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Biomedical subjects

R Wolf

Publications and source records attributed to R Wolf.

At least 109 records · Page 6Linked to original sources

Genetic depletion of histamine from the nervous system of Drosophila eliminates specific visual and mechanosensory behavior.

The role of histamine as a fast neurotransmitter of imaginal insect photoreceptors is firmly established. In adult Drosophila, histamine is also found in mechanosensory receptors of cuticular hair sensilla and in a small number of nonreceptor neurons in head and body ganglia. Here we investigate the function of histamine by immunohistochemical and behavioral analysis of mutants deficient in the hdc gene that codes for histidine decarboxylase. The allele hdcJK910 appears to be a null mutation, as histamine immunoreactivity is almost entirely eliminated. Homozygous flies are blind in various behavioral paradigms. Mutant larvae, on the other hand, show normal photokinetic responses. Thus, adult Drosophila photoreceptors most likely utilize only a single substance, histamine, as a neurotransmitter, whereas larval photoreceptors apparently employ a different transmitter. With the alleles hdcP211, hdcP217, and hdcP218, variable amounts of histamine are found in photoreceptors and mechanoreceptors, but no histamine could be detected in any of the nonreceptor neurons. These mutants show various degrees of visual and mechanosensory impairment, as determined by quantitative behavioral assays. We conclude that histamine is required for normal function of cuticular hair sensilla and for efficient grooming of the body surface. Thus, in Drosophila, histamine represents a major functional neurotransmitter for mechanosensory receptors.

Animals↗

Combined treatment with lithium and nimodipine in a bipolar I manic syndrome.

1. The benefit of a combined treatment with the calcium antagonist nimodipine and lithium in a bipolar I disorder (currently manic, DSM IV 296.44, ICD 10 F 31.1) was explored and documented in a longitudinal single case study. 2. Nimodipine (270 mg/d) was added to lithium (900 mg/d), substituting for previously administered neuroleptics, in an up to then unsatisfactorily treated manic patient. 3. A clear-cut improvement in the patient's condition was achieved within a fortnight, and lasted over the continuation period of this drug regimen. This combined treatment was discontinued after eight weeks and lithium alone was then administered. Within three months another manic episode appeared. 4. Side-effects and changes of lithium blood levels were not observed during the combined treatment with nimodipine and lithium. 5. Further research on the benefits of adding a calcium antagonist, instead of neuroleptics, to lithium therapy for bipolar manic disorder patients who do not respond sufficiently to lithium is recommended. In addition, the benefits of a long term prophylaxis of nimodipine alone or in combination with lithium should be evaluated in those bipolar patients who still show a high relapse frequency on lithium alone.

Adult↗

Leukocyte adhesion and hepatic microvascular responses to intestinal ischemia/reperfusion in rats.

BACKGROUND & AIMS: Although it has been reported that gut ischemia/reperfusion (I/R) elicits neutrophil-dependent liver dysfunction, little is known about the kinetics of leukocyte accumulation in the hepatic microcirculation after gut I/R. The aim of this study was to determine the temporal relationship between leukocyte sequestration and oxidative stress in rat liver after occlusion (30 minutes) and reperfusion (60 minutes) of the superior mesenteric artery and assess the effects of neutrophil depletion or immunoneutralization of either intercellular adhesion molecule 1 (ICAM-1) or the leukocyte adhesion glycoprotein CD11/CD18 on the hepatic microvascular responses to gut I/R. METHODS: Leukocyte accumulation, number of nonperfused sinusoids, and autofluorescence of reduced nicotinamide adenine dinucleotide (NADH) were monitored using intravital videomicroscopy both before and after gut I/R. RESULTS: The number of adherent leukocytes in both midzonal and pericentral regions after gut I/R was elevated. Autofluorescence of NADH increased after reperfusion (indicating hypoxia), particularly in the pericentral region. Neutrophil depletion or antibodies to either ICAM-1 or CD11/CD18 blunted the gut I/R-induced increases in NADH autofluorescence in the pericentral region, leukocyte adherence, and nonperfused sinusoids. CONCLUSIONS: Leukocytes accumulate in the liver after gut I/R via interaction of CD11/CD18 and ICAM-1. The leukocytes appear to mediate an oxidative stress, occurring in proximity to nonperfused sinusoids, that may contribute to liver injury.

Animals↗

Supplemental tests in the evaluation of occupational hand dermatitis in soldiers.

BACKGROUND: Hand dermatitis in soldiers is a considerable problem. The purpose of the study was to evaluate appropriate screening tests to improve the diagnosis of hand dermatitis in soldiers. MATERIALS AND METHODS: A group of 111 soldiers with occupational dermatitis from contact with fuels and oils underwent "tailored patch tests" with allergens relevant to their field of work and their environment. The control group consisted of 24 soldiers with various jobs similar to those of civilian life, who had not been exposed to oils and fuels. Seventy-three civilian patients, attending the clinic for patch testing, were also included. Twenty soldiers, who had a history of intensive contact with oil and fuels, but no contact dermatitis, and who were admitted because of various skin diseases (fungal infections, acne, etc.) also underwent the supplemental testing and served as an additional control group. RESULTS: Of the soldiers, 31 (29%) showed one or more positive skin tests of the oil series and 30 patients of this group one or more positive reactions to the standard patch tests trays. No patient of the control groups had a positive test to the oil series. CONCLUSIONS: Our results show the value of the supplementary tests as a first-step screening test for detection of oil allergy in soldiers and automobile-mechanics or in workers handling other gasoline- or diesel-powered engineering equipment. The test method appears to be practical, easy to perform, reliable and giving clear and accurate results, with a negligible rate of false positive reactions.

Allergens↗

Measurement of the skin-cleaning effects of soaps.

BACKGROUND: In the past 30 years, many tests for assessing the irritancy of soaps have been introduced, but only very few tests for evaluating their cleaning properties. The urgent need for such a method is obvious. METHODS: The method is based on the principles developed by Schrader, with substantial modifications. As in Schrader's method, we used a fat-based ointment to emulate "dirt." The washing process was performed by placing the examined hand in a rotating soap solution for 5 minutes. The capacity of various soaps to remove the "dirt" was assessed by comparing the sebumeter readings before and after the washing process. The difference between the two readings provided a quantitative estimate of the percentage of "dirt" (ointment) that was washed off during the process. RESULTS: The cleansing capacity of two soaps was compared to that of water. Soap 1 showed a cleansing of 81.7 +/- 2.4%, soap 2 a cleansing of 75.3 +/- 2.9%, as compared to water of 29.7 +/- 3.4%. The curve representing the distribution of the data was very smooth, bell-shaped and symmetric about its mean. The difference between the cleaning activity of the two soaps tested was statistically significant (P < 0.0001). CONCLUSIONS: We have presented a new method for testing the cleansing capacity of soaps. We believe, that our method gives better results than that of Schrader; in particular, it enables us to discriminate more effectively among the various soaps. Our results indicate that the method is reliable and reproducible. It is also practical, easy to perform, does not require an expensive and complex washing machine, and can be carried out in every laboratory.

Fats↗

Mortality of patients who dropped out from regular lithium prophylaxis: a collaborative study by the International Group for the Study of Lithium-treated patients (IGSLI).

Excess mortality has repeatedly been found in patients with recurrent affective disorders. In previous studies our group has shown that during long-term lithium treatment the mortality of such patients is not significantly higher than that of the general population. In the present study, we extended our investigation to 273 patients from the earlier IGSLI cohort who subsequently dropped out from regular lithium prophylaxis. The standardized mortality ratio (SMR) for the whole group was 2.5, significantly higher (P < 0.01) than 1.0, which is the SMR of the general population. Furthermore, the SMR of the patients from each of the participating countries, namely Denmark, Germany and Austria, was significantly higher than 1.0. These findings strengthen the evidence accumulated in previous investigations that regular long-term lithium treatment does in fact markedly reduce the excess mortality of patients with recurrent affective disorders.

Antimanic Agents↗

Apolipoprotein A-IV synthesis in proximal jejunum is stimulated by ileal lipid infusion.

Biosynthesis of apolipoprotein A-IV (apo A-IV) is stimulated by dietary lipid, but the precise mechanisms involved are not clearly understood. Using an intestinally infused rat model, we compared the effect of delivery of lipid into different intestinal sites on mucosal synthesis of apo A-IV in the jejunum and ileum to determine 1) the effect of lipid delivered to one region of the intestine on apo A-IV synthesis in another region of the gut, and 2) whether any such effect is dependent on the presence of lipid in the latter region. Duodenal infusion of triolein emulsion (40 mumol/h) increased jejunal apo A-IV synthesis and mRNA levels by two- to threefold but had no effect on ileal apo A-IV synthesis or mRNA abundance. Ileal infusion of lipid emulsion containing monoolein (20 mumol/h) + oleic acid (40 mumol/h) stimulated apo A-IV synthesis in both ileum and proximal jejunum. Retrograde (orad) transport of ileally infused lipid was not a likely explanation for the ileal effect on jejunal apo A-IV synthesis, because there was negligible luminal and mucosal recovery of [14C]oleic acid in the jejunum after ileal infusion. Total bile diversion did not block the effect of ileal lipid on jejunal apo A-IV synthesis. Ileal, but not duodenal, lipid infusion stimulated apo A-IV synthesis in a jejunal Thiry-Vella fistula, and perfusion of an ileal Thiry-Vella fistula marginally stimulated proximal jejunal apo A-IV synthesis. Thus administration of lipid to the distal gut produces an increase in mucosal synthesis of apo A-IV in both proximal and distal gut. This effect appears to be independent of direct jejunal presence of lipid, suggesting that lipid in the distal intestine may elicit a signal capable of stimulating jejunal synthesis of apo A-IV.

Animals↗

Microvascular dysfunction induced by nonsteroidal anti-inflammatory drugs: role of leukocytes.

The objectives of this study were to determine whether 1) the leukocyte-endothelial cell adhesion observed in venules exposed to nonsteroidal anti-inflammatory drugs (NSAIDs) is accompanied by enhanced albumin extravasation, and 2) leukocytes mediate this endothelial cell barrier dysfunction. Intravital video microscopy was used to monitor leukocyte-endothelial cell adhesion and the leakage of fluorescein isothiocyanate-labeled albumin in rat mesenteric venules exposed to either indomethacin or aspirin. Both NSAIDs induced the recruitment of adherent and emigrated leukocytes with temporally related increases in albumin leakage. Agents that effectively decreased or prevented the NSAID-induced leukocyte adherence/emigration (leukotriene B4 receptor antagonist or adhesion molecule-specific monoclonal antibodies) also blocked the corresponding albumin leakage response. These findings indicate that adherent and/or emigrating leukocytes mediate the early endothelial cell barrier dysfunction elicited by NSAIDs.

Animals↗

The lanolin paradox.

Several puzzling aspects of the use of lanolin are discussed as "lanolin paradoxes', in analogy with the 'paraben paradoxes'. Lanolin in topical therapeutic agents sensitizes a high proportion of patients, whereas the same lanolin is 'safe' in cosmetics so widely used by millions of individuals. Patients with an allergic contact dermatitis to lanolin in a medication applied to a stasis ulcer can nevertheless use lanolin-containing cosmetics and not experience a reaction. Lanolin-sensitive individuals often show false-negative patch test reactions to unaltered lanolin. Patch testing with 30% wool wax alcohols used in the standard patch test tray cannot be considered a reliable method for detecting and confirming lanolin allergies. There are too many false-positive and false-negative results using the standard patch test tray.

Cosmetics↗

Oxidative stress during platelet-activating factor-induced microvascular dysfunction.

OBJECTIVE: To assess the potential contribution of hydrogen peroxide (H2O2) to the leukocyte-endothelial cell adhesion and increased microvascular permeability (to fluorescein isothiocyanate [FITC]-albumin) observed in rat mesenteric venules exposed to platelet-activating factor (PAF). METHODS: The production of oxidants derived from H2O2 in mesenteric tissue was monitored using the H2O2-sensitive fluorochrome, dihydrorhodamine 123 (DHR). PAF elicited a rapid increase in both the albumin extravasation and oxidation of DHR, which was followed by an increased adherence and emigration of leukocytes in postcapillary venules. RESULTS: The PAF-induced oxidation of DHR, leukocyte-endothelial cells interactions, and albumin leakage were attenuated by treatment with either catalase or dimethylthiourea. Treatment with monoclonal antibody directed against either CD11b/CD18 on leukocytes or ICAM-1 on endothelial cells attenuated the PAF-induced oxidative stress, albumin leakage, and leukocyte-endothelial cell adhesion. CONCLUSIONS: These findings indicate that most of the oxidants generated in mesenteric tissue exposed to PAF results from the accumulation of activated leukocytes.

Animals↗

Inhibition of the acute-phase response in vivo by anti-gp130 monoclonal antibodies.

The acute-phase response is believed to be an important systemic defence reaction to inflammation during infection, trauma, injury or neoplasia. Although the interleukin-6 (IL-6) family of cytokines appear to be the major regulators of the acute-phase reaction, the exact biological significance of this process remains unknown. In this study, a panel of monoclonal antibodies (Mabs) was raised against the extracellular domain of human gp130 (the common signal transducing chain of the IL-6 cytokine family) in order to inhibit the biological activity of IL-6-like cytokines in vivo. Mabs designated 4B11 and 2H4 were most effective in the inhibition of the in vitro acute-phase response on hepatoma cells and prevented the IL-6-induced growth inhibition of A375 cells. Administration of the antibodies to dogs at a dosage of 8 mg/kg/d showed that 2H4 was a potent inhibitor of the IL-6-induced (40 micrograms/kg/d) acute-phase response, abrogating IL-6-mediated increments in fibrinogen, C-reactive protein and the platelet count. This antibody, the first described to abrogate the acute-phase response in vivo, may not only permit development of a new anti-inflammatory strategy, but provides an excellent tool for defining the function of acute-phase proteins in inflammation and infection.

Acute-Phase Reaction↗

Co-expression of the natriuretic peptides (ANP, BNP, CNP) and their receptors in normal and acutely involuted rat thymus.

The natriuretic peptides (NP) ANP, BNP and CNP constitute circulating hormones as well as neuropeptides. The present investigation reveals that these peptides are also constituents of the immune system. BNP and CNP, in addition to ANP as previously communicated, are synthesized in the rat thymus. The NP seem to be produced by different types of thymic cells. Moreover, expression of NP is differentially affected by acute involution of the organ caused by dexamethasone (DEX). The concentration of BNP and CNP mRNA was not changed in gradually involuted thymi (i.e. at day 2, 3 and 4 after DEX administration). ANP mRNA was increased in parallel with the degree of involution (2-, 5- and 40-fold, respectively). The concentration of immunoreactive CNP (CNP-IR) was not affected by acute involution of the thymus (4th day after DEX); BNP-IR, however, was increased 2-fold and for comparison, ANP-IR as previously shown, was found 10-fold elevated. Our studies also revealed the presence of the specific mRNAs coding for the A-, B-, and C-type NP receptor in the thymus. The thymic NP system may be involved in the communication between the immune and neuroendocrine system.

Animals↗

Impact of clinicopathologic parameters on patient survival in carcinoma of the cervical esophagus.

BACKGROUND: The survival of patients with carcinoma of the cervical esophagus remains poor in spite of multimodality treatment and technical improvements in surgical resection and reconstruction. This study was undertaken to update our experience with cervical esophageal carcinoma and to identify factors that had an impact on patient survival and quality of life. PATIENTS AND METHODS: Clinical data encompassing 132 variables were collected on 67 patients with cervical esophageal carcinoma from 1980 to 1993. Statistical analysis was performed: independent Student's t-tests, Cox regression, Kaplan-Meier curves, and log rank analyses were used in the statistical evaluation. The mean age of the patients was 63 years (range 31 to 88). Dysphagia was the primary symptom in 86% of patients; 80% had received no prior treatment. The most common abnormal finding (21%) on physical examination was a neck mass. RESULTS: Curative resection was performed in 22 patients, 7 had palliative procedures, and 7 were found to be inoperable at exploration and received palliative treatment. Radiation with or without chemotherapy was definitive treatment for 10 patients, whereas 4 patients were treated with chemotherapy alone for cure, and 17 patients received palliative treatment. The mean survival following diagnosis was 17 months (range 1 to 96). Cumulative 5-year survival was 12%. CONCLUSIONS: Persistent disease, chemotherapy prior to presentation, and chemotherapy for cure remained as statistically significant parameters associated with decreased survival by multivariate analysis. There was a trend toward improved survival in patients treated with surgical resection.

Adult↗