Search PubMed⌕ Search

Biomedical subjects

G Schmidt

Publications and source records attributed to G Schmidt.

At least 91 records · Page 5Linked to original sources
PubMed1999

Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction.

BACKGROUND: Identification of high-risk patients after acute myocardial infarction is essential for successful prophylactic therapy. The predictive accuracy of currently used risk predictors is modest even when several factors are combined. Thus, establishment of a new powerful method for risk prediction independent of the available stratifiers is of considerable practical value. METHODS: The study investigated fluctuations of sinus-rhythm cycle length after a single ventricular premature beat recorded in Holter electrocardiograms, and characterised the fluctuations (termed heart-rate turbulence) by two numerical parameters, termed turbulence onset and slope. The method was developed on a population of 100 patients with coronary heart disease and blindly applied to the population of the Multicentre Post-Infarction Program (MPIP; 577 survivors of acute infarction, 75 deaths during a median follow-up of 22 months) and to the placebo population of the European Myocardial Amiodarone Trial (EMIAT; 614 survivors of acute myocardial infarction, 87 deaths during median follow-up of 21 months). Multivariate risk stratification was done with the new parameters and conventional risk factors. FINDINGS: One of the new parameters (turbulence slope) was the most powerful stratifier of follow-up mortality in EMIAT and the second most powerful stratifier in MPIP: MPIP risk ratio 3.5 (95% CI 2.2-5.5, p<0.0001), EMIAT risk ratio 2.7 (1.8-4.2, p<0.0001). In the multivariate analysis, low left-ventricular ejection fraction and turbulence slope were the only independent variables for mortality prediction in MPIP (p<0.001), whereas in EMIAT, five variables were independent mortality predictors: abnormal turbulence onset, abnormal turbulence slope, history of previous infarction, low left-ventricular ejection fraction, and high mean heart rate (p<0.001). In both MPIP and EMIAT, the combination of abnormal onset and slope was the most powerful multivariate risk stratifier: MPIP risk ratio 3.2 (1.7-6.0, p<0.0001), EMIAT risk ratio 3.2 (1.8-5.6, p<0.0001). INTERPRETATION: The absence of the heart rate turbulence after ventricular premature beats is a very potent postinfarction risk stratifier that is independent of other known risk factors and which is stronger than other presently available risk predictors.

Aged↗
PubMed1999

Humoral immune response to p21WAF1/CIP1 in tumor patients, non-tumorous patients and healthy blood donors.

We performed a serological analysis for anti-p21WAF1/CIP1 antibodies in sera of patients with different gynecological diseases such as breast cancer, ovarian carcinoma, cervix carcinoma and benign gynecological tissue alterations and from healthy blood donors using the immunoblotting technique with recombinant p21WAF1/CIP1 as antigen as well as a newly designed ELISA. We detected antibodies specific for p21WAF1/CIP1 in sera derived from cancer patients, as well as from patients with non-malignant diseases and from healthy blood donors. Thus, the presence of antibodies against p21WAF1/CIP1 is not a marker for malignancies. Some of the sera with antibodies against p21WAF1/CIP1 also contained antibodies against the oncoprotein mdm2, and/or the growth suppressor gene product p53. The presence of antibodies against p53 correlates with a malignant disease.

Antibodies, Neoplasm↗
PubMed1999

["Self-inflicted injuries"--psychiatric, forensic and insurance aspects (II)].

German law distinguishes between attempted suicide which is not punishable and self-mutilation which is prohibited. This article describes the historical development of self-injurious behaviour, reviews the social, juridical, and ethical assessments of the past, and examines the statistical and biological results of current research. It relates observations from forensic medicine and psychiatry to specific clinical symptoms, toxicological circumstances, and social influences (stress incurred by everyday life, war, or imprisonment). Drawing on pertinent cases, it clarifies criminal and civil jurisdiction and emphasizes the importance of self-mutilation for private insurers. Intended for insurers, forensic scientists, and psychiatrists, recommendations concern the procedures to be followed in the examination, jurisdiction, and therapy involving cases of self-inflicted injuries.

Forensic Medicine↗
PubMed1999

Isocitrate lyase of Ashbya gossypii--transcriptional regulation and peroxisomal localization.

The isocitrate lyase-encoding gene AgICL1 from the filamentous hemiascomycete Ashbya gossypii was isolated by heterologous complementation of a Saccharomyces cerevisiae icl1d mutant. The open reading frame of 1680 bp encoded a protein of 560 amino acids with a calculated molecular weight of 62584. Disruption of the AgICL1 gene led to complete loss of AgIcl1p activity and inability to grow on oleic acid as sole carbon source. Compartmentation of AgIcl1p in peroxisomes was demonstrated both by Percoll density gradient centrifugation and by immunogold labeling of ultrathin sections using specific antibodies. This fitted with the peroxisomal targeting signal AKL predicted from the C-terminal DNA sequence. Northern blot analysis with mycelium grown on different carbon sources as well as AgICL1 promoter replacement with the constitutive AgTEF promoter revealed a regulation at the transcriptional level. AgICL1 was subject to glucose repression, derepressed by glycerol, partially induced by the C2 compounds ethanol and acetate, and fully induced by soybean oil.

Acetates↗
PubMed1999

Instrumented staircase for ground reaction measurement.

A staircase was developed to record ground reactions during stair climbing at different slopes (inclinations). Each step is instrumented with six strain-gauge-based force transducers which allow the measurement of three-dimensional ground reaction force and moment as well as the centre of pressure (COP) location. A specific sensor arrangement permits accurate recording, especially of the COP location. The overall design of the staircase and details of a single instrumented step are presented. Static and dynamic characteristics have been evaluated by different experimental procedures. Preliminary results of ground reaction forces are shown.

Biomechanical Phenomena↗
PubMed1999

Development of hyperplasias, preneoplasias, and mammary tumors in MMTV-c-erbB-2 and MMTV-TGFalpha transgenic rats.

Human cDNAs corresponding to two epidermal growth factor-related products that are overexpressed in human breast cancers, that for c-erbB-2 (HER-2) and for transforming growth factor alpha (TGFalpha), have been cloned downstream of the mouse mammary tumor virus (MMTV) long terminal repeat promoter and injected into the pronucleus of fertilized oocytes of Sprague-Dawley rats to produce transgenic offspring. Expression of the transgenic mRNAs is not detectable in mammary tissue from virgin transgenic rats but is detected in mammary tissue from certain lines of mid-pregnant transgenic rats. When two such lines of either type of transgenic rat are subjected to repeated cycles of pregnancy and lactation, they produce, primarily in the mammary glands, extensive pathologies, whereas virgin transgenic rats produce no such abnormalities. Multiparous transgenic female offspring from c-erbB-2-expressing lines develop a variety of focal hyperplastic and benign lesions that resemble lesions commonly found in human breasts. These lesions include lobular and ductal hyperplasia, fibroadenoma, cystic expansions, and papillary adenomas. More malignant lesions, including ductal carcinoma in situ and carcinoma, also develop stochastically at low frequency. The mammary glands of transgenic females invariably fail to involute fully after lactation. Similar phenotypes are observed in female MMTV-TGFalpha transgenic rats. In addition, multiparous TGFalpha-expressing female transgenics frequently develop severe pregnancy-dependent lactating hyperplasias as well as residual lobules of hyperplastic secretory epithelium and genuine lactating adenomas after weaning. These transgenic rat models confirm the conclusions reached in transgenic mice that overexpression of the c-erbB-2 and TGFalpha genes predisposes the mammary gland to stochastic tumor development.

Animals↗
PubMed1999

Molecular characterisation of the dnaK operon of Lactobacillus sakei LTH681.

The use of lactobacilli as starter organisms in food fermentation processes requires thorough knowledge of their reaction to the multitude of ecological factors including their response to stress. We have characterised the dnaK gene region of Lactobacillus sakei LTH681. Two chromosomal EcoRI fragments of 2.5 and 4.0 kb were identified using a homologous dnaK probe generated by PCR. The sequence analysis of the cloned fragments showed that the dnaK gene region consists of four heat shock genes with the organisation hrcA-grpE-dnaK-dnaJ. Comparison of the deduced amino acid sequences revealed high similarity to the corresponding heat shock proteins of Gram-positive bacteria. An upstream located orfY was found which exhibited substantial similarity (41.5%) to the chloramphenicol acetyltransferase of Enterobacter aerogenes. Northern hybridisation analysis revealed that the transcription of the genes is induced by heat shock (42 degrees C) as well as salt (6%) or ethanol (10%) stress. Several transcripts were detected including a polycistronic mRNA of 4.9 kb which represents the transcript of the complete dnaK gene region indicating a tetracistronic organisation of the dnaK operon. The other RNA fragments were identified as shorter transcripts (3.7 and 1.3 kb) or cleavage products of the polycistronic mRNAs. The transcription start sites of the dnaK operon were determined under inducing and non-inducing conditions. The site varied with the applied stress condition. A regulatory CIRCE element was identified located between the transcription and translation start site. The promoter region including CIRCE was transcriptionally fused to the beta-glucuronidase reporter gene gusA and expressed in L. sakei LTH681. The kinetics of transcriptional induction of gusA by heat shocking were identical to those of the dnaK operon confirming the involvement of the CIRCE element in regulation of gene expression.

Amino Acid Sequence↗
PubMed1999

The impact of body build on the relationship between body mass index and percent body fat.

OBJECTIVE: The objective of the study was to test the hypothesis that differences in the relationship between percent body fat (%BF) and body mass index (BMI) between populations can be explained (in part) by differences in body build. DESIGN: Cross-sectional, comparative study. SUBJECTS: 120 age, gender and BMI matched Singapore Chinese, Beijing Chinese and Dutch (Wageningen) Caucasians. MEASUREMENTS: From body weight and body height, BMI was calculated. Relative sitting height (sitting height/height) was used as a measure of relative leg length. Body fat was determined using densitometry (underwater weighing) in Beijing and Wageningen and using a three-compartment model based on densitometry and hydrometry in Singapore. Wrist and knee widths were measured as indicators for frame size and skeletal mass was calculated based on height, wrist and knee width. In addition, a slenderness index (height/sum of wrist and knee width) was calculated. RESULTS: For the same BMI, Singapore Chinese had the highest %BF followed by Beijing Chinese and the Dutch Caucasians. Singaporean Chinese had a more slender frame than Beijing Chinese and Dutch Caucasians. Predicted %BF from BMI, using a Caucasian prediction formula, was not different from measured %BF in Wageningen and in Beijing, but in Singapore the formula underpredicted %BF by 4.0 +/- 0.8% (mean +/- s.e.m.) compared to Wageningen. The difference between measured and predicted %BF (bias) was related to the level of %BF and with measures of body build, especially slenderness. Correction for differences in %BF, slenderness and relative sitting height, decreased the differences between measured and predicted values compared to the Dutch group from 1.4 +/- 0.8 (not statistically significant, NS) to -0.2 +/- 0.5 (NS) in Beijing and from 4.0 +/- 0.8 (P < 0.05) to 0.3 +/- 0.5 (NS) in Singapore (all values mean +/- s.e.m.). CONCLUSIONS: The study results confirm the hypothesis that differences in body build are at least partly responsible for a different relationship between BMI and %BF among different (ethnic) groups.

Adipose Tissue↗
PubMed1999

[Lengemann suture versus bone screw osteosynthesis in treatment of ulnar osseous collateral ligament rupture of the thumb metacarpophalangeal joint].

Out of 95 ligamentous lesions of the thumb metacarpophalangeal joint, those with an isolated bony rupture of the ulnar collateral ligament were chosen. Of these, 15 patients treated with Lengemann suture and 16 with screw fixation were followed-up on average 27.3 and 26.4 months, respectively, after operative treatment. Under only "good" and "very good" clinical results, the statistical analysis of the objective and subjective parameters showed no significant difference, except for the measurement of the soft-tissue circumference (p < 0.01) between either procedure. Although both procedures have a low rate of complications, screw fixation is preferable since implant removal is not necessary.

Adult↗
PubMed1999

General form of coupling leading to synchronization of oscillating dynamical systems.

There are numerous examples in nature where oscillating or pulsing physical and biological systems automatically synchronize. Here we pose the question: Is there a general type of coupling that leads to such synchronization? It is demonstrated on numerous examples that dissipative coupling results in synchronization for a variety of systems.

Journal Article↗
PubMed1999

Deamidation of Cdc42 and Rac by Escherichia coli cytotoxic necrotizing factor 1: activation of c-Jun N-terminal kinase in HeLa cells.

Recently, Escherichia coli cytotoxic necrotizing factor 1 (CNF1) was shown to activate the low-molecular-mass GTPase RhoA by deamidation of Gln63, thereby inhibiting intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activities (G. Schmidt, P. Sehr, M. Wilm, J. Selzer, M. Mann, and K. Aktories, Nature 387:725-729, 1997; G. Flatau, E. Lemichez, M. Gauthier, P. Chardin, S. Paris, C. Fiorentini, and P. Boquet, Nature 387:729-733, 1997). Here we report that in addition to RhoA, Cdc42 and Rac also are targets for CNF1 in vitro and in intact cells. Treatment of HeLa cells with CNF1 induced a transient formation of microspikes and formation of membrane ruffles. CNF1 caused a transient 10- to 50-fold increase in the activity of the c-Jun N-terminal kinase. Tryptic peptides of Cdc42 obtained from CNF1-treated cells by immunoprecipitation exhibited an increase in mass of 1 Da compared to control peptides, indicating the deamidation of glutamine 61 by the toxin. The same increase in mass was observed with the respective peptides obtained from CNF1-modified recombinant Cdc42 and Rac1. Modification of recombinant Cdc42 and Rac1 by CNF1 inhibited intrinsic and GAP-stimulated GTPase activities and retarded binding of 2'(3')-O-(N-methylanthraniloyl)GDP. The data suggest that recombinant as well as cellular Cdc42 and Rac are substrates for CNF1.

Bacterial Toxins↗
PubMed1999

The Ras mutant D119N is both dominant negative and activated.

The introduction of mutation D119N (or its homolog) in the NKxD nucleotide binding motif of various Ras-like proteins produces constitutively activated or dominant-negative effects, depending on the system and assay. Here we show that Ras(D119N) has an inhibitory effect at a cell-specific concentration in PC12 and NIH 3T3 cells. Biochemical data strongly suggest that the predominant effect of mutation D119N in Ras-a strong decrease in nucleotide affinity-enables this mutant (i) to sequester its guanine nucleotide exchange factor, as well as (ii) to rapidly bind GTP, independent of the regulatory action of the exchange factor. Since mutation D119N does not affect the interaction between Ras and effector molecules, the latter effect causes Ras(D119N) to act as an activated Ras protein at concentrations higher than that of the exchange factor. In comparison, Ras(S17N), which also shows a strongly decreased nucleotide affinity, does not bind to effector molecules. These results point to two important prerequisites of dominant-negative Ras mutants: an increased relative affinity of the mutated Ras for the exchange factor over that for the nucleotide and an inability to interact with the effector or effectors. Remarkably, the introduction of a second, partial-loss-of-function, mutation turns Ras(D119N) into a strong dominant-negative mutant even at high concentrations, as demonstrated by the inhibitory effects of Ras(E37G/D119N) on nerve growth factor-mediated neurite outgrowth in PC12 cells and Ras(T35S/D119N) on fetal calf serum-mediated DNA synthesis in NIH 3T3 cells. Interpretations of these results are discussed.

3T3 Cells↗
PubMed1999

Mapping of capillary flow, cellular redox state, and resting membrane potential in hypoperfused rat myocardium.

The influence on myocyte viability of ischemia-induced changes in capillary perfusion was studied in the hearts of anesthetized rats subjected to partial occlusion of the left coronary artery for 45 min. Timed plasma labeling was applied to determine perfusion patterns. Changes in the fluorescence of preloaded potential-sensitive dyes [tetramethylrhodamine methyl ester (TMRM) and bis-oxonol], of trypan blue, and of endogeneous NADH were utilized in characterizing myocyte viability in histological sections of the heart. Within the hypoperfused zone, localized areas appeared vascularly nonlabeled for periods of at least 10 min. Within these areas a reduction in TMRM fluorescence occurred in 82. 5% of the tissue, signaling a reduced resting membrane potential. In the same areas 37.7% of the myocytes revealed an NADH fluorescence lower than that regularly found in anoxic tissues. This correlated with an especially low level of TMRM, with increased fluorescence bis-oxonol and with an accumulation of trypan blue. In conclusion, in localized hypoperfusion-induced zones lacking capillary flow, an inhomogeneous pattern of reductions in myocyte viability develops, which appears to be relevant in ischemia-induced arrhythmias.

Animals↗
PubMed1999

Alcohol use and psychosocial well-being among older adults.

OBJECTIVE: The objective of this study was to examine the relationships of three dimensions of alcohol consumption (frequency of drinking, usual total weekly consumption and quantity per occasion) with social and leisure status, stress and psychological well-being among people ages 65 and older. METHOD: Nurse interviewers completed in-house surveys with 826 older persons (65% women) in one community (67% response rate of the census sample). RESULTS: Overall, relationships tended to be modest or nil. Those relationships between negative functioning and heavier alcohol use that did emerge tended to be associated with higher quantity drinking (i.e., drinks per drinking day) and to some extent volume, but not with frequency of drinking. Of the psychosocial variables, poorer psychological well-being, especially depression, was most highly correlated with heavier drinking. These results were the same controlling for sex, age, education, health and use of depressant medications. CONCLUSIONS: Higher quantity and volume of alcohol use among older people show a modest positive association with poorer psychological well-being, independent of other potentially confounding variables such as sex, age, health or use of depressant medications. Frequency of drinking, however, was not related to psychosocial status.

Aged↗
PubMed1999

Kinetics of 123I-MIBG after acute myocardial infarction and reperfusion therapy.

UNLABELLED: Metaiodobenzylguanidine (MIBG) washout from the myocardium has been thought to reflect sympathetic nerve tone. After acute myocardial infarction, however, little is known about this parameter. The aim of this study was to determine the significance of cardiac washout after myocardial infarction and early reperfusion by investigating MIBG kinetics and correlating those kinetics to clinical parameters. METHODS: Sixty patients with acute myocardial infarction underwent planar MIBG and thallium imaging within 14 d of early reperfusion therapy. Global uptake and washout in myocardium, lungs and liver were calculated from early and delayed images. A regional analysis of myocardial kinetics in normal and infarcted myocardium and in an infarct border zone was also performed. Scintigraphic data were correlated with heart-rate variability as an electrophysiologic marker for autonomic tone and prevalence of arrhythmia in 52 patients. Heart-rate variability was described by time-domain indices from long-term electrocardiogram recordings. An age-matched normal control group for MIBG consisted of 10 individuals without heart disease. RESULTS: The infarct patients had preserved left-ventricular ejection fraction (LVEF) (56% +/- 17%). Although late myocardial uptake was expectedly lower in infarct patients compared with healthy volunteers (2.36 +/- 0.66 versus 2.80 +/- 0.55; P = 0.04), global myocardial MIBG washout was faster (11.6% +/- 7.9% versus 0.2% +/- 10.2%, respectively; P = 0.002). Lung and liver kinetics did not differ in patients and healthy volunteers. Global MIBG washout showed a weak but significant positive correlation with the baseline heart rate (r = 0.28, P = 0.03) and an inverse correlation with LVEF (r = -0.28, P = 0.04). Washout was faster in a subgroup of 8 patients with reduced heart-rate variability (16.5% +/- 9.9% versus 10.3% +/- 8.3%; P = 0.04). Regional analysis revealed similar degrees of enhanced MIBG washout for infarcted (low perfusion, low MIBG uptake) and remote myocardium (normal perfusion, high MIBG uptake), whereas the border zone (normal perfusion, low MIBG uptake) showed a nonsignificant trend toward higher washout. CONCLUSION: After myocardial infarction, changes in MIBG kinetics occur specifically in the myocardium, whereas kinetics in lung and liver remain unchanged. Even in patients with left-ventricular function preserved by reperfusion therapy, MIBG washout is abnormal and globally increased. Enhanced washout may reflect increased sympathetic nerve tone and represent increased catecholamine turnover or impaired reuptake in the subacute phase of myocardial infarction.

3-Iodobenzylguanidine↗
PubMed1999

Isolation of a potential neural stem cell line from the internal capsule of an adult transgenic rat brain.

A thermosensitive mutation of simian virus 40 large T antigen (LTA) gene, the tsA58 gene, was cloned downstream of the 6-kbp neurofilament light chain promoter in pPOLYIII and injected into the pronucleus of fertilised oocytes of Sprague-Dawley rats to develop a strain harbouring six copies of the transgene. Immunocytochemical staining of hemizygous adult tissues with antibodies to the C-terminus of LTA showed that the inactive form of LTA was expressed only in the fibres of the internal capsule and in the choroid plexus of the brain. Culturing the former region at 33 degrees C, the permissive temperature for LTA, yielded a cell line, NF2C, which produced active LTA and grew at 33 degrees C but which produced only inactive LTA and eventually died at the non-permissive temperature of 39 degrees C. This clonal cell line was heterogeneous at 33 degrees C, producing the precursor neuronal cell marker nestin and the glial-specific markers glial fibrillary acidic protein, vimentin and S100A1, as well as weakly producing the neuronal cell markers 68-kDa neurofilament protein (NF68) and microtubule-associated protein 2 (MAP2) in different subpopulations of cells. However, at 39 degrees C, the cells produced dendritic, neuronal-like processes and elevated levels of NF68 and MAP2, as well as the neuronal markers synaptophysin, neurone-specific enolase, and low levels of tau, all determined by western blotting and immunofluorescent staining. Basic fibroblast growth factor enhanced the growth of the cells at 33 degrees C but also enhanced the formation of dendritic neuronal-like processes at 39 degrees C. It is suggested that NF2C represents a potential stem cell line from adult brain that expresses precursor and glial cell markers at 33 degrees C but undergoes partial differentiation to a neuronal cell phenotype at 39 degrees C.

Animals↗
PubMed1999

Inhibitors of topoisomerase II as pH-dependent modulators of etoposide-mediated cytotoxicity.

Chloroquine intercalates into DNA and protects cells against topoisomerase II (topo II) poisons such as etoposide by hindering the DNA cleavage reaction of this target enzyme. Chloroquine, in contrast to etoposide, is a weak base and therefore barely enters the cell when the extracellular fluid is acidic, as is the case in most solid tumors. Such a pH-dependent drug interaction could be useful in targeting the cytotoxicity of topo II poisons toward solid tumors. Unfortunately, antagonistic chloroquine concentrations cannot be reached in vivo because of its unacceptable toxicity. Thus, antagonists with a higher therapeutic index are needed. We report here on the structure-activity relationship of several chloroquine and acridine analogues in a clonogenic assay. There were major differences in the cytotoxicity of the different compounds, with acridines being 50-fold more toxic than the chloroquine analogues. Several compounds were, however, able to antagonize etoposide-mediated cytotoxicity in a pH-dependent manner as chloroquine. Dependency on pH was lost if the aminoalkyl side arm of chloroquine was removed or lengthened by one CH2 whereas pH dependency was strong with hydroxychloroquine. In contrast, the aminoalkyl side arm was clearly dispensable in the acridines because both quinacrine and 9-aminoacridine demonstrated profound pH dependency. The results from clonogenic assay were compared with cellular transport measurements and topo II enzyme inhibition. Compounds with the most marked pH-dependent intracellular accumulation were also the best pH-dependent protectors of etoposide cytotoxicity, clearly supporting the hypothesis that extracellular pH can be used to regulate topo II poisoning.

Antineoplastic Agents, Phytogenic↗