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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 235 records · Page 13Linked to original sources
PubMed1998

Haemodynamic results of femoropopliteal percutaneous transluminal angioplasty.

OBJECTIVES: To determine the utility of percutaneous transluminal angioplasty (PTA) of the femoropopliteal segment in patients with claudication and critical leg ischaemia (CLI). DESIGN: Longitudinal observational study. SETTING: A university based vascular surgical centre. MATERIAL: Ninety-five patients with stenosing or occlusive arterial lesions of the femoropopliteal segment underwent 52 primary PTA for claudication and 50 primary PTA for CLI. METHODS: The procedure was considered haemodynamically successful when the increase of immediate postprocedural ABI was 0.15 or more. The criterion for haemodynamic success during follow-up was an ABI having not decreased by more than 0.15 from the immediate postprocedural level. The run-off arteries were graded according to the scoring system proposed by the SVS/ISCVS. RESULTS: Among the technically successful procedures (83%), the haemodynamic success rate was 77% at 1 month, 55% after 1 year, and 51% after 2 years. The cumulative haemodynamic success rates were 83%, 66% and 61% in claudicants, and 70%, 42%, and 38% in CLI (p = 0.03). In patients with a run-off score < or = 7.5, the success rates were 84%, 67%, and 60%, respectively, whereas in those with a crural score > 7.5 these were 61%, 39%, and 39%, respectively (p = 0.04). CONCLUSIONS: The haemodynamic results suggest that PTA to the femoropopliteal segment is seldom a procedure of choice for critically ischaemic legs with poor run-off. The run-off score is useful in identifying patients who may benefit from PTA.

Aged↗
PubMed1998

Inhibition of HLA-DR expression on activated human blood eosinophils by transforming growth factor-beta1.

Peripheral blood, bronchoalveolar lavage and sputum eosinophils of patients with asthma but not peripheral blood eosinophils from normal controls have been shown to express human leucocyte antigen (HLA)-DR on their cell surface. Cytokines implicated in the activation of eosinophils, such as interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), can up-regulate HLA-DR expression. However, little is known about antagonistic factors that might down-regulate HLA-DR expression on eosinophils. In this study we investigated whether transforming growth factor-beta (TGF-beta), which has been shown to reduce survival of activated eosinophils, can also modulate HLA-DR expression on eosinophils. For this purpose, isolated peripheral blood eosinophils were stimulated with IL-3 and GM-CSF for 24 h and HLA-DR expression was measured by flow cytometry. We found that while isolated eosinophils expressed low levels of surface HLA-DR, incubation with GM-CSF and IL-3 increased HLA-DR expression on eosinophils. TGF-beta alone did not change HLA-DR expression on isolated eosinophils. However, co-incubation of eosinophils with TGF-beta and either GM-CSF or IL-3 significantly decreased HLA-DR expression compared to eosinophils incubated with either GM-CSF or IL-3 alone and this was not reversed by addition of IL-5. This effect of TGF-beta on IL-3-induced HLA-DR expression was attenuated dose-dependently in the presence of monoclonal anti-TGF-beta antibodies. Our results suggest that TGF-beta can reduce cytokine-induced HLA-DR expression on eosinophils and could thus influence eosinophil activation.

Cells, Cultured↗
PubMed1998

Diversity of the anti-T-cell receptor immune response and its implications for T-cell vaccination therapy of multiple sclerosis.

More precise understanding of the immune response against T-cell receptors (TCRs) is a prerequisite for successful TCR vaccination therapy of multiple sclerosis and other neurological autoimmune diseases. We conducted a detailed analysis of a paradigmatic anti-TCR response, using synthetic TCR peptides and highly purified recombinant TCR V alpha and Vbeta variable chains for the selection of CD4+ T-cell lines from a healthy volunteer. The target TCR (designated TCR(HWBP-3)) was obtained from HWBP-3, an autologous CD4+ T-cell line specific for myelin basic protein. The V alpha and Vbeta chains of TCR(HWBP-3) were expressed in Escherichia coli and purified by Ni-chelate chromatography and SDS (sodium dodecyl sulphate) gel electrophoresis. Further, we synthesized a set of 13- to 22-mer peptides spanning the complementarity-determining regions (CDR) 1, 2 and 3 and the framework regions (FR) of the alpha and beta chains of TCR(HWBP-3). The TCR peptides and proteins were then used to select a panel of TCR-specific CD4+ T-cell lines from donor HW. Several T-cell lines cross-reacted with a recombinant V chain and synthetic peptide. Cross-reactive immunogenic TCR epitopes were identified in the FR1 and CDR3 regions of the TCR(HWBP-3) alpha chain and in the FR1, CDR1 and CDR2 regions of the TCR(HWBP-3) beta chain. The TCR proteins and peptides were recognized in the context of at least three different HLA-DR molecules [DR2a (DRB5*0101), DR2b (DRB1*1501) and DRB1*1401/DRB3*0202]. Notably, the majority of the TCR peptide-selected T-cell lines did not react with the full-length recombinant V chains, suggesting they recognize 'cryptic' determinants. Based on the diversity of the anti-TCR immune response, we suggest that candidate TCR peptides should be screened in vitro in functional experiments before they are clinically applied for TCR vaccination therapy.

Amino Acid Sequence↗
PubMed1998

A polymorphism in the gene for the atrial natriuretic peptide and diabetic nephropathy. Diabetic Nephropathy Study Group.

BACKGROUND: Atrial natriuretic peptide is involved in blood pressure regulation via its vasodilating and natriuretic actions. Since diabetic nephropathy and hypertension are closely related, ANP is a reasonable candidate gene for diabetic nephropathy (DN). METHODS: We genotyped 410 patients with type I diabetes (without DN n = 307; with DN n = 103) and 658 patients with type II diabetes (without DN n = 464; with DN n = 194). In the patients the duration of diabetes was at least 10 years. Diabetic nephropathy was defined as urinary albumin excretion of > or = 30 mg/24 h. The HpaII polymorphism in intron 2 of the ANP gene was determined using PCR amplification followed by restriction digest. Alleles were separated on agarose gels stained with ethidium bromide. RESULTS: We compared genotype distribution and allele frequencies between patients with and without nephropathy. No significant difference was observed either in type I (allele frequency without DN H1, 0.02/H2, 0.98 vs with DN H1, 0.05/H2, 0.95; P = 0.132) or in type II diabetes (allele frequency without DN H1, 0.04/H2, 0.96 vs with DN H1, 0.05/H2, 0.95; P = 0.551). CONCLUSIONS: The polymorphism in the gene for the atrial natriuretic peptide does not seem to play a major role in the development of diabetic nephropathy in either type I or in type II diabetes.

Adult↗
PubMed1998

Spontaneous classification of complex tones at high and ultrasonic frequencies in the bat, Megaderma lyra.

Megaderma lyra, a bat species using harmonically structured calls for echolocation, exploits the spectral content of its echoes for texture discrimination. It is the aim of the present study to test according to which sensory qualities harmonic complex tones are spontaneously classified by this bat. The applied experimental paradigm is especially adapted to the preference of M. lyra to use absolute pitch cues. Three animals were trained in a 2-AFC procedure to classify three-component stimuli as low or high, with all their harmonics below or above a pure tone reference of 33 kHz, respectively. Later, the original tones were interspersed with "incomplete" test stimuli, with their fundamentals (and lower harmonics) missing. These were ambiguous in that their possible virtual, i.e., collective pitches were below the reference whereas their pure tone pitches were above it. Bat 1 classified 22 of 23 test stimuli with missing fundamentals between 5.3 and 28.3 kHz according to their collective pitches, whereas bat 2 judged all presented ambiguous tones on the basis of their pure tone pitches. Bat 3 failed the pitch control criterion which is why in this case results cannot be interpreted unequivocally. The implications of these findings are discussed with respect to the bats' behavioral context, as well as to psychoacoustical models of the formation of the pitch of complex tones.

Animals↗
PubMed1998

Subforms and in vitro reconstitution of the NAD-reducing hydrogenase of Alcaligenes eutrophus.

The cytoplasmic, NAD-reducing hydrogenase (SH) of Alcaligenes eutrophus H16 is a heterotetrameric enzyme which contains several cofactors and undergoes a complex maturation during biogenesis. HoxH is the Ni-carrying subunit, and together with HoxY it forms the hydrogenase dimer. HoxF and HoxU represent the flavin-containing diaphorase moiety, which is closely related to NADH:ubiquinone oxidoreductase and mediates NADH oxidation. A variety of mutations were introduced into the four SH structural genes to obtain mutant enzymes composed of monomeric and dimeric forms. A deletion removing most of hoxF, hoxU, and hoxY led to the expression of a HoxH monomer derivative which was proteolytically processed at the C terminus like the wild-type polypeptide. While the hydrogenase dimer, produced by a strain deleted of hoxF and hoxU, displayed H2-dependent dye-reducing activity, the monomeric form did not mediate the activation of H2, although nickel was incorporated into HoxH. Deletion of hoxH and hoxY led to the production of HoxFU dimers which displayed NADH:oxidoreductase activity. Mixing the hydrogenase and the diaphorase moieties in vitro reconstituted the structure and catalytic function of the SH holoenzyme.

Alcaligenes↗
PubMed1998

Using gene carrier probability to select high risk families for identifying germline mutations in breast cancer susceptibility genes.

Germline mutations in highly penetrant autosomal dominant genes explain about 5% of all breast cancer, and heritable mutations in the BRCA1 breast and ovarian cancer susceptibility gene account for 2-3% of breast cancer in the general population. Nevertheless, the presence of such mutations is highly predictive of disease development. Since screening for mutations is still technically laborious, we investigated whether the prior probability of being a carrier of a dominant breast cancer susceptibility gene in the youngest affected family member could be used to identify families in which the probability of finding a mutation is sufficiently high. Sixty German families with three or more cases of breast/ovarian cancer with at least two cases diagnosed under the age of 60 were screened for mutations by SSCP/CSGE and subsequent direct sequencing. Thirteen germline truncating/splicing mutations in BRCA1 were found in 33% (6/18) of the breast-ovarian cancer families and in 17% (7/42) of breast cancer only families. All the families showing mutations in BRCA1 had carrier probabilities of 0.65 or higher. In families with prior carrier probabilities above 0.6, the proportion detected was 0.46 in breast-ovarian cancer families and 0.26 in breast cancer only families. The average age at diagnosis of breast or ovarian cancer in families with BRCA1 mutations was 41.9 years and significantly lower than in families without mutations (p < 0.05). Mutation carriers and obligate carriers were also found to have cancers at other sites. The probability of being a susceptibility gene carrier, taking into account the complete pedigree information, allows uniform characterisation of all types of families for identifying those in which mutation analysis for BRCA1/2 is warranted. However, prior probabilities calculated using this method can be reduced when the correlation between genotype and phenotype is imperfect. A larger series of families needs to be investigated in this fashion to provide better estimates of the detection rate for different ranges of carrier probabilities.

Adult↗
PubMed1998

Evaluation of the angiotensinogen locus in human essential hypertension: a European study.

Different family and case-control studies support genetic linkage and association at the human angiotensinogen (AGT) locus with essential hypertension. To extend these previous observations, a European collaborative study of nine centers was set up to create a large resource of affected sibling pairs. The AGT locus was studied using a highly polymorphic dinucleotide repeat in the 3'-flanking region of the gene in 350 European families, comprising 630 affected sibling pairs. Statistical analyses using two different methods did not show any evidence for linkage either in the whole panel or in family subsets selected for severity or early onset of disease. Although several arguments from association studies suggest a role of the AGT gene in essential hypertension, this large family study did not replicate the initial linkage reported in smaller studies. Our results highlight the difficulty of identifying susceptibility genes by linkage analysis in complex diseases.

Adult↗
PubMed1998

Somatostatin receptor scintigraphy in small-cell lung cancer: results of a multicenter study.

UNLABELLED: The aims of this study were to determine the accuracy of somatostatin receptor scintigraphy in the detection of the primary tumor and its metastases in small-cell lung cancer (SCLC) in a large patient population, and to investigate the course of somatostatin uptake in primary tumors during therapy. METHODS: In a total of 100 patients, 134 examinations were performed. Twenty-seven of the patients were examined before and after chemotherapy. Planar whole-body images were acquired 4 hr and 24 hr after injection of approximately 200 MBq (111)In-pentetreotide. SPECT of the thorax was performed after 24 hr. Tumor-to-background (T/B) ratios for the primary tumor were averaged from anterior and posterior projections. RESULTS: Compared to conventional investigations, somatostatin receptor scintigraphy (SRS) visualized the primary tumor with varying degrees of uptake in 96% of the examinations. Regional metastases and distant metastases were detected in 60% and 45% of the examinations, respectively. The uptake of the somatostatin analog by the primary tumor was significantly lower in the patients examined during chemotherapy as compared to those examined before treatment (T/B ratio = 1.94+/-0.79 versus 2.35+/-0.9, p < 0.005). A decrease in T/B ratio was noted in patients with remission at the time of SRS (from 2.40+/-1.56 to 1.63+/-0.72, p < 0.05). No difference in the pretreatment uptake of octreotide by the primary tumor was identified between patients with tumor progression and those with partial or complete remission. CONCLUSION: Somatostatin receptor scintigraphy has a high sensitivity in the detection of the primary tumor in SCLC but fails in the detection of metastases. Thus, SRS does not provide useful information for staging of SCLC. Since somatostatin uptake by the primary tumor is affected by chemotherapy, it may be used to follow up on the course of SCLC.

Adult↗
PubMed1998

[Diagnostic value of somatostatin receptor scintigraphy with indium-111 pentetreotide in small-cell bronchial carcinoma].

Small-cell lung cancer (SCLC) cells may express somatostatin receptors [14]. Receptor-positive tissue can be visualised in vivo by scintigraphy with radiolabelled somatostatin analogues. In a prospective study we examined 18 patients with histologically proven SCLC for the diagnostic value of somatostatin receptor scintigraphy using indium-111 pentetreotide. Planar whole body scanning was performed 4 and 24 hours after administration. Additional SPECT imaging of the thorax and the abdomen was done at 24 hours. The results were compared with conventional staging procedures: ultrasound, x-ray, computed tomography and bone scintigraphy. In all 18 patients the primary tumour was correctly identified. Out of 13 patients with mediastinal lymphoma formation 10 patients showed positive SRS. In 2 more patients SRS showed mediastinal uptake while CT scanning was negative. The detection of distant metastases in patients with extensive disease was true positive in 8 cases (OSS, HEP, BRA), false negative in 4 cases (PLE, ADR, HEP), corresponding to a sensitivity of 67%. In 2 patients cerebral metastases were no longer detectable by SRS after previous local irradiation. Even though the method is limited in respect of revealing distant metastases in the upper abdominal area due to physiological uptake in liver, spleen and kidneys, differentiation between limited disease (LD) and extensive disease (ED) was possible in all cases. We conclude that [111In]pentetreotide scintigraphy is a suitable method for the detection of SCLC primary tumours and a substantial tool for differentiation between LD and ED if combined with ultrasonography of the upper abdomen.

Adult↗
PubMed1998

[Surgical interventional endoscopic treatment concept of bile duct lesions after laparoscopic cholecystectomy].

In this study we analysed 25 patients with bile duct injuries following laparoscopic cholecystectomy retrospectively. Reconstructive surgery was necessary in 24 patients with bile duct lesions that could not be treated endoscopically. After a mean follow-up of 28 months (3-65) we have good functional outcome in the majority of patients, however, one patient required liver transplantation because of secondary biliary cirrhosis.

Bile Ducts↗
PubMed1997

Patterns of chromosomal alterations in metastasizing and nonmetastasizing primary head and neck carcinomas.

In an attempt to define chromosomal alterations that are associated with the metastatic phenotype, we investigated a total of 29 metastasizing (pN+) and 19 non-metastasizing (pN0) head and neck squamous cell carcinomas by comparative genomic hybridization (CGH). The analysis indicated that the pN0 tumors carried preferentially overrepresentations of chromosomes 5p, 6p, and 7p and that the pN+ tumors were frequently characterized by deletions on chromosomes 7q, 10q, 11p, 11q, 15q, and 20p and overrepresentations of the chromosomes 19q and 20q. In particular, the use of difference histograms and statistical analysis indicated that the deletions on chromosomes 10q25-q26 and 11p13-p14 were highly significant for metastasizing carcinomas. The findings on chromosome 10q were supported by loss of heterozygosity analysis in the primary tumors and eight synchronous lymph node metastases using four microsatellite polymorphisms. The data suggest that distinct patterns of genetic lesions are responsible for the metastatic phenotype of head and neck squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed1997

The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U.

The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that is able to modulate gene activity by binding to its response element, interacting with other transcription factors, and contacting several accessory proteins such as coactivators. Here we show that GRIP120, one of the factors we have identified to interact with the glucocorticoid receptor, is identical to the heterogeneous nuclear ribonucleoprotein U (hnRNP U), a nuclear matrix protein binding to RNA as well as to scaffold attachment regions. GR.hnRNP U complexes were identified by blotting and coimmunoprecipitation. The subnuclear distribution of GR and hnRNP U was characterized by indirect immunofluorescent labeling and confocal laser microscopy demonstrating a colocalization of both proteins. Using a nuclear transport-deficient deletion of hnRNP U, nuclear translocation was seen to be dependent on GR and dexamethasone. Transient transfections were used to identify possible interaction domains. Overexpressed hnRNP U interfered with glucocorticoid induction, and the COOH-terminal domains of both proteins were sufficient in mediating the transcriptional interference. A possible functional role for this GR binding-protein in addition to its binding to the nuclear matrix, to RNA, and to scaffold attachment regions is discussed.

Cell Nucleus↗
PubMed1997

Diabetes and hypertension in rodent models.

As shown by ourselves and others, animals models closely resembling human complex diseases like IDDM in BB/OK and hypertension in SHR/Mol rats can be used to dissect a complex disease into discrete genetic factors as has been done for hypertension in (BB/OK x SHR/Mol) cross hybrids. Discrete genetic factors, so-called QTLs, were detected on chromosomes 1, 10, 18, 20, and X. To gain additional information about the physiologic effect of the mapped blood pressure QTLs, genetically defined regions of the SHR rat were transferred onto the genetic background of diabetes-prone BB/OK rats. Four new congenic BB.SHR rats named BB.Sa, BB.Bp2, BB.1K, and BB.Xs were generated and characterized telemetrically for blood pressure, heart rate, and motor activity. The data demonstrate clearly that each single blood pressure QTL of the SHR rat causes a significant increase of the systolic blood pressure and has a different influence on diastolic blood pressure, heart rate, and motor activity. The effects were modified differently by the diabetic state in BB.Sa, BB.Bp2, and BB.Xs rats carrying all diabetogenic genes of the BB/OK rats. The results demonstrate that these newly established congenic strains are a unique tool to study the physiological control of blood pressure by a single blood pressure QTL on the one hand and their interaction with hyperglycemia on the other. It is well within the bounds of possibility that diabetic congenics reflect the diabetic hypertension seen in diabetic patients. Because of the synteny conservation in gene order between different mammals, genes of the appropriate human region could therefore be candidate genes for hypertension in diabetics. Furthermore, these congenic strains can also be used to study interactions between a blood pressure QTL and various selected environmental conditions. In this way, one could learn which QTL can be influenced by environmental factors and to what extent. Another point is the study of gene interactions. Because congenics are genetically identical except for the defined transferred region, congenics can be crossed to investigate the interaction between two or three blood pressure QTLs selected by the investigator and not by nature. These QTL combinations can be studied in the nondiabetic as well as diabetic state. Although the advantage of congenic strains has been shown, the transferred chromosomal regions are too large to pinpoint the gene responsible for the phenotypic change. Therefore, regions on each chromosome must be systematically whittled down, which can be done by crossing the congenics with BB/OK rats and intercrossing their progeny to generate recombinants. These can then be used for the creation of new congenic lines carrying a much smaller region of the SHR/Mol rat. This has been started for the region on chromosome 1 spanning a 16-cM region from the Sa to the Igf2 gene. BB.Sa rats were therefore backcrossed onto BB/OK rats and the resulting progeny were intercrossed. The aim will be to create at least three new congenic BB.Sa rat strains homozygous for the SHR alleles of Sa, Lsn, or Igf2 genes. However, new problems will emerge with these new congenics. To genetically define small regions requires more dense polymorphic markers than are currently available. Dense polymorphic markers will also be necessary to split the other regions on chromosomes 10, 18, 20, and X. We expect that in the near future it will be possible using this approach to define small regions of < 0.5 cM. The recent progress in gene mapping in the rat gives hope that the use of such congenic lines will allow the identification and recovery of the blood pressure genes in the near future.

Animals↗
PubMed1997

Biosynthesis of a cyclic tautomer of (3-methylmaleyl)acetone from 4-hydroxy-3,5-dimethylbenzoate by Pseudomonas sp. HH35 but not by Rhodococcus rhodochrous N75.

Here we report that the bacterial catabolism of 4-hydroxy-3,5-dimethylbenzoic acid 1 takes a different course in Rhodococcus rhodochrous N75 and Pseudomonas sp. strain HH35. The former organism accumulates a degradation metabolite of the acid which we isolated and identified as 2,6-dimethylhydroquinone 2. The latter bacterial strain converts the acid and the hydroquinone into a dead-end metabolite. This novel compound was characterised unequivocally by mass spectrometry and 1H and 18C NMR and UV spectroscopy as 4-acetonyl-4-hydroxy-2-methylbut-2-en-1,4-olide 4, a cyclic tautomer of (3-methylmaleyl)acetone, which exists as the enol carboxylate form 8 in aqueous solution.

4-Butyrolactone↗
PubMed1997

Sce3, a suppressor of the Schizosaccharomyces pombe septation mutant cdc11, encodes a putative RNA-binding protein.

In the fission yeast Schizosaccharomyces pombe, the cdc11 gene is required for the initiation of septum formation at the end of mitosis. The sce3 gene was cloned as a multi-copy suppressor of the heat-sensitive mutant cdc11-136. When over-expressed, it rescues all mutants of cdc11 and also a heat-sensitive allele of cdc14, but not the cdc14 null mutant. Deletion shows that sce3 is not essential for cell proliferation. It encodes a putative RNA-binding protein which shows homology to human eIF4B. Immunolocalisation indicates that Sce3p is located predominantly in the cytoplasm. Elevated expression of sce3 increases the steady-state level of cdc14 mRNA. Possible mechanisms of its action are discussed.

Amino Acid Sequence↗
PubMed1997

Assessment of worldwide tuberculosis control. WHO Global Surveillance and Monitoring Project.

BACKGROUND: Because worldwide tuberculosis (TB) control had never been assessed, WHO set up a surveillance and monitoring project in 1995. The objectives were to assess the performance of national TB programmes; to assess the extent of implementation of the WHO strategy of TB control; and to attempt a comparison between regions that had adopted the WHO strategy and those that had not. METHODS: In June, 1996, we sent data-collection forms requesting information on national TB programmes' control policies, 1995 case notifications, and 1994 treatment results to 216 countries, areas, and territories. We assessed the performance of national TB programmes by comparing case notifications with estimated incidence and by outcome of treatment in cohorts of patients. We also investigated worldwide treatment success and case detection among sputum-smear-positive patients. FINDINGS: 180 (83%) of the 216 countries, areas, and territories surveyed replied to WHO (98% of the worldwide population). In 1995, the WHO control strategy had been implemented in 75 countries, and in 39 of these implementation was countrywide. UP to 23% of the worldwide population lived in regions where the strategy was available. In 1995, 3 297 688 cases of TB (all types) were reported, of which 1161411 (35%) were sputum-smear positive. 54% of all reported cases in countries that used the WHO strategy were sputum-smear positive, compared with 30% in other countries. The worldwide case-detection rate of new sputum-smear-positive cases was 35%. 92% of cases registered for treatment in 1994 in regions that used WHO strategy were assessed for outcome and 76% were treated successfully, compared with 54% and 42%, respectively, in regions that had not implemented the WHO strategy. Among cases reported worldwide in 1994, the documented treatment-success rate was 43%. INTERPRETATION: National TB programmes that have adopted the WHO TB control strategy achieve higher cure rates, but their impact on TB is modest on a worldwide scale. Wider continuous coverage with the WHO strategy is needed for effective worldwide TB control.

Communicable Disease Control↗