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M Classen

Publications and source records attributed to M Classen.

At least 37 records · Page 2Linked to original sources
PubMed1992

Influence of acid secretory state on Cl(-)-base and Na(+)-H+ exchange and pHi in isolated rabbit parietal cells.

Parietal cell apical proton secretion is accompanied by apical Cl- secretion, K+ cycling, and the generation of intracellular base. We examined the ability of the parietal cell to maintain intracellular pH (pHi) during its transformation from the resting to the stimulated state and evaluated the ion transport mechanisms involved in the maintenance of ionic equilibrium. Isolated rabbit parietal cells were loaded with the pH-sensitive fluorescent dye BCECF, and pHi was monitored in maximally stimulated, resting (absence of a secretagogue), and omeprazole-inhibited cells. Although [14C]aminopyrine (AP) accumulation increased up to 30-fold above basal during stimulation, the mean pHi of maximally stimulated cells was not different from that of inhibited cells both immediately and late after stimulation in an extracellular pH range from 6.2 to 7.8 in either HEPES or CO2/HCO3- buffer. When the stilbene DIDS was added 2 min after stimulation of acid formation, pHi rapidly increased (0.09 +/- 0.02 vs. 0.04 +/- 0.02 pH units in unstimulated cells in 6 min), indicating an increased base efflux through a DIDS-sensitive transporter (most likely the Cl(-)-base exchanger). Stimulation of acid secretion did not change the transport capacity, apparent affinity for extracellular Cl-, or dependency of the anion flux rate on pHi of the DIDS-sensitive base exporter. For a given pHi, amiloride-inhibitable proton efflux rates during pHi recovery from an acid load were identical in resting and stimulated cells, suggesting that neither the transport capacity not the pHi set point of the parietal cell Na(+)-H+ exchanger is altered by cAMP-dependent stimulation of acid formation. We conclude that, during the cAMP-mediated stimulation of acid formation in isolated rabbit parietal cells, the pHi remains constant, but an increased base efflux occurs without a change in the transport capacity of the involved base extrusion mechanisms or an inhibition of the parietal cell base loading mechanisms. Whether changes in the intracellular Cl- concentration on stimulation of acid formation initiate the increased base efflux and whether additional ion transporters are involved in the maintenance of ion homeostasis during acid secretion remain to be determined.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Pertussis toxin-sensitive and pertussis toxin-insensitive inhibition of parietal cell response to GLP-1 and histamine.

We have recently shown that in rat parietal cells the glucagon-like peptide 1 (GLP-1) variants 7-36 amide, 1-37, and 1-36 amide stimulate H+ production as indirectly measured by [14C]aminopyrine (AP) accumulation. This response to the GLP-1 peptides was intracellularly mediated by activation of adenylate cyclase and by adenosine 3',5'-cyclic monophosphate (cAMP) as second messenger. In the present study, we compared prostaglandin (PG)E2, somatostatin, and the protein kinase A antagonist Rp-adenosine-3',5'-monophosphorothioate (Rp-cAMPS) with respect to their inhibitory effects on parietal cell function induced by GLP-1 or histamine. PGE2 and somatostatin noncompetitively inhibited AP accumulation and cAMP production in response to the GLP-1 variants and histamine (IC50): [mean inhibitory concn 5 x 10(-9) M PGE2; 3 x 10(-7) somatostatin]; at their maximal concentrations PGE2 (10(-7) M) and somatostatin (10(-6) M) caused 85 and 65% inhibition, respectively. Treatment with pertussis toxin (PT; 250 ng/ml; 4 h) reversed the inhibitory effect of PGE2 and somatostatin on AP accumulation and cAMP production. At 2 x 10(-3) M (IC50: 3 x 10(-4) M) Rp-cAMPS completely inhibited AP accumulation induced by the GLP-1 variants or histamine; this effect was insensitive to PT. Specificity of Rp-cAMPs as protein kinase A inhibitor is suggested by inhibition of AP accumulation in response to Sp-cAMPS and N6,O2-dibutyryl adenosine 3',5'-cyclic phosphate sodium, and forskolin, activators of protein kinase A and adenylate cyclase, respectively. We conclude that the parietal cell responses to GLP-1 and histamine are inhibited by identical mechanisms. Effects of PGE2 and somatostatin are mediated by the PT-sensitive subunit of adenylate cyclase Gi, whereas Rp-cAMPS interferes with cAMP-dependent mechanisms that are insensitive to PT.

Adenylate Cyclase Toxin↗
PubMed1992

Mechanisms of neurotensin-induced inhibition in rat ileal smooth muscle.

The aim of the present study was to determine the mechanisms of neurotensin-induced inhibition in ileal smooth muscle. Isolated rat ileal smooth muscle strips were stimulated in an organ bath using carbachol (CCH) or by KCl depolarization. Neurotensin produced a concentration-dependent inhibition of muscle contraction [mean inhibitory concentration (IC50): 2.8 x 10(-9) M], which was not blocked by phentolamine (10(-6) M), hexamethonium (10(-4) M), indomethacin (10(-6) M), nordihydroguaretic acid (10(-6) M), or tetrodotoxin (10(-6) M). The inhibitory effect of neurotensin during CCH stimulation was blocked concentration dependently in the presence of the K(+)-channel blocker apamin. By contrast, other K(+)-channel blockers such as 9-aminoacridine (10(-6) M to 3 x 10(-5) M), 4-aminopyridine (10(-4) M to 5 x 10(-3) M), tetraethylammonium (10(-4) M to 10(-1) M), or glibenclamide (10(-5) M) were ineffective. The presence of the Ca(2+)-channel antagonist nitrendipine (IC50: 2.4 x 10(-9) M) or verapamil (IC50: 1.1 x 10(-7) M) also blocked the neurotensin inhibitory effect. Ileal contraction, induced by the Ca(2+)-channel activator BAY K 8644 (10(-7) M), was completely inhibited by neurotensin. After depletion of internal Ca2+ stores by repetitive stimulation with CCH and caffeine in Ca(2+)-free buffer, reintroduction of external Ca2+ restored neurotensin inhibition of the contraction induced by CCH. These results demonstrate that the inhibitory effect of neurotensin in rat ileum longitudinal muscle is apamin sensitive and cannot be observed in the presence of the Ca(2+)-channel blockers nitrendipine or verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Ethanol inhibits interferon-gamma secretion by human peripheral lymphocytes.

Clinical and epidemiological evidence exists that subjects who chronically abuse alcohol are disposed to infections and certain types of cancer. In vitro inhibition of mitogen-induced lymphocyte proliferation has been shown suggesting a direct immunosuppressive effect of ethanol. Using human peripheral blood mononuclear cells we could demonstrate in vitro for the first time that even low ethanol concentrations of 6 and 12.5 mM significantly inhibit spontaneous and mitogen-induced secretion of interferon-gamma. This effect was more pronounced with lower mitogen stimulation and it increased in a dose dependent manner when higher ethanol concentrations were used. Inhibition of cell proliferation as measured by 3H-thymidine incorporation did not parallel the inhibition of interferon-gamma secretion. As this lymphokine exerts a great number of immunostimulating effects, diminished secretion might well contribute to the immune defect observed in alcoholics.

Alcohol Drinking↗
PubMed1992

Influence of stress on the healing and relapse of duodenal ulcers. A prospective, multicenter trial of 2109 patients with recurrent duodenal ulceration treated with ranitidine. RUDER Study Group.

The influence of psychologic factors on the healing and relapse of duodenal ulcers under treatment with ranitidine was studied in a prospective, multicenter trial in 2109 patients with an endoscopically proven duodenal ulcer (DU) and a history of recurrent duodenal ulceration. All patient received ranitidine (300 mg daily), and, after healing, 1899 patients continued maintenance treatment (ranitidine, 150 mg daily) for 2 years. A physician's assessment of stress (stress or no stress) was made at every consultation. In the healing phase an overall classification of stress as absent, intermittent, or continuous was made, and in the maintenance phase patients were classified dichotomously as having stress (stress on at least half of the follow-up consultations) or no stress. In addition, at the start of the healing phase stress was measured by means of a standardized questionnaire. Continuous stress, as assessed by the physicians, was associated with a lower 14-day healing rate (35.7%) than intermittent or absent stress (42.4%; relative risk (RR) for delayed healing in patients with continuous stress, 1.19; 95% confidence interval (CI), 1.06-1.33; P < 0.02). Differences in the 14-day healing rate for patients with low and moderate stress scores (43.1%) compared with those with high and very high stress scores (37.9%) just failed to reach statistical significance (RR for patients with stress, 1.14; 95% CI, 0.998-1.29; P = 0.051). During the 1st year of maintenance treatment 18.3% of patients with stress, but 10.9% of patients without stress, had a DU relapse (RR of stress for DU relapse during the first year, 1.73; 95 CI, 1.44-2.09; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Endosonographic diagnosis of submucosal upper gastrointestinal tract tumors.

Endoscopic ultrasound (EUS) was performed in 37 patients with upper gastrointestinal tract submucosal tumors (SMT). Fourteen of these were located in the esophagus, 20 in the stomach, and 3 in the duodenum. In 26 patients histologic confirmation was achieved by operation (n = 15) or biopsy/puncture (n = 11). EUS was able to visualize all tumors and, with one exception, determined their originating wall layer correctly. It became evident that myogenic tumors arise from the echo-poor layers (second layer and fourth--that is, muscularis propria) and that other lesions, such as cysts or fibromas, originate from the third, echo-rich layer (submucosa). Tumor size was correctly (+/- less than 5 mm) predicted in 87% of cases. Computed tomography, performed in 22 patients, was successful in visualizing the SMT in only two-thirds of cases. No single endosonographic criterion could be obtained which enabled accurate differentiation between benign and malignant SMT. However, from a clinical point of view, it seems reasonably safe to regard smaller (less than 3 cm), smoothly demarcated SMT as benign and follow them up by repeated EUS, especially in patients at risk for surgery. Larger masses (greater than 5 cm) and those with irregular borders should be suspected of being malignant. In the future, application of new, small ultrasound probes that can be used during conventional endoscopy (two SMT were visualized successfully) may greatly simplify the procedure.

Diagnosis, Differential↗
PubMed1992

Nonspecific immunostimulation with low doses of cyclophosphamide (LDCY), thymostimulin, and Echinacea purpurea extracts (echinacin) in patients with far advanced colorectal cancers: preliminary results.

Outpatients (n = 15) with metastasizing far advanced colorectal cancers received immunotherapy consisting of low-dose cyclophosphamide (LDCY) 300 mg/m2 every 28 days i.v., thymostimulin 30 mg/m2, days 3-10 after low-dose cyclophosphamide i.m. once daily, then twice a week, and echinacin 60 mg/m2 together with thymostimulin i.m. All patients had had previous surgery and/or chemotherapy and had progressive disease upon entering the study. Two months after onset of therapy a partial tumor regression was documented in one and a stable disease in 6 other patients by abdominal ultrasonography, decrease of the tumor markers carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, and/or chest roentgenography, which may also be attributed to the natural course of disease. Mean survival time was 4 months, 2 patients survived for more than 8 months. Immunotherapy was well tolerated by all patients without side effects.

Adjuvants, Immunologic↗
PubMed1992

[Clinical relevance of endosonography in diagnosis of pancreatobiliary diseases].

Endoscopic ultrasonography allows a high-resolution imaging of the pancreas and the extrahepatic biliary tract due to the high ultrasonic frequencies employed. This is of clinical benefit in the delineation of small pancreatic carcinomas complementary to ERCP and in the preoperative localization of endocrine tumors of potential pancreatic origin. Endosonography is the most accurate method presently available for the local staging of pancreatobiliary malignancy and thus helps avoiding diagnostic laparotomy for staging purposes. The role of endoscopic ultrasonography in the diagnosis of benign diseases such as chronic pancreatitis and choledocholithiasis has not yet fully been established. Endosonography, however, has no role in the differential diagnosis of benign and malignant disorders of the pancreas and biliary tract.

Ampulla of Vater↗
PubMed1992

[Endosonography in gastroenterology--an intermediate evaluation].

Endoscopic ultrasonography has widened the diagnostic spectrum of gastrointestinal disorders in two respects: For the first time it became possible to visualize the gastrointestinal wall with its layer structure. EUS was shown to be highly accurate in the local staging of gastrointestinal tumors (T and N stage). The clinical relevance of endosonography derives from stage-dependent treatment protocols selecting patients for different forms of tumor therapy. The second advantage of endosonography is a high-resolution imaging of the pancreas enabling the detection of small lesions (e.g. endocrine tumors). Endoscopic ultrasonography is furthermore the most reliable method for local staging of pancreatic and ampullary carcinoma. The role of endosonography in benign gastroenterological disorders is less well established. With the increasing use of laparoscopic surgery endosonography may become even more important in the future.

Diagnosis, Differential↗
PubMed1991

[Endoscopic papillotomy (sphincterotomy) in the 1990-s].

This review summarizes the past history and presence of endoscopic papillotomy (EPT, sphincterotomy) in the treatment of biliary and pancreatic tract diseases. The indications of the different techniques used, and the comparison of the effectiveness of EPT with that of the traditional surgical treatment is also discussed. Based on the results, EPT is an up-to-date technique with good effectiveness, low risk for patients and widening indication range. EPT in the future, will play a determining role in the effective treatment of biliary and pancreatic tract diseases.

Ampulla of Vater↗
PubMed1991

Neuropeptide Y and food intake in fasted rats: effect of naloxone and site of action.

Central administration of neuropeptide Y (NPY) induces food intake in freely feeding animals and this effect is mediated by hypothalamic sites. Little is known, however, about the effect of NPY on food intake and site of action in food-deprived animals. To examine this further, 24-h fasted rats received injections of saline or NPY into the lateral cerebral ventricle (10 micrograms/10 microliters; n = 8) or into the lateral (LH) or ventromedial hypothalamus (VMH) (1 microgram/0.5 microliters; n = 44). In addition, intracerebroventricular (i.c.v.) injections of NPY were carried out with or without i.c.v. naloxone (25 micrograms), a specific opioid receptor antagonist. During the first 40 min food intake was not different with or without NPY. After 60 and 120 min, food intake was 5.9 +/- 0.4 g and 8.3 +/- 0.6 g with i.c.v. saline which was significantly augmented by i.c.v. NPY to 8.7 +/- 0.9 g and 14.4 +/- 1.5 g, respectively (P less than 0.05). This increase in food consumption was due to a prolongation of feeding time. The opioid receptor antagonist naloxone significantly augmented latency to feed, both in the absence and presence of NPY (8.0 vs 1.7 min or 14.7 vs 2.8 min, respectively) and abolished the NPY-induced increase in food intake. Following intrahypothalamic injection of NPY, an increase in food intake (greater than 20%) was observed in 50% of the histologically identified LH and VMH sites, but only in 15% of the injection sites outside the LH/VMH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A major fraction of human intraepithelial lymphocytes simultaneously expresses the gamma/delta T cell receptor, the CD8 accessory molecule and preferentially uses the V delta 1 gene segment.

The frequency of T cell receptor (TcR) type and the variable gene segment expression in human intraepithelial lymphocytes (IEL) from the large intestinal mucosa were studied by flow cytometry and immunohistochemistry, and compared to those in peripheral blood lymphocytes (PBL) - or lamina propria lymphocytes (LPL). Employing anti-gamma/delta TcR and anti-alpha/beta TcR monoclonal antibodies (mAb), flow cytometric analysis revealed that a large fraction of IEL (37%) are gamma/delta T cells, whereas within LPL and PBL gamma/delta T cells comprise a minor population (4.6% and 3.8% respectively). At these sites the number of gamma/delta T cells labeled with anti-CD8 mAb were 58.3% (IEL), 43.3% (LPL) and 24.4% (PBL). In situ staining of serial sections of large intestine confirmed these results. Hence, these data suggest a selective accumulation of CD8+ gamma/delta T cells in the human epithelium of the large intestine. Furthermore, analysis of gamma/delta TcR bearing IEL+ disclosed a marked preponderance of cells using the V delta 1 gene segment, whereas gamma/delta TcR+ PBL preferentially express V delta 2. Strikingly, the majority of these V delta 1+ IEL bear the CD8 molecule on their surface. These results are taken as evidence for a selective localization of V delta 1+ CD8+ gamma/delta T cells in the epithelium of the large intestine.

Adult↗
PubMed1991

The effect of glucose and insulin on vagally induced gastrin, bombesin-like immunoreactivity and somatostatin secretion from the perfused rat stomach.

Previous studies in the isolated perfused rat stomach have shown that elevated glucose and insulin concentrations modulate BLI and somatostatin release during arterially administered peptidergic stimuli. In the present study the effect of elevated levels of glucose or insulin was examined on vagally induced changes of gastrin, somatostatin and BLI secretion. The lumen of the stomach was perfused with saline pH 7 or pH 2. Vagal stimulation (5 Hz, 1 msec, 10V) increased gastrin and BLI secretion and inhibited somatostatin release. The increase of the perfusate glucose concentration from 100 mg/dl to 150 or 300 mg/dl or the addition of insulin (100 microU/ml) augmented vagally stimulated gastrin release at luminal pH 7 but not pH2. Vagally induced inhibition of somatostatin was attenuated by both concentrations of glucose at either luminal pH while insulin had no effect. BLI secretion was affected neither by elevated glucose nor by insulin. On the other hand, the noncholinergic component of vagally induced BLI secretion in the presence of atropine was augmented by insulin. These data demonstrate that glucose and insulin can modulate vagally activated gastric neuroendocrine functions which could be of relevance during the ingestion of carbohydrate containing meals.

Animals↗