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Biomedical subjects

R Moser

Publications and source records attributed to R Moser.

At least 19 recordsLinked to original sources
PubMed1995

Migration of skin-homing T cells across cytokine-activated human endothelial cell layers involves interaction of the cutaneous lymphocyte-associated antigen (CLA), the very late antigen-4 (VLA-4), and the lymphocyte function-associated antigen-1 (LFA-1).

The cutaneous lymphocyte-associated Ag (CLA) is expressed by a subset of circulating memory/effector T cells and by the vast majority of skin-infiltrating T cells. CLA is thought to target skin-associated T cells to inflammatory skin sites by interacting with endothelial cell ligand E-selectin (CD62E). We have examined adhesion molecules involved in the migration of human CLA+ and CLA- memory/effector T lymphocytes through IL-1- and TNF-alpha-activated and nonactivated HUVEC layers under static (nonflow) conditions. CLA-enriched memory/effector T lymphocytes migrated more actively across cytokine-activated HUVEC than CLA-depleted memory/effector T cells. This enhanced migration is dependent on the CLA/E-selectin interaction. mAb to very late Ag-4 (VLA-4) and vascular cell adhesion molecule-1 (VCAM-1) blocked the migration of CLA-enriched, but not of CLA-depleted, T cells across activated HUVEC. The observation that anti-VLA-4 and anti-CLA mAb did not show additional inhibition supports the concept that CLA and VLA-4 are sequentially involved in the extravasation. The fact that only CLA+ T cells were inhibited by the anti-VLA-4 mAb suggests that, in this system, CLA engagement is required for using the VLA-4/VCAM-1 pathway. Our studies demonstrate that CLA+ T cells use LFA-1/intercellular leukocyte adhesion molecule-1 (ICAM-1) for transmigration but that CLA expression is not required for the LFA-1/ICAM-1-dependent transmigration because anti-CD18/CD11a mAbs and anti-ICAM-1 mAbs were able to block T cell migration regardless of the activation state of HUVEC or the CLA expression by T cells. Taken together, our results suggest that CLA has a homing function in conducting the T cell to interact with LFA-1/ICAM-1 and/or VLA-4/VCAM-1; this results in enhanced adhesion and migration across cytokine-activated endothelial cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1995

Action of soybean lipoxygenase 1 on 12-iodo-cis-9-octadecenoic acid and 12-bromo-cis-9-octadecenoic acid.

The ferric form of soybean lipoxygenase catalyzes an elimination reaction on 12-iodo-cis-9-octadecenoic acid (12-IODE) to produce iodide ions and 9,11-octadecadienoic acid (9, 11-ODA). If excess 13(S)-hydroperoxy-cis-9,trans-11-octadecadienoic acid (13-HPOD) is present, the reaction proceeds until about one-half of the racemic 12-IODE is consumed; in the absence of excess 13-HPOD, the reaction stops after about three turnovers. Ferric lipoxygenase also catalyzes the conversion of 12-bromo-cis-9-octadecenoic acid (12-BrODE) to 9,11-ODA at a rate that is less than 25% of that observed with 12-IODE. These elimination reactions cannot be detected with ferrous lipoxygenase or with lipoxygenase that has been inactivated by 5,8,11,14-eicosatetraynoic acid. In the case of 12-IODE, elimination is accompanied by a loss of enzymatic activity; at pH 9.0, about 10 iodide ions are produced per molecule of enzyme inactivated. No inactivation can be detected with 12-BrODE. Ascorbate and hydroxylamine, which can act as free-radical traps, block the inactivation by 12-IODE but do not inhibit the elimination reaction. When the enzyme is inactivated by [1-14C]-12-IODE at pH 9.0, the amount of radioactivity that is covalently bound to the protein is less than 30% of that expected for 1:1 incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1995

Effects of lead administration on developing rat kidney. I. Glutathione S-transferase isoenzymes.

The effects of acute and chronic exposure to lead on glutathione S-transferase (GST) isoforms were determined in developing kidney in the rat. The ontogeny of glutathione S-transferase isoforms was characterized as were the effects of depletion of dietary calcium on glutathione S-transferase isoform profiles in control and lead-treated rats. In the acute exposure experiments, rats of 14 and 50 days of age received three daily injections of lead acetate (114 mg/kg) and in the chronic exposure studies, rats received lead acetate at doses ranging from 50 to 500 ppm in their drinking water. Lead acetate administration in these chronic studies began 1 day after conception. Acute and chronic lead exposure had similar effects, causing increases in all but one glutathione S-transferase isoform (Yb3); these increases were markedly exacerbated by dietary calcium depletion. In all lead paradigms, GST subunits Yb1 and Yp showed the largest increases--greater than 25-fold in rats fed a low-calcium diet. GST subunit Yb3 showed small increases in the 14-day acute lead and the 4 week low-calcium animals and did not increase in other groups. Lead-related increases in GSTs were partially reversed by transferring animals previously receiving lead to lead-free water for a 4-week period. Kidneys of rats fed the low-calcium diet did not have detectable GST Yk, but in rats on this low-calcium diet that received 500 ppm lead; this GST isoform was found at levels comparable to those in control rats fed lab chow.

Aging↗
PubMed1995

Effects of lead administration on developing rat kidney. II. Functional, morphologic, and immunohistochemical studies.

The effects of chronic lead administration on renal function and cytoarchitecture and on the immunohistochemical localization of glutathione S-transferase (GST) isoenzymes were determined. Pregnant rats were given 250 ppm lead acetate in drinking water from conception until weaning and mothers and pups received 500 ppm of lead acetate from weaning until termination at either 3 or 7 weeks of age. Light and electron microscopic studies after 3 weeks of lead administration showed tubular injury with frequent mitoses noted in proximal tubular cells and, after 7 weeks of treatment, interstitial fibrosis, characteristic intranuclear inclusions, and tubular injury characterized by both nuclear and cytoplasmic pleomorphism. Rats treated with lead for 7 weeks showed significantly lower body weights and creatinine clearances than age-matched control animals. Immunohistochemical studies of glutathione transferase subunits in control rats showed unique isoform localization in each segment of the nephron; treatment with lead caused large increases in immunoreactive protein of Yc, Yk, Yb1, and Yp GST subunits in proximal tubules. No increases in the antioxidant enzymes copper-zinc superoxide dismutase, catalase, and glutathione peroxidase were found in lead-treated rats, but there was a diffuse lead-related increase in immunoreactive protein for manganese superoxide dismutase throughout the renal cortex. Our results demonstrate large lead-induced increases of specific isoforms of glutathione S-transferase in specific kidney cell types and show that these increases preceded irreversible renal damage.

Aging↗
PubMed1995

Neutrophil activation in response to immune complex-bearing endothelial cells depends on the functional cooperation of Fc gamma RII (CD32) and Fc gamma RIII (CD16).

Leukoclastic vasculitis is thought to be initiated by deposition of immune complexes (ICs) in the vascular wall. To study the neutrophil response in a related in vitro model, we primed human umbilical vein endothelial cell (HUVEC) monolayers with antibodies against human fibronectin. The resulting respiratory burst to the immobilized ICs depended on the antibody concentration used to prime the monolayers and included a marked release of primary and secondary granule constituents. On IC-bearing HUVEC monolayers, but not on ICs directly bound to tissue culture dishes, blocking monoclonal antibodies (mAbs) to crystallizable fragment-gamma receptor II (Fc gamma RII) and Fc gamma RIII markedly inhibited the respiratory burst and the release of elastase. However, on both surfaces the neutrophil response was strongly inhibited by mAbs against CD18. Regardless of whether we used neutrophils from a patient with severe paroxysmal nocturnal hemoglobinuria (PNH) lacking the Fc gamma RIII, or whether the Fc gamma RII-mediated signal transduction was blocked by pertussis toxin, the respiratory burst to the IC-bearing HUVECs was essentially unchanged. With PNH neutrophils, the respiratory burst was predominantly blocked by an anti-Fc gamma RII mAb. In contrast, the response of pertussis toxin treated neutrophils was strongly inhibited by a mAb against Fc gamma RIII. Together these data indicate that the answer of neutrophils to ICs immobilized at the endothelial barrier depends on the cooperative function of both low-affinity Fc gamma Rs.

CD18 Antigens↗
PubMed1995

Aviators at risk.

Human error has been found to cause or contribute to most aviation accidents. Excess emotional stress may have an adverse effect on pilot performance and is known to increase the risk of an aircraft mishap. Family problems, social stressors, career instability, worry, aircraft accidents, and difficult flight schedules are a few of the many potential sources of emotional stress in aviation. Pilots who fail at stress coping may become depressed or even self-destructive. They may externalize their feelings, act out, or blame others for their misfortunes. The aviator at risk may demonstrate "warning signs" such as defensiveness, arrogance, hostility, financial irresponsibility, excesses in routine habits, fatigue, deteriorating pilot performance, or increased risk taking. The aeromedical practitioner's role is to educate aircrew members and help them understand stress and its effect on pilot performance. The time may come when an aviator is confronted by multiple stressors, and inadequate stress coping or failure on the part of the aviation community to recognize the "warning signs" may have disastrous results.

Accidents, Aviation↗
PubMed1995

[Infections caused by Campylobacter jejuni in the pediatric department of the Leoben district hospital 1983-1993].

Over the period 1983-1993 10,344 stool cultures were undertaken in children with gastrointestinal symptoms at the pediatric department of the Landeskrankenhaus Leoben. Campylobacter jejuni was diagnosed as pathogen in 238 cultures taken from 196 patients aged one month to 16 years. Thus, Campylobacter jejuni infections (2.3% of all stool cultures) were second in frequency to various forms of salmonella (6.1% of all stool cultures; 332 patients). Apart from diarrhea (92% of cases), the most frequent clinical features were fever exceeding 38 degrees C (61%), abdominal pain (58%), blood in the stools (48%) and vomiting (34%). Treatment was based on appropriate diet. Fluid replacement with glucose-electrolyte infusions was required in 24% of the patients and erythromycin was administered orally in 30% of cases.

Adolescent↗
PubMed1994

Weekly 5-fluorouracil and high-dose folinic acid in combination with epidoxorubicin as first-line therapy in advanced breast cancer: a phase II study.

A total of 25 patients with advanced breast cancer were treated weekly with i.v. 5-fluorouracil at 350 mg/m2, folinic acid at 500 mg/m2, and epidoxorubicin at 35 mg/m2 as first-line chemotherapy for a maximum of 18 cycles. In all, 24 patients were evaluable for response. Overall, 1 patient achieved a complete response and 11 patients showed a partial response, for an objective response rate of 50%; the median duration of response was 18.3+ months and median survival amounted to 18.8+ months. Side effects were generally mild, with grade II leukopenia occurring in 10 patients and grade III leukopenia, in 1 patient. Other toxicity included nausea and vomiting (82%), diarrhea (48%), stomatitis (48%), and alopecia (92%), all of which were mainly restricted to WHO grades I and II. Our results suggest that leucovorin modulation of 5-fluorouracil can safely be incorporated into combination chemotherapy with epidoxorubicin on the investigated schedule. The observed response rate appears comparable with that obtained with other first-line regimens.

Adult↗
PubMed1994

A phase I/II study of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose leucovorin as first-line therapy in advanced breast cancer patients.

A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

Adult↗
PubMed1994

Development of four donor-specific phenotypes in human long-term lymphokine-activated killer cell cultures.

A series of 62 lymphokine-activated killer cell (LAK) cultures from 44 different donors was investigated for the distribution of various CD markers during a cultivation period of 3 weeks. Great differences in the phenotypic pattern were found between different donors, but similar changes of the subset pattern of various donors allowed a classification of the LAK cultures into four distinct LAK types. LAK type 1 was characterised by low numbers of CD3+ cells and high values for CD56+ cells. In LAK type 2 cultures gamma/delta TCR+ cells extensively proliferated, whereas in LAK type 3 cultures the CD57 and CD8 values increased considerably. LAK type 4 cultures did not show any of these characteristics. The resulting phenotype of a LAK culture was donor-specific, as LAK cultures established from the same peripheral blood mononuclear cells (PBMC), fresh or after cryopreservation, or from PBMC obtained from the same donor at different venous punctures, always developed the same phenotype. A clear correlation between phenotype and killing activity could only be found for LAK type 1 cultures, which always developed high lytic activity. Long-term IL-2 stimulation induced high levels of perforin-positive cells in LAK cultures but the perforin content did not correlate with the cytotoxicity. The transcription pattern for various cytokines only varied slightly between the cultures. Messenger RNA for granulocyte/macrophage- colony-stimulating factor, interferon gamma, tumour necrosis factor alpha, interleukin-4 (IL-4) and IL-5 were found in almost all cultures during the entire cultivation period, whereas mRNA for IL-2 was never detected. Most variations in the transcription pattern were observed for IL-6 and IL-7. However, no correlation could be found between the endogenous cytokine production and the phenotype or lytic activity of the LAK cultures. Further studies are required to determine the factors that cause lymphocyte subsets from a specific donor to proliferate preferentially under long-term IL-2 stimulation.

Animals↗
PubMed1994

Neonatal allo-immune thrombocytopenia due to fetomaternal HPA-1 incompatibility of a homozygous HPA-1a mother and a homozygous HPA-1b father. A case report.

We report a case of neonatal allo-immune thrombocytopenia due to fetomaternal human platelet antigen (HPA)-1 incompatibility. Anit-HPA-1b antibodies were detectable in maternal serum. Repeated treatment of the infant with high-dose IgG effectively raised platelet counts transiently, but the patient remained thrombocytopenic for more than 6 weeks. Serological and DNA analysis revealed that the mother was homozygous HPA-1a and the father homozygous HPA-1b.

Antigens, Human Platelet↗
PubMed1994

Bed occupancy due to HIV/AIDS in an urban hospital medical ward in Uganda.

OBJECTIVE: To determine the proportion of patients with HIV-related illness admitted to a medical ward. DESIGN: A prospective study. SETTING: Rubaga Hospital, the third largest hospital in Kampala, the capital of Uganda. PARTICIPANTS: A total of 449 patients admitted to the medical ward between September and November 1992. RESULTS: Of the 449 patients, 390 (86.8%) agreed to provide a blood sample for HIV serology. Of these, 55.6% (95% confidence interval, 50.7-60.5%) were positive for HIV. Eighty-six (22.2%) of all patients [71 (33%) of the seropositives and six (3.5%) of the seronegatives] met the World Health Organization case definition for AIDS in Africa. The HIV-seropositives had a mortality rate of 17.4%, significantly higher (P = 0.00057) than the 5.8% rate observed in the seronegative group. The overall mortality rate was 13.7% and was significantly associated with HIV infection (P = 0.0005). CONCLUSION: HIV infection is a major contributor to morbidity and mortality in Uganda. Over 50% of the medical admissions were HIV-positive revealing the serious impact of HIV on the health-care system.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Breast cancer in the man: a report of 30 patients].

A retrospective review of male patients suffering from breast cancer seen over an 18-year period was carried out at the Department of Clinical Oncology of the University Hospital of Graz. Thirty evaluable cases were analysed. Eight patients had Stage I, 11 had Stage II, 8 had Stage III, and 3 had Stage IV disease. Local control was achieved in the majority, 29/30 (97%), by either surgery alone or combined surgery and radiation therapy. Local recurrence developed in 2 (7%) patients. Further 7 (23%) patients developed distant metastases and were treated in accordance with policies developed for the appropriate stage of the disease in females, with hormonal manipulation for hormone receptor-positive and -unknown patients and chemotherapy for hormone receptor-negative patients. The corrected five-year survival (Kaplan-Meier) is 83% for the entire group, 100% for patients with Stage I disease, 86% in Stage II, and 67% in Stage III and IV disease, respectively. This corresponds well with the results in recently published series. Stage of disease at initial presentation was a significant factor determining survival in our investigation. Our own data as well as recent data from literature suggest that with respect to TNM Stages in mammary carcinoma, there is no prognostic difference between men and women. To what extent improved local control by adequate local therapy or systemic adjuvant treatment modalities may improve overall survival remains to be discussed.

Adult↗
PubMed1993

Chemotaxins inhibit neutrophil adherence to and transmigration across cytokine-activated endothelium: correlation to the expression of L-selectin.

Non-activated neutrophils strongly adhere to cytokine-activated human umbilical vein endothelial cells (HUVE). However, activation of neutrophils by different chemotactic mediators led to potent inhibition of this endothelial-dependent interaction. For different formylated peptides, concentrations leading to maximal adherence inhibition coincided with those known for inducing maximal chemotactic migration of neutrophils. In terms of maximal adherence inhibition, a rank list was found in the order of N-formyl-Met-Leu-Phe > C5adesArg > interleukin-8 > C5a > or = leukotriene B4, whereas platelet-activating factor, and lipopolysaccharide showed no inhibition. This rank order was congruent to that of down-regulation of neutrophil L-selectin detected by the monoclonal antibody Leu-8. Moreover, the dose-dependent increase of neutrophil adherence inhibition corresponded to the loss of L-selectin expression. Concentrations higher than that required for maximal inhibition led to a dose-dependent decrease of inhibition, which was accompanied by increasing expression of neutrophil CD11/CD18. In contrast to the capacity of non-activated neutrophils to migrate across interleukin-1-activated HUVE monolayers, transmigration was significantly impaired after chemotactic activation.

Antigens, CD↗