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Stephan C Bischoff

Publications and source records attributed to Stephan C Bischoff.

At least 19 recordsLinked to original sources
PubMed2006

Nausea and nutrition.

Nausea and vomiting are symptoms associated with a wide variety of diseases and particular life conditions, such as pregnancy. The symptoms may occur in acute form or chronically depending on the underlying pathogenesis. In some cases, nausea and vomiting are directly triggered by food, e.g. in patients suffering from food allergy or food intolerances. In other cases, food is not the primary cause but dietetic manipulations may still contribute to the management of the nausea and vomiting. Therefore, food plays an important pathophysiological and therapeutic role in nausea and vomiting. In the present article, we describe the most relevant nutrient triggers for nausea and vomiting, discuss food allergy and intolerance as cause of nausea and vomiting, propose a clinical classification of nausea and vomiting, and present in detail dietetic and other therapeutic strategies of relevance for the management of nausea and vomiting.

Female↗
PubMed2006

The German hospital malnutrition study.

BACKGROUND & AIMS: Malnutrition is frequently observed in chronic and severe diseases and associated with impaired outcome. In Germany general data on prevalence and impact of hospital malnutrition are missing. METHODS: Nutritional state was assessed by subjective global assessment (SGA) and by anthropometric measurements in 1,886 consecutively admitted patients in 13 hospitals (n=1,073, university hospitals; n=813, community or teaching hospitals). Risk factors for malnutrition and the impact of nutritional status on length of hospital stay were analyzed. RESULTS: Malnutrition was diagnosed in 27.4% of patients according to SGA. A low arm muscle area and arm fat area were observed in 11.3% and 17.1%, respectively. Forty-three % of patients 70 years old were malnourished compared to only 7.8% of patients <30 years. The highest prevalence of malnutrition was observed in geriatric (56.2%), oncology (37.6%), and gastroenterology (32.6%) departments. Multivariate analysis revealed three independent risk factors: higher age, polypharmacy, and malignant disease (all P<0.01). Malnutrition was associated with an 43% increase of hospital stay (P<0.001). CONCLUSIONS: In German hospitals every fourth patient is malnourished. Malnutrition is associated with increased length of hospital stay. Higher age, malignant disease and major comorbidity were found to be the main contributors to malnutrition. Adequate nutritional support should be initiated in order to optimize the clinical outcome of these patients.

Adolescent↗
PubMed2006

Leptin and insulin response to long-term total parenteral nutrition depends on body fat mass.

BACKGROUND & AIMS: Circulating leptin and insulin concentrations are physiologically representing energy homeostasis. However, the artificial situation of long-term total parenteral nutrition (TPN) and its effects on serum leptin and insulin is not fully understood. METHODS: We studied 42 gastroenterological patients who received TPN for 19+/-11 days. Serum leptin and insulin levels as well as body composition assessed by bioelectrical impedance analysis were evaluated on days 0, 7 and 14. Insulin sensitivity was estimated by calculating the QUICKI. RESULTS: Before the start of TPN, leptin correlated positively with female gender (P<0.03), BMI (P<0.02), fat mass (P<0.02), insulin levels (P<0.001) and QUICKI (P<0.001). Within the first week of TPN, an increase of leptin levels was found only in patients with a body fat mass of >30% (P<0.02). As these were predominantly women, their leptin levels increased likewise (P<0.003). In regression analysis, fat mass (P<0.001), female gender (P<0.04), insulin levels (P<0.03), and i.v. glucose supply rates (P<0.05) were independently associated to leptin levels. CONCLUSIONS: TPN-especially glucose-induces a neurohumoral response as shown here for leptin and insulin that is mainly depending on the fat mass. Better understanding of this regulatory mechanism during artificial nutrition could offer a new approach to improve its therapeutic effects.

Adipose Tissue↗
PubMed2006

Effect of orally administered probiotic E. coli strain Nissle 1917 on intestinal mucosal immune cells of healthy young pigs.

Several beneficial effects of probiotics have been described in studies using rodent disease models and in human patients; however, the underlying mechanisms remained mostly unclear. Only a few studies focused on the effects of probiotics on the intestinal mucosal immune system. Here, we studied the effect of the probiotic strain E. coli Nissle 1917 (EcN) administered orally to young pigs at two concentrations (10(9) and 10(11)CFU/d for 21 days) on the gut-associated lymphatic tissue. This probiotic strain was shown recently to reduce recurrence of inflammation in ulcerative colitis patients. We quantified the number and distribution of intestinal immune cells (granulocytes, mast cells, CD4+, CD8+, CD25+, IgA+ lymphocytes) and the mucosal mRNA expression of cytokines (IFN-gamma, TNF-alpha, TGF-beta, IL-10) and antimicrobial peptides (PR-39, NK-lysin, prepro-defensin-beta 1, protegrins). The number and distribution of cells were highly different between small intestinal and colon segments in all groups, but were not influenced by EcN, except high dose EcN fed pigs (10(11) CFU/d) showing an increase in mucosal CD8+ cells in the ascending colon. The mRNA analysis revealed no changes associated with EcN feeding. In conclusion, according to our analyses EcN has only minor effects on the distribution of mucosal immune cells in the gut of healthy individuals. The well-established preventive effects of EcN might therefore be relate to other mechanisms than simple modulation of immune cell distribution.

Animals↗
PubMed2006

Food allergies.

Food incompatibilities affect approximately 20% of the general population in Western countries. In about one quarter of the affected children and one tenth of affected adults, the incompatibility is based on an allergy, that is, on an immunologically generated incompatibility reaction. Gastrointestinal symptoms occur in a third of these cases. Food allergies are caused by IgE-dependent orIgE-independent immunologic reactions, which lead to an inflammatory reaction, in which mast cells, eosinophilic granulocytes, and other cells are involved. Both genetic and environmental causes are under consideration. New findings concerning the interaction between the innate immune system and intestinal microflora have generated innovative therapeutic concepts, including the use of probiotics to prevent food allergies. The development of recombinant allergens and varieties of allergens will improve diagnostic possibilities and bring new therapeutic options, such as hyposensitization and induction of immunologic tolerance. Food intolerances (non-immunologic food incompatibilities often caused by specific enzyme deficiencies) must be diagnostically differentiated from food allergies.

Adult↗
PubMed2006

Isolation, culture, and characterization of intestinal mast cells.

Mast cells are bone-marrow-derived tissue cells typically located at barrier sites of the body, such as skin, mucosal barriers, or blood barriers, that is, around blood vessels. This location suggests that mast cells might have a function as immunological "gate-keepers" or "watch dogs" and, indeed, some recent functional data support this idea. Mast cells derive from myeloid progenitors, but in contrast to other myeloid cells, they leave the bone marrow in an immature state; therefore, mast cells are not found in the blood under normal conditions. For full maturation, the tissue environment is necessary. Thus, mature mast cells can be only isolated from tissue such as skin or mucosal sites, which makes mast cell isolation rather complicated. Alternatively, mast cell progenitors can be isolated from the bone marrow, peripheral blood, or cord blood, which is easier but requires subsequent in vitro maturation of mast cells as far as possible using cytokines. This chapter describes a rather new technique of mast cell isolation from human intestinal mucosal tissue yielding approx 1-5 million pure and viable human mast cells suitable to perform functional and cell culture experiments.

Animals↗
PubMed2005

IL-4-induced priming of human intestinal mast cells for enhanced survival and Th2 cytokine generation is reversible and associated with increased activity of ERK1/2 and c-Fos.

In synergy with stem cell factor (SCF), IL-4 strongly enhances mast cell proliferation and shifts IgE-dependent cytokine production in mature human mast cells toward an increased release of Th2 cytokines such as IL-3, IL-5, and IL-13 and a decreased IL-6 expression. In this study we analyzed the kinetics and the mechanisms of these IL-4 effects on mast cells purified from intestinal tissue. If the cells were first cultured with IL-4 for 14 days and then without IL-4 for another 14 days, mast cells lost the capacity of producing higher amounts of Th2 cytokines and regained the capacity of producing IL-6. The IL-4-induced up-regulation of mast cell proliferation and FcepsilonRI expression was also reversible if IL-4 was withdrawn for 14 days. Interestingly, in contrast to IL-4, proliferation and phenotype of human intestinal mast cells were not affected by IL-13 although both cytokines were capable of inducing STAT6 activation. Instead, IL-4 treatment (but not IL-13 treatment) was associated with an increased activity of ERK1/2 and c-Fos, the downstream target of ERK1/2 and component of the transcription factor AP-1. Consistently, mast cell proliferation and cytokine expression in response to IL-4 was blocked by the MEK inhibitor PD98059. In summary, our data show that the IL-4 effects on human intestinal mast cell functions are reversible and accompanied by an increased activity of ERK1/2 and c-Fos.

Cell Proliferation↗
PubMed2005

beta2-Adrenoceptor-mediated suppression of human intestinal mast cell functions is caused by disruption of filamentous actin dynamics.

Previous studies indicated potent inhibitory effects of beta2-adrenoceptor (beta2AR) activation on the immunological mediator release of mast cells (MC). Here, we studied effects of beta2AR agonists on human MC mediator release, and in particular on MC proliferation, adhesion, and migration. MC were isolated from human intestinal mucosa, purified, and cultured in the presence of stem cell factor (SCF). beta2AR activation by epinephrine, norepinephrine, and salbutamol suppressed the IgE receptor-dependent release of histamine, lipid mediators, and TNF-alpha, and inhibited SCF-dependent MC proliferation and migration. Moreover, beta2-adrenergic stimulation interfered with MC adhesion to fibronectin and human endothelial cells. Using fluorescent phallacidin, we found that beta2AR activation reduced the amount of filamentous actin (F-actin) within minutes, whereas MC stimulation by either IgE receptor cross-linking or SCF caused F-actin accumulation. Interestingly, this activation-induced F-actin increase was abolished by previous beta2-adrenergic stimulation. Finally, we demonstrated that disruption of the F-actin cytoskeleton by latrunculin B mimicked the effects of beta2AR agonists on MC adhesion and migration. Our results argue for an important role of F-actin interference in beta2AR-mediated MC inhibition. Furthermore, the data support the concept of neuroimmune interactions regulating intestinal MC distribution, density, and functionality in vivo.

Actins↗
PubMed2004

The European Competence Network on Mastocytosis (ECNM).

The European Competence Network on Mastocytosis (ECNM) is a Europe-wide, multinational cooperative approach attempting to improve recognition, diagnosis, and therapy of mastocytosis. The network is composed of local centers, physicians, and scientists who have dedicated their work to patients with mastocytosis. However, because of the rarity and complexity of the disease, each single component in the network alone would fail to meet important demands and to reach solid conclusions in this field of applied medicine. The ECNM represents an attempt to overcome this restriction as a cooperative multicenter platform that should serve as an important basis for the development of new therapeutic strategies and diagnostic concepts, and for the standardization of techniques used to determine diagnostic and prognostic parameters. Moreover, using future central databases and registries, a suitable infrastructure for the development of co-operative multicenter clinical trials will be established. In addition, the ECNM is dedicated to provide the best available information about the disease to patients and physicians.

Clinical Competence↗
PubMed2004

Human intestinal fibroblasts prevent apoptosis in human intestinal mast cells by a mechanism independent of stem cell factor, IL-3, IL-4, and nerve growth factor.

In rodents, fibroblasts (FBs) mediate stem cell factor (SCF)-dependent growth of mast cells (MCs). In humans, SCF is mandatory for MC differentiation and survival. Other factors such as IL-3, IL-4, and nerve growth factor (NGF) act in synergism with SCF, thus enhancing proliferation and/or preventing apoptosis in MCs. In this study, we studied in vitro interactions between human MCs and human FBs, both isolated from the intestine and purified to homogeneity. In coculture with FBs, MCs survived for up to 3 wk, whereas purified MCs cultured alone died within a few days. TNF-alpha and IL-1beta, which both did not affect MC survival directly, enhanced FB-dependent MC growth. We provide evidence that FB-derived MC growth factors are soluble, heat-sensitive molecules which down-regulate MC apoptosis without enhancing MC proliferation. However, only low amounts of SCF were measured in FB-conditioned medium (<0.2 ng/ml). Moreover, blocking of SCF/c-kit interaction by anti-SCF or anti-c-kit Abs and neutralization of IL-3, IL-4, and NGF did not affect MC survival in the coculture system. In conclusion, our data indicate that human FBs promote survival of human MCs by mechanisms independent of SCF, IL-3, IL-4, and NGF. Such interactions between MCs and FBs may explain why MCs accumulate at sites of inflammatory bowel disease and intestinal fibrosis.

Apoptosis↗
PubMed2003

Role of activator protein 1, nuclear factor-kappaB, and nuclear factor of activated T cells in IgE receptor-mediated cytokine expression in mature human mast cells.

BACKGROUND: On activation by cross-linking the high-affinity IgE receptor (FcepsilonRI), expression of TNF-alpha, IL-3, IL-5, and IL-13 is induced in human intestinal mast cells. OBJECTIVE: We sought to examine, for the first time, FcepsilonRI signaling in mature human mast cells. METHODS: Mast cells were isolated from intestinal tissue and cultured in the presence of stem cell factor. The cells were treated with specific inhibitors before stimulation by means of FcepsilonRI cross-linking. Cytokine mRNA expression was analyzed by means of RT-PCR, and activation of signaling molecules was determined by means of immunocytochemistry, RT-PCR, Western blotting, and protein kinase C (PKC) assay. RESULTS: We found that nuclear factor-kappaB (NF-kappaB), as well as c-Fos and c-Jun, the components of activator protein 1 (AP-1), are activated after FcepsilonRI cross-linking in human intestinal mast cells. Treatment of the cells with specific inhibitors revealed an involvement of NF-kappaB and nuclear factor of activated T cells, as well as the necessity of extracellular signal-regulated kinase 1/2 (ERK-1/2), PKC, and AP-1 for the induced cytokine gene expression. Consistently, we found that activation of c-Fos corresponds with the induced cytokine gene expression and that ERK-1/2, an activator of c-Fos, was activated in response to FcepsilonRI cross-linking. CONCLUSION: Our data on human mast cells show that the activity of ERK-1/2, PKC, and subsequent activation of AP-1 are necessary for the FcepsilonRI-mediated cytokine expression. Nuclear factor of activated T cells and NF-kappaB seem to be necessary for the induction of TNF-alpha, IL-3, and IL-13 but are less important for the transcription of IL-5.

Cytokines↗
PubMed2002

Regulatory effects of stem cell factor and interleukin-4 on adhesion of human mast cells to extracellular matrix proteins.

Mast cells are inflammatory and immunoregulatory cells resident in tissues. They develop from bone marrow-derived progenitor cells that enter the tissue through the blood circulation. The specific localization and migration of mast cells in tissues is dependent on their interaction with extracellular matrix (ECM) proteins. Adhesion of human mast cells isolated from intestinal mucosa and cultured in the presence of stem cell factor (SCF) to ECM proteins is analyzed. It was observed that SCF is a unique cytokine enhancing mast cell adhesion to all tested ECM proteins (fibronectin, laminin, collagen I, III, IV, VI, XIV) up to 5-fold, particularly to fibronectin (54% +/- 12% of mast cells) and to denatured collagens (40% +/- 12% on cyanogen bromide-cleaved peptides of collagen I). Most noteworthy, preculture of mast cells with interleukin-4 (IL-4), in addition to SCF, reduced their potency to adhere to ECM proteins to one third compared to mast cells cultured with SCF alone. Mast cell adhesion was preferentially mediated by beta1 integrins, and most cells expressed the ECM-binding integrins alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1, and alphaVbeta3. SCF-induced mast cell adhesion was totally blocked by wortmannin and apigenin, indicating an involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase, and it was related to an up-regulation of the HUTS-21 beta1 epitope, which is associated with an activated conformation of beta1. In conclusion, these data indicate that SCF induces the adhesion of cultured mast cells to ECM proteins, whereas IL-4 may promote detachment from the ECM.

Cell Adhesion↗
PubMed2002

Mast cell dynamics and involvement in the development of peritoneal adhesions in the rat.

Mast cells have been implicated in the ethiopathology of post-operative peritoneal adhesions. However an evaluation of their role in this condition is missing. Adhesions were induced in rats using small intestinal scraping. These rats or rats injected ip with either Stem Cell Factor (SCF) or nedocromil sodium or compound 48/80 (day 0-20) were sacrificed for grading of peritoneal adhesions, for evaluating mast cells and inflammatory cells in adhesions and peritoneal lavage (histochemical staining) and for histamine content (peritoneal lavage, radioenzymatic assay) on days 1-21. Mast cell sonicate was added to intestinal fibroblast and their proliferation was assessed (cell counting). All the rats developed adhesions (day 1) and after 3 days the adhesion score remained constant. Early adhesions were avascular and made of fibrinous exudate containing many mast cells. Thereafter adhesions became denser, and the number of stainable mast cells decreased and then stabilized. On the first few days, inflammatory cells in the peritoneal lavage increased while mast cells and histamine content were significantly reduced indicating their activation. Injection of SCF for 1 week slightly increased peritoneal adhesion formation while nedocromil sodium reduced their development. Compound 48/80 had no significant influence. Addition of mast cell sonicate to normal intestine or to peritoneal adhesion fibroblasts resulted in a significant increase of fibroblast proliferation. In conclusion, mast cell presence correlated with the establishment of peritoneal adhesions, and their pharmacological modulation influenced adhesion formation. In vitro mast cell induced fibroplasia. Therefore, mast cells have a profibrogenic role in this model of peritoneal adhesions.

Animals↗
PubMed2002

Cultured human intestinal mast cells express functional IL-3 receptors and respond to IL-3 by enhancing growth and IgE receptor-dependent mediator release.

Mast cells are immunoregulatory effector cells capable of releasing different mediators and cytokines implicated in inflammatory tissue processes. Previous studies suggested that IL-3 regulates growth and function of murine mast cells and human mast cell precursors, but does not affect mature human mast cells. In the present study, we found expression of IL-3 receptors (IL-3R) in freshly isolated human intestinal mast cells by reverse transcriptase (RT)-PCR and in mast cells cultured with stem cell factor (SCF) using RT-PCR and flow cytometry. IL-3R expression was enhanced when the culture medium was supplemented with IL-4 in addition to SCF. In the presence of SCF, IL-3 significantly enhanced mast cell growth in a dose-dependent fashion (179+/-51% of control, p</=0.004, n=9, ED(50) approximately 15 ng/ml) by decreasing mast cell apoptosis rather than inducing proliferation. Furthermore, IL-3 selectively enhanced histamine (from 39.6+/-12.4 to 51.2+/-15.7% specific release, p<0.02, n=8) and leukotriene C(4) (LTC(4), 5.1+/-3.4 to 10.8+/-5.5 ng/10(6) mast cells, p<0.03, n=6) release triggered by IgE receptor cross-linking without affecting prostaglandin D(2) production. In conclusion, our data show that human intestinal mast cells express functional IL-3R, indicating that IL-3 not only regulates growth and function of immature, but also that of mature human mast cells.

Cell Division↗
PubMed2002

Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis.

BACKGROUND: The management of acute pancreatitis (AP) frequently includes parenteral nutrition, but conditionally essential amino acids such as glutamine are not included in conventional total parenteral nutrition (TPN). AIM: This study was conducted to determine whether the inclusion of glutamine has a beneficial effect in patients with AP receiving TPN. METHODS: In a randomized, controlled study 28 patients with AP received either a standard TPN with 1.5 g/kg body weight protein or an isonitrogen, isocaloric TPN which contains 0.3 g/kg L -alanine- L -glutamine. Patients were assessed for nutritional and inflammatory parameters, infectious complications, length of TPN, length of hospital stay (LOS) and cost of TPN. RESULTS: There were no side-effects related to glutamine substitution observed. Glutamine was associated with a significant increase of cholinesterase, albumin and lymphocyte count in AP as well a decrease of C-reactive protein compared to standard TPN at day 14. There was a reduced length of TPN (10 [6-16] vs 16 [10-18] days, P<0.05) and a trend of reduced LOS (21 [14-32] vs 25 [19-40] days) in AP patients receiving glutamine. The overall cost per patient for TPN did not differ (gln+: 929+/-586 vs gln-: 981+/-507 euro/patient). CONCLUSION: Our results suggest that glutamine substitution is beneficial and does not increase the overall cost of parenteral feeding in patients with acute pancreatitis.

Acute Disease↗
PubMed2002

The stem cell factor-c-kit system and mast cells in human pancreatic cancer.

Stem cell factor (SCF) and its receptor c-kit take part in the regulation of developmental processes of mast cells, hematopoietic stem cells, and melanocytes, as well as in the growth control of human malignancies. To explore the possible role of the SCF-c-kit system and of mast cells in pancreatic cancer, the concomitant expression and distribution of the two molecules were examined in 17 normal and 26 cancerous human pancreatic tissues and in 6 cultured pancreatic cancer cell lines. Mast cell distribution was also evaluated in the same tissue samples. In addition, the effects of SCF and of the c-kit tyrosine-kinase inhibitor STI571 on the growth of the cancer cell lines and of the normal pancreatic ductal cell line TAKA-1 were assessed. SCF immunoreactivity was absent in acinar, ductal, and islet cells of the normal pancreas and faint in pancreatic cancer tissues and cell lines. In contrast, c-kit was clearly present in some normal and hyperplastic ducts of the normal pancreas, in the cancer cells of 73% of the tumor samples, and in all the cell lines tested. Mast cells, identified by tryptase and chymase immunostaining on consecutive tissue sections, showed immunoreactivity for SCF and c-kit in both normal and cancerous specimens and their number was significantly increased (p = 0.03) in pancreatic cancer compared with the normal pancreas. SCF showed a dose-dependent growth inhibitory effect on TAKA-1 cells (p < 0.001), whereas pancreatic cancer cells were resistant to the SCF-induced growth inhibition. Nonetheless, the growth of TAKA-1 cells and pancreatic cancer cells was inhibited by the c-kit tyrosine kinase inhibitor STI571. In conclusion, the SCF-c-kit system, possibly with the contribution of mast cells, may have a growth-regulating role in the normal pancreas, which is altered during malignant transformation.

Adolescent↗
PubMed2002

Cutting-edge technology. III. Imaging and the gastrointestinal tract: mapping the human enteric nervous system.

Monitoring membrane potentials by multisite optical recording techniques using voltage-sensitive dyes is ideal for direct analysis of network signaling. We applied this technology to monitor fast and slow excitability changes in the enteric nervous system and in hundreds of neurons simultaneously at cellular and subcellular resolution. This imaging technique presents a powerful tool to study activity patterns in enteric pathways and to assess differential activation of nerves in the gut to a number of stimuli that modulate neuronal activity directly or through synaptic mechanisms. The optical mapping made it possible to record from tissues such as human enteric nerves, which were, until now, inaccessible by other techniques.

Digestive System↗