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H Schmidt

Publications and source records attributed to H Schmidt.

At least 109 records · Page 6Linked to original sources
PubMed2002

A cohort mortality and nested case-control study of French and Austrian talc workers.

OBJECTIVES: To study whether the mortality from non-malignant and malignant respiratory diseases of workers employed in French and Austrian talc mines and mills is related to their long term occupational exposure. METHODS: Two historical cohorts were set up comprising all male subjects who had been working continuously for at least 1 year in a series of talc producing companies in France and Austria. The French cohort consisted of those employed at a site in the French Pyrenees and working between 1 January 1945 and 31 December 1994. The Austrian cohort consisted of the workers employed between 1 January 1972 and 31 December 1995 in one of four industrial sites in the Austrian Alps. The mortality within the cohorts was compared with local death rates. Two nested case-control studies focusing on non-malignant and malignant respiratory diseases were set up to estimate possible dose-response relations with cumulative exposure to talc dust based on an industry specific job exposure matrix. RESULTS: Mortality from lung cancer was in small excess in both cohorts (France, standardised mortality ratio (SMR) 1.23, 21 cases observed, 95% confidence interval (95% CI) 0.76 to 1.89; Austria, SMR 1.06, seven observed, 95% CI 0.43 to 2.19). A non-significant excess mortality was found for all non-malignant respiratory diseases in the French cohort due to a significant excess for pneumoconiosis (SMR 5.56, three observed, 95% CI 1.12 to 16.2). The case-control study of non-malignant respiratory disease showed an increased mortality in the highest exposure groups (odds ratio (OR) 2.5 for a cumulative exposure > or = 800 y.mg/m(3)) with a significant trend (OR/100 y.mg/m(3) 1.08) with cumulative exposure to talc. On the contrary, no increasing trend could be found in the case-control study of lung cancer. This result must be interpreted considering the small cohort size. Adjustment on smoking and exposure to quartz did not influence these results to any extent. CONCLUSIONS: The mortality from non-malignant respiratory disease was found to be related to high cumulative exposure to talc dust. The small excess in lung cancer does not seem to be attributable to talc.

Austria↗
PubMed2002

[Regelsberger's intravenous oxygen therapy--an interpretation of results in practice from a biochemical and physiological point of view].

Results of intravenous (i.v.) application of medical oxygen described by users are interpreted by means of biochemical and physiological knowledge. It is shown that i.v. oxygen therapy produces changes in metabolism which can also occur independently of the course of illness. Apart from the general improvement in oxygen availability, i.v. oxygen therapy causes eosinophilia, which can be valued as an increase in undetermined cellular immunological resistance. Furthermore, rheological qualities of the blood as well as diuresis are improved, the release of oxygen into the tissue is increased, and the blood pH is normalized. Compared with hyperbaric oxygen therapy, i.v. oxygen therapy seems to have less side effects. Application is less complicated, less expensive but probably of higher efficacy. This statement does not apply to issues related to diving medicine.

Blood Chemical Analysis↗
PubMed2002

Human paraoxonase 1 gene polymorphisms and the risk of coronary heart disease: a community-based study.

Published data on the association between paraoxonase1 (PON1) polymorphisms and coronary heart disease (CHD) have yielded controversial results. The objective of this study was to determine the possible relationship between the two human PON1 amino acid variants, the Leu55Met and the Gln192Arg polymorphism, and the risk of CHD in a community-dwelling cohort of European ancestry. PON1 genotypes of 152 women and 151 men out of 1,998 randomly selected individuals aged 44-75 years were determined by polymerase chain reaction-based restriction enzyme digestion. Study participants underwent cardiological examination including a structured clinical interview, resting ECG, exercise testing and echocardiography. The diagnosis of CHD was based on history and/or appropriate findings during cardiac examination. Evidence for CHD was found in 43 (14.2%) study participants. The Leu/Leu (LL), Leu/Met (LM) and Met/Met (MM) genotypes at position 55 were noted in 131 (43.2%), 128 (42.2%) and 44 (14.5%) subjects; the Gln/Gln (QQ), Gln/Arg (QR) and Arg/Arg (RR) genotypes at codon 192 occurred in 167 (55.1%), 118 (38.9%) and 18 (5.9%) individuals, respectively. Homozygosity for the 55L-allele was significantly associated with CHD (p = 0.02), while the Gln192Arg polymorphism had no effect (p = 0.16). Logistic regression analysis demonstrated age (odds ratio 1.06/year), smoking (odds ratio 2.86), HDL cholesterol (odds ratio 0.94/mg/dl) and the paraoxonase LL genotype (odds ratio 2.25) to be significant predictors of CHD. These data suggest that the paraoxonase LL genotype at position 55 may present a risk factor for CHD.

Adult↗
PubMed2001

Increased survivin transcript levels: an independent negative predictor of survival in soft tissue sarcoma patients.

Survivin, a recently identified inhibitor of apoptosis protein (IAP), is expressed in diverse embryonic tissues and in various human cancers. We have investigated the quantitative expression of survivin mRNA by a sensitive TaqMan-based RT-PCR assay in tissue samples from 94 patients with soft tissue sarcomas (STS). Survivin transcript levels were measured and normalized to GAPDH transcripts. By using a multivariate Cox regression analysis, we found an inverse correlation between the level of survivin mRNA (ratio >2 zmol survivin/amol GAPDH) and the rate of overall survival (p = 0.009, RR = 2.7). Survivin transcript variants as detected by qualitative RT-PCR analysis were revealed in 36 of 56 STS patients (64%). Only survivin DeltaEx3 and/or full-length survivin variants but not survivin 2B were identified. Our results suggest that a higher level of survivin mRNA is an independent predictor of survival for STS patients.

Adolescent↗
PubMed2001

Deregulation of FCGR2B expression by 1q21 rearrangements in follicular lymphomas.

We report here the molecular cloning and characterization of a t(1;14)(q21;q32) in a follicular lymphoma (FL) with an unusual BCL2 aberration. Fluorescence in situ hybridization (FISH) and Southern blot analysis of tumor cells identified the translocation breakpoint within the 5' switch region of IGHG (Sgamma). We cloned the chimeric breakpoint region approximately 1.5 kbp downstream from the HindIII site of 5'Sgamma2 on chromosome 14q32 and identified a 360-bp novel segment with homology to the CpG island clone 11h8. Two BAC clones containing this sequence were isolated and mapped to 1q21 by FISH. BAC 342/P13 contained sequences homologous to Fcgamma receptors 2A, 3A, 2B, 3B, and a heat shock protein gene HSP70B. The translocation brought the Sgamma2 region of a productive IGH allele 20 approximately 30 kbp upstream of FCGR2B. As a result of the translocation, the b2 isoform of FCGR2B was overexpressed in the tumor. Screening of a panel of 76 B-cell lymphomas with 1q21-23 cytogenetic aberrations by Southern blot analysis using breakpoint probes identified an additional FL with a t(14;18)(q32;q21) and a breakpoint in the FCGR2B region. These results suggest that FCGR2B may be deregulated by 1q21 aberration in BCL2 rearranged FLs and possibly play a role in their progression.

Adult↗
PubMed2001

Detection and characterization of Shiga toxin-producing Escherichia coli in feral pigeons.

Escherichia coli strains producing a variant of Shiga toxin 2 (Stx2), designated Stx2f, have been recently described in the stools of feral pigeons. During 1997-1998, 649 pigeons were trapped and examined in three different squares of Rome. Stool samples were collected from each bird and enrichment cultures were examined for the presence of Stx by the vero cell assay. Stx-producing E. coli (STEC) were isolated from the positive cultures and characterized by serotyping and PCR analysis of stx and other virulence-related genes. Stx was detected in 10.8% of the stool enrichment cultures. The percentage of positive birds did not differ significantly for the three flocks considered and the season of sample collection. Conversely, STEC carriage was significantly more frequent in young than in adult birds (17.9 versus 8.2%). None of the birds examined showed signs of disease. STEC strains were isolated from 30 of 42 Stx-positive cultures examined. All the strains produced Stx2f, and most of them possessed genes encoding for intimin and the cytolethal distending toxin (CLDT). Six serogroups were identified, but most of the isolates belonged to O45, O18ab, and O75. Molecular typing indicated that most of the isolates within a flock were clonally-related. This work confirms that pigeons represent a natural reservoir of STEC strains characterized by the production of the toxin variant Stx2f, and by the frequent presence of eae and cldt genes. Further work is needed to clarify whether these STEC may represent a cause of avian disease or even a potential health hazard for humans.

Animals↗
PubMed2001

Low detection rate of p53 antibodies in sera of soft tissue sarcoma patients.

Accumulation of the p53 gene product can lead to its immunogenic appearance and the generation of p53 serum antibodies (p53ab). In different cancer types the occurrence of detectable p53ab has an independent prognostic impact. In spite of the known p53 protein overexpression rate in soft tissue sarcomas (STS), up to 70%, there have been no investigations done on p53ab in serum in STS patients. In this prospective study of 50 STS patients, we investigated the presence of serum p53ab using an enzyme-linked immunosorbent assay system and the presence of p53 overexpression in the appropriate tissue specimen immunohistochemically. Using Kruskal-Wallis chi(2) and Kaplan-Meier tests the results were then correlated to histopathological and clinical data. Six of the 50 patients (12%) showed p53ab detectable in the serum, and 56% (28/50) of the tumors were p53 immunohistochemically positive. Four of the six p53ab positives (66%) had immunohistochemically p53 positive and two (33%) had negative tumors. Altogether four of the 50 patients (8%) were positive for p53ab in serum as well as for p53 immunohistochemistry in tumor tissue specimens. Twenty patients (40%) were negative for both. All of the p53ab positive patients had stage I or II tumors. Excluding tumor stage there was no p53ab correlation to histopathological, clinical or prognostic parameters. We conclude that in STS patients, p53ab also occurs but in contrast to other tumor types at a relatively low frequency. According to our results, the clinical value of p53ab seems to be limited in STS patients.

Adult↗
PubMed2001

Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis.

OBJECTIVE: The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however. METHODS: In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers. RESULTS: The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the epsilon4 allele (n = 85) had a significantly higher progression index of disability (0.46 +/- 0.4 versus 0.33 +/- 0.26; p < 0.004) and a worse ranked MS severity score (5.1 +/- 1.9 versus 5.7 +/- 1.7; p = 0.05) than their non-epsilon4 counterparts, despite significantly more frequent long-term immunotherapy in epsilon4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in epsilon4 carriers (0.87 +/- 0.56) was significantly higher than in patients with MS without an epsilon4 allele (0.71 +/- 0.47; p = 0.03). CONCLUSIONS: These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE epsilon4 allele with a more severe course of the disease.

Adult↗
PubMed2001

Cytogenetic characterization of six malignant peripheral nerve sheath tumors: comparison of karyotyping and comparative genomic hybridization.

We analysed six malignant peripheral nerve sheath tumors (MPNSTs) from four patients using metaphase preparations and compared the results with those obtained by using comparative genomic hybridization (CGH). All six tumors showed structural and numerical chromosomal aberrations, mostly of chromosomes 1, 5, 7-10, 14-17, 19, 21, and 22. The number of chromosomes per tumor cell ranged from 42 to 104. We could not find a recurrent specific pattern of structural changes after comparing the MPNSTs of different patients. However, aberrations of different tumors from the same patient were nearly identical. In the four patients, we found a total of 117 breakpoints, mostly in 21q11.2 (seven times), in 8q11.2 and 14q10 (six times each), in 5q11.2 and 15q26 (four times each), in 8p11.2, 10q11.2, 16q22, 19q13.3, and 22q10 (three times each). In three MPNSTs, double minute chromosomes (dmin) we detected with metaphase investigations and high-level amplifications by using CGH, respectively. C-MYC gene amplification and loss of the P53 gene could be ruled out by locus-specific probes for the common gain of 8q and for losses of 17p. When comparing the CGH results with those of karyotyping an overlap in the most frequent gains in 7q, 8q, 15q, and 17q was observed. However, we found more frequent losses in 19q in the metaphase investigations.

Aged↗
PubMed2001

Essential roles for four cytoplasmic intermediate filament proteins in Caenorhabditis elegans development.

The structural proteins of the cytoplasmic intermediate filaments (IFs) arise in the nematode Caenorhabditis elegans from eight reported genes and an additional three genes now identified in the complete genome. With the use of double-stranded RNA interference (RNAi) for all 11 C. elegans genes encoding cytoplasmic IF proteins, we observe phenotypes for the five genes A1, A2, A3, B1, and C2. These range from embryonic lethality (B1) and embryonic/larval lethality (A3) to larval lethality (A1 and A2) and a mild dumpy phenotype of adults (C2). Phenotypes A2 and A3 involve displaced body muscles and paralysis. They probably arise by reduction of hypodermal IFs that participate in the transmission of force from the muscle cells to the cuticle. The B1 phenotype has multiple morphogenetic defects, and the A1 phenotype is arrested at the L1 stage. Thus, at least four IF genes are essential for C. elegans development. Their RNAi phenotypes are lethal defects due to silencing of single IF genes. In contrast to C. elegans, no IF genes have been identified in the complete Drosophila genome, posing the question of how Drosophila can compensate for the lack of these proteins, which are essential in mammals and C. elegans. We speculate that the lack of IF proteins in Drosophila can be viewed as cytoskeletal alteration in which, for instance, stable microtubules, often arranged as bundles, substitute for cytoplasmic IFs.

Animals↗
PubMed2001

Amplification of the MDM2 gene, but not expression of splice variants of MDM2 MRNA, is associated with prognosis in soft tissue sarcoma.

The MDM2 gene encodes a 90-kDa oncoprotein that is overexpressed in several human carcinomas, osteosarcomas, gliomas and soft tissue sarcomas (STSs). This overexpression is the result of several mechanisms, for example, enhanced transcription or translation, gene amplification and alternative splicing. We found that 19 of 67 (28.4%) STS specimens contained an amplified MDM2 gene. The amplification was more likely to be present in grade 1 tumors than in grade 2 or 3 tumors (58% of grade 1 tumors vs. 15% of grade 2 or 3 tumors, p = 0.001, chi(2) test). Furthermore, patients with tumors that contained an amplified MDM2 gene had a survival estimate (87 months) that was longer than that of patients with tumors that lacked an amplified gene (40 months; p = 0.02, log-rank test). Alternatively and aberrantly spliced MDM2 mRNAs were detected in human STSs by a highly sensitive reverse transcription-polymerase chain reaction method. Of 71 tumor samples, 38 (54%) showed evidence of the spliced forms, which included MDM2-A, MDM2-B and several variants exclusively expressed in STSs. A common feature of all forms was the absence of the MDM2 N-terminal region, which includes the TP53-binding region. Furthermore, the presence of the spliced forms was associated with elevated levels of TP53 (p = 0.01, chi(2) test). Although the presence of spliced forms was associated with late-stage tumor phenotypes (p = 0.05, chi(2) test), we observed no relationship between the presence of splice variants and patient outcome.

Alleles↗
PubMed2001

Loss of G2/M arrest correlates with radiosensitization in two human sarcoma cell lines with mutant p53.

We have examined the modulation of radiosensitivity by using caffeine in two human sarcoma cell lines both with a p53 mutation (US8-93 and LMS6-93). In both cell lines a strong irradiation-induced G2/M arrest was coupled with a low rate of apoptosis. Incubation with caffeine resulted in a low percentage of S and G2/M cells, associated with an accumulation in G1. With a higher caffeine concentration, we detected a lower clonogenic survival with IC(50) at 2 mM. In both cell lines incubation with caffeine completely prevents the irradiation-induced G2/M arrest. This was connected to radiosensitization, but without direct correlation to an induction of apoptosis. The effect of radiosensitization rose with higher irradiation doses. However, in comparison with LMS6-93, it was stronger in cell line US8-93. A higher radiosensitization in US8-93 correlated with the prevention of strong irradiation-induced G2/M response and higher initial DNA damage. Results of Western hybridization reveal a p53-independent mechanism of radiosensitization caused by caffeine. Our findings suggest that modulation in G2/M regulation may affect a common checkpoint for tumor cells with defective p53 function. Furthermore, our results show that the enhancer effect of caffeine is dependent on a strong reduction in the number of G2/M arrested cells and on an inhibition of DNA damage repair after irradiation.

Adenocarcinoma↗
PubMed2001

Organotypic hippocampal cultures. A model of brain tissue damage in Streptococcus pneumoniae meningitis.

Hippocampal slices of newborn rats were exposed to either heat-inactivated Streptococcus pneumoniae R6 (hiR6) equivalent to 10(6) and 10(8) CFU/ml, lipoteichoic acid (LTA) (0.3 microg/ml and 30 microg/ml), peptidoglycans (PG) (0.3, 30, 50 and 100 microg/ml), pneumococcal DNA (pDNA) (0.3 and 30 microg/ml) or medium only (control). Cell injury was examined by Nissl staining, Annexin V and NeuN immunohistochemistry, and quantified by propidium iodide (PI) uptake and by determining neuron-specific enolase (NSE) concentration in the culture medium. Necrotic and apoptotic cell damage occurred in all treatment groups. Overall damage (Nissl and PI staining) was most prominent after hiR6 (10(8) CFU/ml), followed by LTA (30 microg/ml), pDNA (30 microg/ml), and not detectable after PG (30 microg/ml) exposure. PG (100 microg/ml) induced severe damage. Apoptotic cells were most frequent after exposure to LTA and hiR6. Damage in the neuronal cell layers (NeuN, NSE) was most severe after treatment with hiR6 (10(8) CFU/ml), followed by PG (100 microg/ml), pDNA (30 microg/ml), and LTA (30 microg/ml).

Animals↗
PubMed2001

Electrophysiological responses to thermal stimuli in peripheral nerves of the African giant snail, Archachatina marginata S.

In Archachatina marginata S. the activity of 264 single units of the lip nerves and the tentacle nerve was recorded during thermal stimulation of the lip region. 17.8% of all fibres responded with an increase in neuronal activity to temperature changes in the range from 12 to 36 degrees C. The amount of fibres responding to peripheral warm or cold stimuli varied between the investigated nerves. In the tentacle nerve (N. olfactorius) 30.5% of the neurons responded either to peripheral warming or cooling. In the three lip nerves N. labialis internus, N. labialis externus, and N. labialis medianus 20, 17, and 9.5%, respectively, proved to be thermoresponsive. Additional behavioural tests revealed that the thermopreferendum of Archachatina marginata S. is in the broad range between 13 and 32 degrees C.

Journal Article↗
PubMed2001

A potentiometric and 51V NMR study of the aqueous H+/H2VO4-/H2O2/L-alpha-alanyl-L-histidine system.

The speciation in the quaternary aqueous H+/H2VO4-/H2O2/L-alpha-alanyl-L-histidine (Ah) system has been determined from quantitative 51V NMR measurements and potentiometric data (glass electrode). The study was performed in 0.150 M Na(Cl) medium at 25 degrees C. Data were evaluated with the computer program LAKE, which is able to treat combined EMF and NMR data. The pKa values for Ah were determined as 8.06, 6.72 and 2.64. In the ternary H+/H2VO4-/Ah system, two complexes, (H+)p(H2VO4-)q(Ah)r, for which (p, q, r) values of (0, 1, 1) and (1, 1, 1) with log beta(0,1,1) = 2.52 +/- 0.03 and log beta(1,1,1) = 9.40 +/- 0.05 (pKa = 6.88), respectively, explain all data. The errors given are 3sigma. In the quaternary H+/H2VO4-/H2O2/Ah system, eight complexes were determined in addition to all binary and ternary complexes, four with a V/X/Ah ratio 1:1:1 and four with a ratio 1:2:1 (X = peroxo ligand). VX2Ah2- and VX2Ah- (pKa = 8.19) are the main complexes and predominate in the pH range 5 to 9. Three additional minor species have also been found but their compositions could not be determined owing to their small amounts. Equilibria are slow, significant decomposition of peroxide occurs only in acidic solutions. Data in the pH range 5 to 10 have been used for the LAKE calculations. Chemical shifts, compositions, and formation constants for the eight quaternary complexes are given, and equilibrium conditions are illustrated in distribution diagrams. Structural proposals for VX2Ah2- and VX2Ah- are made from 1H and 13C NMR measurements.

Dipeptides↗