PubMed Health⌕ Search

Biomedical subjects

G Schürmann

Publications and source records attributed to G Schürmann.

At least 19 recordsLinked to original sources
PubMed1999

Ecotoxicological hazard and risk assessment of heavy metal contents in agricultural soils of central Germany.

Heavy metal content of agricultural topsoils has been experimentally determined at 14 areas in the German Leipzig-Halle-Bitterfeld region covering ca. 3700 km2. For most of the locations and elements, the contamination levels are comparable to those of other agricultural sites in Germany and Europe. Application of a sequential extraction technique revealed relatively low contamination levels in the mobile fractions, which indicates a correspondingly low degree of bioavailability of the heavy metals under the current milieu conditions. In contrast, acidification of the soil due to a drastic decrease in the deposition of calciferous fly ash would lead to a significantly increased ecotoxicological hazard potential, as is analyzed by a probabilistic distribution method that quantifies the overlap of normalized exposure and effect data. The discussion includes recommendations for further improvement of risk assessment schemes addressing soil contamination.

Acid Rain↗
PubMed1999

[Foreign research position in the career development of academic surgeons].

Since there are no data concerning the results/efficiency of research stipends in foreign countries, the aim of this study was to analyze the experience of German surgeons doing research work abroad. Seventy-four fellows (residents) in surgical training who conducted research outside Germany between 1986 and 1995 were interviewed using a detailed questionnaire. Back in Germany, the results and experience gained from research abroad led in the majority of cases to a PhD degree ("habilitation"), a high number of publications, and intensified research efforts in the same field using the methods learned abroad. In Germany, better support for researchers in terms of better clinical and scientific perspectives is urgently needed according to numerous comments.

Adult↗
PubMed1999

Transepithelial transport processes at the intestinal mucosa in inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) of unknown etiology. Oral absorption studies have shown an increased intestinal permeability for various sugar molecules in patients with IBD and their healthy relatives as a possible pathogenetic factor. However, the various transport pathways through the mucosal barrier have not yet been examined. This study therefore investigated whether antigens pass the epithelial barrier by a transcellular or a paracellular pathway. Mucosa of freshly resected specimens from CD (n = 10) or UC (n = 10) patients was investigated by immunoelectron microscopy and compared with healthy mucosa. Epithelial transport was studied with the antigens ovalbumin and horseradish peroxidase after defined incubation. Labeling density of subunit c of ATP synthetase was determined in mitochondria of enterocytes of all specimens. In all specimens epithelial transport of OVA and HRP was principally transcellular through enterocytes with normal ultrastructure, although some tight junctions in CD and UC were dilated. Antigens were transported within vesicles to the basolateral membrane 2.5 min after incubation. The level of enterocytes with electron-lucent cytoplasm containing a high amount of antigens was higher in CD and UC than in healthy mucosa, depending on the grade of inflammation. ATP synthetase was significantly decreased in electron-lucent cytoplasm of CD and UC to normal ultrastructure of healthy mucosa. Our study shows that ovalbumin and horseradish peroxidase taken up by the apical membrane reach the paracellular space by vesicular transport in healthy and IBD enterocytes within a few minutes. Transcellular pathway is affected in both CD and UC, which is indicated by a high level of antigens within the cytosol. We speculate that increased intestinal permeability in IBD results substantially from enhanced transcellular transport.

Adult↗
PubMed1998

Cytokine gene transcription by NF-kappa B family members in patients with inflammatory bowel disease.

We examined the expression of the transcription factor NF-kappa B, a nuclear trans-acting factor known to play a key role in cytokine gene regulation, in patients with inflammatory bowel disease (IBD). It was found that LP macrophages in Crohn's disease (CD) and ulcerative colitis (UC) display high levels of NF-kappa B DNA-binding activity accompanied by an increased production of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) alpha. Western blot studies showed an increased expression of the p50 and c-rel subunits of NF-kappa B; however, the most striking finding was an increased expression level of NF-kappa B p65 in patients with CD and UC. Selective downregulation of p65 in IBD macrophages by a specific antisense phosphorothioate oligonucleotide was sufficient to considerably reduce production of proinflammatory cytokines. These results demonstrate a characteristic increase of NF-kappa B binding levels in patients with IBD. The data suggest that antisense DNA targeting NF-kappa B p65 can be used as a novel molecular approach for the treatment of patients with IBD.

Adolescent↗
PubMed1998

In situ expression of interleukin-10 in noninflamed human gut and in inflammatory bowel disease.

A dysregulated secretion of contra-inflammatory cytokines such as interleukin-10 (IL-10) could play a role in the pathogenesis of inflammatory bowel disease (IBD). We have investigated the expression of IL-10 in gut tissues from patients with Crohn's disease (CD), ulcerative colitis (UC) and controls by mRNA in situ hybridization and immunohistochemistry. Intestinal epithelial cells were found to express IL-10 mRNA and IL-10 protein in all of the tissues investigated without any major differences in the expression patterns. However, compared with noninflamed gut, significantly increased numbers of mononuclear cells (MNCs) producing IL-10 were present in inflamed gut, both in CD and UC. This cytokine was expressed most prominently by inflammatory infiltrates enriched in macrophages, although T cells seem to contribute to its production as well. Elevated IL-10 expression in IBD was mainly detected in the submucosa, whereas IL-10 production by lamina propria cells remained comparably low. In contrast, the expression of IL-1beta mRNA was preferentially increased in the lamina propria. Our data argue against a general deficiency in IL-10 production in IBD. The results suggest rather that the local production of IL-10 by mucosal MNCs in IBD is insufficient to down-regulate pro-inflammatory cytokines such as IL-1beta in the lamina propria compartment.

Adult↗
PubMed1998

Terminal differentiation of chondrocytes is arrested at distinct stages identified by their expression repertoire of marker genes.

During endochondral bone formation, cells in the emerging cartilaginous model transit through a cascade of several chondrocyte differentiation stages, each characterized by a specific expression repertoire of matrix macromolecules, until, as a final step, the hypertrophic cartilage is replaced by bone. In many permanent cartilage tissues, however, late differentiation of chondrocytes does not occur, due to negative regulation by the environment of the cells. Here, addressing the reason for the difference between chondrocyte fates in the chicken embryo sternum, cells from the caudal and cranial part were cultured separately in serum-free agarose gels with complements defined earlier that either permit or prevent hypertrophic development. Total RNA was extracted using a novel protocol adapted to agarose cultures, and the temporal changes in developmental stage-specific mRNA expression were monitored by Northern hybridization and phosphor image analysis. Kinetic studies of the mRNA accumulation not only showed significant differences between the expression patterns of cranial and caudal cultures after recovery, but also revealed two checkpoints of chondrocyte differentiation in keeping with cartilage development in vivo. Terminal differentiation of caudal chondrocytes is blocked at the late proliferative stage (stage Ib), while the cranial cells can undergo hypertrophic development spontaneously. The differentiation of cranial chondrocytes is reversible, since they can re-assume an early proliferative (stage Ia) phenotype under the influence of insulin, fibroblast growth factor-2 and transforming growth factor-beta in combination. Thus, the expression pattern in the latter culture resembles that of articular chondrocytes. We also provide evidence that the capacities of caudal and sternal chondrocytes to progress from the late proliferative (stage Ib) to hypertrophic stage (stage II) correlate with their differing abilities to express the Indian hedgehog gene.

Animals↗
PubMed1998

[Classification of neuroendocrine tumors and the effect on surgical technique].

Neuroendocrine tumors of the gastrointestinal tract are heterogenous regarding hormone production and tumor biology and have a varying disease course and survival time. In 1995 Capella et al. proposed a new classification of neuroendocrine tumors combining characteristics of the primary (i.e. histological differentiation, size, extension into surrounding tissues, hormonal activity and angioinvasion) and its suspected biological behavior (benign, uncertain, low-grade malignant, high-grade malignant). The extent of surgical therapy depends on the malignant potential of the primary tumor. To evaluate the usefulness of this classification in practical work neuroendocrine tumors have to be categorized by this classification and these data have to be correlated with the individual long-term course of patients.

Gastrointestinal Neoplasms↗
PubMed1998

[Length of overseas research sojourn in the career path of academic surgeons].

Since there are no data concerning the results/efficiency of research stipends in foreign countries, the aim of this study was to analyze the experience of German surgeons doing research work abroad. Seventy-four fellows (residents) in surgical training who conducted research outside Germany between 1986 and 1995 have been interviewed using a detailed questionnaire. Back in Germany, the results and the experience gained from research abroad led in the majority of cases to a post doctoral degree, a high number of publications, as well as to intensified research efforts in the same field, using the methods learned abroad. Back home, the possibilities of pursuing research were often compromised by clinical workload. In general, better support for researchers in terms of better clinical and scientific perspectives is urgently needed, a demand that is voiced in numerous comments.

Career Choice↗
PubMed1997

[Cell adhesion. Molecular principles and initial implications for surgery].

This article reviews the molecular basis of cell adhesion and its possible implications in surgery. Adhesion of circulating cells to endothelial cells is mediated by a variety of celladhesion molecules. The first steps in the cell adhesion cascade (rolling, tethering) are regulated by selectins (P, E, L selectin). Stable adhesion and transmural migration predominantly involve integrins (LFA-1, etc.) and members of the immunoglobulin supergene family (ICAM-1, etc). The mechanisms of leucocyte-endothelial interaction are markedly similar in various organs under both physiological and pathophysiological conditions. However, it is likely that cell trafficking to specific tissues/organs (e.g., homing) is regulated by additional organ-specific, topical adhesion molecules (e.g., MAdCAM-1). In surgery, cell adhesion molecules are involved in organ-transplantation pathology (ischemia/reperfusion injury, rejection), inflammation (e.g., chronic inflammatory bowel diseases), tumor metastasis. Animal experiments with anti-adhesive substances show that blocking the leukocyte-endothelial interaction reduces the cellular inflammatory infiltrate and organ rejection. The transfer of experimental data into clinical practice requires further understanding of the regulators of cell adhesion (cytokines, chemoattractant substances, etc.) and the specificity of the process. Current experimental data suggest that early intervention in cell-adhesion mechanisms may offer innovative therapeutic strategies.

Animals↗
PubMed1997

T cells of the human intestinal lamina propria are high producers of interleukin-10.

BACKGROUND AND AIM: Some of the recently observed functional features characteristic of immunocompetent cells residing in the human intestinal lamina propria could be mediated by interleukin-10 (IL-10). To investigate the role of IL-10 in the human intestinal mucosa, the regulation of IL-10 production by lamina propria T lymphocytes (LPL-T) was determined and compared with that of peripheral blood T lymphocytes (PBL-T). METHODS: Following activation by using different stimuli, IL-10 release by LPL-T and PBL-T into the supernatant was measured by enzyme linked immunosorbent assay (ELISA). In parallel, cell growth was determined by [3H]-thymidine incorporation. RESULTS: Neither LPL-T nor PBL-T release IL-10 constitutively. Triggering through CD2 or the T cell receptor (TCR)/CD3 complex in the presence of autologous monocytes induces significantly greater IL-10 secretion by LPL-T than by PBL-T. Engagement of the CD45 receptor enhances IL-10 release and proliferation of CD2 triggered CD45RO+ PBL-T. In contrast, it reduces CD2 induced IL-10 production by LPL-T without altering cell growth significantly. CONCLUSIONS: Activated LPL-T release relatively high amounts of IL-10. Enhanced IL-10 production by activated LPL-T, in comparison with activated PBL-T, is not only related to the presence of a higher proportion of CD45RO+ T cells in the intestinal lamina propria, but is also caused by increased sensitivity of LPL-T to CD2 co-stimulation. The differential responsiveness of LPL-T, compared with PBL-T, to CD45 engagement demonstrates that CD45 could be involved in the altered CD2 reactivity of LPL-T.

Blood↗
PubMed1996

Differential regulation of human T cell responsiveness by mucosal versus blood monocytes.

Human intestinal T lymphocytes are constantly exposed to a large number of foreign antigens without developing a systemic immune response. One crucial mechanisms leading to this intestinal hyporesponsiveness is based on impaired signal transduction through the T cell receptor/CD3 complex in lamina propria T lymphocytes (LP-T). In this study, we addressed the question whether a lack of co-stimulatory/progression signals might also contribute to LP-T hyporesponsiveness. To this end, isolated human monocyte populations from the intestinal lamina propria were obtained and their phenotypes as well as their capacity to promote T cell activation studied. Here, we demonstrate that lamina propria macrophages (LP-MO), in contrast to peripheral blood monocytes (PB-MO), do not support proliferation of either LP-T or PB-T. This may be due to the low expression of ligands (CD54, CD58, CD80) for the T cell accessory receptors CD11/18, CD2 and CD28/CTLA-4 on mucosal macrophages. Thus, down-regulation of both recognition/competence and co-stimulatory/progression signals contribute to intestinal hypo- or unresponsiveness.

Antigens↗
PubMed1996

The impact of disease pattern, surgical management, and individual surgeons on the risk for relaparotomy for recurrent Crohn's disease.

OBJECTIVE: The authors provide a multivariate analysis of a large single-center experience with limited surgery for Crohn's disease. SUMMARY BACKGROUND DATA: During the past decade, the aim of surgery for Crohn's disease has shifted from radical operation, achieving inflammation-free margins of resection, to "minimal surgery," intended to remove just grossly inflamed tissue or performing strictureplasties. METHODS: Seven hundred ninety-three cases of resection and/or strictureplasty in 689 individuals with histologically verified Crohn's disease were followed for a mean period of 50 months (range, 5-166 months). Two different end points were analyzed: 1) any relaparotomy for recurrent (or persistent) Crohn's disease and 2) relaparotomy for site-specific recurrence. More than 30 variables of patient/disease characteristics and surgical management were included in a proportional hazard model. RESULTS: Five parameters were associated independently with the risk for relaparotomy: increased risk coincided with young age at onset of disease, involvement of jejunum, enterocutaneous fistula, or performed strictureplasty, and decreased risk followed ileocecal resection. Site-specific risks of reoperation were calculated on the basis of 1260 intestinal resections or anastomoses performed in these patients. Young age at onset, duodenal and jejunal involvement, presence of enterocutaneous or perianal fistula, and a single surgeon (of 23) were associated significantly with increased risk of regional recurrence but not strictureplasty or inflammation at margins of resection. CONCLUSIONS: Limited surgery for Crohn's disease is not associated with increased risk of regional recurrence requiring reoperation. However, patients with juvenile onset, proximal small bowel disease, and some types of fistulae are at a considerable risk of experiencing early surgical recurrence.

Adolescent↗
PubMed1996

T cell receptor V beta expression in human intestine: regional variation in postnatal intestine and biased usage in fetal gut.

A panel of T cell receptor V beta specific monoclonal antibodies was used to analyse V beta gene usage at different sites in human postnatal and fetal intestine. In normal small intestine, at a single site, different patients showed expansion of T cells expressing individual V beta s. Lamina propria and epithelial T cells from the same patient showed overlapping but not identical V beta dominance. V beta dominance was also shown in the T cells of the colonic lamina propria. Analysis of two separate regions of intestine from the same patient (5-100 cm apart) showed that T cells expressing a dominant V beta region were often present at both sites. In most patients, however, major biases in T cell V beta usage (two to 12-fold variation) were also apparent between the two sites. Analysis of V beta expression in human fetal intestine also showed considerable skewing, although the most common dominant V beta in postnatal intestine (V beta 22) was never predominant in fetal intestine. Patchy local variation in the expression of individual V beta s therefore occurs against a background of V beta dominance over large regions of the human gut. Furthermore the results from fetal gut show that factors other than luminal antigen control V beta expression in the gut.

Adolescent↗