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R Meier

Publications and source records attributed to R Meier.

At least 73 records · Page 4Linked to original sources

[Difficulties in differentiation between Crohn disease and ulcerative colitis].

We report on the medical history of a 44 year old woman, who has been diagnosed to suffer from ulcerative colitis, first diagnosed in 1991. Until 1994, when she had finally a colectomy, recurrent episodes occurred under full medical treatment. After colectomy the diagnosis had to be revised as histology revealed Crohn's disease. Only a few months after surgery a new episode of Crohns disease developed including the occurrence of an anal fistula.

Adult↗

[Validation of the "Digest Questionnaire" for consistency and reproducibility with reference to upper abdominal symptoms].

"Digest" is a international effort to record the prevalence of digestive symptoms in the general population. The international questionnaire was tested in German translation for reliability and reproducibility. The questionnaire consists of 14 symptoms, which were investigated by standardized questions. Each symptom was described in 3 dimensions: frequency, severity and impact on daily activities. 127 successive patients referred for upper gastrointestinal endoscopy were interviewed twice by a young assistant and by an experienced gastroenterologist before the diagnostic work-up. A further 72 volunteers served as a control group. In these volunteers no upper gastrointestinal endoscopy was performed. Reliability and reproducibility were calculated by the Spearman rank test. The most frequent diagnoses were: organic diseases (oesophagitis [28], gastric ulcer/erosive gastritis [32] and duodenal ulcer [18]); functional diseases (dyspepsia [32] and irritable bowel syndrome [14]). Reproducibility was satisfactory by accepted standards (p > 0.7). Reliability was very good, with r-values for each symptom between p 0.96-0.99. The impact on daily activities was highest in the case of heart-burn or localized upper gastrointestinal pain, and lowest in the case of belching and fullness. The questionnaire can be easily administered by the non-specialist and the results discriminate well between functional/organic diseases and healthy people, thanks to excellent reproducibility and reliability.

Activities of Daily Living↗

Deuterium in comet C/1995 O1 (Hale-Bopp): detection of DCN.

Deuterated hydrogen cyanide (DCN) was detected in a comet, C/1995 O1 (Hale-Bopp), with the use of the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. The inferred deuterium/hydrogen (D/H) ratio in hydrogen cyanide (HCN) is (D/H)HCN = (2.3 +/- 0.4) x 10(-3). This ratio is higher than the D/H ratio found in cometary water and supports the interstellar origin of cometary ices. The observed values of D/H in water and HCN imply a kinetic temperature >/=30 +/- 10 K in the fragment of interstellar cloud that formed the solar system.

Deuterium↗

A determination of the HDO/H2O ratio in comet C/1995 O1 (Hale-Bopp).

Deuterated water (HDO) was detected in comet C/1995 O1 (Hale-Bopp) with the use of the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. The inferred D/H ratio in Hale-Bopp's water is (3.3 +/- 0.8) x 10(-4). This result is consistent with in situ measurements of comet P/Halley and the value found in C/1996 B2 (Hyakutake). This D/H ratio, higher than that in terrestrial water and more than 10 times the value for protosolar H2, implies that comets cannot be the only source for the oceans on Earth.

Deuterium Oxide↗

Nerve growth factor promotes activation of the alpha, beta and gamma isoforms of protein kinase B in PC12 pheochromocytoma cells.

The activation of phosphatidylinositol (PtdIns) 3-kinase is considered to be a key event occurring after stimulation of cells with growth factors. The proto-oncogenic protein kinase B (PKB; also known as RAC protein kinase or Akt) has recently been shown to be a downstream target of PtdIns 3-kinase and may be involved in cell survival. We therefore asked whether stimulation of neuronal cells with nerve growth factor (NGF), on which certain types of neurons are dependent for survival, causes activation of PKB. Stimulation of serum-starved PC12 rat pheochromocytoma cells with NGF caused an increase of up to 14-fold in PKB activity. This activation was detected within 1 min of stimulation and occurred at NGF concentrations that are consistent with TrkA-mediated signaling. PKB activation was accompanied by a decrease in electrophoretic mobility of the kinase, which is characteristic of phosphorylation. Both PKB activation and mobility changes were prevented by wortmannin, indicating the upstream involvement of PtdIns 3-kinase in these events. Analyses employing isoform-specific antibodies for immunoprecipitation suggested that all three isoforms of PKB (alpha, beta and gamma) are activated in response to NGF. G-protein-coupled-receptor agonists, lysophosphatidic acid (lyso-PtdH) and thrombin, which induce rapid neurite retraction, neither stimulated PKB activity, nor affected NGF-induced or insulin-induced kinase activation. Wortmannin treatment did not prevent neurite retraction induced by lyso-PtdH or thrombin. These data suggest that PtdIns 3-kinase and PKB are not involved in cytoskeletal changes mediated by the small GTPase Rho.

Androstadienes↗

Phylogeny of fungus-growing ants (Tribe Attini) based on mtDNA sequence and morphology.

We examined the phylogenetic relationships among taxa of attine or "fungus-growing" ants (Tribe Attini) using parsimony analyses of molecular and morphological data. We sequenced a region of mitochondrial DNA from 13 taxa of attines and from one closely related outgroup species, Wasmannia auropunctata. Our study sequence included the 3' end of the cytochrome c oxidase subunit I (CO I) locus (183 to 198 total sites; 91 informative sites), an intergenic spacer region of variable size (0 to 152 sites), the tRNA leucine locus (65 to 74 sites), and the 5' end of the cytochrome c oxidase subunit II (co II) locus (292 total sites; 140 informative sites). The inferred relationships among the attine taxa based on an unweighted analysis of the nucleotide sequence data closely matched the relationships inferred from an analysis of larval morphological characters from 11 of the taxa. In fact, the inferred relationships were completely congruent among the protein parsimony analysis of amino acid data, the morphology analysis, and "total evidence" analysis combining the amino acid and morphology data. The congruent conclusions we obtained from two independent data sets increases our confidence in the reliability of our analyses.

Animals↗

Effects of a partially hydrolyzed guar gum on intestinal absorption of carbohydrate, protein and fat: a double-blind controlled study in volunteers.

UNLABELLED: Some dietary fibres have been shown to affect the rate of absorption of dietary carbohydrate, protein and fat as well as exocrine pancreatic function. The aim of the study was to examine the effect of partially hydrolysed guar gum (BENEFIBER), on normal absorption of glucose, amino acid (arginine) and fat. In addition hepatic, pancreatic, renal and haematological side effects were evaluated. METHODS: A double blind, randomized and cross-over design was used. Each subject served as its own control. Ten healthy male volunteers participated in the study. Each subject was randomly assigned to two different dietary regimes for a period of 7 days each. The study was repeated with the other diet for another 7-day period after an interval of at least 1 week. In one study period the subjects took liquid formula diet without fibre and during the other study period they took the same diet with fibre. RESULTS: The results of the study demonstrated that BENEFIBER did apparently not interfere with the normal absorption of glucose, amino acid and fat. In keeping with these observations, insulin release and exocrine pancreatic function were not affected. Haematological, renal and hepatic toxicity were not observed in association with BENEFIBER consumption. CONCLUSION: We conclude that BENEFIBER is a safe source of soluble fibre.

Adult↗

Effect of transdermal application of nicotine on colonic transit in healthy nonsmoking volunteers.

The radio-opaque marker technique (ROMT) is a safe and noninvasive method to determine total colonic (TCTT) and segmental colonic transit times (SCTT). Previous results have shown that smoking volunteers had significantly longer TCTT than nonsmokers, but the underlying mechanism was not clear. We investigated the effect of transdermal nicotine application in two different doses in a non-blind randomized experiment involving three distinct phases. In phase 1 baseline transit times were determined with an abdominal X-ray after a 6-day period of marker ingestion and again after the following bowel movement to study the influence of a bowel movement just before the X-ray. TCTT was nearly twice as high before than after defaecation (42.6 h vs. 25.1 h, P < 0.05). The main acceleration was found in the rectosigmoid (RS) (18.6 h vs 7.1 h, P < 0.05) with no significant changes in right (RC) and left colon (LC). In phase 2 and 3 nicotine was applied in two doses of 17.5 mg day-1 and 35 mg day-1 in random order. Both doses resulted in a significant decrease of TCTT compared to the predefaecation baseline (42.6 h vs 32.2 h/28.2 h, respectively, P < 0.05). Again the main effect was located in the RS (18.6 h vs 9.9 h/7.6 h, P < 0.05). Short-term application nicotine results in a decrease of TCTT which is due to an accelerated transit in the RS.

Administration, Cutaneous↗

Role of translocation in the activation and function of protein kinase B.

We have investigated the role of subcellular localization in the regulation of protein kinase B (PKB) activation. The myristoylation/palmitylation motif from the Lck tyrosine kinase was attached to the N terminus of protein kinase B to alter its subcellular location. Myristoylated/palmitylated (m/p)-PKBalpha was associated with the plasma membrane of transfected cells, whereas the wild-type kinase was mostly cytosolic. The activity of m/p-PKBalpha was 60-fold higher compared with the unstimulated wild-type enzyme, and could not be stimulated further by growth factors or phosphatase inhibitors. In vivo 32P labeling and mutagenesis demonstrated that m/p-PKBalpha activity was due to phosphorylation on Thr308 and Ser473, that are normally induced on PKB following stimulation of the cells with insulin or insulin-like growth factor-1 (IGF-1). A dominant negative form of phosphoinositide 3-kinase (PI3-K) did not affect m/p-PKBalpha activity. The pleckstrin homology (PH) domain of m/p-PKBalpha was not required for its activation or phosphorylation on Thr308 and Ser473, suggesting that this domain may serve as a membrane-targeting module. Consistent with this view, PKBalpha was translocated to the plasma membrane within minutes after stimulation with IGF-1. This translocation required the PH domain and was sensitive to wortmannin. Our results indicate that PI3-K activity is required for translocation of PKB to the plasma membrane, where its activation occurs through phosphorylation of the same sites that are induced by insulin or IGF-1. Following activation the kinase detached from the membrane and translocated to the nucleus.

Amino Acid Substitution↗

Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta.

Protein kinase B (PKB) is a member of the second messenger-dependent family of serine/threonine kinases that has been implicated in signaling pathways downstream of growth factor receptor tyrosine kinases and phosphatidylinositol 3-kinase. Here we report the characterization of the human beta-isoform of PKB (PKBbeta). PKBbeta is ubiquitously expressed in a number of human tissues, with mRNA and protein levels elevated in heart, liver, skeletal muscle, and kidney. After transfection into HEK-293 or COS-1 cells, PKBbeta is activated 2- to 12-fold by mitogens and survival factors. Activation was due to phosphorylation on Thr-309 and Ser-474, which correspond to Thr-308 and Ser-473 implicated in the regulation of PKBalpha. Both phosphorylation and activation were prevented by the phosphatidylinositol 3-kinase inhibitor wortmannin. Moreover, membrane-targeted PKBbeta was constitutively activated when overexpressed in HEK-293 cells. Although the specific activity of PKBbeta was lower than that of PKBalpha toward Crosstide as a substrate (23 nmol/min/mg compared with 178 nmol/min/mg for PKBalpha), both enzymes showed similar substrate specificities. Using confocal microscopy, we show that activation of PKBbeta results in its nuclear translocation within 20 to 30 min after stimulation. These observations provide evidence that PKBbeta undergoes nuclear translocation upon mitogenic activation and support a role for PKB in signaling from receptor tyrosine kinases to the nucleus through phosphatidylinositol 3-kinase.

Amino Acid Sequence↗

Measurements of 12C/13C, 14N/15N, and 32S/34S ratios in comet Hale-Bopp (C/1995 O1).

The 12C/13C, 14N/15N, and 32S/34S isotope ratios in comet Hale-Bopp (C/1995 O1) were determined through observations taken with the James Clerk Maxwell Telescope. Measurements of rare isotopes in HCN and CS revealed isotope ratios of H12CN/H13CN = 111 +/- 12, HC14N/HC15N = 323 +/- 46, and C32S/C34S = 27 +/- 3. Within the measurement uncertainties, the isotopic ratios are consistent with solar system values. The cometary volatiles thus have an origin in the solar system and show no evidence for an interstellar component.

Carbon↗

Clinical pharmacodynamics of SDZ HTF 919, a new 5-HT4 receptor agonist, in a model of slow colonic transit.

OBJECTIVES: To explore the pharmacodynamic effects of the new promotile agent SDZ HTF 919, a selective partial 5-HT4 receptor agonist, in healthy subjects. METHODS: A pharmacodynamic model was applied to prolong colonic transit by dietary means. Subsequently, the effects of twice-daily multiple doses of SDZ HTF 919 (1, 5, 25, and 100 mg) were investigated in a randomized, double-blind, placebo-controlled parallel-group study with 12 subjects per dose level. The sequential design with three study periods of 7 days each included intake of a self-selected diet, a liquid formula diet with soluble fiber supplementation, and a fiber-supplemented diet together with either SDZ HTF 919 or placebo administration. Stool characteristics (frequency and consistency) and total colonic transit times (with use of radiopaque markers) were recorded in each study period. RESULTS: SDZ HTF 919 was well tolerated at all dose levels. The frequency of loose stool and headache increased with higher doses. After a fiber-supplemented diet intake, the median stool frequency decreased from 8 1/2-9 to 5-7 defecations per study period. SDZ HTF 919 in doses of 25 and 100 mg twice a day increased the stool frequency (p < 0.05). Stool consistency was softened by all but the lowest SDZ HTF 919 dose. A fiber-supplemented diet prolonged total colonic transit time in all groups by 45 hours on average. Twice-a-day administration of SDZ HTF 919 for 6 days in addition to a fiber-supplemented diet significantly shortened the total colonic transit time only at the 5 mg dose. The lack of effect at lower and higher SDZ HTF 919 doses suggests a biphasic dose-response relationship for total colonic transit time. CONCLUSIONS: The suitability of total colonic transit time measurements in healthy subjects as a surrogate marker should be confirmed by patient studies.

Adult↗

Differential phosphorylation of lamin B2 in normal and leukemic cells.

Lamins constitute the nuclear lamina, which underlie the inner membrane of the cell nucleus. Phosphorylation of lamins is a key factor in the regulation of nuclear structure during the cell cycle and of gene transcription. Since an uncontrolled cell cycle and altered gene transcription are major characteristics of neoplasms, we looked for differences in lamin B2 phosphorylation between PBMC, ALL and AML cells. Using different lamin B2-specific antibodies, we detected two different lamin B2 species termed lamin B2 and B2A. Although phosphorylation of lamin B2 in leukemic cells was reminiscent of resting cells, the majority of ALL and AML samples showed significantly higher and more altered lamin B2A phosphorylation compared to PBMC. It remains to be elucidated which mechanism leads to these alterations and whether it could explain the extended G1-phase frequently observed in ALL cells.

Acute Disease↗

Comparison between esophageal Wallstent and Ultraflex stents in the treatment of malignant stenoses of the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.

Adult↗