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Biomedical subjects

S Weber

Publications and source records attributed to S Weber.

At least 199 records · Page 11Linked to original sources

Continuous dosimetry of the biologically harmful UV-radiation in Antarctica with the biofilm technique.

For the first time, a continuous biological dosimetry experiment for cytotoxic solar UV-radiation has been performed in Antarctica. The biologically harmful UV-radiation on the ground was measured at the German Antarctic Georg von Neumayer Station (70 degrees 37' S, 80 degrees 22' W) from December 1990 to March 1992 using the biofilm technique. The UV-sensitive targets were dried spores of Bacillus subtilis which were immobilized on the film surface. The UV-induced inhibition of biological activity, determined photometrically from the protein synthesized after incubation and staining, was taken as a measure for the absorbed UV-dose. Films were exposed in horizontal position for time intervals ranging from 4 days during summer up to 51 and 41 days before and after the polar night respectively. The use of different cut-off filters allowed the calculation of the biologically effective UVA, UVB and the complete UV-radiation (UVA + B). The data were compared with the global radiation and the ozone column thickness indicating an increase of biologically harmful UVB radiation during austral spring at reduced ozone concentrations yielding a radiation amplification factor (RAF) of 1.4, whereas for the total UV(A + B) range the RAF amounted to 0.3.

Antarctic Regions↗

Inhibition of substance P-induced microvascular leakage by inhaled methoxamine in rat airways.

1. The effect of the inhaled alpha-adrenoceptor agonist, methoxamine (MTX), was studied on experimental airway oedema induced by injection of substance P (SP) in the rat. Sprague-Dawley rats (300-350 g) were anaesthetized with sodium thiopentone, tracheotomized and artificially ventilated. 2. MTX or its vehicle was administered by inhalation. Airway resistance and blood pressure were monitored continuously. Evans Blue dye (EB, 20 mg kg-1) was injected through a jugular catheter 1 min before SP (14.8 nmol kg-1). Airways were dissected out, weighed and placed in formamide for EB extraction and determination by spectrophotometry. 3. EB extravasation induced by SP was significantly reduced in distal intraparenchymal bronchi by inhaled MTX at doses of 50 micrograms kg-1 (58 +/- 9 vs 96 +/- 9 ng EB mg-1 tissue after vehicle, P < 0.001) and 100 micrograms kg-1 (69 +/- 11 vs 137 +/- 26 ng EB mg-1 tissue after vehicle, P < 0.01). Inhaled MTX by itself (100 micrograms kg-1) increased blood pressure: 172 +/- 6 vs 132 +/- 10 mmHg baseline (P < 0.02), but neither induced extravasation nor increased airway resistance. 4. In another set of experiments without SP, MTX was administered intravenously 1 min after EB. At 100 micrograms kg-1, i.v. MTX increased blood pressure to a similar extent as inhaled MTX (180 vs 147 mmHg baseline, P < 0.01), increased airway resistance and caused leakage of plasma proteins in distal intraparenchymal bronchi (79 +/- 7 vs 47 +/- 1 ng EB mg-1 tissue, P < 0.02). 5 Similarly, after sequential i.v. injections of doubling doses of MTX (50-800 microg kg-1), a marked EB extravasation was found in the airways. This was abrogated by pretreatment with prazosin (100 microg kg-1)but not with propranolol (2 mg kg-1).6 These results suggest that microvascular leakage and airway oedema induced by i.v. MTX may be linked to an increase in pressure in the pulmonary circulation, resulting from vasoconstriction of the pulmonary vasculature and acute cardiac dysfunction due to systemic hypertension.7 Our results with inhaled MTX show that direct deposition of MTX at the bronchial vasculature induces a reduction in SP-induced microvascular leakage in rat airways and that inhaled MTX does not share the untoward effect of i.v. MTX inducing airway oedema.

Administration, Inhalation↗

Monoclonal antibodies to leucosialin (CD43) induce homotypic aggregation of the human mast cell line HMC-1: characterization of leucosialin on HMC-1 cells.

CD43 (leucosialin, sialophorin) is the major sialoprotein of nearly all circulating leucocytes and has important biological activities in cellular differentiation and activation. Recently, the expression of CD43 has also been demonstrated on mast cells and basophils by flow cytometry. In order to further characterize mast cell/basophil leucosialin we have investigated CD43 on the human mast cell line HMC-1, the human basophilic precursor cell line KU-812, and the human promonocytic cell line U-937. The apparent molecular weights (MW) were 123,000 (HMC-1 and KU-812) and 144,000 (U-937) by Western blot analysis. Expression of CD43 on HMC-1 was down-regulated after stimulation with phorbol myristate acetate (PMA). Three monoclonal antibodies (mAb) specific for human CD43 induced homotypic mast cell line (HMC-1) aggregation in a semi-quantitative assay, a phenomenon that has not been described before with mast cells. Monoclonal antibodies specific for seven other surface antigens and an irrelevant mAb of the same isotype had no effect. The level of aggregation was dependent on anti-CD43 mAb concentration, time and temperature. Anti-leucosialin-induced aggregation of HMC-1 cells was completely inhibited by mAb against CD11a (LFA-1) and CD18 (beta 2-chain). Monoclonal antibody to CD54 (ICAM-1) partially inhibited anti-CD43-induced homotypic aggregation, while anti-CD11b (CR3), anti-CD11c (p 150, 95) and a control mAb had no inhibitory effect. We conclude that mast cell line CD43 antigen expression is differentially regulated during cell activation, and speculate that anti-CD43-induced homotypic aggregation of HMC-1 cells is closely associated with modulation of beta 2-integrins.

Antibodies, Monoclonal↗

[Cold labile serum and plasma proteins: clinical and diagnostic significance of cryoglobulins, cryofibrinogen and cold agglutinins].

Cold labile serum and plasma proteins can cause a variety of clinicopathological symptoms. Due to altered physicochemical properties, cryoglobulins and cryofibrinogens may cause increased serum viscosity, cold dependent protein precipitation or, in rare cases, serum gelification. Cold agglutinins, on the other hand, cause temperature dependent agglutination of erythrocytes and eventually hemolysis. All pathological cold dependent serum and plasma phenomena are associated with either neoplasma, autoimmune disorders, various infections or are considered as "essential". While the diagnosis of these conditions remained largely unchanged during the last 10 years, new aspects regarding etiology, pathogenesis, and therapy have arisen.

Agglutinins↗

[Introduction of an infection registration program for surgical wound infection based on the WHOCARE software of WHO].

Surveillance of surgical wound-infection (SWI) is an important instrument in the internal and external quality control in surgery. In the past it has been shown that statistics on surgical wound infection are helpful for reduction of wound infection rates. With the engagement of nurses for clinical hygiene at our hospital we had the possibility to evaluate programs for surveillance of nosocomial infection. In a pilot study we began with the surveillance of SWI. The set of data registered was defined by WHOCARE, the software-package used in the study which is distributed by the WHO Europe. Criteria of the NNIS-Study for SWI were applied. Between March and December 1992 approximately 1.300 surgical interventions had been registered. Although the dataset in WHOCARE is limited with regard to an easy surveillance, it was possible to find out infection rates dependent on all major parameters. Additionally reports on individual infection rates and tables containing information of infected cases were sent to every surgeon. By analyzing some of the problems detected during the study, we developed an improved protocol for routine surveillance of SWI. In the future it will save time and will allow the best quality of collected data in narrow collaboration between the departments of microbiology, clinical hygiene and surgery. This protocol should be transferable to other hospitals and represents an anticipated precautious measure with regard to legal regulations on quality control in medicine.

Cross Infection↗

Determination of bleeding risk in thrombocytopenic patients with platelet transfusion therapy.

In a clinical study (50 thrombocytopenic patients) we determined the bleeding risk and the platelet transfusion efficacy by a special modification of the in vitro bleeding test (IVBT, Thrombostat 4000). Additionally, cell count, hematocrit, body temperature, platelet volume and distribution width, Simplate bleeding time and a bleeding score were investigated. The use of the modified IVBT proved to be promising to find a clearer indication of platelet transfusion and to estimate its efficacy.

Bleeding Time↗

The formation of the haemostatic plug--a special case of platelet aggregation. An experiment and a survey of the literature.

The formation of the haemostatic plug is an extremely fast process. This excludes, at least in its first phase, the involvement of soluble activating agents released from or produced by the platelets. An experiment with ADP-activated, formaldehyde-fixed platelets shows that platelets with activated fibrinogen receptors will bind inactive platelets in the presence of fibrinogen and Ca(2+)-ions. A survey of the literature shows that platelet activation is accompanied by the clustering of the fibrinogen receptors. The surface of an activated platelet, which makes part of the growing haemostatic plug therefore is covered with patches of tightly packed fibrinogen. This allows the multisite combination with the statistically distributed low affinity receptors of the newly arriving platelets. Tightly packed fibrinogen, as present on clusters of the activated GP IIb/IIIa receptors as well as when absorbed to artificial surfaces acts as an activator of platelets. Thus, the propagation of the activation process is possible without a requirement for other, external activators. Such agents, which are released from platelets and, finally, thrombin formation, are nonetheless of vital importance, not for the formation but for the consolidation of the haemostatic plug.

Adenosine Diphosphate↗

The occurrence of sleep-disordered breathing among middle-aged adults.

BACKGROUND: Limited data have suggested that sleep-disordered breathing, a condition of repeated episodes of apnea and hypopnea during sleep, is prevalent among adults. Data from the Wisconsin Sleep Cohort Study, a longitudinal study of the natural history of cardiopulmonary disorders of sleep, were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health. METHODS: A random sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep (the apnea-hypopnea score). We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score (> or = 5, > or = 10, and > or = 15); we used logistic regression to investigate risk factors. RESULTS: The estimated prevalence of sleep-disordered breathing, defined as an apnea-hypopnea score of 5 or higher, was 9 percent for women and 24 percent for men. We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome (an apnea-hypopnea score of 5 or higher and daytime hypersomnolence). Male sex and obesity were strongly associated with the presence of sleep-disordered breathing. Habitual snorers, both men and women, tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher. CONCLUSIONS: The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women. Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence.

Adult↗

Organic dust exposures from compost handling: case presentation and respiratory exposure assessment.

Inhalation of dust from contaminated organic materials may result in acute respiratory tract illness. Possible mechanisms include toxic and cellular reactions to microbial and other organic products or immunologic responses after prior sensitization to an antigen. A case is presented of a 52 year old male who developed fever, myalgia, and marked dyspnea 12 hr after shoveling composted wood chips and leaves. Inspiratory crackles, hypoxemia, and bilateral patchy pulmonary infiltrates were seen. Precipitating antibody tests for the usual antigens were inconclusive. He improved over 3 days. In order to assess the environmental conditions the patient had experienced, we returned to the site to reproduce and measure respiratory exposures during hand loading of the compost. Visible clouds of fine particulate were easily generated during handling activities. Microscopic examination of these dusts indicated a predominance of spores. Endotoxin concentrations from inspirable and respirable dust samples ranged from 636 to 16,300 endotoxin units/m3. Levels of contaminants found were consistent with those associated with respiratory illness in other agricultural settings. Two respiratory disorders, hypersensitivity pneumonitis (HP) and organic dust toxic syndrome (ODTS), may occur after exposure to organic dusts containing fungal spores and endotoxins. Despite extensive clinical and environmental investigations, we were unable to differentiate these two disorders, and suggest they may represent parts of a spectrum of responses to complex organic dusts, rather than completely distinct clinical entities.

Agriculture↗

Constitutive expression of high levels of soluble mouse CD4 in transgenic mice does not interfere with their immune function.

Interactions of CD4 with the major histocompatibility complex (MHC) class II molecules are crucial during thymic development and subsequently for the function of single-positive CD4+CD8- T lymphocytes. Here, we have investigated the potential effects of soluble CD4 (sCD4) on the immune system. We generated two different transgenic mouse lines, which constitutively expressed either approximately 100 micrograms/ml of monovalent or approximately 20 micrograms/ml of decavalent mouse sCD4 molecules in their sera. Analysis of these mice revealed no differences compared to control littermates, e.g. the single-positive CD4+ cells developed normally and these cells responded to allogeneic and anti-CD3 antibody stimuli like the cells from control mice. Furthermore, the T helper cell function for antibody responses in vivo were not affected. Our data provide evidence that, in mouse, the CD4-MHC class II-interaction has very low affinity. Since sCD4 is considered to be a therapeutical agent for human immunodeficiency virus infection, these findings are not only of basic, but also of clinical interest.

Animals↗

A long-term longitudinal isotypic study of anti-topoisomerase I autoantibodies.

In this first retrospective longitudinal study of anti-topoisomerase I autoantibodies (anti-topo I) we examined the isotypic expression in 13 patients with scleroderma by enzyme-linked immunosorbent assay. Titers were stable for up to 16 years. However, one patient lost the antibody, while another developed high levels of IgM with myositis and another, high levels of IgA with cardiac disease. For the first time the de novo development of anti-topo I was observed.

Adult↗

An orthostatic uterovascular syndrome--a prospective, longitudinal study.

OBJECTIVE: The interaction between maternal hemodynamics and uterine activity in the upright position was investigated longitudinally (358 measurements) in 40 healthy pregnant women from 20 gestational weeks to term. STUDY DESIGN: Maternal-fetal hemodynamic parameters and uterine contractions were measured noninvasively in four different postures. RESULTS: Hemodynamic disturbances caused by compression of pelvic vessels by the gravid uterus in the upright position were detected in two of 40 (5%) women as early as 24 weeks' gestation; a peak was reached at 38 weeks (71%). With a decrease in the stroke volume (22%, p < 0.001) neither the cardiac output (-11%, p < 0.05) nor the systolic blood pressure (-1.4%, p < 0.05) remained constant, although there was a compensatory heart rate increase. CONCLUSION: A significantly increased number of spontaneous uterine contractions in the upright position is associated with release of the blocked venous return flow and restoration of normal maternal hemodynamics.

Adult↗

Mouse CD4 binds MHC class II with extremely low affinity.

Interaction of CD4 with MHC class II molecules plays a crucial role during thymic development and activation of single-positive CD4 T lymphocytes. The quantitation of this interaction is, therefore, important for understanding the role of CD4 during these events. To this end, we have developed a rosette assay, which enabled us to study this molecular interaction. By coupling soluble mouse CD4 onto beads, we could show specific binding of CD4 to MHC class II molecules on A20 B lymphoma cells. These binding studies revealed an extremely low affinity (Ka < or = 10(4) M-1) between CD4 and MHC class II molecules in mouse.

Animals↗

[Value and indication of the use of 2 internal mammary arteries in repeated coronary surgery].

Forty-nine patients who had coronary artery reoperations were divided into two groups: the 29 patients of the first group were operated conventionally with use of one internal mammary artery or a saphenous vein; the 20 patients of the second group were reoperated using both internal mammary arteries. Three patients (6%) died prematurely: two in the first and one in the second group. The rates of peri-operative infarction were 7% and 15% respectively. The average postoperative bleeding was 472 +/- 385 ml in the first group and 700 +/- 628 ml in the second group (NS). All patients are pauci-symptomatic and have a negative exercise stress test. The mortality and morbidity of coronary reoperation does not seem to be greater with double internal mammary artery bypass grafting. However, this technique should be reserved for patients who can derive long-term benefit from reoperation with arterial grafts, that is to say in patients in good clinical condition, less than 65 years of age with good left ventricular function. In these patients, double internal mammary artery bypass grafting may avoid a third operation for myocardial revascularisation.

Aged↗

Antinociceptive profile of biphalin, a dimeric enkephalin analog.

The dimeric enkephalin biphalin (Try-D-Ala-Gly-Phe-NH)2 was evaluated in mice using antinociceptive, gastrointestinal and physical dependence paradigms and compared with that of morphine (reference mu agonist) and etorphine (ultrapotent opioid agonist). Intracerebroventricular biphalin was 6.7- and 257-fold more potent than etorphine or morphine in eliciting antinociception. When administered i.t., biphalin produced only a 60% maximal antinociceptive effect in the tail-flick test even when given at doses up to 3 orders of magnitude higher than those effective i.c.v.; morphine was equipotent in this assay when given i.c.v. or i.t. Both morphine and biphalin were equipotent after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration, only a small fraction of [125I]biphalin was shown to penetrate to the brain (0.051 +/- 0.011%, at 20 min). After i.c.v. administration, biphalin antinociception was antagonized by receptor selective doses of beta-funaltrexamine (mu antagonist), naloxonazine (mu 1 antagonist), ICI 174,864 (delta antagonist) and [D-Ala2,Cys4]deltorphin (delta 2 antagonist), but not by [D-Ala2,Leu5,Cys6]enkephalin (delta 1 antagonist) or nor-binaltorphimine (kappa antagonist), whereas etorphine antinociception was significantly antagonized only by beta-funaltrexamine and naloxonazine. Intracerebroventricular biphalin inhibited gastrointestinal propulsion at doses 8-fold higher than those producing i.c.v. antinociception; i.c.v. morphine showed a similar antinociceptive and gastrointestinal propulsion A50. Intraperitoneal biphalin, but not i.p. morphine, showed little, if any, physical dependence, but both biphalin and morphine produced significant physical dependence when equiantinociceptive doses were infused i.c.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗