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Biomedical subjects

S Roth

Publications and source records attributed to S Roth.

At least 217 records · Page 12Linked to original sources

Post-ischemic hyperemia in the cat retina: the effects of adenosine receptor blockade.

Significant hyperemia results after 1 h of retinal ischemia in cats. Adenosine receptor blockade significantly attenuates the increase in retinal blood flow that occurs in response to systemic hypoxia. Synthesizing these findings, I hypothesized that adenosine receptor antagonism would attenuate the increase in blood flow that follows retinal ischemia. In these experiments, blood flows were measured with radioactively labeled microspheres in the retina and choroid of adult cats anesthetized with chloralose and acepromazine. Ischemia was induced for 1 h in both eyes by elevation of intraocular pressure above systolic arterial pressure. Blood flows were measured before ischemia and 5 min after the return of normal intraocular pressure. In each animal, after baseline blood flows were determined and approximately 10-15 min before ischemia was induced, one eye received 0.1 ml of intravitreal 0.01M 8-sulfophenyltheophylline, a polar adenosine receptor antagonist, while the opposite eye, the control, received an equal volume of intravitreal saline. Arterial blood gas tensions, systemic arterial pressure, hematocrit, and anesthetic level were kept constant during the experimental protocol. Compared with control eyes, hyperemia was significantly attenuated in the retinal circulation after ischemia in eyes injected with 8-sulfophenyltheophylline. Increase in post-ischemic choroidal blood flow was not affected. Although adenosine is involved in the vasodilatation that occurs when blood flow is restored after retinal ischemia, adenosine receptor blockade did not completely abolish hyperemia, implying that blockade was incomplete or other vasoactive substances also affect post ischemic hyperemia in the retina.

Adenosine↗

DNA-damage detection in man after radiation exposure--the comet assay--its possible application for human biomonitoring.

The exposure of human beings to ionizing radiation is still of great concern to occupational and environmental medicine. The goal of this workshop is to identify a panel of biological markers that could be used in humans after exposure to ionizing radiation. The comet assay or single cell gel (SCG) assay is a new method that allows efficient determination of single-strand breaks (SSB) and double-strand breaks (DSB), as well as alkali-labile sites in the DNA of single cells. In order to demonstrate the practicability of the comet assay for the detection of DNA damage caused by low doses of ionizing radiation, we exposed human peripheral blood cells to radiation in vitro. The extent of DNA damage in blood cells irradiated with x-rays (0.05-1 Gy) was significantly increased above the control values even at 0.05 Gy and shows a clear dose-relationship. To investigate the repair kinetics for x-ray-induced DNA damage following acute and chronic (fractionated) irradiation, we exposed peripheral blood to 1 Gy and examined the tail moment at different time intervals. The effect of one acute dose is repaired within two h, whereas the effect of fractionated irradiation gives a totally different result. The tail moment of the initial damage increased indicating an accumulation of the damage, and the repair activity clearly decreased. Until now, there was no data available concerning DNA damage in vivo. For this reason, we explored patients subjected to radioiodine therapy as well as a Chernobyl liquidator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Risk of bowel dysfunction with diarrhea after continent urinary diversion with ileal and ileocecal segments.

PURPOSE: In a retrospective study we evaluated the risk of diarrhea after continent urinary diversion using ileal and ileocecal segments. MATERIALS AND METHODS: We interviewed 100 patients of whom 65 underwent ileal and 35 underwent ileocecal resection. RESULTS: Of the 65 patients who underwent ileal resection 7 (11%) and of the 35 who underwent ileocecal resection 8 (23%) reported chronic diarrhea of greater than 6 months in duration, which subsided spontaneously in 2 patients in each group. In each group 3 patients responded well to cholestyramine treatment and 3 responded to loperamid or psyllium. Two patients with ileocecal resection failed to respond to drug therapy. CONCLUSIONS: The risk of diarrhea after ileocecal resection seems to be twice as high as after ileal resection. Most patients responded to symptomatic drug therapy. Alternative surgical therapies should be considered when risk factors are present.

Cecum↗

Effect of nitric oxide synthase inhibition on blood flow after retinal ischemia in cats.

PURPOSE: To determine the effect of nitric oxide synthase inhibition on blood flow in the cat retina and on changes in the electroretinogram after 1 hour of ocular ischemia. METHODS: After the induction of general anesthesia, one eye in each of 18 cats was subjected to 60 minutes of ischemia by raising intraocular pressure above systolic arterial pressure. One group (n = 9) was administered 30 mg/kg L-NG-nitro-arginine-methylester (L-NAME) intravenously 60 minutes before ischemia. The other group (n = 9) was administered an equivalent volume of saline intravenously. Five minutes after the end of ischemia, blood flow in the retina, choroid, and iris-ciliary body was measured using injections of radioactively labeled microspheres. Electroretinographic studies were carried out before, during, and 1, 2, 3, and 4 hours after ischemia ended. Arterial blood gas tension, systemic arterial pressure, hematocrit, and anesthetic levels were controlled in each experiment. RESULTS: Basal blood flow in iris-ciliary body was decreased by L-NAME, whereas retinal and choroidal blood flow was unchanged. Postischemic hyperemia was unaltered in the choroid and reduced in the retina. There was enhancement of postischemic hyperemia in the iris-ciliary body, but this effect may have resulted from a decrease in basal flow in the L-NAME group. Electroretinographic a- and b-wave recoveries were not altered by L-NAME; L-NAME infusion significantly decreased b-wave amplitude. CONCLUSIONS: Nitric oxide appears to be a significant factor in the regulation of uveal circulation and may contribute to the regulation of retinal, but not choroidal, blood flow after ischemia. The authors could not detect a difference in outcome by electroretinography with or without nitric oxide synthase inhibition.

Animals↗

[Combined endocrine autoimmune syndrome--incidence, forms of manifestation and clinical significance].

UNLABELLED: In a retrospective case finding study we collected data from patients with polyglandular autoimmune syndrome type II (PGAS Type II) who had been treated in our endocrine outpatient clinic between 1975 and 1989. 31 adult patients (25 females and 6 males) fulfilled the criteria for PGAS Type II (association of autoimmune endocrine disease with at least one other--usually endocrine--autoimmune disease or autoantibodies against another organ). Among these patients, 18 had hypothyroidism due to autoimmune thyroiditis, 8 were hyperthyroid (Graves' disease), and 4 had silent autoimmune thyroiditis (without thyroid dysfunction). Insulin dependent (type I) diabetes mellitus (IDDM) was seen in 11, Addison's disease in 7, primary hypogonadism in 5, vitiligo in 6 and pernicious anemia in 5 cases. The presence of antiparietal cell antibodies was demonstrated in 21 of 30 investigated patients. These patients also showed other evidence of autoimmune gastritis, such as increased gastrin (in 10 out of 13), diminished vitamin B12 levels (6 out of 13), atrophic gastritis (9 out of 9), pernicious anemia (6 out of 30) and funicular myelosis (2 out of 30). CONCLUSION: The most common endocrine diseases in our patient group were autoimmune thyroid diseases (97%) followed by IDDM (35%) and Addison's disease (23%). A high percentage (70%) of our subjects had elevated titers of antiparietal cell antibodies. Polyglandular autoimmune syndrome must be suspected in all patients with autoimmune endocrine disease, especially in the presence of relatives suffering from PGAS. Patients at risk should be screened regularly by measuring thyrotropin (ultrasensitive assay), fasting blood glucose levels, and by checking red blood count and antiparietal cell antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Glutathione reverses the inhibition of T cell responses by superoptimal numbers of "nonprofessional" antigen presenting cells.

"Professional" antigen-presenting cells (APC) such as macrophages or dendritic cells display not only antigens to specific T cell receptors but deliver in addition certain "costimulatory signals." Macrophages also release substantial amounts of cysteine and raise thereby the intracellular glutathione (GSH) levels of activated T cells in their vicinity. We therefore studied the hypothesis that stimulation with "nonprofessional" APC that fail to deliver cysteine may induce a type of immunological unresponsiveness that is caused by GSH deficiency and prevented by administration of exogenous GSH. Our experiments showed that cytotoxic T cell (CTL) responses are indeed strongly suppressed in vivo and in vitro by different types of nonprofessional APC and reconstituted by administration of GSH at the time of immunization if these APC are administered at relatively high doses. At lower doses, however, the same cell types may stimulate CTL responses without exogenous GSH, and the responses may be even inhibited in these cases by GSH. CTL responses were not suppressed by high numbers of professional APC, and GSH had no substantial effect on CTL responses after in vivo immunization with professional APC or a cysteine-releasing tumor variant. However, exogenous GSH reconstituted the otherwise weak CTL response in vitro against splenic adherent cells from athymic (nude) mice. Experiments with cloned T cells (D10.G4.1) finally showed that stimulation with graded concentrations of mitogen causes a dose-dependent decrease of intracellular GSH levels. These effects are expected to play a role in "high zone tolerance," in CTL responses against certain types of tumors, and in pathological conditions with a GSH deficiency.

Animals↗

Effect of glutathione depletion and oral N-acetyl-cysteine treatment on CD4+ and CD8+ cells.

HIV-infected individuals and SIV-infected rhesus macaques have, on the average, decreased plasma cysteine and cystine concentrations and decreased intracellular glutathione levels. We show that the cysteine supply and the intracellular glutathione levels have a strong influence on the T cell system. A study of healthy human subjects revealed that persons with intracellular glutathione levels of 20-30 nmol/mg protein had significantly higher numbers of CD4+ T cells than persons with either lower or higher glutathione levels. Persons who moved during a 4-week observation period from the optimal to the suboptimal range (10-20 nmol/mg) experienced, on the average, a 30% decrease in CD4+ T cell numbers. This decrease was prevented by treatment with N-acetyl-cysteine (NAC). NAC caused this relative increase of CD4+ T cell numbers in spite of decreasing glutathione levels and not by increasing the glutathione level. Our studies suggest that the immune system may be exquisitely sensitive not only against a cysteine and glutathione deficiency but also against an excess of cysteine.

Acetylcysteine↗

A quantitative ultrastructural investigation of tyrosine hydroxylase-immunoreactive axons in the hairy skin of the guinea pig.

Besides its thermoregulatory role, the sympathetic innervation of the skin is involved in a modulation of sensory processing and trophic functions that has not been fully characterized. To investigate possible sites at which such sympathosensory interactions might occur, a quantitative ultrastructural study of the sympathetic innervation of the skin was attempted. The hairy skin of the guinea pig was studied because the sympathetic and sensory nerve axons in this species can easily be discriminated by the presence of immunoreactivity to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH). The thermoregulatory role of the sympathetic skin innervation was highlighted by the almost exclusive sympathetic innervation of piloarrector muscles which contained 62% (n = 195) of randomly selected TH-immunoreactive (TH-IR) axon profiles. Of TH-IR pilomotor axons, 53% were filled with vesicles. Vesicle-containing axonal profiles were equally frequent around dermal arterial blood vessels (partly associated with mast cells), hair follicles, and within nerve fibre bundles surrounded by a perineural sheath, in each case accounting for about 3% of all dermal TH-IR axonal profiles. In contrast to piloarrector muscles, at these locations TH-IR (sympathetic) and non-reactive (sensory) axons were found in close association. These findings are in line with the previously reported inhibitory influence of sympathetic stimulation upon hair follicle afferents and perivascular sensory nerve terminals. In addition, they point to a yet underestimated target of sympathetic axon terminals, i.e. preterminal nerve fibre bundles.

Animals↗

Crotonobetaine reductase from Escherichia coli--a new inducible enzyme of anaerobic metabolization of L(-)-carnitine.

Crotonobetaine reductase from Escherichia coli 044 K74 is an inducible enzyme detectable only in cells grown anaerobically in the presence of L(-)-carnitine or crotonobetaine as inducers. Enzyme activity was not detected in cells cultivated in the presence of inducer plus glucose, nitrate, gamma-butyrobetaine or oxygen, respectively. Fumarate caused an additional stimulation of growth and an increased expression of crotonobetaine reductase. The reaction product, gamma-butyrobetaine, was identified by autoradiography. Crotonobetaine reductase is localized in the cytoplasm, and has been characterized with respect to pH (pH 7.8) and temperature optimum (40-45 degrees C). The Km value for crotonobetaine was determined to be 1.1 x 10(-2M). gamma-Butyrobetaine, D(+)-carnitine and choline are inhibitors of crotonobetaine reduction. For gamma-butyrobetaine (Ki = 3 x 10(-5M)) a competitive inhibition type was determined. Various properties suggest that crotonobetaine reductase is different from other reductases of anaerobic respiration.

Anaerobiosis↗

"I felt like a slut": the cultural context and women's response to being raped.

This paper examines how cultural beliefs (cultural constructions) about women influence how women survivors of rape make sense of their traumatic experience. A thematic content analysis of interviews with female survivors of rape was undertaken to provide a systematic description of the phenomenology of the experience. This paper reports on one major finding which highlighted the ways in which cultural beliefs about women, sexuality, and rape become salient to women, and are accessed by them as they struggle to bring meaning to the experience of being raped. The nature of these beliefs and their implications for response and recovery are discussed.

Adolescent↗

Analysis of chromosomal aberrations, sister-chromatid exchanges and micronuclei in peripheral lymphocytes of pharmacists before and after working with cytostatic drugs.

The frequencies of chromosome aberrations, SCEs and micronuclei (cytokinesis-block method) in blood lymphocytes were compared among six nonsmoking female pharmacists before and after 1 year of working with cytostatic drugs. All possible precautions were taken to avoid exposure to cytostatics, including proper protective clothing and a monitored, negative-pressured working environment with vertical laminar flow cabinet. As referents, an age-matched group of six nonsmoking female hospital workers not dealing with cytostatics was simultaneously sampled twice with the same time interval. The pharmacists showed a marginally higher mean frequency of SCEs/cell (6.3; P = 0.049) after the working period than 1 year earlier (5.8). On the other hand, the referents, with no obvious exposure, had a higher mean number of cells with chromatid-type aberrations, gaps excluded, in the second sampling (2.0%; P = 0.048) than in the first one (0.5%). In addition, a slight (P = 0.055) trend towards a higher frequency of micronucleated binucleate cells was observed in the second sampling for both the exposed and control subjects. As such findings suggest technical variation in the cytogenetic parameters, the small difference observed in SCEs for the pharmacists between the two samplings was probably not related to the cytostatics exposure. No statistically significant differences were observed for any of the cytogenetic parameters in comparisons between the pharmacists and the referents. The findings suggest that caution should be exercised in comparing results obtained from two different samplings in prospective cytogenetic studies.

Adult↗

Dorsoventral patterning in Drosophila oogenesis.

Dorsoventral polarity in the egg chamber of Drosophila involves the localization of maternal gurken RNA to the dorsal side of the oocyte. The gurken protein has homology to secreted growth factors and may bind to the torpedo/DER receptor tyrosine kinase present on the adjacent follicle cells. This localized signal from the oocyte to the follicle cells appears to initiate a cascade of events leading to dorsal follicle cell differentiation, and delimiting and orienting the future dorsoventral axis of the embryo.

Animals↗

The Alcock syndrome: temporary penile insensitivity due to compression of the pudendal nerve within the Alcock canal.

Penile insensitivity is a symptom commonly observed after traumatic or iatrogenic nerve lesions, or in association with neurological or vascular diseases. In contrast, we report 2 cases of intermittent genital hypesthesia that occurred in cyclists after long-term bicycle riding. Anatomical studies show that this condition was probably caused by an irritation of the pudendal nerve during its course through the Alcock canal as reported in the literature. No pathological findings were demonstrated on extensive physical examinations, medical history and all medical imagings (sonography of abdomen, prostate and testes, and magnetic resonance imaging of the pelvis and lumbar spine) as well as radiodiagnostics and Doppler sonography, nor was there evidence of other neurological disturbances. The symptoms in the 2 patients spontaneously resolved after 4 and 7 weeks, respectively, without specific medical therapy.

Bicycling↗

Erythrocyte polyamines and prognosis in stage D2 prostatic carcinoma patients.

We studied 43 patients with newly diagnosed, untreated, stage D2 prostatic carcinoma, and correlated the initial performance status, hemoglobin, prostate specific antigen levels, tumor Gleason grade, extent of disease on the bone scan, and erythrocyte spermidine and spermine levels with progression. Three patients died of unrelated causes and were excluded from the study, 16 remained in remission with a mean 28 +/- 11 months of followup and 24 had progression (18, or 75%, of whom died of the cancer) with a mean 12 +/- 9 months of followup (p < 0.05 for followup) after initiation of hormonal therapy. Pretreatment performance status, hemoglobin, and erythrocyte spermidine and spermine levels were correlated with progression, hemoglobin and spermine being the most significant independent variables (p = 0.006 and p = 0.001, respectively). Concerning cause-specific survival, only hemoglobin and spermine erythrocyte levels were significant independent variables (p = 0.02 and p = 0.0025, respectively). If confirmed, polyamine erythrocyte levels obtained by a simple blood sample could discriminate at diagnosis patients with a high risk of rapid hormonal relapse who may benefit from a more aggressive primary management.

Aged↗