Biomedical subjects

W Domschke

Publications and source records attributed to W Domschke.

At least 145 records · Page 8Linked to original sources

PubMed1998

Human intestinal epithelial cells down-regulate IL-8 expression in human intestinal microvascular endothelial cells; role of transforming growth factor-beta 1 (TGF-beta1).

Cytokines produced from intestinal epithelial cells may function as signals to neighbouring immune cells. In the present study we analysed the effects of colonic epithelial cell lines (HT-29, Caco-2, HCT-116, Colo-320) and freshly isolated intestinal epithelial cells on IL-8 expression in the SV-40T transfected human microvascular endothelial cell line (HMEC-1). Epithelial cell-conditioned media and transwells preventing physical contact between epithelial and endothelial cells were used. TGF-beta1 and IL-8 levels were determined by ELISA and Northern blot analysis. Increasing concentrations of IL-1beta led to increasing production of IL-8. The addition of epithelial cell-conditioned medium or epithelial cells to HMEC-1 cells in a two-compartment co-culture system resulted in a strong decrease in IL-8 at the protein and mRNA level. Decrease of IL-8 was markedly stronger when epithelial cells were co-cultured in contact with HMEC-1 cells, indicating that not only soluble factor(s) play a role in the induction of IL-8 suppression in HMEC-1 cells. MoAbs against TGF-beta1 partially inhibited down-regulation of endothelial IL-8 expression. In further studies, IL-8 expression in freshly isolated human intestinal microvascular endothelial cells (HIMEC) was also down-regulated by intestinal epithelial cells. Our results demonstrate that intestinal epithelial cells down-regulate IL-8 expression in HMEC-1 cells. TGF-beta1 is a candidate factor of epithelial-endothelial communication in the colonic mucosa.

Caco-2 Cells↗

PubMed1998

Intraductal ultrasonography may localize islet cell tumours negative on endoscopic ultrasound.

Two patients with suspected insulinoma and one patient with a gastrinoma were referred to our hospital for preoperative tumour localization. Conventional imaging methods and even endoscopic ultrasonography did not detect any tumour in the pancreatic parenchyma. During endoscopic retrograde cholangiopan-creatography ultrasound miniprobes with a 2-mm diameter were applied via the biopsy channel of the duodenoscope. After insertion of the ultrasound probe into the pancreatic duct intraductal sonography (IDUS) was able to depict the tumours. The two insulinomas (1.8 x 2 mm and 5 x 8 mm, respectively) could be localized, as could the gastrinoma, which had a diameter of 6 mm. IDUS diagnosis was confirmed by surgery as the tumours were resected. Follow-up showed no evidence of tumour recurrence.

Adult↗

PubMed1998

Physiological role of cholecystokinin in gastroprotection in humans.

OBJECTIVE: Cholecystokinin (CCK) is able to protect gastric mucosa against acute injury in experimental animals but little is known about the role of this hormone in maintaining mucosal integrity in humans. This double-blind, placebo controlled study was performed in 16 healthy volunteers. It describes the effects of CCK-8 infused intravenously (i.v.) at physiological doses and endogenous CCK released by intraduodenal (i.d.) oleate on gastric mucosal damage, as brought about by ethanol without or with pretreatment with loxiglumide, a selective CCK-A receptor antagonist. METHODS: CCK-8 was infused i.v. 30 min before and throughout the study or i.d. oleate was instilled through a separate duodenal tube. Thirty minutes after the start of i.v. infusion of CCK or i.d. oleate instillation, 100 ml of 50% ethanol spray was applied to the gastric mucosa using an endoscope. Gastroscopy was performed and mucosal lesions were quantified using modified Lanza score. Gastric biopsies were taken from oxyntic mucosa for histological evaluation and gastric content was aspirated for radioimmunoassay of somatostatin. RESULTS: In placebo-treated subjects ethanol caused endoscopic damage, with an average score of 2.8+/-0.2. Histologically, a widespread disruption of surface epithelium and deep hemorrhagic necrotic lesions were observed. Pretreatment with CCK or i.d. oleate markedly reduced the endoscopic lesion score to 0.7+/-0.1 and 0.3+/-0.1, respectively, and in both cases this reduction was accompanied by a significant rise in plasma CCK. Histologically, surface epithelium was still disrupted but deep necrotic lesions were absent. Gastric content collected before and after CCK or oleate showed a several-fold increase of luminally released somatostatin. CONCLUSIONS: Pretreatment with loxiglumide abolished the protective effects of i.v. CCK-8 and i.d. oleate on mucosal lesions induced by ethanol and prevented the rise in intragastric somatostatin, but failed to affect the increments in plasma CCK. Endogenous CCK plays a physiological role in the maintenance of mucosal integrity. This occurs through activation of CCK-A receptors and is associated with an increased gastric luminal release of somatostatin.

Adult↗

PubMed1998

Human intestinal M cells exhibit enterocyte-like intermediate filaments.

BACKGROUND: The derivation and ultrastructural composition of M cells covering the lymphoid follicles of Peyer's patches is still unknown. Results from different animal models have shown that there are species specific differences in the composition of intermediate filaments between M cells and neighbouring enterocytes. Little is known, however, about intermediate filaments of human M cells. AIMS: To compare components of the cytoskeleton of human M cells with those of adjacent absorptive enterocytes. METHODS: The expression and localisation of different cytokeratins, vimentin, and desmin in M cells was determined on follicle associated epithelia of human appendix using immunohistochemistry and immunogold electron microscopy. RESULTS: Cytokeratins specific for human intestinal epithelial cells such as cytokeratins 8, 18, 19, and 20 were expressed in both absorptive enterocytes and M cells with no differences in intensity and cellular distribution between both cell types. Vimentin and desmin, tissue specific markers of either mesenchymal or myogenic cells, as well as other cytokeratins were not detectable in enterocytes or M cells. CONCLUSION: This is the first study on the structure of intermediate filaments in human intestinal M cells. Our results show that in contrast to several animal models, human M cells apparently do not differ from adjacent enterocytes in the composition of their intermediate filament cytoskeleton. The presence of enterocyte like cytokeratins and the absence of other cytokeratins as well as of vimentin and desmin supports the hypothesis of an epithelial origin of human intestinal M cells and suggests that M cells may derive from differentiated enterocytes.

Adult↗

PubMed1998

[Metal stents in the biliopancreatic duct system--assessment of current status].

By the end of the eighties mesh stents were implanted in malignant stenoses of the biliary and pancreatic ducts for the first time. In the following years, self-expanding as well as balloon-expandable mesh stents were increasingly implanted in malignant stenoses by radiologists or interventional gastroenterologists, either percutaneously or endoscopically retrograde. In randomized comparative studies different teams showed relevant advantages of this new type of prosthesis in comparison to the commonly used plastic stents. Especially the significantly lower rate of late complications and longer patency rates speak in favor of the mesh stents. The higher cost of the mesh stent makes it important to carefully select patients before implantation, to let patients with potentially longer survival time profit from the advantages of the procedure. Expandable mesh stents were successfully implanted in benign stenoses of the biliopancreatic ducts as well, although the lack of randomized comparative studies makes a final assessment difficult. Concluding from already presented results, there might be a new therapeutical option for selected patients with benign stenoses of the biliopancreatic ducts.

Bile Duct Neoplasms↗

PubMed1998

Disturbed gastric motility and pancreatic hormone release in diabetes mellitus.

BACKGROUND AND AIMS: The influence of glucose metabolism and postprandial release of glucagon on gastric emptying in diabetes mellitus is still unclear. The aim of this study was to assess the relationship between glucose, insulin and glucagon and alterations of gastric motility in symptomatic diabetic subjects with delayed gastric emptying. METHODS: Scintigraphy for solids and liquids, 13C-acetate breath test, electrogastrography and antral manometry were assessed in 20 symptomatic subjects with diabetes mellitus type II and in 20 healthy controls. Simultaneously, serum glucose, glucagon and insulin levels were determined during the functional studies. RESULTS: Postprandial increase in antral motility and myoelectrical activity were seen in controls, but were missing in the group with diabetes mellitus. Moreover, in the fasting state the dominant frequency instability coefficient observed in healthy individuals and in subjects with diabetes of short (<5 years) duration was significantly reduced in subjects with longer duration of diabetes while the postprandial increase in dominant frequency instability coefficient was missing in all diabetics. Following the standard test meal, serum glucose and plasma glucagon in the diabetics increased to a significantly higher degree when compared to controls. CONCLUSIONS: Symptomatic subjects with delayed gastric emptying present abnormal patterns of gastric motor and electrical activity. Higher than normal postprandial plasma levels of glucagon may, at least in part, be responsible for disturbed gastric motility in non-insulin-dependent diabetic subjects.

Acetates↗

PubMed1998

[A system of nonspecific defense in chronic inflammatory bowel diseases--pathophysiologic and therapeutic aspects].

Monocytes/macrophages are a prominent feature of the inflammatory infiltrate in inflammatory bowel disease (IBD). Progress in the development of monoclonal antibodies has provided a powerful means to identify and study various subsets of macrophages in the intestinal mucosa. In both Crohn's disease and ulcerative colitis distinct macrophage populations have been found being prominent in active disease, but absent from normal mucosa. Studies of our group show that the Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epitope) can be immunolocalized in the majority of granulocytes and macrophages in active but not inactive IBD. Serum MRP8/14 concentrations are significantly increased in patients with active IBD compared with patients suffering from inactive/mild disease. In vitro studies revealed that IL-13, IL-10 and IL-4 strongly suppress secretion of monocytic proteins. Differential responses of monocytes and macrophages towards the inhibitory effects of TH2-cytokines can be observed in both patients with IBD and control groups. Combined treatment with TH2-cytokines may effectively suppress the response of activated monocytes/macrophages thus being of potential therapeutic benefit for patients with IBD.

Antigens, Differentiation↗

PubMed1998

Metastatic pancreatic VIPoma: deteriorating clinical course and successful treatment by liver transplantation.

Gastrointestinal neuroendocrine tumors are slowly growing and metastases are often limited to the liver. As a result of their favorable biological behavior these tumors have a relatively good prognosis even in metastatic stage. Due to a variety of therapeutic options patients with malignant neuroendocrine tumors may survive for extended periods of time up to ten years. Often a combination of different treatments and also alternation between the different therapeutic regimes is needed. A patient with excessive WDHA-syndrome and severe metabolic disturbances due to a pancreatic VIPoma with metastatic spread into the liver and abundant hormonal secretion is presented. Cytotoxic agents (streptozocin, 5-fluorouracil and adriamycin) were able to alleviate clinical symptoms and to control tumor growth for six years. Analogues of somatostatin (octreotide) and interferon alpha had been very useful in controlling clinical symptoms and tumor progress for 18 months. Cytotoxic agents or octreotide were not able, however, to achieve any permanent cure. Eventually, treatment failure occurred with dramatic progression of symptoms and tumor growth, unresponsive to any medical therapy. Consequently, total hepatectomy and liver transplantation together with extirpation of the pancreatic primary tumor was performed and succeeded in providing a normal life to the patient. In our opinion the overall outcome of patients with metastatic VIPoma may be improved best by maintaining the patients on medical therapy until treatment failure occurs. In case of extended hepatic metastases orthotopic liver transplantation might be considered for patients with symptomatic disease who no longer respond to conventional treatment modalities.

Chemotherapy, Adjuvant↗

PubMed1998

Current concept of the role of monocytes/macrophages in inflammatory bowel disease--balance of proinflammatory and immunosuppressive mediators.

Macrophages are important in providing the first line of intestinal defence against microorganisms or toxins that break the epithelial barrier, by presenting antigen to sensitised T cells and releasing a variety of cytokines and inflammatory mediators. During active states in inflammatory bowel disease, large numbers of monocytes leave the bloodstream and migrate into the inflamed mucosa and submucosa. Phenotypic studies have previously shown the presence of much more marked macrophage heterogeneity in inflammatory bowel disease mucosa than in normal mucosa. In both Crohn's disease and in ulcerative colitis, distinct macrophage populations have been found, being prominent in active disease, but absent from normal mucosa. Studies in our institution have shown that the Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epitope) are expressed in the majority of granulocytes and macrophages in active but not inactive inflammatory bowel disease. Furthermore, a strong complex MRP8/14 immunoreactivity was present in epithelial cells of the terminal ileum adjacent to ulcerative and fissuring lesions, while epithelial cells of large bowel tissues were consistently negative. In vitro studies revealed that interleukin-13, interleukin-10 and interleukin-4 strongly suppress secretion of different monocytic proteins. A combination of TH2-cytokines even at suboptimal concentrations significantly suppressed protein secretion, much more than using interleukin-13, interleukin-10 or interleukin-4 at a double concentration alone. Our morphological findings demonstrate the presence of MRP8/14 (27E10 antigen) both in monocytes/macrophages and in epithelial cells in active inflammatory bowel disease. Systemic or topical application of combined cytokine treatment might be a new effective therapeutic approach for chronic inflammatory bowel disease especially in those cases in which monocytes/macrophages lose their ability to respond, to some degree, to anti-inflammatory cytokines.

Animals↗

PubMed1998

[Role of protease activation in pathophysiology of acute pancreatitis].

For over a century it has been assumed that acute pancreatitis represents an autodigestion of the pancreas by its own, physiologically inactive proteases. Whether, how and where digestive proteases are being activated in the pancreas has remained the topic of much controversy and speculation. We review a number of recent studies that have been undertaken to elucidate the mechanisms and identify the initial subcellular localization of this process. These studies suggest that a premature and intrapancreatic protease activation does, indeed, occur early in pancreatitis and can be experimentally induced in vivo and in vitro. Activation begins within minutes of the induction of pancreatitis and is initially confined to cytoplasmic vacuoles at the apical pole of acinar cells. From here trypsin activity as well as its activation peptide are transferred to the cytosol of acinar cells where autodigestion may begin.

Animals↗

PubMed1998

[Preoperative staging of stenosing esophageal carcinoma--prospective comparison of mini-endosonography with conventional endosonography].

Staging of esophageal malignancies can easily and safely be performed with ultrasonic miniprobes. Unlike large-diameter ultrasonic instruments, miniprobes may pass even high-grade malignant esophageal strictures without prior bouginage. Image quality and resolution of miniprobe sonography exceeds that of conventional endosonography, thus achieving higher accuracy rates for T staging, while those for N staging have found to be similar. As miniprobe sonography is able to improve patients' convenience and security and is highly cost effective compared to conventional endosonography, miniprobe sonography appears to be a valuable addition to the staging armamentarium in esophageal carcinoma.

Adenocarcinoma↗

PubMed1997

Effects of extracellular Mg2+ concentration on intracellular signalling and acid secretion in rat gastric parietal cells.

In the present study, the effects of extracellular magnesium concentration ([Mg2+]ex) on stimulus-secretion coupling processes were investigated in rat gastric parietal cells in vitro. Extracellular magnesium reduction resulted in (1) an increase of basal intracellular free calcium concentration ([Ca2+]in), (2) an enhancement of both carbachol and thapsigargin-induced calcium responses, (3) an improved filling state of intracellular calcium stores, (4) an increase of both basal and carbachol-induced acid secretion, whereas intracellular adenosine 3',5'-cyclic monophosphate (cyclicAMP) levels and histamine stimulated acid secretion were not affected. The effects of high [Mg2+]ex were opposite to the described results, except that high [Mg2+]ex was able to decrease significantly histamine-stimulated cyclicAMP levels and acid secretion. These findings indicate a modulatory role of [Mg2+]ex on the intracellular signalling processes and acid secretory properties in rat parietal cells. These effects seemed to be mediated by regulating (1) calcium loading capacity of intracellular stores, (2) the permeability of the calcium influx pathway, and (3) the formation of cyclicAMP.

Animals↗

PubMed1997

[Intraductal ultrasound in the pancreaticobiliary duct system].

BASIC PROBLEM AND OBJECTIVE OF STUDY: The power of resolution of conventional imaging methods is too low for the diagnosis of very small pancreaticobiliary tumours. High-frequency ultrasound transducers (20 MHz), adapted to the dimensions of the pancreaticobiliary systems (2 mm diameter), make intraductal ultrasound examination possible during endoscopic retrograde cholangiopancreatography (ERCP). In a prospective study the invasiveness and diagnostic value of intraductal ultrasound (IDUS) was compared with ERCP, endosonography (ES) and computed tomography (CT). PATIENTS AND METHODS: During ERCP in 51 consecutive patients an intraductal ultrasound transducer was introduced into the pancreaticobiliary duct system, the results being compared with those obtained with the other imaging modalities and histopathological findings, if available. RESULTS: IDUS of the pancreatic and bile duct systems is a rapid, simple and reliable method during ERCP and provides valuable additional information on periductal tissues. In the diagnosis of carcinoma of the pancreas its sensitivity was 75% (six of eight cases), that of ERCP 37% (3/8), ES 50% (4/8) and CT 37% (3/8). In the diagnosis of biliary tract tumour the sensitivity of the different modalities (in the above order) was 89% (8/9), 78% (7/9), 33% (3/9) and 33% (1/3). Specificity was 67% (2/3), 67% (2/3), 67% (2/3) and 33% (3/9); predictability 89%, 88%, 75% and 60%. CONCLUSIONS: The use of small ultrasound catheter transistor system in the biliary and pancreatic ducts, introduced during ERCP, is technically simple and has few complications. It is a valuable addition to ERCP in the precise diagnosis of small pancreaticobiliary lesions.

Adult↗

PubMed1997

Scintigraphic evaluation of hepatic blood flow after intrahepatic portosystemic shunt (TIPS).

In patients with liver cirrhosis a transjugularly placed intrahepatic portocaval shunt (TIPS) is a non-surgical portosystemic device which aims to reduce portal venous pressure. In comparison with Doppler sonography, we evaluated in 28 patients the diagnostic impact of liver perfusion scintigraphy (with technetium-99m diethylene triamine penta-acetic acid) in the assessment of changes in the hepatic blood flow after TIPS shunting. The arterial and portal contributions to hepatic flow were calculated from the areas under the biphasic time-activity curve. In the course of TIPS shunting, patency is threatened by reocclusion. Angiography is the gold standard for TIPS shunt reassessment. However, there is a need for a less invasive diagnostic procedure, such as scintigraphy or Doppler sonography, for the early detection of shunt insufficiency. Scintigraphy demonstrated that prior to TIPS shunting the portal venous contribution to hepatic perfusion was reduced to 29.2%, this reduction being due to portal hypertension. After TIPS placement a significant increase in portal venous perfusion was observed (38.2%; P<0.02). TIPS shunt occlusion was identified in patients by a significant reduction in the scintigraphically measured portal venous contribution to hepatic blood flow. Hepatic perfusion scintigraphy appears to be a valuable method to determine the immediate effect of TIPS on hepatic blood flow. Post-TIPS follow-up studies of hepatic haemodynamics by liver perfusion scintigraphy appear able to contribute to the detection of TIPS shunt occlusion before the clinical consequences of this complication have become apparent.

Blood Flow Velocity↗

PubMed1997

Simultaneous restitution of matrix and cells in gastric ulcer: use of a combined in-situ hybridization and immunohistochemistry technique applicable to paraffin-embedded tissue.

The restoration of gastric tissue after ulceration involves cellular and matrix components. Our aim was to investigate the kinetics of collagen expression and cellular proliferation in an animal model of gastric ulcer. To demonstrate the expression of type I and IV collagen mRNAs by proliferating cells, a method combining in-situ hybridization and immunohistochemistry was devised. In order to avoid the disadvantages of radioisotopes, digoxigenin-labeled RNA-riboprobes were utilized and combined with single-step immunohistochemistry. This method proved sensitive enough to detect type I and IV procollagen mRNA transcripts in the submucosal area beneath the ulcer crater or adjacent to the ulcer rim. In addition, a subset of cells transcribing either procollagen type I or IV RNA was concomitantly positive for proliferating cell nuclear antigen by immunohistochemistry. Focal proliferation of cells simultaneously expressing extracellular matrix components may therefore occur in the gastric submucosa after ulceration, starting as soon as 3 days after the insult and continuing for several weeks. The devised method of combined in-situ hybridization and immunohistochemistry can be used with standard paraffin-embedded tissues, yields results within 2 days, and avoids radioisotopes.

Acetic Acid↗

PubMed1997

Cytomegalovirus encephalomyelomeningoradiculitis in acquired immunodeficiency syndrome (AIDS).

Acute inflammatory polyradiculitis represents an uncommon peripheral nerve complication during HIV infection. The case of an HIV-seropositive patient who was admitted to hospital for a cauda equina syndrome is reported. Despite early application of anticytomegalic medication, a cytomegalovrirus (CMV) infection spread out to the central nervous system (CNS), causing the patient's death. A post-mortem examination confirmed the diagnosis of CMV-encephalomyelomeningoradiculitis. To the authors' knowledge, such a progress of a CMV-related polyradiculitis to an encephalomyelomeningoradiculitis has not yet been described. The clinical features of this case will aid in the recognition of CMV-related neurological complications, and may permit earlier and perhaps more successful treatment.

AIDS-Related Opportunistic Infections↗

PubMed1997

Synergistic effect of immunoregulatory cytokines on peripheral blood monocytes from patients with inflammatory bowel disease.

Active inflammatory bowel disease (IBD) is characterized by increased monocyte secretion of proinflammatory cytokines. Immunoregulatory cytokines such as Interleukin (IL)-4, IL-10, and IL-13 are capable of inhibiting the proinflammatory cytokine response of activated monocytes. The aim of our study was to determine the effect of different antiinflammatory cytokines under various culture conditions and to evaluate combinations of antiinflammatory cytokines in down-regulating monocyte response in IBD. Peripheral monocytes from patients with active IBD were isolated and stimulated with pokeweed mitogen (PWM). IL-4, IL-10, IL-13 and a combination of IL-4/IL-10 and IL-10/IL-13 were added at different concentrations and different times. Secretion of IL-1beta and TNF-alpha was assessed using sandwich ELISA systems. There was a diminished down-regulation of TNF-alpha by IL-4 and IL-13 in IBD when the cytokines were added at the time of stimulation, while there was a significantly higher down-regulation when monocytes were primed with these Th-2 cytokines 24 hr before activation. IL-10 plus IL-4 and IL-10 plus IL-13, respectively, inhibited the proinflammatory cytokine response of monocytes as well as matured macrophages much more than IL-4, IL-10, or IL-13 alone. Even at suboptimal concentrations for each cytokine alone, a combination of cytokines showed synergistic inhibitory effects. In summary, a combination of antiinflammatory cytokines is more effective in down-regulating the response of activated monocytes than using the cytokines alone and thus may have a potential therapeutic benefit for patients with IBD.

Cells, Cultured↗

PubMed1997

Oral budesonide therapy for steroid-dependent ulcerative colitis: a pilot trial.

BACKGROUND: Budesonide, a corticosteroid with high topical anti-inflammatory activity and low systemic activity, has been shown to prolong time to relapse in Crohn's disease. In the present study, the efficacy of budesonide in an oral pH-modified-release formulation was evaluated for maintenance treatment in patients with steroid-dependent ulcerative colitis. METHODS: Fourteen patients with steroid-dependent ulcerative colitis in the reduction phase of conventional glucocorticosteroids (c-GCS) following a severe attack, were treated with budesonide 3 mg t.d.s. for 6 months. The primary investigation parameters were changes in the clinical activity index (CAI) and in the daily dose of c-GCS. RESULTS: In 11 cases the CAI improved significantly and treatment with c-GCS could be terminated. Three patients experienced relapse and needed further c-GCS treatment. The average daily dose of c-GCS and the average value of the CAI before treatment with budesonide were significantly higher in the relapse group than in the remission group. CONCLUSIONS: In patients with c-GCS-dependent ulcerative colitis, a dose of 9 mg budesonide daily in an oral pH-modified-release formulation was well tolerated, significantly decreased the CAI, and rendered c-GCS unnecessary in the majority of cases.

Administration, Oral↗