Biomedical subjects

B Simon

Publications and source records attributed to B Simon.

At least 109 records · Page 6Linked to original sources

PubMed1995

Effect of gastrin receptor blockade on gastrin and histidine decarboxylase gene expression in rats during achlorhydria.

BACKGROUND: Gastrin stimulates histidine decarboxylase (HDC) activity and proliferation of enterochromaffin-like (ECL) cells. Furthermore, it has been suggested that gastrin controls HDC gene expression. We therefore analysed the effect of gastrin receptor blockade by PD 136 450 (CAM 1189) on HDC gene expression. The influence of PD 136 450 on gastrin, somatostatin, and chromogranin A was also evaluated. METHODS: Gene expression of HDC, gastrin, somatostatin, and chromogranin A (CgA) was analysed by Northern blot analyses after 14 days' application of the proton pump inhibitor BY 308 and/or the gastrin/cholecystokinin B receptor antagonist PD 136 450. RESULTS: PD 136 450 had no significant effect on gastrin mRNA or somatostatin mRNA in controls and during proton pump inhibition. BY 308 treatment resulted in a marked induction of HDC and CgA mRNA, whereas concomitant PD 136 450 in a concentration previously shown to suppress maximal pentagastrin-induced gastric acid secretion and to prevent BY 308-induced ECL cell proliferation did not result in significant alteration. PD 136 450 increased HDC significantly and CgA mRNA to a lesser extent in normogastrinaemic rats, whereas previous work showed a decreased ECL cell labelling index. CONCLUSIONS: These data suggest that there are independent regulatory pathways for ECL cell proliferation and gene expression. Other factors besides gastrin may act through PD 136 450-insensitive pathways to control HDC and CgA gene expression.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1995

Tumor cell-induced platelet aggregation in vitro by human pancreatic cancer cell lines.

BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is considered to be a critical step in hematogenous metastasis. METHODS: TCIPA was studied in vitro in six human pancreatic carcinoma cell lines (PC 3, PC 44, AsPC1, BxPC3, Capan2, Panc1). RESULTS: Whereas all cell lines induced aggregation of washed platelets in the presence of minimal amounts of platelet-poor plasma, five cell lines also induced aggregation of platelets in platelet-rich plasma. The thrombin-antagonist hirudin inhibited TCIPA in all cell lines indicating that TCIPA is thrombin-dependent. Since pretreatment of tumor cells with phospholipase A2 or C inhibited TCIPA, the thrombin-generating activity might be confined to the tumor cell surface. Further support for a prothrombinase activity was provided by the observation that all cell lines were able to induce the aggregation of washed platelets after addition of purified coagulation factors II and V. CONCLUSIONS: Pancreatic carcinoma cells are able to induce platelet aggregation via activation of thrombin. This might support metastasis in pancreatic cancer and possibly explain the incidence of thrombosis in this tumor.

Antithrombins↗

PubMed1995

[Effects of hydrostatic pressure on malondialdehyde (MDA) determination in brain from yellow freshwater eels].

Malondialdehyde (MDA) content in a tissue can be an indicator of lipoperoxidation and thus of membrane alteration. MDA concentrations have been measured in the brain of yellow freshwater eels (Anguilla anguilla) submitted to 1.51 or 101 ATA of hydrostatic pressure. Exposure to pressure was performed for 6 h at constant water temperature and in normoxic conditions. The results thus obtained show a significant increase (P < 0.05 or better) of MDA brain concentrations at 51 ATA (+ 124%) and 101 ATA (+ 290%). These results mean that hydrostatic pressure is able to activate lipoperoxidation and can alter membrane functions together with the decrease in membrane fluidity it induces. Such a membrane alteration can explain, at least in part, the excitation periods which are observed during and after animal compression.

Anguilla↗

PubMed1995

[Protective effects of ranitidine in ibuprofen gastroduodenopathy. An endoscopic controlled double blind study].

Protective Effect of Ranitidine in Ibuprofen Gastroduodenopathy/An endoscopically controlled double-blind study in healthy volunteers. In a randomized parallel double-blind study the gastroduodenal effects of 600 mg ibuprofen racemate (CAS 15687-27-1) tid in the presence of 150 mg ranitidine (CAS 66357-35-5, Sostril) bid or placebo was evaluated in 32 healthy volunteers undergoing upper gastrointestinal endoscopy. Drugs were taken during a period of 7 days. Endoscopic controls were performed at entry and repeated after 7 days of treatment. A damaging score was used to asses the lesions. At entry both groups showed comparable mucosal damages. The median values under ibuprofen/placebo were 1 (range 0-1) and under ibuprofen/ranitidine 1 (range 0-2). After 7 days of treatment the median lesions score increased under ibuprofen/placebo to 8 (range 1-20) whereas corresponding values in the ibuprofen/ranitidine group were constant at 1 (range 1-9). The differences between both groups were statistically significant (p < 0.05). Our data underline the protective effect of ranitidine 150 mg bid against ibuprofen both on the stomach as well as on the duodenum.

Adolescent↗

PubMed1995

[Protective effect of omeprazole against low-dose acetylsalicylic acid. Endoscopic controlled double-blind study in healthy subjects].

Protective Effects of Omeprazole against Low-dose Acetylsalicylic Acid/An endoscopic controlled double-blind study in healthy volunteers. In a randomized double-blind parallel study the gastroduodenal tolerability of 300 mg acetylsalicylic acid (CAS 50-78-2, ASA) daily (8 p.m.) has been evaluated in the presence of 20 mg and 40 mg omeprazole (CAS 73590-58-6) daily (8 p.m.) or placebo in 36 healthy volunteers using upper GI-endoscopy. The treatment periods lasted 14 days. Endoscopic controls were performed at entry and repeated at day 14. At entry the mean endoscopic score averaged 0.9 +/- 0.08 in the ASA/placebo (n = 12), the ASA/omeprazole 20 mg (n = 12) and the ASA/omeprazole 40 mg group (n = 12). The median values were 1.0. In the placebo experiments 300 mg ASA daily induced marked gastroduodenal lesions at day 14 (12.4 +/- 1.7). The median value was 10.0. Concomitant administration of 20 mg omeprazole daily afforded significant protection against 300 mg ASA daily on day 14 (2.9 +/- 0.9) (p < 0.0005 vs. ASA/placebo). 300 mg ASA + 40 mg omeprazole daily reduced the damaging score to 1.8 +/- 0.5 (p < 0.00002 vs. ASA/placebo). The median values in the ASA/omeprazole 20 mg and in the ASA/omeprazole 40 mg group were 1.0. The difference in the damaging score between ASA/omeprazole 20 mg and ASA/omeprazole 40 mg after 14 days did not reach statistical significance. Our data suggest that coadministration of 20 mg omeprazole daily reduces almost completely gastroduodenal lesions evoked by 300 mg ASA.

Adult↗

PubMed1994

Activation of gastrin gene transcription in islet cells by a RAP1-like cis-acting promoter element.

Gastrin transcription in islet cells is activated by a cis-regulatory sequence containing a binding site for the yeast transcription factor RAP1. The DNA-protein interactions between RAP1 protein and the gastrin DNA element determined by methylation interference assays are identical to those of RAP1 and yeast genes. Point mutations in the gastrin RAP1 binding site, which abolished RAP1 binding, decreased transcriptional activation by this sequence. Islet cells revealed a DNA binding protein with RAP1-like binding specificity. These findings support the conclusion that gastrin transcription is activated in mammalian cells by a RAP1-like transcription factor.

Animals↗

PubMed1994

Modulation of the osteoclast Ca2+ receptor by extracellular protons: possible linkage between Ca2+ sensing and extracellular acidification.

We report a sensitivity of the osteoclast cell surface Ca2+ receptor to extracellular protons. Freshly isolated rat osteoclasts were exposed to the known agonists of the Ca2+ receptor, Ca2+ and Ni2+, in extracellular solutions set at different pH values. Decreasing the extracellular pH from 7.8 to 4.0 units markedly potentiated the cytosolic Ca2+ signals elicited in response to Ca2+ receptor activation by either Ni2+ (50 microM, 500 microM or 5 mM) or Ca2+ (5 mM). Each response consisted of a rapid and usually transient elevation of cytosolic [Ca2+]. Maximal cytosolic [Ca2+] responses were obtained at pH values of 6.6 (for 5 mM-[Ni2+]) and 4.0 units (for 5 mM-[Ca2+]). Finally, the effects of extracellular pH persisted in Ca(2+)-free, EGTA-containing solutions, suggesting a modulation of intracellular Ca2+ release.

Animals↗

PubMed1994

Frequent alterations of the tumor suppressor genes p53 and DCC in human pancreatic carcinoma.

BACKGROUND/AIMS: The pathogenesis of pancreatic cancer is poorly understood. The multigenetic nature of carcinogenesis has been best documented in colon cancer. The relevance of this model was suggested for other epithelial tumors. Only advanced stages of pancreatic cancer are usually detected because of late diagnosis. Analysis of accumulated, diverse genetic changes could allow further understanding of putative mechanisms involved in tumor development. Activated c-Ki-ras oncogene has been shown to be a frequent event. However, additional alterations of tumor suppressor genes are expected. Therefore, concomitant genetic changes of p53 and deleted in colon carcinoma (DCC) in pancreatic carcinoma cell lines and primary tumors were analyzed. METHODS: p53 protein and transcript expression were revealed by immunocytochemistry and immunohistochemistry, immunoassay, and Northern blot analysis. p53 mutations were identified by sequence analysis. DCC expression was investigated by reverse-transcription polymerase chain reaction. RESULTS: p53 overexpression was observed in 9 of 12 cell lines. p53 point mutations were confirmed in seven cell lines overexpressing p53. The majority of cell lines showed concomitant p53 and DCC alterations. Four of 6 primary tumors overexpressing p53 also showed loss of DCC expression. CONCLUSIONS: p53 and DCC genetic changes are associated with pancreatic cancer and the frequently activated c-Ki-ras oncogene. Therefore, the multihit model of carcinogenesis could prove relevant for pancreatic cancer.

Base Sequence↗

PubMed1994

Cytogenetic and fluorescence in situ hybridization studies on sporadic and hereditary tumors associated with von Hippel-Lindau syndrome (VHL).

We performed cytogenetic and fluorescence in situ hybridization (FISH) studies on 29 sporadic or familial tumors associated with von Hippel-Lindau [correction of Landau] disease. Four of five renal cell carcinomas with detectable alterations showed clones with chromosome 3 alterations. These changes led to loss of genetic material visible with cytogenetic resolution: either an unbalanced translocation involving 3p or loss of a whole homolog 3, resulting in monosomy of 3p. We have previously mapped the VHL gene to chromosomal region 3p25-p26. We applied FISH using the single copy probes cA233 and cA479, sequences close to the VHL gene, in a search for submicroscopic deletions of 3p. Use of FISH with differentially labeled probes indicated cA479 to be distal to cA233, but both were located within bands 3p25-26. FISH with single copy probes for interphase cytogenetics detected four subclones with deletions in the VHL region in 8/22 tumors, including four tumors which appeared cytogenetically normal. FISH proved to be a powerful tool in tumor genetic studies, especially helpful in detecting tumor subclones in benign and slowly growing tumors.

Adrenal Gland Neoplasms↗

PubMed1994

Self-stereotyping and social context: the effects of relative in-group size and in-group status.

In 2 laboratory experiments, the tendency to stereotype oneself in terms of one's group membership as a function of the social context was examined. Experiment 1 examined the effects of relative in-group size on self-stereotyping. The results confirmed the prediction that minority members are more likely than majority members to stereotype themselves. Experiment 2 examined the interactive impact of relative in-group size and in-group status. As predicted, a high (relative to a low) status of the in-group increased self-stereotyping primarily for minority members, but not for majority members. Moreover, analyses of the differences in perceived in-group and out-group homogeneity suggest that the in-group homogeneity effect should also be interpreted in terms of self-stereotyping processes. Finally, the interplay between cognitive and motivational determinants of self-stereotyping is discussed as well as a possible distinction between self-stereotyping effects on individual level versus group level self-representations.

Adult↗

PubMed1994

Short report: long-term management of peptic ulcer disease with ranitidine in Germany.

One hundred and twenty-five patients with duodenal ulcer disease were given continuous ranitidine therapy after initial acute healing. Cumulative remission rates indicated that 95% of patients were ulcer-free after 1 year, 89% at 2 years, 81% at 3 years, 70% at 4 years and 60% at 5 and 6 years. Nine patients had a second recurrence after healing of the first. No patient developed an ulcer complication. These results support the view that long-term continuous ranitidine therapy prevents ulcer recurrence and complications.

Duodenal Ulcer↗

PubMed1994

Dimensional analysis of osteoclastic bone resorption and the measurement of biologically active calcitonin.

Calcitonin inhibits bone resorption through a direct action on the osteoclast. We report a quantitative analysis of bone resorption by disaggregated rat osteoclasts. We then used our findings to develop a formal bioassay for calcitonin. Osteoclasts were mechanically disaggregated from neonatal rat long bones and dispersed at low densities on slices of devitalized bovine cortical bone. The resulting areas of bone excavation were quantified to micrometric precision by scanning electron microscopy together with computer-assisted image analysis. These findings were correlated with the volumes of bone resorption in the same slices measured by confocal scanning microscopy for the first time. The total planar areas of bone resorption per slice correlated linearly (r = 0.78) with the confocal microscopic measurements of total volume resorbed, provided that volume was expressed to its two-thirds power. The latter transformation resulted in representations of the determined areas ([length]2) and volumes ([length]3) which were dimensionally consistent. These findings thus demonstrate that osteoclastic bone excavations show a consistent relationship between area and volume and that assessments of the area of excavations accordingly provide an empirical representation of the volume of bone resorbed. Furthermore, in view of the skewed nature of the distributions of area measurements, we assessed the effect of transforming the response variable to derive a metameter, (planar area of resorption)1/2. Such transformed data points, which expressed the data in the dimensions of [length], were more normally distributed than the raw data points and had more stable variances over a wider concentration range. We accordingly determined relative potencies using parallel line analyses on the transformed data. The latter offered a consistent correlation to the volume measurements when these were also converted to dimensions of [length] (r = 0.805). It was confirmed that the inhibition of bone resorption by calcitonins from various species, namely, pig, salmon and eel, was quantitatively dependent upon concentration of the respective peptides. The resulting assay was also found to be sufficiently sensitive to measure picomolar peptide concentrations with a precision, lambda (standard deviation/slope), ranging between 0.3 and 0.8. Finally, we identified factors affecting assay precision and sensitivity.

Animals↗

PubMed1994

Expression of the gastric H+/K(+)-ATPase and histidine decarboxylase during omeprazole treatment.

The gastric proton pump H+/K(+)-ATPase in the parietal cell is central to acid secretion into the stomach. We performed the following experiment to examine the pattern of expression of the alpha- and beta-subunits of the H+/K(+)-ATPase at the transcriptional level during 7 days' application of the proton pump inhibitor omeprazole, in relation to the expression of gastrin and histamine, two stimuli of gastric acid secretion. Serum gastrin concentrations and mRNA levels of antral gastrin, fundic histidine decarboxylase (HDC) and H+/K(+)-ATPase alpha- and beta-subunits were determined after 8 h, 1, 3 and 7 days. Omeprazole treatment rapidly caused an increase in the serum gastrin concentration and the antral gastrin mRNA level after 3 days. HDC mRNA expression showed a steady increase with a 5-fold induction after 1 week. However, mRNA levels of the alpha- and beta-subunits of the H+/K(+)-ATPase were unchanged during the course of omeprazole treatment. These results suggest that omeprazole inhibition of the gastric proton pump does not result in feedback activation of H+/K(+)-ATPase gene expression despite adaptive changes of the endocrine stomach.

Animals↗

PubMed1994

Characteristics of psychoanalytic patients under a nationalized health plan: DSM-III-R diagnoses, previous treatment, and childhood trauma.

OBJECTIVE: This article reports the results of a survey to collect data on the characteristics of patients in psychoanalysis under a nationalized health insurance scheme. METHOD: A questionnaire, to be answered anonymously, was sent to all 174 accredited psychoanalysts in Ontario, Canada. Part 1 of the questionnaire consisted of 38 questions on the analyst's pattern of practice. Part 2, also to be filled out by the analyst, consisted of 452 questions on the demographic characteristics, childhood traumas, DSM-III-R diagnoses, and indications for psychoanalysis of each of the analyst's patients. RESULTS: One hundred seventeen analysts responded--a survey response rate of 67%--with data on 580 patients. Fifty-nine percent (N = 344) of patients were women, and 41% (N = 236) were men. Eighty-two percent had attempted other forms of treatment, including briefer forms of psychotherapy and medication, prior to psychoanalysis. During childhood, 23% had had traumatic separations, 23% had been sexually abused, 22% had been physically abused, and 21% had had a parent or sibling die. The mean number of adult psychiatric disorders at the beginning of analysis was four, and the mode was two. CONCLUSIONS: In a nationalized health insurance scheme, the psychoanalytic patients were mostly women, they had high rates of trauma and psychopathology, and they had attempted other forms of briefer treatment before resorting to psychoanalysis.

Adolescent↗

PubMed1994

Nizatidine in therapy and prevention of non-steroidal anti-inflammatory drug-induced gastroduodenal ulcer in rheumatic patients.

Two hundred and sixty-nine patients with various rheumatic disorders who had been treated with non-steroidal anti-inflammatory drugs (NSAID) for at least 3 weeks were enrolled in this randomized double-blind multicentre trial. Entry criteria were the presence of an ulcer in the gastric and/or duodenal mucosa (> 3 mm and < 20 mm in diameter) and dyspeptic symptoms. The patients were treated with 150 mg nizatidine nocte (n = 86), 2 x 150 mg/d (n = 93) and 2 x 300 mg/d (n = 90) nizatidine. All patients continued to take their original NSAID medication. The three nizatidine groups were well matched with respect to important patient characteristics. After 8 weeks of treatment more than 90% of gastric and duodenal ulcers (DU) had healed under all three nizatidine dosages. There was a tendency to higher healing rates in the case of gastric ulcers after 4 weeks following the higher dose of nizatidine. Erosion, in the stomach and duodenum as well as oesophagitis, improved to a similar degree with all nizatidine doses. There were similar improvements in clinical symptoms such as epigastric pain, heartburn etc. Consumption of additional antacids were similar in all three groups. In the subsequent prevention trial, 237/221 patients were followed for 3/6 months. In addition to their continued antirheumatic medication 116/107 received nizatidine 150 mg nocte and 121/114 patients 2 x 150 mg nizatidine daily. The cumulative relapse rates within 6 months averaged 5.5% in the low and 1.8% in the high dose group (NS). The safety of nizatidine was assessed as good in both the therapeutic and the preventive trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1994

[Comparison of the protective effects of roxatidine and misoprostol on diclofenac gastroduodenal pathology. An endoscopic, controlled study of volunteers].

For prophylaxis of gastroduodenal lesions induced by non-steroidal antirheumatic drugs (NSAID) acid-lowering as well as mucosa protective substances are used. Direct comparison of both therapeutic regimens are lacking. In randomized parallel studies the gastroduodenal tolerability of 100 mg diclofenac daily in slow-release form was evaluated in the presence and absence of 150 mg roxatidine (CAS 78273-80-0) daily as well as in the presence of 75 mg bid roxatidine or 200 micrograms bid misoprostol (CAS 59122-46-2). The drugs were taken over a period of 14 days. Endoscopic controls were performed at entry, as well as after 14 days of treatment. A quantitative damaging score was used. Study A: Both treatment groups (n = 20) had at entry comparable mucosal damages: placebo/diclofenac: 0.9 +/- 0.1 (+/- SEM), roxatidine/diclofenac: 0.9 +/- 0.1; after 14 days of treatment the score increased in the diclofenac/placebo group to 7.6 +/- 1.9 and, in the corresponding diclofenac/roxatidine group, only to 2.1 +/- 0.9. The difference between the two treatment groups after 14 days was significant (p < 0.05). Study B: Both treatment groups (n = 24) had comparable mucosal damages at entry: diclofenac/roxatidine: 0.9 +/- 0.1, diclofenac/misoprostol: 0.8 +/- 0.1. Following 14 days treatment with 100 mg diclofenac daily the damaging score in both group rose to comparable levels: roxatidine group 2.1 +/- 0.7 and misoprostol group 2.0 +/- 0.4 (n.s.). The data suggest that for prophylaxis of NSAID-induced gastroduodenal lesions substances with different mechanism of action can be used. The findings underline the complex way by which NSAID can damage the mucosa of the upper gastrointestinal tract.

Adult↗

PubMed1994

Ranitidine in the treatment of non-ulcer dyspepsia. A placebo-controlled study in the Federal Republic of Germany.

The trial randomly assigned 652 patients with non-ulcer dyspepsia (NUD), defined as chronic or recurrent complaints of acid-related (heartburn, acid regurgitation, epigastric pain) and non-acid related (fullness/vomiting, nausea) symptoms and with no evidence of organic disease, to treatment for 4 weeks with 150 mg of ranitidine (Zantic, CAS 66357-59-3) twice a day, or placebo, according to a double-blind design. The presence and duration of all dyspeptic symptoms were recorded by interviews at the beginning and after 2 and 4 weeks of treatment as well as by diaries. The complete disappearance of all dyspeptic symptoms after 4 weeks in the placebo group was 36%; ranitidine treatment resulted in a significant improvement after 4 weeks (p < 0.05). The effect of ranitidine was slightly more pronounced in acid-related than in non-acid-related symptoms. We conclude that suppression of gastric acid secretion is of clinical value in NUD patients, especially in those suffering from epigastric pain, acid regurgitation and heartburn.

Adult↗

PubMed1994

Fact and fantasy in the history of Freud's views on incest and seduction.

This article surveys the history of Freud's attitudes and theories about the etiologic role of actual incest and seduction and neurosis. It also surveys the debate in historical writing on that topic, much of which oversimplifies complex and contradictory data. Here is an instance in which history is being written and used as part of current debates and polemics, principally to either monolithically defend or attack Freud. This article argues that Freud's motives for downplaying the etiologic role of seduction in the neuroses were complex, did not involve cowardice, and need to be understood both in terms of internal developments in Freud's thinking as well as in terms of relevant external (for example, historical) factors.

Austria↗