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Biomedical subjects

S Kudlacek

Publications and source records attributed to S Kudlacek.

28 records · Page 2Linked to original sources

Differential expression of various T cell surface markers in young and elderly subjects.

The purpose of this study was to investigate the expression of lymphocyte markers in the peripheral blood of aged individuals and of young healthy blood donors. Results showed significant changes in the distribution of various T cell subpopulations. The CD3, CD4 and CD8 surface expression was not different in the elderly patients when compared to the young subjects. The number of CD4+ T cells expressing CD45 RO isoform (memory cells) was increased in aged people; CD45 RA+ CD4+ cells (naive cells) were decreased. The expression of the CD45 RB on the CD4+ cells was significantly lower in the elderly when compared to the young subjects. In contrast, the surface expression of CD45 RO and CD45 RB in the CD8+ cells was not statistically different in the young and aged subjects. The proportion of CD8+ cells coexpressing CD57 was significantly increased in the elderly subjects. These results indicate age-dependent alterations of various surface markers of T cells. These observations may be of importance in the investigation of immunoregulatory mechanisms in geriatric patients with infection, autoimmune disease or cancer.

Adult↗

Influence of sex and age on biochemical bone metabolism parameters.

Age-related changes in bone metabolism are of interest in the pathogenesis of postmenopausal and senile osteoporosis; however, data in the literature give conflicting results. Thus, the aim of our study was to measure serum levels of osteocalcin, a specific biochemical parameter of bone formation, as well as serum levels of midregional parathyroid hormone (PTH) and alkaline phosphatase in healthy males and females of various age groups. We studied 155 healthy subjects (91 females, 64 males, mean age: 43 years, age range: 20-81 years). Serum levels of osteocalcin, alkaline phosphatase and PTH increased with age and were significantly higher in the postmenopausal than in the premenopausal females (osteocalcin: 8.7 +/- 0.4 vs. 6.5 +/- 0.3 ng/ml, p < 0.0001; alkaline phosphatase: 126 +/- 7 vs. 89 +/- 5 U/l, p < 0.0003; PTH: 111 +/- 10 vs. 61 +/- 9 pmol/l, p < 0.0001). In contrast, serum levels of osteocalcin, alkaline phosphatase and PTH were similar in the male subjects above or below the age of 50 years (osteocalcin: 6.5 +/- 0.5 vs. 7.2 +/- 0.4 ng/ml, non significant; alkaline phosphatase: 104 +/- 8 vs. 105 +/- 5 U/l, non significant; PTH: 59.6 +/- 6 vs. 61 +/- 5 pmol/l, non significant. Serum calcitonin levels were significantly lower in postmenopausal women and men above 50 years of age. Our data suggest different age-related alterations in bone metabolism in males and females. The increased levels of osteocalcin, alkaline phosphatase and PTH in postmenopausal females give evidence of increased bone turnover in these subjects. In healthy men bone-specific markers remained unchanged, indicating no relationship between bone turnover and age.

Adult↗

Insensitivity to cyclosporine may explain the HLA-DRw6 recipient effect.

Clinical as well as experimental studies have found an interindividual variability in the immunosuppressive effect of cyclosporine (CsA). In renal transplant patients treated with CsA and prednisolone alone, biopsy-verified rejections were significantly more frequent in DRw6-positive than in DRw6-negative graft recipients. The relative risk for developing a graft rejection independently of the CsA blood levels increased in HLA-DRw6-positive transplant patients. Although no statistical significance of the CsA levels within different DR phenotypes could be assessed, HLA-DR2-positive graft recipients with biopsy-verified rejection episodes had significantly lower CsA levels than DR2-negative patients (P = 0.01). Our results would indicate a very low CsA sensitivity of HLA-DRw6-positive graft recipients and might explain previous results describing an increased incidence of rejection and decreased graft survival rates in these patients.

Antilymphocyte Serum↗

The effect of insulin treatment on HbA1c, body weight and lipids in type 2 diabetic patients with secondary-failure to sulfonylureas. A five year follow-up study.

No conclusive data are available about the long-term effect of insulin treatment in type 2 diabetic patients failing to maximal doses of sulfonylureas and caloric restriction. In total 160 non-obese type 2 diabetic patients with secondary failure were substituted with insulin using a diabetic teaching and care program. From these 160 patients 40 died within the observation period of five years; 102 patients had a complete five year follow-up, whereas the remaining 18 patients did not come to regular follow-up visits. Metabolic control parameters improved significantly in the 102 patients with the complete five year follow-up. Postprandial plasma glucose (16.0 mM vs 10.9 mM; p < 0.0001) and HbA1c values (8.7% vs 7.1%, p < 0.0001) decreased significantly from the state before to five years after insulin substitution. In addition, plasma lipid levels could be significantly lowered under insulin therapy (cholesterol 6.2 +/- 1.5 mM vs 5.4 +/- 3.6 mM, p < 0.0002; triglycerides 2.8 +/- 1.6 mM vs 2.4 +/- 2.1 mM, p < 0.01). However, we observed a significant weight gain (mean: 10.6 kg) associated with insulin application during the five year follow-up. Thus, the body-mass-index decreased from 28.9 at onset of type 2 diabetes to 24.5 (p < 0.0001) at time of secondary failure and increased again to 28.5 (p < 0.0001) at five years after onset of insulin treatment. Furthermore, small increases of plasma creatinine from 88.4 microM to 115 microM, as well as systolic (19.3 kPa to 20.7 kPa) and diastolic (10.7 kPa to 11.3 kPa) blood pressures were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Evidence that sensitivity to cyclosporine is influenced by the HLA-DR phenotype of kidney graft recipients.

Clinical as well as experimental studies have shown a great interindividual variability in the immunosuppressive efficacy of CsA. Evaluating previous in vitro findings of a correlation between sensitivity of alloresponsiveness to CsA and the HLA-DR phenotype CsA levels were compared in kidney transplant recipients with and without rejections during the early posttransplant period and tested for a possible relationship to the HLA-DR phenotype of the recipient. In patients treated with CsA and prednisolone only, rejection frequency was significantly higher in HLA-DRw6 positive than in DRw6 negative graft recipients (77% vs. 53%, P = 0.045). In the DRw6 positive group incidence of rejection was independent of CsA blood levels, whereas in DRw6 negative patients frequency of rejection episodes decreased as a function of increasing CsA levels. Therefore the relative risk in developing graft rejection continuously increased in HLA-DRw6 positive patients. In HLA-DR2 positive graft recipients, however, a decrease in the relative risk could be observed with increasing CsA levels. Within patients with bioptically verified rejection episodes HLA-DR2 positive recipients had significantly lower CsA levels than DR2 negative patients (P = 0.01). In other HLA-DR phenotypes no association with CsA blood levels could be assessed. Also no statistically significant difference could be found in nonrejecting patients. These clinical findings demonstrate an association of sensitivity to immunosuppressive treatment and the HLA-DR phenotype of the graft recipient. Our results would indicate a very low CsA sensitivity of HLA-DRw6 positive graft recipients and thus might offer an explanation for previous findings about an increase in the incidence of rejection reported on those patients.

Adult↗

Influence of brachytherapy (192Ir afterloading) on cell-mediated immune reactions in patients with stage I endometrial cancer.

The influence of radiation therapy on cell-mediated immune reactions in cancer patients seems to depend on source, dose, and area of irradiation, as well as on the variables reflected by the patient population investigated. In the present study we demonstrated that brachytherapy (192Ir afterloading), applied to patients with inoperable stage I endometrial cancer, has no immediate or sustained effect on lymphocyte function. Both lymphocyte mitogen response and natural killer cell (NK) activity are not significantly changed in terms of baseline values compared with test results during and after therapy. Brachytherapy, as used in this study, has no influence on cell-mediated immunity in patients with endometrial cancer stage I.

Aged↗

Use of CA 125 monoclonal antibody to monitor patients with ovarian cancer.

The monoclonal antibody (mAb) OC 125 reacts with an antigen on human ovarian carcinoma (OVCA) cells that is also shed into the body fluids and can be detected in patients' sera and/or ascites with a radioimmunometric assay. For the present study, serum CA 125 levels of patients (n = 36) with different stages of OVCA were investigated. Serum levels seem to correlate with tumor burden. In stages I and II (n = 12), 33% of patients were CA 125 positive, whereas 70% of stage III and IV patients (n = 24) were CA 125 positive. Mean serum levels were in 93 U/ml (stages I, II) and 279 U/ml (stages III, IV). CA 125 levels in ascites and in pleural effusions were manyfold higher than serum levels of the same patients (P less than 0.0001). Immunohistochemical investigations of CA 125 in different ovarian tumors (n = 91) revealed that 85% of malignant and 75% of borderline serous cystadenocarcinomas had detectable CA 125 surface expression. Furthermore, 71% of benign tumors showed the CA 125 epitope, whereas mucinous tumors were negative for this marker. One of six ovarian cancer cell lines was CA 125 positive, whereas in 6 of 11 patients, ascites-derived ovarian cancer cells (fresh and gradient isolated) were positive for this marker. The proportion of positive cells ranged from 10 to 90% in these samples. Intraperitoneal recombinant interferon-gamma (rIFN-gamma) therapy resulted in an increase in the number of cells reacting with CA 125. The results of monitoring in patients receiving different therapeutic regimens and/or agents demonstrate the usefulness of this marker.

Antibodies, Monoclonal↗

[Tumor markers. Their current diagnostic status].

Many tumor markers have been described in the hope of finding a blood test for cancer, and some have found their way into widespread but indiscriminate clinical use. Classically, a marker is synthesized by the tumor and released into the circulation, but it may be produced by normal tissue in response to invasion by cancer cells. Several characteristics define the ideal tumor marker: It should be produced by the tumor cell and be readily detectable in body fluids, not present in health or benign disease, reflect the bulk of the disease and correlate with the results of anticancer therapy. No marker described to date meets all of these criteria. Application of monoclonal antibodies to detect tumor markers promises to greatly expand the number of diagnostic tests available. Monoclonal antibodies have found to provide a degree of specificity not possible using conventional heterogeneous population of antibodies. Antibodies to tissue specific markers are being used to label tissue sections by immune labelling techniques such as immunofluorescence and immunoperoxidase. Identification of a particular marker in the tumor cells of a metastatic lesion may aid in determining the primary site of a tumor. Furthermore radiolabelled antibodies have been used to localize antigen-bearing tumors. Some occult neoplasms have been localized by this procedure, however the practical usefulness remains to be determined. There is still a need for new markers, specific for certain tumoral tissues. Perhaps by aid of monoclonal antibodies it will be possible to identify molecules having a functional significance for tumor-growth (e.g. oncogene products). Such markers may circulate in ultra small amounts, but may still have significance for the monitoring of patients. The continuing improvements of tumor-associated markers may help to approach in cancer treatment and diagnosis.

Biomarkers, Tumor↗

The impact of a senior dancing program on spinal and peripheral bone mass.

Because activity and regular exercise are important factors to maintain general good health in senior citizens, we investigated whether senior dancing has any effect on peripheral or lumbar bone density. We performed a prospective study over a12-mo period on bone density at a spinal and peripheral measuring site in 28 female senior members (mean age: 67 +/- 2 yr) of a dancing group in Vienna. Lumbar bone mineral density was assessed by quantitative computed tomography (qCT) and radial bone density by single photon absorptiometry of the distal forearm. The mean training time per week was 3.2 +/- 0.8 h. In the entire group of female dancers, no significant effects of dancing on radial or lumbar bone density could be observed. Linear regression analysis showed that the lower the qCT at the beginning of the observation period, the higher was the percentage increase of spinal qCT in the entire group during 12 mo of dancing (r = 0.52, P < 0.0001). For additional evaluation, females were divided into two subgroups, osteoporotic or nonosteoporotic, based on x-rays and lumbar bone mineral density (BMD) as measured by qCT. The group classified as dancers with osteoporosis (group I) showed a significant increase in lumbar bone density, whereas in the group of dancers without signs of osteoporosis (group II), BMD remained unchanged. Additionally, radial bone density did not show any changes in either group. Group I showed a significant correlation between basal spinal BMD and the percentage change of BMD during the observation period (r = 0.7, P < 0.001). Changes of the biochemical parameters were observed in the bone-specific isoenzyme of alkaline phosphatase, a marker of osteoblastic activity, in group I giving additional evidence of increased bone formation.

Absorptiometry, Photon↗