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Biomedical subjects

M Betzler

Publications and source records attributed to M Betzler.

At least 19 recordsLinked to original sources
PubMed1992

Soluble interleukin-2 receptor, interleukin-6 and interleukin-1 beta in patients with Crohn's disease and ulcerative colitis: preoperative levels and postoperative changes of serum concentrations.

Crohn's disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins (IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1 beta were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 +/- 62 U/ml (mean +/- SEM; healthy controls; 210 +/- 25 U/ml; p less than 0.02) in CD and 705 +/- 120 U/ml (p less than 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 +/- 6 U/ml in CD (controls: 11 +/- 0.6 U/ml; p less than 0.0036) and 33 +/- 6 U/ml (p less than 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Down-regulation of protein kinase C activation in human lamina propria T lymphocytes: influence of intestinal mucosa on T cell reactivity.

Human lamina propria T lymphocytes (LPL-T) were shown to have lower proliferative responses to CD3 triggering than autologous peripheral blood T lymphocytes (PBL-T), yet preserved their responsiveness to CD2 stimulation. In order to elucidate the basis of these differences, freshly recovered human LPL-T and autologous PBL-T were stimulated with CD2 monoclonal antibodies anti-T11(2/3) plus sheep red blood cells and phorbol 12,13-dibutyrate (PBu2) plus ionomycin, respectively. LPL-T showed invariably lower responses to PBu2 plus ionomycin than PBL-T. In contrast, LPL-T still preserved proliferation to CD2 activation even when their responses to PBu2 plus ionomycin were decreased almost to background levels. Preincubation of PBL-T with intestinal mucosa supernatant led to a similar reactivity as observed in fresh LPL-T. Moreover, the protein kinase C (PKC) inhibitor sphinganine was able to inhibit DNA synthesis to stimulation with PBu2 plus ionomycin but not to CD2 triggering. This study suggests that CD2-induced proliferation is not dependent on PKC activation and that down-regulation of PKC activation may be one of the mechanisms for inhibition of the CD3-Ti-dependent activation pathway in LPL-T by intestinal mucosa-derived influences in vivo.

Antigens↗
PubMed1991

Mononuclear cells in peripheral venous blood of patients with Crohn's disease: preoperative status and postoperative course, influence of duration, activity and extent of disease.

In Crohn's disease (CD) the intestinal lesion is supposed to be the cause of the observed systemic immunologic changes. Based on this assumption, peripheral blood mononuclear cells (PBMC) are of specific interest as a possible indicator of intestinal activity of the disease. From 151 surgical patients CD3+, CD4+, CD8+, B cells, macrophages, leucocytes and the relative number of lymphocytes were analysed preoperatively and 10 days, 3 and 6 months postoperatively. The cell data were correlated with the main clinical data of disease. There was a highly significant preoperative increase of leucocytes, macrophages, CD8+, and B cells in the CD group, and a marked decrease of CD3+, CD4+ cells, and the relative lymphocyte count in the same group. Six months postoperatively, highly elevated macrophages, and leucocytes, and a depressed number of CD4+ cells were the only changes. The preoperative cell data did not correlate with the duration of illness, CDAI, localisation, and extent of the intestinal lesion nor did they correlate with any modality of preoperative drug treatment. Thus, the determination of PBMC characteristics in CD is only of limited value for routine diagnostic purposes. However, the persistence of some pathological values long after operation might be caused by residual microscopic lesions and thus reflect the intestinal process.

Adolescent↗
PubMed1991

Activation and signaling status of human lamina propria T lymphocytes.

In this study, proliferative responses of human lamina propria T lymphocytes were examined in vitro. The response of lamina propria T lymphocytes to Sepharose-bound anti-CD3 antibody plus interleukin 2 was significantly lower than the response of autologous peripheral blood T lymphocytes, whereas the responses of lamina propria T lymphocytes to anti-T11(2/3) antibodies plus sheep erythrocytes or anti-CD28 antibody plus interleukin 2 were largely preserved. After coculture with mucosa supernatant, peripheral blood T lymphocytes showed a similar pattern of reactivity as lamina propria T lymphocytes. This reduced reactivity to T-cell antigen receptor stimulation appears to exist at the level of signal transduction, because triggering of CD3 induces low amounts of intracellular inositol 1,4,5-triphosphate and no free calcium increase in lamina propria T lymphocytes when compared with peripheral blood T lymphocytes. This study indicates that the antigen receptor-dependent activation pathway of lamina propria T lymphocytes for proliferation is down-regulated by intestinal mucosa derived factor(s) and that the alternative pathways mediated by CD2 or CD28 are largely preserved. Based on previous data that lamina propria T lymphocytes can provide help to B cells, it is possible that these alternative activation pathways play an important role in T-B cell interaction in the gut.

Antibodies, Monoclonal↗
PubMed1991

Risks of intestinal anastomoses in Crohn's disease.

Six hundred fifty-eight intestinal anastomoses in 429 operations for Crohn's disease were studied prospectively during an 8-year period to detect variables connected with perioperative morbidity. Postoperative complications occurred in 9.7% of the patients, 4% had to be reoperated on, and the overall mortality rate was 0.5%. In multivariate analysis by stepwise logistic regression, the only variable significantly (p = 0.03) associated with overall rate of complications was long-term corticosteroid therapy. Serious complications were more common in cases of intra-abdominal abscesses (p = 0.01) and preoperative steroid medication (p = 0.03). The combination of both of these risk factors increased the rate of reoperations from 0.6% (no steroids, no abscess) to 16% (steroids and abscess). No significant association with postoperative complications could be found for age, sex, duration of disease, previous operations, nutritional status, emergency surgery, extent of disease, type, number, and localization of anastomoses, presence of proximal ileo-/colostomy, or histologically inflamed margins of resection.

Abscess↗
PubMed1991

An amplifiable and deletable chloramphenicol-resistance determinant of Streptomyces lividans 1326 encodes a putative transmembrane protein.

A genetically unstable chloramphenicol resistance gene from Streptomyces lividans 1326 was cloned and characterized. This gene and adjacent DNA regions can be lost spontaneously or amplify within variants. Biochemical studies proved that chloramphenicol is not modified by an acetyltransferase or any other enzyme and that ribosomes of the resistant strain are sensitive to chloramphenicol. Sequence data revealed that the resistance gene encodes a hydrophobic protein predicted to have 12 membrane-spanning alpha-helices and a hydropathic profile similar to the membrane of proteins required for the efflux of tetracycline. Variable proportions of the amino acids (about 16-24%) within the presumed chloramphenicol-resistant protein are identical to various aligned tetracycline-resistant proteins from Gram-negative and Gram-positive bacteria and to transporters for citrate in Klebsiella pneumonaie and for ferrichrome in Escherichia coli.

Amino Acid Sequence↗
PubMed1991

Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations.

The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment.

Adult↗
PubMed1990

Differential responsiveness to CD3-Ti vs. CD2-dependent activation of human intestinal T lymphocytes.

Human lamina propria lymphocytes were recovered from surgical specimens of unaffected large bowel and compared with peripheral blood lymphocytes (PBL) from the same individual. We investigated their capacities to respond to triggering stimuli delivered by mitogenic monoclonal antibodies directed at the T cell receptor/CD3 complex or, alternatively, the CD2 glycoprotein. In marked contrast to PBL, expression of the interleukin 2/interleukin 2 receptor system was markedly reduced in LPL following activation through the CD3/T cell receptor. Perhaps, more important, responses to CD2 triggering were similar or even stronger in LPL as opposed to PBL. This indicates that the CD2-dependent alternative pathway of T cell activation might serve a functional role in local immunity in the gut.

Antibodies, Monoclonal↗
PubMed1990

Partial recovery of lymphocyte activity in patients with colorectal carcinoma after curative surgical treatment and return of plasma glutamate concentrations to normal levels.

Glutamate was recently found to inhibit the membrane transport of cystine and to impair the function of macrophages and lymphocytes in vitro. Elevated plasma glutamate concentrations in patients with advanced carcinoma were also found to be quantitatively correlated with reduced lymphocyte reactivity in these persons. We now investigated the questions whether glutamate levels in tumor patients would decline to approximately normal levels after tumor resection and, if so, whether this would be correlated with a recovery of lymphocyte reactivity. We report that plasma glutamate levels as well as the concomitantly elevated plasma lactate levels of patients with colorectal carcinoma return to practically normal levels within 1 week after curative surgery. This is accompanied by a rapid recovery of the lymphocyte reactivity against concanavalin A. Lymphocyte responses against pokeweed mitogen and phytohemagglutinin, in contrast, remain impaired for at least 6 months, indicating that elevated glutamate levels in patients with colorectal carcinoma are associated with a long-lasting defect in the immune system.

Adult↗
PubMed1990

Chromogranin A, neuron-specific enolase and synaptophysin as neuroendocrine cell markers in the diagnosis of tumours of the gastro-entero-pancreatic system.

Neuroendocrine (NE) tumours of the gastro-entero-pancreatic tract were analysed immunohistochemically for the expression of chromogranin A, neuron-specific enolase and synaptophysin. In all cases at least one marker was present and in 17 out of 19 investigated neoplasms, at least one of the three markers could be demonstrated in more than 75% of the NE tumour cells. Monoclonal antibody chromogranin A stained a much higher proportion of NE cells in tumours with hormonal activity than in hormonally inactive ones. Immunostaining of the primary tumour as compared to its respective metastases was almost identical. Thus, chromogranin A, neuron-specific enolase and synaptophysin identify NE tumours and their metastases regardless of their localization and their state of hormonal activity. As 'panendocrine' markers of NE tumours they are of special diagnostic value in NE tumours that do not produce hormones and peptides.

Adult↗
PubMed1989

Sutureless large bowel anastomosis: European experience with the biofragmentable anastomosis ring.

Sutureless colonic anastomosis using a biofragmentable anastomosis ring (BAR) has been evaluated in a prospective randomized comparison with sutures and staples for elective colorectal surgery. One hundred and one patients underwent BAR anastomosis, 85 a sutured anastomosis, and 16 a stapled anastomosis. There were two anastomotic leaks in the patients undergoing BAR anastomosis, seven in patients having a sutured anastomosis, and one in a patient who had a stapled anastomosis. Wound infection occurred in ten BAR patients, ten sutured patients and no stapled patient. There was no statistically significant difference in these or in other postoperative complications between the groups. The BAR was easy to use and is a safe alternative to sutures and staples for large bowel anastomosis.

Adolescent↗
PubMed1989

Cloning and analysis of a deletable tetracycline-resistance determinant of Streptomyces lividans 1326.

An unstable determinant encoding resistance to tetracycline and minocycline has been cloned and characterized. It could be demonstrated that this determinant shares extensive homology with the otrA gene identified in Streptomyces rimosus. Tetracycline-sensitive variants of Streptomyces lividans derive mostly by deletion of this resistance determinant and neighbouring DNA regions.

Chromosomes, Bacterial↗