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Biomedical subjects

M Classen

Publications and source records attributed to M Classen.

At least 127 records · Page 7Linked to original sources
PubMed1994

RUDER--a prospective, two-year, multicenter study of risk factors for duodenal ulcer relapse during maintenance therapy with ranitidine. RUDER Study Group.

In a prospective study of the risk factors for duodenal ulcer relapse during maintenance (150 mg daily) ranitidine therapy, 1899 patients with chronic ulcer disease were recruited to a multicenter, German trial. Healing of all ulcers was confirmed endoscopically; endoscopy was also obligatory after one and two years or if the patients presented in the interim with symptoms of ulcer relapse. By the end of the first year, 247 patients had experienced at least one relapse and, by the end of the second year, 432 patients had relapsed at least once. The crude one- and two-year relapse rates were 13.0% (95% CI 11.5-14.5) and 22.7% (20.9-24.6%), respectively. Univariate analysis indicated that all seven prospectively defined risk factors were associated with an increased two-year relapse rate; of these, duodenal erosions distant from the healed ulcer [odds ratio (95% CI): 2.23 (1.59-3.15); P < 0.0001], smoking, past or present [1.46 (1.12-1.90); P = 0.0050], psychological stress [1.38 (1.09-1.74); P = 0.0085], heavy physical labor [1.45 (1.06-1.98); P = 0.0219], and absence of NSAID intake [1.54 (1.01-2.29); P = 0.0464] were independent risk factors on stepwise logistic regression analysis, whereas persistent symptoms at healing [1.29 (1.03-1.62), P = 0.0310] and frequent prior relapses [1.45 (1.01-2.04); P = 0.0454] were not. Multiple relapses in 107 patients [5.63% (4.60-6.67%)] were associated with duodenal erosions, smoking, stress, and heavy physical labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Endosonographic possibilities in the pancreatobiliary area.

ES is certainly the most accurate technique presently available for visualizing small lesions in the pancreas and (distal) bile duct. However, this technique can at present not be utilized for improving the earlier diagnosis of pancreatic carcinoma but is of great help in the preoperative localization of pancreatic endocrine tumours. ES makes significant contributions to the preoperative loco-regional staging of pancreatic, ampullary and distal biliary malignancies, but it has distinct limitations in large masses and more remote areas (superior mesenteric vein) and in the differentiation between malignant and inflammatory lesions.

Biliary Tract Diseases↗
PubMed1994

Oligoclonality and skewed T cell receptor V beta gene segment expression in in vivo activated human intestinal intraepithelial T lymphocytes.

Intraepithelial intestinal T lymphocytes (IEL) bearing alpha beta or gamma delta T cell receptors (TCR) are positioned to serve as a first line of defense against enteric pathogens. To investigate whether intestinal IEL are subject to antigenic selective forces distinct from that influencing (xp T cells in the peripheral blood (PBL), we performed a comparative analysis of V beta gene segment usage in IEL and PBL of immunologically normal donors by quantitative PCR. Primers for 22 different human TCR V beta gene segments of V beta gene segments families were used to analyze the repertoire of TCR beta chain transcripts in colonic IEL (c-IEL), in corresponding colonic lamina propria lymphocytes (c-LPL), and in peripheral blood lymphocytes. In each of the three individuals examined, a limited number (1-4 out of 22) of TCR V beta families predominated and accounted for more than 50% of the total beta chain transcripts from c-IEL, whereas in PBL and c-LPL a more even distribution of V beta gene families was observed. The dominating V beta gene families were V beta 2, V beta 3, V beta 6, V beta 8 and V beta 14. In one individual, V beta 3 comprised more than 40% of the entire repertoire of c-IEL beta chain transcripts. Sequence analysis of the predominant V beta 3 family in this individual revealed identical sequences in 13 of 17 clones analyzed. Human alpha beta TCR+ c-IEL could not be driven to proliferate or exhibit cytotoxic function in vitro however, PCR analysis for detection of lymphokine mRNA revealed constitutive production of several lymphokines known to exert trophic effects on intestinal epithelial cells and pro-inflammatory activities. Taken together, the striking degree of oligoclonality may indicate that the intraepithelial intestinal immune system is targeted to a limited set of hitherto unknown self- or foreign antigens present in the intestine and orchestrates intramucosal inflammatory and regenerative processes.

Base Sequence↗
PubMed1994

pHi and HCO3- dependence of proton extrusion and Cl(-)-base exchange rates in isolated rabbit parietal cells.

In many cell types, the regulation of intracellular pH (pHi) is different in the presence vs. absence of HCO3-. We investigated the pHi and HCO3- dependence of proton extrusion and anion exchange rates in isolated rabbit parietal cells loaded with the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). In Cl(-)-depleted parietal cells, the dependence of maximal proton efflux rate on pHi showed a strong inverse correlation but was identical in the presence and absence of HCO3-. Amiloride and Na+ removal inhibited proton extrusion rates to a similar degree with or without HCO3-, whereas 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) had no effect. This suggests that a Na(+)-H+ exchanger is the major acid extrusion ion transporter under these experimental conditions. In Cl(-)-containing cells, there was also some Na(+)-independent, extracellular HCO(3-)- and intracellular Cl(-)-dependent, DIDS-inhibitable pHi recovery from an acid load, most likely due to intracellular Cl(-)-extracellular HCO3- exchange. Recovery from an alkaline load was primarily mediated by anion exchange, and the dependence of maximal anion exchange rates on pHi was very different in the absence and presence of HCO3-. In its absence, maximal anion exchange (Cl(-)-OH-) rates increased slowly over the tested pHi range from 6.4 to 7.8. In the presence of HCO3-, however, there was an S-shaped dependence of maximal flux rates on pHi, with a steep increase in flux rates between 6.8 and 7.5.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Stimulation of rat parietal cell function by histamine and GLP-1-(7-36) amide is mediated by Gs alpha.

It was the aim of the present study to determine in rat parietal cells whether Gs alpha, the stimulatory subunit of adenylate cyclase, mediates adenosine 3',5'-cyclic monophosphate (cAMP)-dependent parietal cell function in response to histamine and glucagon-like peptide 1 (GLP-1)-(7-36) amide. Cytoplasmic membrane from enriched (83 +/- 5%) rat parietal cells were incubated for 30 min with 30 microCi/ml [32P]NAD+ and 40 micrograms/ml preactivated cholera toxin (CT), a pharmacological tool for activation of Gs alpha. Subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography revealed [32P]ADP ribosylation of Gs alpha represented by three proteins with molecular masses ranging from 42 to 45 kDa. In intact parietal cells, CT (10(-12)-10(-8) M) caused marked stimulation of [14C]aminopyrine accumulation and cAMP production confirming the functional importance of Gs alpha in regulation of H+ production. Identical membrane preparations were preincubated (2 h, 4 degrees C) in parallel with and without RM/1, a rabbit polyclonal anti-Gs alpha-antibody. Subsequently, adenylate cyclase was stimulated by histamine, GLP-1-(7-36) amide, CT, or forskolin. At a 1:10 dilution, the antiserum completely abolished adenylate cyclase activity in response to maximal concentrations of histamine, GLP-1-(7-36) amide, and CT while reducing forskolin stimulation by only 22.0 +/- 4.9%. At 1:50, RM/1 reduced responses to histamine, GLP-1-(7-36) amide and CT by 20-30% but failed to inhibit forskolin-stimulated enzyme activity. At 1:100, the antiserum was ineffective versus all stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1994

Rat parietal cell receptors for GLP-1-(7-36) amide: northern blot, cross-linking, and radioligand binding.

The intestinal peptide hormone glucagon-like peptide-1 (GLP-1) (7-36) amide is a potent stimulus of H+ production in isolated rat parietal cells, suggesting the presence of specific GLP-1-receptors on this cell type. Our aim was to characterize these receptors. Enzymatically isolated rat gastric mucosal cells (F0) were fractionated by counterflow elutriation, resulting in five fractions (F1-F5) according to increasing cell diameter and parietal cell content (3, 5, 4, 27, 81%). Additional density gradient centrifugation of F4 yielded enriched chief cells (74%; parietal cells: 1%; F6), whereas density gradient centrifugation of F5 almost purified parietal cells (97%; chief cells: 1%; F7). Northern blot of total cellular RNA from F0-F7 with a probe specific for the GLP-1-(7-36) amide receptor revealed two RNA species of 2.7 and 3.6 kb. These messages were present to some extent in small cells (F1, F2), much more pronounced in F5, abundant in F7, barely detectable in F3 and F4, and absent from F6. Cross-linking of 125I-labeled GLP-1-(7-36) amide to parietal cell membranes revealed a single 59-kDa band that was abolished by unlabeled GLP-1-(7-36) amide. Throughout fractions F1-F7 specific binding of 125I-GLP-1-(7-36) amide was correlated with parietal cell content (r = 0.99; P < 0.01) and H+ production ([14C]aminopyrine accumulation) in response to GLP-1-(7-36) amide or histamine (r = 0.96; P < 0.01). Binding was maximal in purified parietal cells (F7), whereas almost no binding was detectable in enriched chief cells (F6). In F7, Scatchard analysis revealed a single class of high-affinity binding sites (KD = 2.8 +/- 0.6 x 10(-10) M, Bmax = 6.8 +/- 1.4 fmol/10(6) cells, 4,096 +/- 793 receptors/parietal cells). The following half-maximal inhibition values were found for GLP-1-(7-36) amide and (1-37) and (1-36) amide: 6.6 +/- 0.9 x 10(-10), 1.4 +/- 0.7 x 10(-7), and 2.6 +/- 0.4 x 10(-7) M, respectively. Pancreatic glucagon, GLP-2, and oxyntomodulin, products of the proglucagon gene, were 3-4 log units less potent displacers while gastric inhibitory peptide, vasoactive intestinal peptide, and secretin were ineffective. We conclude that rat parietal cells are equipped with specific high-affinity receptors for GLP-1-(7-36) amide, which, in addition, are present in as yet unidentified small cells (F1, F2) but not in chief cells.

Aminopyrine↗
PubMed1994

Concanavalin-A-extractable non-mucous glycoprotein concentrations in gallbladder bile of cholesterol gallstone patients.

BACKGROUND: The relationship between protein concentrations and the nucleation activity of bile in cholesterol gallstone patients has already been investigated. Nucleation promoters are mucins and concanavalin A (Con-A)-extractable glycoproteins. Nucleation inhibitors are apolipoproteins. We wanted to investigate whether a change in concentration of apolipoprotein A-I (Apo A-I) or Con-A in the bile of cholesterol stone carriers is dependent on the nucleation time. METHODS: Total protein was measured by fluorescence photometry, and Con-A-extractable glycoproteins were separated by their affinity to lectins and measured by photometry. Apolipoproteins were measured by radioactive competitive protein binding assay. RESULTS: The protein concentrations in our bile samples were 2.41 +/- 1.08 mg/ml for the whole group, 2.73 +/- 1.07 mg/ml for a nucleation time less than 3 days, and 2.04 +/- 1.00 for a longer nucleation time. The concentration of the Con-A fraction accounted for 0.289 +/- 0.096 mg/ml, 0.306 +/- 0.081 mg/ml, and 0.274 +/- 0.109, respectively. The Apo A-I concentration was 52 +/- 64 micrograms/ml; 50 +/- 56 micrograms/ml for a nucleation time less than 3 days and 85 +/- 133 micrograms/ml for a longer nucleation time. CONCLUSIONS: Obviously, individual protein fractions have an effect on the nucleation behaviour of gallbladder bile in cholesterol gallstone patients.

Apolipoprotein A-I↗
PubMed1994

[Chemoimmunotherapy of malignancies of the gastrointestinal tract].

Stimulation of the immune response could be obtained in outpatients with inoperable locally advanced or metastasizing gastrointestinal tumors (n = 56), who were palliatively treated with cyclophosphamide (cy), 350 mg/m2 i.v., thymostimulin, echinacin i.m. and in part additionally with epirubicin, 15 mg/m2 i.v. At present, outpatients with pancreatic (n = 7) or colon carcinomas (n = 1) receive interleukin 2 (IL-2) intralesionally, 2 x 10(5) Cetus units (CU), days 3, 5 and 7 after cy, and by portable continuous infusion systems i.v., 3 x 10(5) CU/day, days 3-8 after cy. Subsets of lymphocytes slightly decreased in the patients' peripheral blood, recall antigen reactivity slightly increased. Patients' mean survival time was 5.7 +/- 1.7 months.

Cyclophosphamide↗
PubMed1994

Double blind placebo controlled study on the effect of the nitric oxide donor molsidomin and the 5-HT3 antagonist ondansetron on human esophageal motility.

The aim of the present study was to investigate the effects of acute administration of the NO-donor molsidomin (2 mg) and the 5-HT3 antagonist ondansetron (8 mg) on esophageal motility and lower esophageal sphincter pressure (LESP) in 10 healthy volunteers by stationary side hole manometry in a double-blind placebo controlled study design. LESP, contraction amplitudes (5, 10, 15 cm above the LES) and propagation velocity (10-15 cm above the LES) for dry and wet swallows were analysed and additional blood samples were taken for determination of plasma levels of VIP and gastrin. Molsidomin significantly decreased basal LESP from 16.8 +/- 1.6 mmHg to 11.4 +/- 1.0 mmHg, while ondansetron had no influence. Molsidomin also reduced contraction amplitudes of dry swallows (saline 61.9 +/- 7.2 mmHg, molsidomin 40.1 +/- 8.1 mmHg), while it did not influence contraction amplitudes of wet swallows. Ondansetron had no effect on contraction amplitudes. Both substances did not influence propagation velocity of wet swallows, while they reduced propagation velocity of dry swallows significantly (saline 3.9 +/- 0.4 cmls, ondansetron 3.1 +/- 0.2 cm/s, molsidomin 3.1 +/- 0.2 cmls). There were no effects on plasma levels of gastrin or VIP. These data strongly suggest a possible therapeutic role of molsidomin in the treatment of esophageal motility disorders. Effects of ondansetron have to be further evaluated in patients with disturbed esophageal motility.

Adult↗
PubMed1993

[Globus pharyngis: indications for flexible endoscopy?].

Flexible endoscopy of the upper gastrointestinal tract usually does not form part of the primary diagnostic evaluation of the globus syndrome. In order to find out the value of this investigation in the differential diagnosis of globus sensation, 51 globus patients were examined by flexible endoscopy of the upper gastrointestinal tract. Pathological findings requiring therapy were diagnosed in 70.6% of cases. The most frequent findings were reflux esophagitis (n = 24; 47%) and hiatal hernia (n = 25; 49%). In 16 cases (31.4%) these were accompanied by other pathological lesions. A total of 32 patients (62.7%) suffered from esophageal diseases as sole etiological factors of the globus syndrome, which allowed us to postulate a causative relationship in these cases. Flexible endoscopy, therefore, can contribute significantly to the differential diagnosis of the globus syndrome. The investigator should consider the potentially high diagnostic "yield" of flexible endoscopy for this indication, also.

Adult↗
PubMed1993

[Pneumonia due to a rare atypical Mycobacterium in AIDS].

A 38-year-old man, HIV-positive for 6 years, developed fever and cough with deterioration in his general state. Chest radiography demonstrated an infiltration in the left upper lobe and computed tomography showed a septated cavity. Three bronchioalveolar lavages over 4 weeks recovered Klebsiella, Candida, Pseudomonas and Staphylococcus in the lavage fluid. Acid-fast rods were not found in any of the microscopic preparations. His clinical condition and the radiological findings deteriorated despite appropriate antibiotic administration. A further cavity occurred in the right upper lobe and the inflammatory infiltrations extended further. Although no acid-fast organism had been demonstrated, tuberculostatic treatment was begun (daily 300 mg isoniazid, 600 mg rifampicin, 900 mg streptomycin, 2 g pyrazinamide). His general condition and the radiological findings rapidly improved. Four weeks after culturing the lavage fluid atypical Mycobacterium xenopi was isolated. This case illustrates the difficulty of diagnosing an atypical mycobacterial infection. It takes time and effort, but it is of great importance because up to 50% of patients with AIDS contract such infection. Early and appropriate treatment will significantly improve quality of life and life expectancy.

AIDS-Related Opportunistic Infections↗
PubMed1993

In man histamine and muscarinergic mechanisms are essential mediators of acid secretion in response to synthetic human gastrin (1-17).

It is still controversial whether gastrin stimulates acid secretion by interacting with specific gastrin receptors on parietal cells or via endogenous mediators, e.g., histamine. Therefore, it was our aim to determine in healthy human volunteers (n = 14; 3 females, 11 males; age 23-28 years) the degree by which the specific histamine H2-receptor antagonist famotidine or the muscarinergic antagonist atropine block acid secretion in response to synthetic human gastrin (hG) (1-17). Famotidine was deliberately administered at a supramaximal dose (40 mg i.v. bolus) to reliably block any and all effects of endogenous histamine on the parietal cells. After an overnight fast famotidine or saline were injected i.v., and gastric secretions were collected via a nasogastric tube for the ensuing 60 min to assess basal secretion. Thereafter, hG (1-17) was infused for 60 min in randomized order at two different rates: 0.75 ng/kg/min resulting in postprandial plasma gastrin levels (55-66 pg/ml), and 1.5 ng/kg/min yielding supraphysiologic levels (110-136 pg/ml). Both rates increased basal acid secretion (meq/10 min) from 0.5 +/- 0.2 to 3.8 +/- 0.6 and 4.7 +/- 0.5, respectively. Famotidine abolished basal acid secretion and completely blocked acid and volume secretion in response to both hG (1-17) doses. After injection of famotidine both hG (1-17) doses resulted in plasma levels exceeding those in controls by 18-27 pg/ml. A similar increase (14-16 pg/ml) was observed after famotidine injection without simultaneous hG (1-17) infusion indicating that this increase was due to the release of endogenous gastrin when the acid feedback inhibition was blocked by famotidine. To study a potential additional role of cholinergic mechanisms the effect of atropine (7 micrograms/kg i.m.) on hG (1-17)-induced acid secretion was examined. Atropine reduced basal acid secretion from 0.8 +/- 0.1 to 0.1 +/- 0.08 meq/15 min. Similarly, the response to 0.75 ng/kg/min hG (1-17) was reduced by 72.9%. Basal gastrin release was not altered by atropine which, however, tended to increase serum gastrin levels during infusion of hG (1-17) by 16-24 pg/ml. We conclude that in man histamine and muscarinic mechanisms are essential mediators of gastrin-stimulated acid secretion. The present data argue against a significant direct effect of gastrin alone on human parietal cells but rather support potentiating interaction with histamine and cholinergic mechanisms.

Adult↗
PubMed1993

Pertussis toxin-sensitive inhibition of glucagon-like peptide 1-stimulated acid production by epidermal growth factor and transforming growth factor alpha in rat parietal cells.

We have recently shown that the intestinal hormone glucagon-like peptide-1 (GLP-1)-(7-36) amide is a cAMP-dependent stimulant of rat parietal cell H+ production. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are known to inhibit histamine-stimulated parietal cell function by reducing cAMP production in a pertussis toxin-sensitive manner. Pertussis toxin blocks Gi alpha, the inhibitory subunit of adenylate cyclase, thereby preventing inhibitors from acting via Gi alpha. Therefore, we used pertussis toxin as a tool to determine whether EGF and TGF alpha inhibit GLP-1-stimulated parietal cell function via Gi alpha. In enriched (76 +/- 4%) rat parietal cells [14C]aminopyrine accumulation and cAMP production were maximally stimulated by GLP-1-(7-36) amide (10(-8) and 10(-7) M, respectively) or by histamine (10(-4) and 10(-3) M, respectively). EGF and TGF alpha (10(-13)-10(-7) M) caused concentration-dependent inhibition of GLP-1-stimulated parietal cell function. Maximal inhibition (33% and 37% of the response to GLP-1-(7-36) amide was observed at 10(-8) M EGF and 10(-9) M TGF alpha, respectively. There was a close correlation (r = 0.83; P < 0.05; n = 7) between the inhibition by EGF and TGF alpha of [14C]aminopyrine accumulation and the fall in cAMP production in GLP-1-stimulated parietal cells. The identical concentrations of both growth factors which maximally reduced GLP-1-stimulated parietal cell function inhibited [14C]aminopyrine accumulation in response to histamine by approximately 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗