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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 163 records · Page 9Linked to original sources

Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R.

The extracellular matrix glycoprotein tenascin-R (TN-R), colocalizing with hyaluronan, phosphacan, and aggregating chondroitin sulphate proteoglycans in the white and grey matter, is accumulated in perineuronal nets that surround different types of neurons in many brain regions. To characterize the role of TN-R in the formation of perineuronal nets, we studied their postnatal development in wild-type mice and in a TN-R knock-out mutant by using the lectin Wisteria floribunda agglutinin and an antibody to nonspecified chondroitin sulphate proteoglycans as established cytochemical markers. We detected the matrix components TN-R, hyaluronan, phosphacan, neurocan, and brevican in the perineuronal nets of cortical and subcortical regions. In wild-type mice, lectin-stained, immature perineuronal nets were first seen on postnatal day 4 in the brainstem and on day 14 in the cerebral cortex. The staining intensity of these nets for TN-R, hyaluronan, phosphacan, neurocan, and brevican was extremely weak or not distinguishable from that of the surrounding neuropil. However, all markers showed an increase in staining intensity of perineuronal nets reaching maximal levels between postnatal days 21 and 40. In TN-R-deficient animals, the perineuronal nets tended to show a granular component within their lattice-like structure at early stages of development. Additionally, the staining intensity in perineuronal nets was reduced for brevican, extremely low for hyaluronan and neurocan, and virtually no immunoreactivity was detectable for phosphacan. The granular configuration of perineuronal nets became more predominant with advancing age of the mutant animals, indicating the continued abnormal aggregation of chondroitin sulphate proteoglycans complexed with hyaluronan. As shown by electron microscopy in the cerebral cortex, the disruption of perineuronal nets was not accompanied by apparent changes in the synaptic structure on net-bearing neurons. The regional distribution patterns and the temporal course of development of perineuronal nets were not obviously changed in the mutant. We conclude that the lack of TN-R initially and continuously disturbs the molecular scaffolding of extracellular matrix components in perineuronal nets. This may interfere with the development of the specific micromilieu of the ensheathed neurons and adjacent glial cells and may also permanently change their functional properties.

Age Factors↗

Interaction of the G protein beta 3 subunit T825 allele and the IRS-1 Arg972 variant in type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus is a common late-onset disease with a strong genetic component. It is characterized by insulin resistance which results from alterations in insulin signal transduction. The G protein beta 3 subunit 825T allele was recently found to be associated with hypertension and obesity which makes it a sensible candidate gene for type 2 diabetes. METHODS: In a case-control study on 320 male patients and 962 male healthy controls we investigated the association of two candidate genes with diabetes, i.e. (i) the GNB3 825T allele, associated with a G protein beta 3 subunit splice variant and enhanced intracellular signal transduction, and (ii) the insulin receptor substrate-1 (IRS-1) 972Arg variant, which encodes a protein variant associated with cellular insulin resistance. RESULTS: The GNB3 825T allele and the IRS-1 972Arg variant were significantly associated with diabetes (odds ratios for either variant 1.4 1.8). Odds ratios were 3 4 in males carrying both alleles. CONCLUSIONS: The results document an association of a hypertension susceptibility gene with type 2 diabetes which may partially explain the frequent coexistence of both disorders.

Adult↗

No association of serum levels of interleukin-6 and its soluble receptor components with a genetic variation in the 3'flanking region of the interleukin-6 gene in patients with multiple sclerosis.

Interleukin-6 (IL-6) plays an important role in the regulation of the inflammatory response in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous reports indicated that a variable number tandem repeat (vntr) polymorphism in the 3'flanking region of the IL-6 gene (C allele) is associated with altered activity of IL-6 in vivo. Therefore, we analyzed the frequency distribution of IL-6 gene C allele vntr poymorphism in 96 MS patients and 106 ethnically matched healthy controls. Moreover, possible correlations between genotypic differences of IL-6 gene and serum levels of IL-6, soluble IL-6 receptor (sIL6-R), soluble gp130 (sgp130), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were investigated. There were no differences in the allelic distribution of the IL-6 gene C allele between MS patients and healthy controls, and no association of the IL-6 gene C allele with serum levels of IL-6, sIL-6R, spg130, sICAM and sVCAM-1 was found.

Adolescent↗

Observation of a BCS spectral function in a conventional superconductor by photoelectron spectroscopy

We present high-resolution photoelectron spectra on the A15-type conventional superconductor V 3Si, where-for the first time-both singularities of the BCS density of states can be resolved by photoemission spectroscopy (PES). With a transition temperature of about T(c) approximately 17 K the gap Delta(gap) of this compound has a magnitude of approximately 5 meV. A measurement by PES on this small energy scale requires a very high energy resolution (DeltaE less, similar5 meV) and sample temperatures significantly below T(c).

Journal Article↗

Association of dietary antioxidants on the severity of gastritis in a high risk population.

PURPOSE: This study is to examine the role of dietary antioxidant intake on the severity of gastritis at the baseline in an intervention study, Chemoprevention of Gastric Dysplasia.METHODS: The Chemoprevention of Gastric Dysplasia is an intervention study conducted in the towns of Pasto and Tuquerres, Colombia. A 79-item food frequency questionnaire was administered to 1,219 subjects at baseline. Endoscopic screening for precancerous gastric lesions was performed in all subjects by biopsy and histologic diagnosis. Subjects without adequate diagnostic material (n = 18) and subjects identified as histologically normal (n = 12) or with gastric cancer (n = 4) were excluded from these analyses. Analysis of Variance on logarithm-transformed data was conducted on dietary antioxidants and the stages of gastritis (atrophic gastritis, intestinal metaplasia, and gastric dysplasia).RESULTS: After adjusting for age, body mass index, smoking status, year of education, total calorie intake, and H-pylori infection status, dietary vitamin C and vitamin E were found to be inversely associated with the severity of gastritis (p < 0.05). Decreased dietary alpha-carotene was found to be marginally associated with gastric dysplasia. Data were then stratified by town where subjects were recruited. The trends for the observed associations were apparent for dietary alpha-carotene, vitamin C and E. However, the association was significant only for vitamin C in Pasto. Compared to subjects with atrophic gastritis, subjects diagnosed with gastric dysplasia have an approximately 15% lower intake of vitamin C.CONCLUSIONS: This study confirmed the protective effect of specific dietary antioxidants on the severity of gastritis. Dietary vitamin C, and to a lesser extent, dietary vitamin E are potentially important for the prevention of gastric cancer.

Journal Article↗

Phagocytosis, oxidative burst, and killing of Candida dubliniensis and Candida albicans by human neutrophils.

Candida dubliniensis is a phylogenetically closely related species to Candida albicans. So far virtually nothing is known about the virulence factors of C. dubliniensis. Cell surface hydrophobicity (CSH) plays a critical role in adhesion of microorganisms to phagocytic cells; hydrophobic cells of C. albicans have been reported to be less sensitive to phagocytic killing than hydrophilic cells. C. dubliniensis displays CSH at 37 degrees C in contrast to C. albicans. To elucidate this issue, we determined levels of phagocytosis, oxidative burst and killing by human neutrophils of C. dubliniensis (n=10) compared to C. albicans (n=10) both cultured at 37 degrees C. Obtained test results revealed no statistically significant differences between these two yeast species for the level of phagocytosis (77.3 vs. 76.2% after 60 min), evoked oxidative burst (64.5 vs. 67.3% after 30 min) and killing (72.7 vs. 73.1% after 240 min). Therefore, human neutrophils can be considered to be equally efficient against these two yeast species.

Candida↗

Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction.

Clonal composition and T cell receptor (TCR) repertoire of CD4(+) and CD8(+) T cells infiltrating actively demyelinating multiple sclerosis (MS) lesions were determined with unprecedented resolution at the level of single cells. Individual CD4(+) or CD8(+) T cells were isolated from frozen sections of lesional tissue by micromanipulation and subjected to single target amplification of TCR-beta gene rearrangements. This strategy allows the assignment of a TCR variable region (V region) sequence to the particular T cell from which it was amplified. Sequence analysis revealed that in both cases investigated, the majority of CD8(+) T cells belonged to few clones. One of these clones accounted for 35% of CD8(+) T cells in case 1. V region sequence comparison revealed signs of selection for common peptide specificities for some of the CD8(+) T cells in case 1. In both cases, the CD4(+) T cell population was more heterogeneous. Most CD4(+) and CD8(+) clones were represented in perivascular infiltrates as well as among parenchymal T cells. In case 2, two of the CD8(+) clones identified in brain tissue were also detected in peripheral blood. Investigation of the antigenic specificities of expanded clones may help to elucidate their functional properties.

Adult↗

Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila.

Correct pathfinding by Drosophila photoreceptor axons requires recruitment of p21-activated kinase (Pak) to the membrane by the SH2-SH3 adaptor Dock. Here, we identify the guanine nucleotide exchange factor (GEF) Trio as another essential component in photoreceptor axon guidance. Regulated exchange activity of one of the two Trio GEF domains is critical for accurate pathfinding. This GEF domain activates Rac, which in turn activates Pak. Mutations in trio result in projection defects similar to those observed in both Pak and dock mutants, and trio interacts genetically with Rac, Pak, and dock. These data define a signaling pathway from Trio to Rac to Pak that links guidance receptors to the growth cone cytoskeleton. We propose that distinct signals transduced via Trio and Dock act combinatorially to activate Pak in spatially restricted domains within the growth cone, thereby controlling the direction of axon extension.

Adaptor Proteins, Signal Transducing↗

T-cell/natural killer cell lymphoblastic lymphoma with an unusual coexpression of B-cell antigens.

Lymphoblastic lymphomas are usually B- or T-cell neoplasms. There exists a small group of T-cell lymphomas additionally coexpressing cytotoxic or natural killer (NK)-cell markers, supporting the hypothesis of a common T/NK-cell precursor and respective neoplasms. Clinically, lymphatic neoplasms of T/NK-cell phenotype are either extranodal lymphomas or acute leukemias. The clinical course of these T/NK neoplasms cannot be predicted by morphology and/or phenotype alone. However, the expression of a heterogeneous (T + NK or myeloid) marker profile or of "early" antigens (such as TdT, CD10, RAG1, RAG2) render them more likely to be in the acute leukemia group. We present a case of a 63-year-old woman with a bone marrow infiltrate, enlarged lymph nodes, and B-symptoms. A cervical lymph node biopsy showed a monomorphic blastic infiltrate with a T-cell phenotype, coexpressing NK markers (CD56, CD57, NK1) and B-cell antigens (CD20, CD79). To the best of our knowledge, this is a newly recognized phenotype that has not been reported before. T/NK-cell lymphomas, including blastic NK-cell leukemia/lymphoma and T-lymphoblastic lymphomas, have to be included in the differential diagnosis. Both groups have a different clinical behavior and prognosis. In particular, T/NK-cell lymphomas associated with an Epstein Barr virus infection are clinically very aggressive neoplasms.

Antigens↗

The role of echolocation in the hunting of terrestrial prey--new evidence for an underestimated strategy in the gleaning bat, Megaderma lyra.

The observation that gleaning bats detect prey by its noises, together with difficulties in recording their faint sonar calls, have led some authors to conclude that gleaning bats may not use echolocation in certain hunting situations. In particular, it is conjectured that echolocation plays no role in the classification and tracking of prey. In the present study, we show that the gleaning bat, Megaderma lyra, is able to find silent and motionless prey on the ground. The significance of sonar for catching a variety of terrestrial prey is established in a standardized situation. Sonar calls were found to be emitted during all stages, i.e. approach, hovering above the prey, and return to the roost, of every hunting flight. The harmonic pattern of the calls differed significantly between these stages, calls with three or more prominent components prevailing during hovering. Bats identified prey and rejected dummies while hovering above them. During this stage, increased call rates and reduced call durations were found. Echolocation activity during, and the duration of, the hovering phase depended on prey type, in particular on prey movement. The prey-dependent shifts in sonar activity, the broadband call structure with an emphasis on higher harmonics, and a systematic shift of the calls' peak frequencies during hovering, are discussed as adaptations to identifying prey by sonar.

Animals↗

Predicting the outcome of infertility surgery.

We studied a group of 187 infertile patients who had electromicrosurgery after laparoscopy, and falloposcopy. Follow-up information about 154 of these patients (82.4%) was available. Success rates in terms of intrauteine pregnancy was inversely related to the severity of peritubal and intratubal adhesions. Electromicrosurgery should only be preformed when clinical benefit is reasonably likely.

Adult↗

Discriminative power of fatty acid methyl ester (FAME) analysis using the microbial identification system (MIS) for Candida (Torulopsis) glabrata and Saccharomyces cerevisiae.

Candida (Torulopsis) glabrata is frequently isolated in cases of fungal infection and commonly shows acquired or innate fluconazole resistance. Saccharomyces cerevisiae, an emerging opportunistic yeast pathogen, causes serious systemic infections in immunocompromised, and vaginitis and superficial infections in immunocompetent patients. For both species reliable identification in the routine laboratory is mandatory, but species identification of strains, e.g. trehalose-negative C. glabrata, may be difficult. Therefore, gas-liquid chromatography (GLC) of whole cell fatty acid methyl ester (FAME) profiles, that is independent of assimilation profiles of strains and suitable for reliable and rapid identification of clinically important yeasts, was applied. However, frequent misidentification of C. glabrata as S. cerevisiae has been reported when using the Yeast Clinical Database of MIS. Accuracy of MIS identification may be strongly influenced by the amounts of cell mass analyzed. Therefore, the present study compared the MIS results of these two yeasts achieved with different cell masses. Primarily we optimized, especially with respect to cost-effectiveness, the recommended streaking technique yielding a maximal recovery of 90-130 mg of cell mass from one plate, enabling testing of poor growing strains of C. glabrata. For all C. glabrata strains tested (n = 10) the highest identification scores (SI [Similarity Index] range 0.525-0.963, median 0.832) were achieved with 30 to 45 mg of cell mass. Only 5 of 10 S. cerevisiae strains revealed good library comparisons (SI > or = 0.5) when using 30 mg of cell mass, whereas with 45 mg all strains but two revealed this SI-level. For S. cerevisiae a higher amount of cell mass processed (up to 90 mg) was correlated with better identification scores (SI range using 90 mg: 0.464-0.870, median, 0.737). Several passages prior to FAME analysis of C. glabrata strains on recommended media revealed narrowing of SI ranges, but differences in SI values were not statistically significant.

Biomass↗

Studying the dynamics of emotional expression using synthesized facial muscle movements.

Synthetic images of facial expression were used to assess whether judges can correctly recognize emotions exclusively on the basis of configurations of facial muscle movements. A first study showed that static, synthetic images modeled after a series of photographs that are widely used in facial expression research yielded recognition rates and confusion patterns comparable to posed photos. In a second study, animated synthetic images were used to examine whether schematic facial expressions consisting entirely of theoretically postulated facial muscle configurations can be correctly recognized. Recognition rates for the synthetic expressions were far above chance, and the confusion patterns were comparable to those obtained with posed photos. In addition, the effect of static versus dynamic presentation of the expressions was studied. Dynamic presentation increased overall recognition accuracy and reduced confusions between unrelated emotions.

Adult↗

A cell surface-displayed anti-c-myc single-chain antibody: new perspectives for the genetic improvement of cellular tumor vaccines.

We have shown recently that cell surface-bound, single-chain Fv antibodies (scFv) are a powerful tool for the improvement of cellular tumor vaccines. To simplify this approach and to develop a general tool for the generation and improvement of cellular tumor vaccines, we chose an scFv against a peptide from the human proto-oncogene c-myc that could anchor any c-myc-tagged protein to the cell surface. The retroviral vector p50-Mx-neo (pMESV) was used to express scFv on the surface of the human melanoma line SkMel63. The cell-bound anti-c-myc scFv bound specifically to a soluble purified anti-CD28 scFv carrying a c-myc peptide-tag at its C terminus. Proof of principle was determined by incubating human peripheral blood lymphocytes with a mixture of (a) anti-c-myc-transfected SkMel63 cells binding the anti-CD28 scFv and (b) SkMel63 cells transfected with an anti-CD3 scFv. A clear synergistic effect on T-cell activation was observed that was comparable with that obtained in previous studies using SkMel63 cells transfected with the gene for the anti-CD28 scFv. As the cell surface-displayed anti-c-myc scFv can bind any c-myc-tagged protein of interest, this technique facilitates the genetic engineering of cellular vaccines for the therapy of virtually all human neoplasias.

Antibodies, Monoclonal↗