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Biomedical subjects

B Simon

Publications and source records attributed to B Simon.

At least 73 records · Page 4Linked to original sources
PubMed1998

MEN1 gene mutations in 12 MEN1 families and their associated tumors.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumor syndrome characterized by the development of multiple endocrine tumors. The gene responsible for the disease, termed MEN1 gene. has recently been isolated and germline mutations have been described in affected MEN1 individuals. Twelve unrelated (German MEN1 families and their associated tumors (5 parathyroid tumors, 1 vipoma, 1 gastrinoma, 1 insulinoma) were characterized for MEN1 gene mutations by single-strand conformational variant (SSCV) analysis and DNA sequence analysis as well as for loss of heterozygosity on chromosome 11q13. We identified nine different heterozygous germline mutations (6 frameshift, 2 missense, 1 nonsense), eight of them were novel. Four of five informative MEN1-associated tumors revealed deletion of the second MEN1 allele, supporting the concept of a tumor suppressor gene. Furthermore. SSCV analysis proved an effective and sensitive method for the detection of menin mutations providing a reliable genetic screening approach supporting genetic counseling and clinical management of MEN1 family members.

Adenoma↗
PubMed1998

[The action of the proton pump inhibitor pantoprazol against acetylsalicylic acid-induced gastroduodenopathy in comparison to ranitidine. An endoscopic controlled, double blind comparison].

In a randomised double-blind parallel study the gastroduodenal tolerability of 300 mg acetylsalicilic acid daily (ASA, CAS 50-78-2) has been evaluated in the presence of placebo (n = 8), 40 mg pantoprazole (CAS 102625-70-7) daily (8 a.m.) (n = 16) and 300 mg ranitidine (CAS 66357-35-5) daily (8 a.m.) (n = 16) in healthy volunteers using upper GI-endoscopy. The treatment period lasted 14 days, endoscopic controls were performed at entry and repeated at day 14. At entry, the mean endoscopic score averaged 1.0 +/- 0.0 (+/- SEM) in the ASA/placebo, in the ASA/pantoprazole and the ASA/ranitidine group. In the placebo experiments 300 mg ASA daily induced marked gastroduodenal lesions at day 14 (lesion score of 6.8 +/- 1.4 (+/- SEM). Concomitant administration of 40 mg pantoprazole daily offered significant protection against 300 mg ASS daily on day 14 (2.1 +/- 0.6) (+/- SEM) (p < 0.05) vs ASA/placebo. 300 mg ASA plus 300 mg ranitidine daily reduced the damaging score to 4.9 +/- 1.2 (+/- SEM) (n.s. vs ASA/ placebo). Our data suggest that coadministration of 40 mg pantoprazole daily reduces significantly gastroduodenal lesions evoked by 300 mg ASA daily.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Immunological and biological properties of Bet v 4, a novel birch pollen allergen with two EF-hand calcium-binding domains.

We have isolated a cDNA clone coding for a birch pollen allergen, Bet v 4. The deduced amino acid sequence of Bet v 4 contained two typical EF-hand calcium-binding domains. Sequence similarities of Bet v 4 to calmodulin are primarily confined to the calcium-binding domains. However, significant sequence similarities extending outside the Ca2+-binding sites were found with a recently described group of pollen-specific allergens of Brassica and Bermuda grass. Both EF-hand domains of Bet v 4 are able to bind Ca2+, as demonstrated by 45Ca2+ blot overlay of wild type and calcium-binding deficient mutants of Bet v 4. Among pollen-allergic patients, protein-bound Ca2+ was not an absolute requirement for IgE recognition of Bet v 4. However, disruption of the carboxyl-terminal Ca2+-binding domain indicated that most IgE antibodies from allergic patients are directed against this site. IgE inhibition experiments suggested that Bet v 4 represents a highly cross-reactive pollen allergen. Pre-absorption of allergic sera with Bet v 4 drastically reduced IgE binding to proteins of similar molecular weight in pollen extracts from distantly related plant species (e.g. timothy grass, mugwort, lily) but not in extracts from plant-derived foodstuff. To test for a possible biological role in pollen germination and tube growth, we introduced recombinant Bet v 4 protein into growing lily pollen tubes by iontophoresis. As a result, cytoplasmic streaming stopped in the vicinity of the electrode tip, and a slight depolarization of the membrane voltage was measured. These effects were not observed with Ca2+-binding deficient mutants of Bet v 4. Thus, Bet v 4 and homologous proteins represent a new class of pollen-specific Ca2+-binding allergens that may have a physiological role as inhibitors of cytoplasmic streaming in outgrowing pollen tubes.

Allergens↗
PubMed1997

ZBP-89, a Krüppel-type zinc finger protein, inhibits cell proliferation.

ZBP-89 is a Krüppel-type zinc finger transcription factor that binds to GC-rich sequences. Overexpression of this factor prevents EGF induction of the gastrin promoter; therefore, we postulated that ZBP-89 may modulate cellular proliferation. To test this hypothesis, ZBP-89 was overexpressed in immortalized (GH4) and malignant (AGS) cell lines. Growth parameters, e.g., 3H-thymidine, BrdU labeling, flow cytometry and ornithine decarboxylase promoter activity were analyzed. The results show that DNA synthesis is inhibited and progression to S phase is blocked in GH4 cells. Collectively, these studies demonstrate that ZBP-89 inhibits cellular proliferation at least in part through its ability to bind and repress ornithine deacarboxlyase promoter activity.

Adenocarcinoma↗
PubMed1997

RAP1-like binding activity in islet cells corresponds to members of the Sp1 family of transcription factors.

Deletion and mutational analyses of the gastrin promoter have identified a binding site for the yeast transcription factor RAP1 relevant for transcriptional activation in islet cells. We here report that the mammalian transcription factors binding to this site in islet cells are the Sp transcription factor members Sp1 and Sp3. Furthermore, functional analyses revealed Sp1- and Sp3-mediated transcriptional activation of gastrin. These data reveal that the zinc finger proteins Sp1 and Sp3 do have similar binding specificities as the multifunctional yeast RAP1 protein.

Animals↗
PubMed1997

Transient transcriptional activation of gastrin during sodium butyrate-induced differentiation of islet cells.

Transient expression of pancreatic gastrin corresponds to a period of rapid islet cell development. After birth gastrin expression silencing is coincidental with islet cell terminal differentiation, while persistent expression is accompanied with nesidioblastosis and reexpression observed in islet cell tumors. Experiments with transgenic animals suggested that gastrin might act synergistically with growth factors to stimulate islet cell development. The present study intended to establish an in vitro cell culture model to analyse the molecular events controlling gastrin gene activation and repression dependent on islet cell differentiation. Sodium butyrate, a proliferation-arresting compound has previously been shown to differentiate insulinoma cells while increasing insulin production. The present paper demonstrates concomitant transient increase in gastrin mRNA, intracellular and secreted gastrin during sodium butyrate treatment. Increased gastrin expression was due to activation or derepression of gastrin promoter activity as revealed by promoter analyses. This in vitro model mimics the expression pattern of gastrin and insulin observed during fetal islet cell development and provides an excellent tool to analyse the molecular mechanisms controlling gastrin gene activation and selective repression during islet cell differentiation.

Animals↗
PubMed1997

Dopaminergic and serotonergic properties of fluoxetine.

1. Rats were trained to discriminate i.p. injections of a 5-HT agonist, LSD (0.08 mg/kg, n = 12) or a DA agonist, cocaine (10 mg/kg; n = 16) in a two lever, drug discrimination situation. 2. Animals were tested with fluoxetine (0.625-10 mg/kg) alone and in combination with low doses of the training drugs. 3. Fluoxetine did not substitute for either LSD or cocaine at any dose tested. A relatively low dose of fluoxetine (2.5 mg/kg) potentiated the discriminability of cocaine (2.5 mg/kg) from saline. A higher dose of fluoxetine (5.0 mg/kg) significantly enhanced the effects of a low dose of LSD (0.02 mg/kg), but only to 41.7% responses on the LSD-appropriate lever. 4. The data suggest that fluoxetine alters the discriminative stimulus properties of cocaine to a greater extent than those of LSD. 5. The ability of fluoxetine to potentiate the cocaine cue (but not to substitute for cocaine) suggests that both of those drugs affect DA systems, but do so through different mechanisms. For example, fluoxetine may not inhibit DA reuptake (to the same extent as cocaine), but may have other dopaminergic actions such as increasing DA receptor density.

Animals↗
PubMed1997

When self-categorization makes sense: the role of meaningful social categorization in minority and majority members' self-perception.

The authors examined the joint influence of meaningful social categorization and relative in-group size on the depersonalization of self-perception. Meaningfulness of social categorization was varied following the fit principle, introduced by self-categorization theory. In Experiment 1, the authors predicted and found that minority members show more depersonalized self-perception than majority members if, and only if, the meaningfulness of the underlying in-group-out-group categorization is high as opposed to low. Experiment 2 further substantiated that a meaningful social categorization affects only minority members' self-perception. Finally, the conceptual relationship between fit, meaning, and identity is discussed.

Adult↗
PubMed1997

Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia.

BACKGROUND & AIMS: The mechanisms causing progression of fundic gastritis and changes in argyrophil cell morphology in patients undergoing long-term treatment with proton pump inhibitors are unknown. The hypothesis of this study was that Helicobacter pylori is a risk factor for both gastritis and argyrophil cell hyperplasia. METHODS: Forty-two patients with peptic disorders resistant to H2-blockers were treated with 30-90 mg lansoprazole daily for up to 5 years. Serum gastrin levels, antral gastrin cells, fundic argyrophil cells, parameters of gastritis, and H. pylori infection were evaluated regularly. RESULTS: In nonantrectomized patients, serum gastrin levels increased from a median of 76 pg/mL to 163 pg/mL within 3 months. Antral gastrin cell density increased from 175 to 267 cells/mm2 (P < 0.001), and fundic argyrophil cell density increased from 83 to 149 cells/mm2 (P < 0.001). Chronic inflammation, activity, and atrophy of the oxyntic mucosa worsened exclusively in patients with H. pylori infection. Linear and/or micronodular argyrophil cell hyperplasia was diagnosed in 2.6% of patients before lansoprazole and in 29.2% after 5 years treatment. These changes were significantly related to serum gastrin levels, H. pylori infection, chronic inflammation, and atrophy of the oxyntic mucosa. CONCLUSIONS: H. pylori represents an important factor for the progression of fundic gastritis and the development of argyrophil cell hyperplasia during long-term treatment with lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

High levels of circulating adrenomedullin in severe illness: correlation with C-reactive protein and evidence against the adrenal medulla as site of origin.

Adrenomedullin (AM) is a novel vasorelaxing peptide which was originally isolated from the extracts of human pheochromocytoma. It is produced by a number of organs among which the adrenal gland exhibits by far the highest concentrations. The peptide circulates in blood and its plasma levels have been reported to be increased in several diseases such as renal failure and sepsis. In the present study plasma concentrations of AM were measured in various forms of severe illness and compared to clinical and biochemical parameters in order to gain an insight into the factors controlling the plasma levels of this peptide. The highest concentrations of AM were found in patients with sepsis (344.4 +/- 60.4 pg/ml, n = 16) who exhibited up to 12-fold higher levels than a group of healthy subjects (74.1 +/- 4.1 pg/ml, n = 20). Markedly elevated levels were also measured in hemorrhagic (250.1 +/- 37.9 pg/ml, n = 9) and cardiogenic (216.2 +/- 29.4 pg/ml, n = 7) shock as well as in patients with cancer of the gastrointestinal tract (155.6 +/- 32.5 pg/ml, n = 11) or the lungs (146.5 +/- 19.1 pg/ml, n = 22). Plasma AM levels were positively correlated with serum creatinine concentrations in shock (r = 0.06, p < 0.001) and with C-reactive protein levels in patients with cancer (r = 0.64, p < 0.001) or sepsis (r = 0.63, p < 0.01). In order to examine the potential role of the adrenal gland as a site of AM release, hypoglycemia was induced in a group of healthy volunteers by graded infusion of insulin. Despite a more than 20-fold increase in plasma adrenalin indicating maximal stimulation of the adrenal medulla, no significant alterations of the plasma AM levels were observed. The study demonstrates that not only sepsis but also various forms of cancer and shock are associated with high levels of circulating AM. The correlation with C-reactive protein levels suggests a role of cytokines in mediating the elevations in plasma AM observed in sepsis and cancer. Reduced clearance of the peptide by the kidneys may be one of the mechanisms involved in the accumulation of AM in shock. The adrenal gland appears not to be a major source for circulating AM.

Adrenal Medulla↗
PubMed1997

[Studies on the protective effect of lansoprazole on human gastric mucosa against low-dose acetylsalicylic acid. An endoscopic controlled double-blind study].

In a randomized double-blind parallel study the gastroduodenal tolerability of 300 mg acetylsalicylic acid (ASA) daily has been evaluated in the presence of placebo, 15 mg lansoprazole (CAS 103577-45-3, Agopton) and 300 mg ranitidine daily (8 a.m.) in 30 healthy volunteers using upper gastrointestinal tract 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 1.0 +/- 0.0 (+/- SEM) in the ASA/placebo (n = 10), in the ASA/ lansoprazole 15 mg (n = 10) and the ASA/300 mg ranitidine group. In the placebo experiments 300 mg ASA daily induced marked gastroduodenal lesions at day 14 (lesion score of 10.1 +/- 1.4) (+/- SEM). Concomitant administration of 15 mg lansoprazole daily offered significant protection against 300 mg ASA daily on day 14 (3.6 +/- 1.2) (p < 0.05), 300 mg ASA plus 300 mg ranitidine daily reduced the damaging score to 5.8 +/- 1.3 (p n.s. vs ASA/placebo). Our data suggest that co-administration of 15 mg lansoprazole daily reduces significantly gastroduodenal lesions evoked by 300 mg ASA.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

[Influence of mechanisms of Pseudomonas aeruginosa resistance on the bactericidal activity of third generation cephalosporins].

Survey of resistance of beta-lactam's resistance of P. aeruginosa have to be conducted. 410 strains of P. aeruginosa ticarcilline resistant have been studied. 52% of these strains were cephalosporinase producing alone or in combination with penicillinase. beta-lactam's inhibitors are not fully efficient upon these strains. Upon cephalosporinase producing strains bactericidal activity of C3G is difficult to obtain. At low concentration selection of strains with upper MICs is observed. This phenomenon is not observed at high concentration of antibiotics. Cefepime show a good bactericidal activity against P. aeruginosa.

Cefepime↗
PubMed1996

[Helicobacter pylori eradication: modified triple therapy with lansoprazole].

For the eradication of Helicobacter pylori in H.p.-positive patients with peptic ulcer, preference is presently being given worldwide to the modified triple therapy-comprising an acid suppressant and two antibiotics. This relatively new form of treatment is highly effective, relatively well tolerated, patient-friendly (5 to 6 tablets daily), and inexpensive. In 12 studies involving more than 600 patients, the new proton pump inhibitor, lansoprazole, has proved to be an effective component of this eradication regimen. In combination with clarithromycin and metronidazole or amoxicillin and clarithromycin, consistently high eradication rates of more than 85% are obtained, with treatment of only seven days duration. Since in terms of clinical efficacy 30 mg lansoprazole daily presumably correspond to 40 mg omeprazole daily, the new proton pump inhibitor represents a more economic alternative for H.p. eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗