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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 217 records · Page 12Linked to original sources

Perception of complex tones and its analogy to echo spectral analysis in the bat, Megaderma lyra.

The gleaning bat Megaderma lyra emits broadband echolocation sounds consisting of multiple frequency components. The present study investigates into which perceptual qualities the spectral characteristics of echoes may be translated in the auditory system of M. lyra. Three bats were trained in a 2-AFC behavioral experiment to classify nine complex tones, which spectrally resembled M. lyra's sonar calls, into two perceptual categories. Then the bats' spontaneous responses to unknown complex tones were recorded. The results show that the animals based their classifications of the complex tones on a sound quality which was mediated by their broadband frequency spectra. The bats used the training stimuli as spectral templates and classified the test stimuli according to their broadband spectral similarity with the learned patterns. Assuming that passive hearing and echo processing are governed by similar perceptual qualities and subject to similar limitations, the perceptual mode which was used by the bats to compare the multicomponent spectral patterns in the reported experiments could serve as a powerful tool for the spectral analysis of M. lyra's multicomponent echoes. The analogy between the perception of complex tones and echo spectral analysis in M. lyra is theoretically elaborated in the "formant-mode" model.

Animals↗

PCR and blood culture for detection of Escherichia coli bacteremia in rats.

Critically ill patients often develop symptoms of sepsis and therefore require microbiological tests for bacteremia that use conventional blood culture (BC) techniques. However, since these patients frequently receive early empirical antibiotic therapy before diagnostic procedures are completed, examination by BC can return false-negative results. We therefore hypothesized that PCR could improve the rate of detection of microbial pathogens over that of BC. To test this hypothesis, male Wistar rats were challenged intravenously with 10(6) CFU of Escherichia coli. Blood was then taken at several time points for detection of E. coli by BC and by PCR with E. coli-specific primers derived from the uidA gene, encoding beta-glucuronidase. In further experiments, cefotaxime (100 or 50 mg/kg of body weight) was administered intravenously to rats 10 min after E. coli challenge. Without this chemotherapy, the E. coli detection rate decreased at 15 min and at 210 min after challenge from 100% to 62% of the animals with PCR and from 100% to 54% of the animals with BC (P, >0.05). Chemotherapy decreased the E. coli detection rate at 25 min and at 55 min after challenge from 100% to 50% with PCR and from 100% to 0% with BC (P, <0.05). Thus, at clinically relevant serum antibiotic levels, PCR affords a significantly higher detection rate than BC in this rat model. The results suggest that PCR could be a useful adjunct tool supplementing conventional BC techniques in diagnosing bacteremia.

Animals↗

Candidate autoantigens in multiple sclerosis.

Multiple sclerosis is an inflammatory demyelinating CNS disease of putatively autoimmune origin. Novel models of experimental autoimmune encephalomyelitis (EAE) have demonstrated that T cells specific for various myelin and even nonmyelin proteins are potentially encephalitogenic. The encephalitogenic T cell response directed against different CNS antigens not only determines the lesional topography of CNS inflammation but also the composition of the inflammatory infiltrates. The heterogeneity of the lesional distribution seen in EAE might therefore be useful for the understanding of the various clinical subtypes seen in MS. In this review the possible candidate autoantigens in MS are discussed with special regard to the human T cell and B cell responses against various myelin and nonmyelin proteins.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Selection of an anti-CD20, single-chain antibody by phage ELISA on fixed cells.

Cloning the correct genes that code for antibody-variable domains from hybridomas is often complicated by the presence of several immunoglobulin transcripts, some of them arising from a myeloma cell line. For the rapid functional evaluation of recombinant antibody fragments against cell-surface antigens, we established an efficient expression and screening system using phagemid antibodies and fixed cells. VL and VH-polymerase chain reaction (PCR) products, amplified from hybridoma cDNA, were cloned into the phagemid vector pSEX81. After transduction into E. coli and phage rescue, clones were tested for antigen binding using a phage-enzyme-linked immunosorbent assay (ELISA) procedure with whole cells fixed to ELISA wells. This procedure facilitated the successful cloning of a functional anti-CD20, single-chain antibody from hybridoma cDNA. The CD20 B-lymphocyte surface antigen expressed by B-cell lymphomas is an attractive target for cancer treatment using immunoconjugates or bi-specific antibodies.

Antibodies, Monoclonal↗

[The diagnostic report as an aid for determination of referral to inpatient rehabilitation].

The investigation analyzes some 206 standardized diagnostic reports submitted by office-practice physicians, demonstrating the role of diagnostic reports in determining access to medical rehabilitation. It is found that the practitioners added no further information about their patients' health status in half of the diagnostic reports given, and no further medical documents in one third. On the other hand, diagnostic reports that included details about the patients' ability to work as well as information about previous treatments resulted to a greater degree in direct award of a medical rehabilitation measure.

Decision Support Techniques↗

Genetic factors in IgA nephropathy.

Immunoglobulin A glomerulonephritis (IgA-GN) or Berger's disease is the most common glomerulonephritis when diagnosis is based on renal biopsy. The disease has a variable clinical course. Abnormalities in the production and/or catabolism of IgA are thought to play an important role in the etiology and pathogenesis of IgA-GN. Some evidence suggests that genetic factors determine the susceptibility to develop IgA-GN. Furthermore it has been proposed that genetic factors determine also the rate of progression. Since hypertension is an important predictor of progression, genes involved in blood pressure regulation have been analysed. A polymorphism in the gene for the angiotensin converting enzyme has been reported to be associated with progression. Further studies and progress in molecular biology will help to further elucidate the genetic factors which contribute to the development and progression of IgA-GN.

Biopsy↗

Specific mucosal immunity in the pathophysiology of bacterial prostatitis in a rat model.

Mucosal immunity was established in the rat prostate by stimulating the common mucosal system through serosal exposure of formalin-killed Escherichia coli. Immunized but not sham-immunized rats developed bacterial specific IgG and IgA in prostatic fluid, and IgA in urine. Immunized (n = 21) and sham-immunized control rats (n = 30) were challenged by transurethral injection of E. coli into the prostate ducts. Mortality, gross and microscopic pathology, tissue bacterial counts, bacterial associated immunoglobulins, and antibody titers in serum and urine were assessed at 7 days following the challenge. Increased E. coli specific immunoglobulin titers were seen in immunized rats, and E. coli, but not Proteus, found in the prostates of immunized animals were coated with IgG and IgA. Immunization protected against toxaemia and septicemia, seen as a rare complication of acute prostatitis, but did not protect against acute prostatitis, nor alter the degree of tissue damage seen in the rat model.

Acute Disease↗

Late onset immunodeficiency in a patient with recurrent thymic carcinoma and myasthenia gravis.

The most common autoimmune disease associated with thymoma is myasthenia gravis. In addition, cellular and humoral immune defects have been frequently reported in association with thymic neoplasms. Here we report the case of a patient with myasthenia gravis receiving long-term immunosuppression with azathioprine and recurrent well-differentiated thymic carcinoma who developed CD4+ T-cell depletion and CNS cryptococcosis after multiple courses of chemotherapy and mediastinal irradiation. We hypothesize that in thymectomized patients bone marrow suppression and abrogation of the peripheral T-cell pool can result in a delayed T-cell regeneration due to the lack of functional thymic epithelium.

Adult↗

Mapping of novel genes predisposing or protecting diabetes development in the BB/OK rat.

By several crossing studies it has been demonstrated that the MHC class-II genes of the RT1u haplotype, Iddm1, and the lymphopenia, Iddm2, are essential, but not sufficient for diabetes development in the BB rat. Using diabetic BB/OK and diabetes-resistant DA rats it has been shown that a third non-MHC gene, Iddm3, on chromosome 18 cosegregates with diabetes in the BB/OK rat subline. Because mapping results need not be consistent among different crosses, we genetically analysed a new cross population using diabetic BB/OK and diabetes-resistant SHR/Mol rats analysing 73 microsatellite markers. The genetic analysis of Iddm1 and Iddm2 homozygous [(BB/OK x SHR)F1 x BB/OK] first backcross hybrids (BC1) confirmed the action of Iddm3 and one predisposing non-MHC locus, Iddm4, near Ighe/D6Mgh2 on chromosome 6 and one protective locus, Iddm5r(esistance), detected around Igf2/Tnt on chromosome 1. From these novel findings it is concluded that the diabetogenic phenotype of the BB/OK rat subline is the result of the interaction of predisposing and protecting diabetes genes.

Alleles↗

Multiple receptor interaction domains of GRIP1 function in synergy.

Nuclear hormone receptors are exerting their effect on transcription by interacting with basal factors of the transcription machinery and/or by recruiting intermediary factors, such as the mouse protein GRIP1. GRIP1 is one of the recently identified coactivators for nuclear hormone receptors. Upon interaction with the hormone-binding domain of the receptors, GRIP1 increases their transcriptional activity. Here we show that GRIP1 contains at least two receptor-interacting regions using the hormone-binding domain of several receptors as bait in the yeast two-hybrid assay. GRIP1 interacts in a hormone-dependent manner with the C-termini of nuclear hormone receptors such as GRalpha, TRalpha, TRbeta, RARalpha and RXRalpha but not with v-ErbA. GRIP1 contains several LXXLL motifs which were shown to be required for receptor interaction. A protein fragment containing all of the three LXXLL motifs, but having the activation domain deleted, is able to repress the transcriptional activity of human TRbeta, whereas a region harbouring only one LXXLL motif fails to do so. A protein fragment with two LXXLL motifs exhibits an intermediate modulation of the TRbeta transactivation. While one motif seems to be sufficient for receptor interaction, more than one motif is needed for functional interference.

Amino Acid Sequence↗

Asymmetric segregation on spindle poles of the Schizosaccharomyces pombe septum-inducing protein kinase Cdc7p.

Schizosaccharomyces pombe divides by means of a centrally placed division septum. The initiation of septation must be tightly coordinated with events in mitosis, as premature formation of the septum can lethally cut the undivided nucleus. The Spg1p GTPase and the Cdc7p kinase, with which it interacts, play a central role in signaling the initiation of septum formation. Loss-of-function mutations in either gene prevent septation, whereas inappropriate activation of Spg1p can induce septum formation from G1 or G2 interphase cells. Increased expression of either gene leads to multiple rounds of septation without cell cleavage, emphasizing the need for precise cell cycle regulation of their activity. To understand the mechanisms underlying this regulation, we have investigated whether these key initiators of septum formation are controlled by changes in their activity and/or location during mitosis and cytokinesis. We demonstrate that Spg1p localizes to the spindle pole body in interphase and to both spindle poles during mitosis. In contrast, Cdc7p shows no discrete localization during interphase, but early in mitosis it associates with both spindle pole bodies and, as the spindle extends, is seen on only one pole of the spindle during anaphase B. Spg1p activity is required for localization of Cdc7p in vivo but not for its kinase activity in vitro. Staining with an antiserum that recognizes preferentially GDP-Spg1p indicates that activated GTP-Spg1p predominates during mitosis when Cdc7p is associated with the spindle pole body. Furthermore, staining with this antibody shows that asymmetric distribution of Cdc7p may be mediated by inactivation of Spg1p on one spindle pole. Deregulated septation in mutant cells correlates with segregation of Cdc7p to both spindle poles.

Cell Cycle Proteins↗

Genomic alterations associated with malignancy in head and neck cancer.

BACKGROUND: Comparative genomic hybridization (CGH) was performed on 50 primary head and neck squamous cell carcinomas (HNSCC) to discover molecular genetic alterations underlying the progression of these tumors. METHODS: In CGH, equal amounts of differently labeled tumor deoxyribonucleic acid (DNA) and normal reference DNA were hybridized simultaneously to normal metaphase chromosomes. They were visualized by different fluorochromes, and the signal intensities were quantitated separately as gray levels along the single chromosomes. The over- and underrepresented DNA segments were determined by computation of ratio images and average ratio profiles. RESULTS: Prevalent changes observed in more than 50% of the HNSCC included deletions of chromosomes 1p, 4, 5q, 6q, 8p, 9p, 11, 13q, 18q, and 21q and DNA overrepresentations of 11q13 as well as 3q, 8q, 16p, 17q, 19, 20q, and 22q. The calculation of ratio profiles of tumor subgroups revealed that well differentiated carcinomas (G1) were defined by the deletions of chromosomes 3p, 5q, and 9p together with the overrepresentation of 3q, suggesting the association with early tumor development. Accordingly, the undifferentiated tumors (G3) were characterized by additional deletions of chromosomes 4q, 8p, 11q, 13q, 18q, 21q, and overrepresentations of 1p, 11q13, 19, and 22q. CONCLUSION: Our data indicate that the CGH patterns of chromosomal imbalances may help to define the malignant potential of head and neck squamous cell carcinomas.

Carcinoma, Squamous Cell↗

Detectability improvements in capillary zone electrophoresis by combining single capillary isotachophoretic preconcentration and frequency doubled argon ion laser-induced fluorescence detection.

Due to the small path length and low injection volume the concentration limit of detection is comparatively poor in capillary electrophoresis (CZE) with UV detection. This limitation can be overcome by means of preconcentration methods and/or improved detection techniques. This paper describes a strategy where isotachophoresis (ITP) is used to preconcentrate a new cholinesterase inhibitor (NXX-066) prior to a capillary zone electrophoresis analysis in the same single capillary. A hydrodynamic backpressure is used to prevent the analyte from migrating out of the capillary. Laser-induced fluorescence (LIF) is used to further increase the detectability. The total gain in detectability with ITP-CZE-LIF compared to CZE-UV was at least 5500-fold, and it is possible to determine NXX-066 at the 1 nM level. The ITP-CZE method was further evaluated for two beta-blockers; the mean coefficient of variation of the peak areas was 3.4% and the linearity of the calibration plots was satisfying.

Argon↗

[S100B: pathogenetic and pathophysiologic significance in neurology].

S100B is a multifunctional member of the S100-calmodulin-troponin superfamily of proteins and can modulate the activity of other intracellular proteins following binding of calcium. S100B has been shown to exhibit regulatory effects on cell growth and differentiation as well as on cell shape and energy metabolism. S100B has neurotrophic properties and stimulates glial cell proliferation in vitro and in vivo. Overexpression of S100B has been proposed as a pathogenetic factor in plaque formation in patients with Alzheimerís disease and Down syndrome. Furthermore, S100B-specific T-lymphocytes have been shown to be encephalitogenic in the animal model of experimental autoimmune panencephalitis (EAP). Phenotypically and functionally similar S100B-specific T-cells can also be recovered from the peripheral blood of humans making S100B a potential candidate autoantigen in multiple sclerosis. Here the basic biochemical, molecular and functional properties of S100B are reviewed with special regard to the potential pathogenetic role of S100B in Alzheimerís disease, Down syndrome and multiple sclerosis.

Alzheimer Disease↗

Breast cancer risk assessment: use of complete pedigree information and the effect of misspecified ages at diagnosis of affected relatives.

Reliable risk estimates for hereditary breast cancer are important for the genetic counseling of women who have one or more first- and/or second-degree relatives affected by the disease. If no mutation analysis of known high-penetrance breast cancer genes is performed, risk estimation is often based on published reference tables. These tables express a woman's age-specific risk of breast cancer as a function of the ages at diagnosis of one or two affected relatives with different degrees of relationship to the counselee. However, unaffected relatives are not taken into account when these estimates are derived. We report here the extent to which risk estimation is influenced by the number and ages of any unaffected relatives and by the exact genealogical relationship between the proband and affected relative rather than merely the degree. Additionally, we describe the sensitivity of risk estimates when ages at diagnosis of affected relatives are misspecified because of inaccurate information supplied by the counselee. We determined a proband's probability of being a carrier of a highly penetrant breast cancer susceptibility gene, such as BRCA1 or BRCA2, by likelihood calculations that take into account information from the entire pedigree. This genetic risk was used to estimate a phenotypic lifetime breast cancer risk, which was compared with the risks derived from the published reference tables. We demonstrate numerically that the tabulated values tend to over-estimate the probands risk and that the extent of over-estimation depends greatly on the number and ages of unaffected relatives. The validity of the relatives ages at diagnosis can affect risk predictions considerably in small families with two or three affected relatives. Furthermore, the magnitude of the estimated breast cancer risks depends upon the assumed genetic model and can therefore vary appreciably when different penetrance estimates are used.

Adult↗

Efficacy of a self-management program for childhood asthma--a prospective controlled study.

Asthma training programs for parents and children have been developed to increase both the self-management skills of asthmatic children and compliance with medical regimes. In order to evaluate two training programs for asthmatic children aged 7-14, 81 patients were randomly assigned to three groups. Group 1 consisted of 27 patients and their parents who participated in a five-day standardized family-oriented clinical asthma training program. They had monthly follow-up meetings with the training team for a period of six months. Group 2 (n = 29) had the same clinical training without follow-up interventions; a control group (n = 25) received regular medical treatment according to the international guidelines at the asthma clinics without a training program and served as control group. Questionnaires regarding self-management aspects, coping and anxiety were filled out by patients, parents, family doctors and the training team prior to as well as twelve months after the training. The results indicate that Training group 1 benefitted most with respect to active asthma self-management, Training group 2 to some degree while the control group showed no significant effects. The differences after one year between the three groups regarding physical parameters such as lung-function and days missed in school did not reach the level of significance. Our results indicate that the long-term efficacy of self management courses for asthmatic children is enhanced by regular follow-up training sessions.

Adolescent↗

Biodegradation of phenol and p-cresol by the hyphomycete Scedosporium apiospermum.

A hyphomycete with the ability to utilize phenol and p-cresol as carbon and energy source was isolated from soil and subsequently identified as Scedesporium apiospermum. The identification of degradation metabolites and the detection of the corresponding catabolic enzymes in crude extracts enabled us to propose different pathways for the degradation of both phenol and p-cresol in this organism. Generally, the catabolism proceeded via three different dihydroxylated intermediates (catechol, hydroxyhydroquinone and protocatechuate) which were intradiolically cleaved by the corresponding inducible dioxygenases and further catabolized via the 3-oxoadipate pathway.

Biodegradation, Environmental↗