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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 91 records · Page 5Linked to original sources

Evidence for two-band superconductivity from break-junction tunneling on MgB2.

Superconductor-insulator-superconductor tunnel junctions have been fabricated on MgB2 that display Josephson and quasiparticle currents. These junctions exhibit a gap magnitude, Delta approximately 2.5 meV, that is considerably smaller than the BCS value, but which clearly and reproducibly closes near the bulk T(c). In conjunction with fits of the conductance spectra, these results are interpreted as direct evidence of two-band superconductivity.

Journal Article↗

Determination of acetone, 2-butanone, diethyl ketone and BTX using HSCC-UV-IMS.

A combination of a custom-designed ion mobility spectrometer (IMS) with a UV ionization source and a high speed capillary column (HSCC) has been developed as an analytical device for the sensitive detection of volatile organic compounds (VOCs), e.g. 2-propanone (acetone), 2-butanone and 3-pentanone (diethyl ketone) in the gas phase. A fast separation of the three selected substances and benzene, toluene and m-xylene (BTX) - all of which occur in human breath - has been achieved within less than four minutes at a carrier gas flow rate of 4.5 mL x min(-1). Multi-dimensional correlations presented support the interpretation of the acquired spectra of mixtures. Method detection limits were 2.7 microg x L(-1) for acetone and 2-butanone and 3.0 microg x L(-1) for diethyl ketone in nitrogen, respectively. The assay linear dynamic range is 4-320 microg x L(-1).

Journal Article↗

The deubiquitinating enzyme Ubp21p of fission yeast stabilizes a mutant form of protein kinase Prp4p.

The protein kinase Prp4p of Schizosaccharomyces pombe is involved in control of the formation of active spliceosomes, phosphorylating the spliceosomal component Prp1p. The kinase domain of Prp4p is closely related to cyclin-dependent kinases (CDKs) and mitogen-activated kinases (MAPKs). A mutational analysis of the highly conserved amino acid sequence ALKHP in subdomain XI of this kinase showed that structural features of this sequence are important for the function of the kinase. We identified ubp21 as a high-copy-number suppressor of a mutation in the ALKHP motif. Characterization of this gene revealed that it encodes a deubiquitinating enzyme belonging to the family of ubiquitin-specific processing proteases (Ubps). The results presented in this report are consistent with the notion that the deubiquitinating activity of Ubp21p may be involved in regulating the steady-state levels of proteins including Prp4p.

Amino Acid Sequence↗

Gains of 12q are the most frequent genomic imbalances in adult fibrosarcoma and are correlated with a poor outcome.

Comparative genomic hybridization was used to analyze 41 adult fibrosarcomas from 34 patients. Thirty-one patients showed in their tumors DNA sequence copy number changes (mean 11, range 3-25). The minimal common regions for the most frequent gains were narrowed down to 12q21 (18 cases); 12q14-q15 and 14q22 (16 cases each); 4q22, 7q31, and 14q23-q24 (15 cases each); and 4q21, 4q23-q24, 8q22, and 12q22 (14 cases each). Twenty-five high-level amplifications were observed in 12 samples. 12q21 and 18p were affected three times each; and 1p21, 4q31.3, 7p21, 12q14-q15, Xp22.1-p22.2, and Xq22-q23 two times each. Losses were less frequent than gains. Early stages of adult fibrosarcomas were characterized by frequent gains of chromosomes 2, 4q, and 14q, whereas gains of chromosomes 7 and 8q were associated with progression. Gains of 12q were frequent in all of the developmental steps of this soft-tissue sarcoma. By investigation of several tumors of the same patient, a number of corresponding changes were always detected. Adult fibrosarcomas from patients who died during the observation time showed statistically significant more frequent gains of 8q, 12q, 13q, and 15q compared to the fibrosarcomas of patients who are alive. Gains and high-level amplifications of 12q14-q22, which were the most frequent genomic imbalances, partly reflected an MDM2 amplification, indicating the importance of this region in the tumorigenesis of sarcomas. In adult fibrosarcomas, a gain of 12q22 correlated significantly (P = 0.028) with a poor overall survival rate.

Abdominal Neoplasms↗

Risk factors and progression of small vessel disease-related cerebral abnormalities.

A three year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate and clinical predictors of progression of small vessel disease related cerebral abnormalities including white matter changes and lacunes. White matter hyperintensity progression was found in 17.9% of individuals over the 3 year period. New lacunes occurred in 2.2% of subjects. The overall frequency of progression of small vessel disease related brain changes was 19%. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline predicted lesion progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study described that polymorphisms in the renin angiotensin system (RAS) increase the susceptibility for progression of cerebral small vessel disease. Homozygosity for the T allele of the M235T polymorphism of the angiotensinogen gene was associated with a 3.19-fold increased risk for lesion progression independently of arterial hypertension. These data suggest that drugs influencing the RAS system may allow to intervene with an unfavorable course of cerebral small vessel disease.

Aged↗

Microangiopathy-related cerebral damage and angiotensinogen gene: from epidemiology to biology.

Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the best accepted risk factors for MARCD. Genes involved in blood pressure regulation, like genes encoding the proteins of the renin-angiotensin system (RAS) therefore represents good candidate genes for MARCD. Plasma angiotensinogen level is a major determinant of the RAS activity. Positive correlation between angiotensinogen gene expression and RAS activity, as well as blood pressure were observed. Common mutations described in the AGT promoter were able to alter AGT expression in cell culture. We described that 4 frequent mutations at the AGT promoter are combined in 5 haplotypes coded as A (-6:g, -20:a, -152:g, -217:g), B (-6:a, -20:c, -152:g, -217:g), C (-6:a, -20:c, -152:a, -217:g), D (-6:a, -20:a, -152:g, -217:g), and E (-6:a, -20:a, -152:g, -217:a). The B haplotype was significantly associated with MARCD in the cohort of the Austrian Stroke Prevention Study (p = 0.005). The association was independent of hypertension, which pinpointed to a possible role of the local RAS in this relationship. Investigation of the promoter activity of the AGT gene in astrocytes suggests that expression of this gene may be modulated by the haplotype.

Aged↗

An international study of the interobserver variation between interpretations of vaginal smear criteria of bacterial vaginosis.

An international workshop on vaginal smear-based diagnosis of bacterial vaginosis was organized where 13 investigators scoring 258 slides with smears from vaginal fluid. Interobserver reproducibility of interpretations of Nugent scores, Hay/Ison scores and wet smear scores for the diagnosis of bacterial vaginosis was shown to be high. Detailed analysis of individual scoring results however indicated that basic standards of quality control to ensure robust individual readings of slides must be adhered to.

Bacteriological Techniques↗

Modified magnetic resonance imaging score compared with orthopaedic and radiological scores for the evaluation of haemophilic arthropathy.

Twenty-four joints (10 knees and 14 ankles), with at least one manifestation of bleeding (proven by sonographic assessment), of 15 patients with haemophilia were investigated prospectively. For magnetic resonance imaging (MRI) evaluation, the MRI scale of Nuss et al. was modified to a MRI score (max. 13 points/joint) to allow a comparison with the physical examination score (max. 12 points) and the radiological score (Pettersson score; max. 13 points). The number of joint bleeds correlated well with the degree of arthropathy P < 0.01). In all 16 joints with a maximum of two bleeds, no alterations were found by physical examination, or radiological and MRI assessment. Joints with three bleeds had physical examination scores between 0 and 2, Pettersson scores from 0 to 3 and MRI scores of 2. Joints with four or more bleeds had physical examination scores ranging between 3 and 7, radiological scores between 7 and 12 and MRI scores between 3 and 8. The MRI score describes initial joint alterations more precisely and earlier than other assessments, allowing a discerning estimation of the degree of arthropathy, as well as a follow-up of haemophilic arthropathy and an improvement after change of treatment. In addition, the modified MRI score seems to differentiate better between early and advanced signs of arthropathy than the MRI scale of Nuss et al.

Adolescent↗

[Evaluation of haemophilic arthropathy--a comparison of MRI and Pettersson score].

PURPOSE: In order to compare score values, joint alterations in haemophilic patients on early and late prophylaxis were assessed and evaluated by X-ray radiography and magnetic resonance imaging (MRI) in a prospective study. PATIENTS AND METHODS: 24 joints (10 knees and 14 ankles) of 15 haemophilic patients, with at least one manifestation of bleeding (proven by sonographic assessment) were investigated. Radiological and MRI investigations were done after complete resorption of bleeding. For radiological evaluation a Petterson score (max. 13 points), and for MRI evaluation a modified MRI score (max. 13 points) according to Nuss et al. were used. RESULTS: Good correlation could be demonstrated between the number of joint bleedings and the degree of arthropathy. 16 joints with maximal 2 bleedings had no alteration on both MRI and radiological assessment. Joints with 3 bleedings had Pettersson score from 0 - 3 points and MRI scores of 2 points. Joints with greater-than-or-equal 4 bleedings had a radiological score between 7 and 12 points, MRI scores ranged from 3 to 8 points. CONCLUSION: Increasing severity of heamophilic arthropathy could be demonstrated initially by the MRI score and later by the Pettersson score depending on the number of bleedings. The MRI score describes initial joints alterations more precisely and earlier than the Pettersson score, allowing a discerning estimation of the degree and a follow-up of haemophilic arthropathy.

Adolescent↗

Expression of cathepsin B, D and L protein in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common childhood autoimmune rheumatic disease and like rheumatoid arthritis (RA), it is characterized by inflammation and the progressive destruction of joints. In RA, cathepsins as proteinases play a major role in destroying synovial tissue and cartilage matrix. So far no data on cathepsin expression in pannus tissue of HA patients exist. The aim of this study was to characterize the expression levels of cathepsins B, D, H, and L in HA and to compare them with those in RA. Synovectomy tissue from 16 HA and 12 RA patients was investigated for cathepsin expression levels by Western blot analysis. Expression of cathepsins B, D and L was on comparable levels in the synovectomy tissue of HA and RA patients. The following graduation of expression was determined: cathepsin D > cathepsin L > cathepsin B. Cathepsin H was neither found to be expressed in HA nor in RA patients. The expression levels of cathepsins in pannus tissue showed no clear difference between patients with systemic JIA and patients with monoarticular JIA. In summary, the comparable expression of cathepsins B, D and L in RA and JIA synovectomy tissue suggests that they may play a similarly important role in destroying synovial tissue and cartilage matrix in the course of HA and RA.

Adolescent↗

A phase II study of outpatient subcutaneous histamine dihydrochloride, interleukin-2 and interferon-alpha in patients with metastatic melanoma.

BACKGROUND: Experimental data had suggested a synergistic effect of histamine with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). PATIENTS AND METHODS: Forty-one patients with metastatic melanoma received IL-2 9 MU subcutaneously (s.c.) twice daily on days 4-8 and 25-29, and once daily on days 11-15 and 32-36. IFN-alpha-2b was given as 5 MU s.c. on days 1-3 and then daily to day 43. Histamine 1 mg s.c. was administered twice daily, following IL-2 and IFN injections starting on day 4. Efficacy and toxicity were compared with those of 42 patients included on exactly the same criteria and receiving the same regimen but without histamine. RESULTS: Two patients achieved a partial response (PR) for an objective response rate of 5% [95% confidence interval (CI) 1% to 17%]. Median overall survival was 7.8 months (95% CI 6.4-9.1). In the control group, two complete responses and one PR were achieved. Median overall survival was 7.1 months (95% CI 5.4-8.9). CONCLUSIONS: This IL-2 and IFN regimen was well tolerated on an outpatient basis. However, the applied regimen cannot be recommended because of the low clinical efficacy. Histamine did not add efficacy or toxicity in combination with this moderate-dose schedule of IL-2 and IFN.

Adult↗

Quantitative RT-PCR assessment of melanoma cells in peripheral blood during immunotherapy for metastatic melanoma.

Circulating malignant cells in peripheral blood are thought to be precursors and surrogate markers of distant metastases and hence markers of a poor clinical outcome. In this study, we used the detection of MART-1 and tyrosinase (TYR) mRNA with a quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay to identify circulating melanoma cells. Blood samples were obtained from 35 patients with metastatic melanoma before, during and after treatment with interleukin-2, interferon-alpha and cisplatin. In addition, MART-1 and TYR protein was identified by immunohistochemistry in consecutive biopsies from 15 of the patients. Analysis of three daily blood samples for 3 days demonstrated that four out of 11 patients examined were negative for both markers on all occasions, and two patients were positive for both markers on all occasions but one. The remaining five patients showed sporadic low positive results for one or the other of the two markers. By comparing the immunohistochemistry results from consecutive biopsies with the RT-PCR results, we demonstrated that patients with MART-1 and TYR protein in their tumour cells had circulating MART-1 and TYR mRNA in 77% and 54% of the cases, respectively. During treatment, the majority of patients who were positive for MART-1 and TYR mRNA converted to being negative. However, these conversions did not significantly correlate with objective response. The presence of TYR mRNA in one of the first two samples showed a trend towards being an independent prognostic factor for poor survival.

Adult↗

Measurements and modeling of acoustic scattering from partially and completely buried spherical shells.

The use of low-frequency sonars (2-15 kHz) is explored to better exploit scattering features of buried targets that can contribute to their detection and classification. Compared to conventional mine countermeasure sonars, sound penetrates better into the sediment at these frequencies, and the excitation of structural waves in the targets is enhanced. The main contributions to target echo are the specular reflection, geometric diffraction effects, and the structural response, with the latter being particularly important for man-made elastic objects possessing particular symmetries such as bodies of revolution. The resonance response derives from elastic periodic phenomena such as surface circumferential waves revolving around the target. The GOATS'98 experiment, conducted jointly by SACLANTCEN and MIT off the island of Elba, involved controlled monostatic measurements of scattering by spherical shells which were partially and completely buried in sand, and suspended in the water column. The analysis mainly addresses a study of the effect of burial on the dynamics of backscattered elastic waves, which can be clearly identified in the target responses, and is based on the comparison of measurements with appropriate scattering models. Data interpretation results are in good agreement with theory. This positive result demonstrates the applicability of low-frequency methodologies based on resonance analysis to the classification of buried objects.

Acoustics↗

Genetic diversity of intimin genes of attaching and effacing Escherichia coli strains.

In this study, we determined the sequences of four intimin variant genes detected in attaching and effacing Escherichia coli isolates of human origin. Three of them were novel and were designated eae-eta (eta), eae-iota (iota), and eae-kappa (kappa). The fourth was identical to the recently described eae-zeta (zeta), isolated from a bovine E. coli O84:NM isolate. We compared these sequences with those of published intimin-alpha, intimin-beta, intimin-gamma1, intimin-gamma2, intimin- epsilon, and intimin-theta alleles. Sequence analysis of these 10 intimin alleles confirmed extensive genetic diversity within the intimin gene family in E. coli. The genetic diversity was more prominent in the 3' region (starting at bp 2,112), which encodes the binding domain of intimin. Phylogenetic analyses revealed four groups of closely related intimin genes: alpha and zeta; beta and kappa; gamma1 and gamma2/theta; and epsilon and eta. Calculation of homoplasy ratios of sequences of the 5' region of eae (positions 1 to 2,111) revealed evidence for intragenic recombination. Split decomposition analysis also indicates that recombination events have played a role in the evolutionary history of eae. In conclusion, we recommend an eae nomenclature system based on the Greek alphabet and provide an updated PCR scheme for amplification and typing of E. coli eae.

Adhesins, Bacterial↗