Biomedical subjects

R Brezinschek

Publications and source records attributed to R Brezinschek.

9 recordsLinked to original sources

PubMed2005

Blockade of tumour necrosis factor {alpha} significantly alters the serum level of IgG- and IgA-rheumatoid factor in patients with rheumatoid arthritis.

OBJECTIVE: To determine the effect on the humoral immune system of long term treatment of patients with RA with etanercept. METHODS: 12 consecutive patients with seropositive RA treated with etanercept were studied and followed up for 9 months. Clinical efficacy of treatment was evaluated using the 28 joint count Disease Activity Score (DAS28). Serum samples were collected at baseline and after 9 months and serum immunoglobulin, RF isotypes, and anti-cyclic citrullinated peptide (aCCP), antinuclear, nucleosome, and dsDNA antibodies determined. For comparison 7 patients with seropositive RA treated with adalimumab were studied. RESULTS: DAS28 decreased significantly after the first month and then was constant for the whole study (5.7 (0.3) v 3.8 (0.2), p< or=0.000). Serum IgA-RF and IgG-RF increased significantly after 9 months' etanercept treatment (mean (SEM) IgA-RF rose from 19.5 (4.8) to 30.5 (5.9) IU/ml, p< or=0.01; IgG-RF from 20.6 (8.1) to 33.8 (11.5) IU/ml, p< or=0.04). Serum levels of total immunoglobulin and specific autoantibodies remained unchanged during the study. In patients treated with adalimumab, no significant changes in serum levels of RF isotypes and aCCP antibodies were seen. CONCLUSION: Etanercept, although effective in treating the clinical symptoms of RA, seems to have a pivotal effect on RF-producing B cells either directly or indirectly.

Aged↗

PubMed1998

Mutation analysis of the PTEN/MMAC1 gene in lung cancer.

We studied PTEN/MMAC1, a newly discovered candidate tumor suppressor gene at 10q23.3, for mutations in lung cancer. One hundred and thirty-six lung cancer cell line DNAs (66 small cell lung cancers, SCLC, 61 non-small cell lung cancers, NSCLC, four mesotheliomas, five extrapulmonary small cell cancers) were analysed for PTEN/MMAC1 homozygous deletions and five (8%) SCLC lines showed homozygous deletions interrupting the PTEN/MMAC1 gene. Using single stranded conformation polymorphism (SSCP) analysis, we screened the PTEN/MMAC1 open reading frame of 53 lung cancer cell line cDNAs for point mutations and found that 3/35 SCLCs and 3/18 NSCLCs contained homozygous amino acid sequence altering mutations. Northern blot analysis revealed that expression of the PTEN/MMAC1 gene was considerably lower in all the tumor cell lines with point mutations while no expression was detected for cell lines with PTEN/MMAC1 homozygous deletions. Mutation analysis of 22 uncultured, microdissected, primary SCLC tumors and metastases showed two silent mutations, and two apparent homozygous deletions. We also discovered a processed pseudogene (PTEN2) which has 98.5% nt identity to PTEN/MMAC1, that needs to be accounted for in cDNA mutation analysis. Our findings suggest that genetic abnormalities of the PTEN/MMAC1 gene are only involved in a relatively small subset of lung cancers.

Carcinoma, Small Cell↗

PubMed1994

Phenotypic characterization of CD4-/alpha beta TCR+ and gamma delta TCR+ T cells with a transendothelial migratory capacity.

During inflammation, both CD4+ and CD4- T lymphocytes extravasate into perivascular tissues by adhering to and migrating through the vascular endothelium. These studies were undertaken to characterize the phenotype of CD4- T cells that have a capacity to migrate through endothelium. Results show that CD4- T cells exhibit a greater capacity to migrate through endothelial cells (EC) than CD4+ T cells; and that TCR-gamma delta+ T cells exhibited the greatest migratory capacity. The migrating CD8+ T cell population was enriched in CD45RO+/L-selectin-/LFA-1bright/CD29bright/CD 44bright cells. TNF-alpha-activated EC did not support increased CD4- T cell transendothelial migration and changes in the phenotype of the migrating CD8+ T cells. The migrating CD4- T cell population was enriched in VLA-2+ T cells and expressed increased densities of VLA-4, VLA-5, and VLA-6. The migrating TCR-gamma delta+ T cell population contained both CD8dim and CD8- T cells. Moreover, the migrating gamma delta T cell population was not different from the initial or nonadherent population in that it contained CD45RO+, CD45RA+, and L-selectin+ cells. Finally, migrating TCR-gamma delta+ T cells contained cells expressing V delta 2 and V gamma 9 TCR chains, but these were not enriched compared with the initial population. These studies have characterized the CD4- T cells that are capable of transendothelial migration in vitro. The results are consistent with the conclusion that unique subpopulations of CD8+ alpha beta and CD8+ and CD8- gamma delta T cells gain access to inflammatory sites by virtue of their intrinsic ability to migrate across the endothelium.

CD4 Antigens↗

PubMed1994

Cell-type specific response of peripheral blood lymphocytes to methotrexate in the treatment of rheumatoid arthritis.

The mode of action of methotrexate in the treatment of rheumatoid arthritis is still questionable. Although in vitro results suggest an immunosuppressive effect of methotrexate, several clinical studies have failed to confirm these effects in patients treated with oral low-dose methotrexate. With respect to the highly variable bioavailability of methotrexate, we investigated the effects of an intravenous administration of 15 mg methotrexate per week on peripheral blood lymphocyte subsets in eight patients with rheumatoid arthritis. Methotrexate after 12 weeks significantly (P < 0.01) reduced total peripheral blood lymphocytes and led to a pronounced redistribution of lymphocyte subsets with a preferred reductive effect on B-lymphocytes (P < 0.005) and T-lymphocytes (P < 0.05). Natural killer cells and killer cell-like T cells, on the other hand, were unaffected by the treatment. Our results suggest a cell-type specific effect of intravenously administered low-dose methotrexate on peripheral blood lymphocytes. This effect, in our opinion, may contribute to the mode of action of methotrexate as an immunosuppressive drug in the treatment of rheumatoid arthritis.

Adult↗

PubMed1994

Prevalence of Helicobacter pylori antibodies in the serum of gastroenterologists in Austria.

Eighty-eight endoscopists (mean age 41 years, range 29-76 years) and a control group of 100 persons of similar ages were investigated for the prevalence of antibodies (ABs) to Helicobacter pylori, using a quantitative enzyme-linked immunosorbent assay (ELISA) to IgG, two semiquantitative ELISAs to IgG and IgA, and a latex test to IgG and IgM antibodies. The prevalence of antibodies to H. pylori in endoscopists was 48% (quantitative ELISA), 56% (semiquantitative ELISA to IgG), 62% (latex test), and 57% by combined evaluation of semiquantitative ELISAS to IgG and IgA. The respective numbers in the control group were 47%, 48%, 48% and 51%. None of the differences was significant. In both groups, endoscopists and controls, there was a significantly higher H. pylori positivity in older subjects compared to younger persons, but there was no difference between the two groups. The prevalence of ABs was independent to the number of endoscopies previously performed, and independent of protective measures taken, such as wearing gloves during the procedures. Antibody titers as measured with quantitative ELISA showed a positive correlation with the length of time the subject had been active as an endoscopist, but no correlation with the total number of endoscopies performed. In conclusion, the prevalence of ABs to H. pylori in endoscopists follows the age-dependent pattern known from the general population. The regular performance of gastrointestinal endoscopies poses no additional risk of infection with H. pylori in Austria.

Adult↗

PubMed1994

Serum levels of interleukin-6 and tumour-necrosis-factor-alpha are not correlated to disease activity in patients with rheumatoid arthritis after treatment with low-dose methotrexate.

Cytokines are major mediators of inflammatory responses in rheumatoid arthritis. Some of them have been shown to correlate with the disease activity and thus are proposed to be used for monitoring patients. Therefore the effects of a low-dose therapy with methotrexate on serum concentrations of interleukin-6 (IL-6) and tumour-necrosis-factor-alpha (TNF-alpha) were examined in eight patients with seropositive rheumatoid arthritis. Serum levels of IL-6 and TNF-alpha were significantly elevated in patients compared to healthy controls. Before the onset of MTX treatment IL-6 concentrations were correlated to the c-reactive protein (P < 0.05) but the correlation was abolished after treatment. For TNF-alpha no correlations neither before nor after treatment were observed. Both cytokines remained substantially elevated after MTX treatment despite a clear reduction in disease activity. Thus we suggest that one of the effects of MTX might be the inhibition of some of the actions of IL-6 and TNF-alpha.

Arthritis, Rheumatoid↗

PubMed1993

Increased immune activation during and after physical exercise.

The present study has been performed to examine the pattern of immune response during and following a long-duration of physical exercise. We have measured plasma concentrations of serum soluble immune activation markers namely soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8), soluble intercellular adhesion molecule 1 (sICAM-1), soluble CD23 (sCD23), soluble tumor necrosis factor receptor (sTNF-R) and neopterin in 18 individuals before, during (ascent: 3 h, descent: 2 h) and after an alpine tour. Compared to baseline levels, all the parameters were significantly increased on top of the mountain and/or after descent. Within 36 hours after the tour sIL-2R, sCD8 and sICAM-1 decreased. In contrast, sTNF-R and neopterin levels remained higher than baseline throughout the study, only partially decreasing 24 and 36 hours from start. These data show immune system activation induced by physical exercise. The increase of parameters sTNF-R and neopterin, reflecting activation of macrophages, was sustained. The data suggest that immune activation phenomena may be involved in the pathogenesis of impaired immune function after exercise and the exercise-induced asthma.

Adult↗

PubMed1992

Involvement of the immune system in iodine deficient goiter.

Iodine deficient goiters were studied by immunohistochemistry and showed extensive presence and typical arrangement of dendritic cells, known to have excellent antigen presenting capacity. These cells were positive for all MHC-class II epitopes and for ICAM-1. Epithelial follicle lining cells were also seen to be class II positive but lacked ICAM-1. Thyroglobulin seemed not to be iodinated at the C-terminal hormogenic site, as shown by reactions with monoclonal antibodies. Iodine therapy, as well as thyroxine therapy were effective in reducing thyroid size. Both forms of therapy were found to decrease the pretreatment levels of circulating thyroid growth stimulating immunoglobulins (TGI).

Antibodies, Monoclonal↗

PubMedDate not supplied

Cytokine levels in the seminal plasma of infertile males.

Cytokines released by various cell subsets in the male urogenital tract are capable of markedly influencing sperm function and fertility. We determined the cytokine content in the seminal plasma of patients with unexplained infertility and correlated the results with urogenital infections and sperm parameters. Routine sperm parameters, bacterial culture of seminal plasma and blood follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were obtained from 14 infertile males and 8 healthy control subjects. Interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF alpha) levels in the seminal plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-1 beta, IL-6, and TNF alpha levels in the seminal plasma were negatively correlated with the number of progressively motile sperm, but there was no correlation with total sperm counts, viability, pH, morphological alterations, type of abnormality, and hormone parameters. Cytokine levels were significantly elevated in seminal plasma exhibiting bacterial or mycoplasmal infections of the urogenital tract. Urogenital infections lead to an release of inflammatory cytokines, most probably by immunocompetent cells of the lymphocyte/macrophage origin. Cytokines such as IL-1, IL-6, and/or TNF alpha might influence sperm motility via direct or indirect effects, resulting in reduced mucosa penetration properties. Therefore, our data suggest that cytokines may be involved in reduced male fertility.

Adult↗