Search PubMed⌕ Search

Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 181 records · Page 10Linked to original sources
PubMed2000

Effects of interferon-gamma and tumour necrosis factor-alpha on CD95/Fas ligand-mediated apoptosis in human blood eosinophils.

Many cells, including eosinophils, express CD95 (Fas), a surface receptor that mediates apoptosis when ligated by specific antibodies or its natural ligand, Fas ligand (FasL). As apoptosis may play an important role in the regulation of tissue eosinophilia, factors that modulate eosinophil sensitivity to apoptosis are of great interest. It has previously been shown that interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) together increase CD95 surface expression on eosinophils. However, the functional consequences of this increase in CD95 expression have not been demonstrated in detail. We therefore investigated whether the increase in CD95 expression mediated by IFN-gamma/TNF-alpha indeed translates into increased, FasL-mediated apoptosis of eosinophils. For this purpose, purified eosinophils from normal donors were incubated with different concentrations of FasL and induction of apoptosis was assessed by annexin-V/propidium iodide assay. Unlike Jurkat cells, which became apoptotic within 2 h after incubation with FasL, an increase in eosinophil apoptosis could first be dedicated after 6 h incubation with FasL. Prestimulation with IFN-gamma/TNF-alpha for 24 h significantly enhanced FasL-induced apoptosis in eosinophils. This increase in CD95/FasL-mediated apoptosis was correlated with an IFN-gamma/TNF-alpha-mediated increase in CD95 expression. From these findings we conclude that the combination of IFN-gamma and TNF-alpha enhances CD95 expression, which results in an increase in FasL-mediated apoptosis of eosinophils in vitro.

Apoptosis↗
PubMed2000

Three-dimensional (3-D) ultrasonography for obtaining the four and five-chamber view: comparison with cross-sectional (2-D) fetal sonographic screening.

OBJECTIVES: To assess the ability of Doppler-gated 3-D fetal echocardiography to reconstruct and display specific cardiac structures routinely visualized during antenatal ultrasound in a population at low risk for cardiac anomalies. To determine whether any advantage is offered by 3-D sonographic cardiac examination over conventional sonographic fetal screening techniques. DESIGN: After routine two-dimensional sonographic examination, 3-D cardiac data were collected prospectively in 30 fetuses with gestational ages between 19 and 23 weeks from a low risk patient population. Basic echocardiographic key views were derived from 3-D data and selected for reconstruction and analysis. Four- and five-chamber views were rated and only those views judged to be well visualized were considered as positive results. RESULTS: The four- and five-chamber views were well visualized in all but one fetus using conventional 2-D imaging. Gated 3-D volume data sets enabled visualization of these structures in only 19 of 30 fetuses but provided additional structural depth and allowed a dynamic 3-D perspective of valvar morphology and ventricular wall motion. The right ventricular outflow tract was available from the 3-D volumes in 16 subjects. CONCLUSIONS: Considering the versatility of gated 3-D fetal cardiac imaging we believe that it may soon become an important component of fetal screening thus helping to retrieve standard cardiac cross sections when 2-D imaging is limited by lack of sonographer experience or sonographic windows. Diagnostically acceptable echocardiographic views were obtained more consistently with 2-D ultrasound than with 3-D volume data.

Echocardiography, Doppler↗
PubMed2000

[Effects of an herbal crataegus-camphor combination on the symptoms of cardiovascular diseases].

One hundred and ninety (190) patients presenting with "functional cardiovascular disorders" (ICD 10, F 45.3) received purely herbal combination therapy comprising crataegus and camphor (Korodin Herz-Kreislauf-Tropfen) or a placebo, identical in colour and taste to the active treatment, over a period of four weeks within the scope of a multi-centre, placebo-controlled, double-blind study. The principal criterion was the fall in the overall score obtained for a heart-related symptom complex (HSK) during administration of the herbal combination or randomly allocated placebo. The overall score fell significantly by 5.5 or 4.5 points, respectively, from a baseline value of 10.0 points each (p = 0.0165). The sub-score for exhaustion, joint pain, heart disorders, pain on pressure and the total score on the Giessen discomfort chart (GBB) indicated better efficacy with the crataegus-camphor combination than with the placebo. On completion of treatment, the investigators assessed the efficacy of the active drug as "very good to good" in 70.5% of their patients compared with a similar evaluation in just 49.5% of the placebo patients. The degree of satisfaction with the drug therapy according to physician and patient reflected the objective results obtained. 71.6% of subjects in the active drug group were satisfied with their treatment compared with just 52.7% in the placebo group. Adverse events (undesirable side effects) were recorded in 8.3% and 8.5% of patients, respectively. A correlation with the active drug therapy was established in only two cases. Tolerance was therefore positively assessed.

Adult↗
PubMed2000

[Prognostic value of Fallopian tube endoscopy].

OBJECTIVE: Progress in sterility-therapy demands diagnostic methods, that ensure the right indication for certain therapies in order to avoid unsuccessful attempts. In this retrospective study we tried to find out, whether we could predict and influence the success rate of therapies with the use of falloposcopy prior to further treatment. MATERIAL AND METHODS: In 62 sterile patients the endotubal state was evaluated with a falloposcope (Imagyn, Irvine, USA), a system of linear everting catheter (LEC) and microendoscope, prior to further treatment. RESULTS: Twenty of the 62 patients had endotubal pathology of both tubes, 15 patients showed pathology of one tube and 25 patients were diagnosed to have a normal endotubal morphology. In 2 patients falloposcopy could not be performed because of blockage due to intramural myomas. Pregnancy rate of those patients with a normal endosalpinx was 52% altogether, following microsurgery 80% and following insemination even 100%. No extrauterine pregnancies were described in this group. Pregnancy rate of those patients with endotubal pathology of both tubes was 35%. In this group no pregnancy followed microsurgery and following insemination one extrauterine pregnancy could be noticed. Furthermore, IVF results were improved if morphologic evaluation showed normal mucosa. CONCLUSIONS: The falloposcopy is a helpful diagnostic procedure to evaluate endotubal pathology prior to microsurgery and insemination.

Adult↗
PubMed2000

Serum levels of substance P are decreased in patients with type 1 diabetes.

Morphological and immunohistochemical studies in diabetic subjects have shown a depletion of the neuropeptide substance P (SP) in the central and peripheral nervous system. This is the first study investigating serum levels of substance P in type 1 diabetes patients (n=50) and controls (n=75) by means of an enzyme immunoassay. The serum level of SP was significantly decreased in the diabetic group compared to the control group (10.12+/-0.29 vs. 12.25+/-0.38 pg/ml; p<0.0001). In diabetic patients, there was no correlation of substance P levels with age, serum creatinine, albuminuria, total cholesterol, HDL- or LDL-cholesterol, triglycerides, HbA1c, type or duration of diabetes and gender. Furthermore, there was no difference in serum levels of SP in patients with or without retinopathy, but SP was significantly decreased in patients with neuropathy (9.59+/-0.48 vs. 10.78+/-0.83 pg/ml; p=0.04). These data show that SP is decreased in serum of type 1 diabetes patients, especially in those with diabetic neuropathy. Subsequent and already ongoing prospective studies in well validated diabetic patients with neuropathy may characterize the impact of this neurogenic marker in the course of diabetic neuropathy.

Adolescent↗
PubMed2000

[Deletion of chromosome 10q--a marker for metastasis of head-neck carcinomas?].

BACKGROUND: Comparative genomic hybridization (CGH) was applied to squamous cell carcinomas of the head and neck to define genetic alterations that are associated with the metastatic phenotype. METHODS: CGH is a molecular cytogenetic method allowing the comprehensive analysis of a tumor genome for chromosomal imbalances. In total, 23 primary squamous cell carcinomas without evidence of metastasis formation and 20 lymph node metastases were investigated. RESULTS: Prevalent changes observed in more than 50% of the primary tumors included deletions on chromosomes 3p, 4p/q, 5q, 6q, 9p, 11q, 13q, and 18q, and DNA overrepresentations on chromosomes 1p, 3q, 5p, 8q, 9q, 11q13, 16p, 17q, 19p, 20q, and 22q. To evaluate the differences between both groups we used a histogram representation, calculation of a difference histogram, and statistical analysis. The analysis revealed that the lymph node metastases were frequently characterized by deletions on chromosomes 10, 11, and 14. In particular, DNA loss of the chromosomal bands 5p12, 10p11.2-12, 10q21, 10q22-23, 10q24-26, 11p13-14, 11q24-25, and 14q22-24 were significantly associated with metastases formation. The statistical analysis indicated that particularly the deletions on chromosome 10q were highly significant markers for the incidence of lymph node metastases. CONCLUSION: Our data indicate that tumor phenotypes are determined by patterns of chromosomal alterations, and that 10q deletions may predict the metastatic phenotype in head and neck squamous cell carcinomas.

Biomarkers, Tumor↗
PubMed2000

Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects: epitope spreading versus clonal persistence.

Autoantigen-specific T-lymphocytes are present in patients with autoimmune disease and in normal subjects. Little is currently known about the temporal variation (dynamics) of the immune repertoire of these autoreactive T cells. We analysed the long-term variation of the immune repertoire of T cells specific for myelin basic protein (MBP) in five untreated patients with multiple sclerosis and four normal control subjects over a mean observation period of 6 years. MBP-specific CD4(+) T-cell lines were selected with purified human MBP, and their epitope specificity was mapped with overlapping synthetic peptides. Three distinct patterns of repertoire development were observed. (i) Two patients and three control subjects maintained a broad epitope response with fluctuations over time. (ii) Two patients initially showed a focused response that broadened over the course of 6 years; this finding could be described as intramolecular epitope spreading. (iii) In one patient and one control subject, a strikingly focused response, which was directed to a cluster of nested epitopes in the MBP region 83-102, persisted over time. T-cell receptor Vbeta sequence analysis allowed us to trace individual clones of MBP-specific T cells for up to 7 years in the peripheral circulation in four of the five patients and three of the four controls, suggesting that the long-term persistence of MBP-specific T-cell clones is a common feature of the T-cell repertoire not unique to multiple sclerosis. The persisting MBP-specific T-cell clones were not detectable in the blood of one of the patients by complementarity-determining region (CDR)-3 spectratyping, indicating that their frequency does not exceed 1 in 5000 T cells. The temporal characteristics of the MBP-specific T-cell repertoire described here are relevant to therapeutic strategies targeting autoantigen-specific T cells in multiple sclerosis and other autoimmune diseases.

Adult↗
PubMed2000

Toward a developmental family therapy: the clinical utility of research on adolescence.

Tremendous advances have been made in our understanding of the intrapersonal, interpersonal, familial, and contextual characteristics and processes that contribute to adaptive as well as maladaptive developmental outcomes with high-risk and clinically referred adolescents. This empirical knowledge base offers clinically rich opportunities for systematic treatment development. An important step in this process is distinguishing which research findings in basic science areas such as developmental psychology and developmental psychopathology might have clinical relevance. Toward this goal, we review relevant but selective research in areas that are central to clinical work with adolescents (parent-adolescent relationship, biological aspects, and affect and cognition), and we offer examples of how basic research in these areas can inform treatment.

Adolescent↗
PubMed2000

Differentiation between Candida dubliniensis and Candida albicans by fatty acid methyl ester analysis using gas-liquid chromatography.

Candida dubliniensis is often found in mixed culture with C. albicans, but its recognition is hampered as the color of its colonies in primary culture on CHROMagar Candida varies. Furthermore, definite identification of C. dubliniensis is difficult to achieve, time-consuming, and expensive. Therefore, a method to discriminate between these two closely related yeast species by fatty acid methyl ester (FAME) analysis using gas-liquid chromatography (Sherlock Microbial Identification System [MIS]; MIDI, Inc., Newark, Del.) was developed. Although the chromatograms of these two species revealed no obvious differences when applying FAME analysis, a new library (CADLIB) was successfully created using Sherlock Library Generation Software (MIDI). The amount and frequency of FAME was analyzed using library training files (n = 10 for each species), preferentially those comprising reference strains. For testing the performance of the CADLIB, clinical isolates genetically assigned to the respective species (C. albicans, n = 32; C. dubliniensis, n = 28) were chromatographically analyzed. For each isolate tested, MIS computed a similarity index (SI) indicating a hierarchy of possible strain fits. When using the newly created library CADLIB, the SIs for C. albicans and C. dubliniensis ranged from 0.11 to 0.96 and 0.53 to 0. 93 (for all but one), respectively. Only three isolates of C. albicans (9.4%) were misidentified as C. dubliniensis, whereas all isolates of C. dubliniensis were correctly identified. Resulting differentiation accuracy was 90.6% for C. albicans and 100% for C. dubliniensis. Cluster analysis and principal component analysis of the resulting FAME profiles showed two clearly distinguishable clusters matching up with two assigned species for the strains tested. Thus, the created library proved to be well suited to discriminate between these two species.

AIDS-Related Opportunistic Infections↗
PubMed2000

TrioGEF1 controls Rac- and Cdc42-dependent cell structures through the direct activation of rhoG.

Rho GTPases regulate the morphology of cells stimulated by extracellular ligands. Their activation is controlled by guanine exchange factors (GEF) that catalyze their binding to GTP. The multidomain Trio protein represents an emerging class of &Rgr; regulators that contain two GEF domains of distinct specificities. We report here the characterization of Rho signaling pathways activated by the N-terminal GEF domain of Trio (TrioD1). In fibroblasts, TrioD1 triggers the formation of particular cell structures, similar to those elicited by RhoG, a GTPase known to activate both Rac1 and Cdc42Hs. In addition, the activity of TrioD1 requires the microtubule network and relocalizes RhoG at the active sites of the plasma membrane. Using a classical in vitro exchange assay, TrioD1 displays a higher GEF activity on RhoG than on Rac1. In fibroblasts, expression of dominant negative RhoG mutants totally abolished TrioD1 signaling, whereas dominant negative Rac1 and Cdc42Hs only led to partial and complementary inhibitions. Finally, expression of a Rho Binding Domain that specifically binds RhoG(GTP) led to the complete abolition of TrioD1 signaling, which strongly supports Rac1 not being activated by TrioD1 in vivo. These data demonstrate that Trio controls a signaling cascade that activates RhoG, which in turn activates Rac1 and Cdc42Hs.

Actins↗
PubMed2000

Clinical usefulness of pulse oximetry in the fetus with non-reassuring heart rate pattern?

UNLABELLED: The objective of this study was the evaluation of intrapartum pulse oximetry as an indicator of fetal distress and the condition of the newborn during clinical routine surveillance in an University Perinatal Center. Between 1998 and 1999 pulse oximetry (SpO2) was used additionally to routine fetal monitoring by electronic fetal heart rate tracing (CTG) and fetal blood sampling (FBA) in 128 cases with nonreassuring heart rate pattern. Cut off values were FIGO Score < 8 for the heart rate pattern and for fetal blood sampling during labor results of < 7.25 (preacidosis). The condition of the newborn was defined by the APGAR score with the cut off < 7 at 1 minute, while the biochemical status was evaluated by means of arterial blood sampling of the umbilical artery directly after birth using a pH of < 7.20 to verify acidosis. Predictive values of critically low SpO2 values (< 30%) for at least 10 minutes as well as corresponding sensitivities and specificities were calculated together with 95% confidence intervals to identify fetal distress or a depressed condition of the newborns. Of 128 fetuses included in this study 66 (52%) were born spontaneously, 23 (18%) were born by operative vaginal delivery and 39 (31%) by means of cesarean section. The high rate of cesarean section was due to cephalopelvic disproportion in 29 cases. Fetal outcome was evaluated with a clinical score: mean APGAR score value 8.5 SD +/- 1. The mean value of the pH in the umbilical artery was 7.23 +/- 0.04. During a SpO2 monitoring period of 18,381 minutes we analyzed a contact time of 63%. Comparing SpO2 values of < 30% with preacidosis in the fetal blood sampling, we found a positive predictive value of merely 0.17 (95% CI: 0.00-0.64). Of 9 preacidotic cases during delivery only 1 was indicated by a saturation value below 30% (sensitivity 0.11, 95% CI: 0.00-0.48). The specificity and negative predictive value were calculated as 0.83 (95% CI: 0.65-0.94) and 0.76 (95% CI: 0.58-0.89) respectively. Of eleven cases with acidosis in the blood of the umbilical cord artery, pH < 7.20, only 2 were indicated by a SpO2 values below 30%. Which is equivalent to a sensitivity of 0.18 (95% CI: 0.03-0.52). Results of a receiver operator curve analysis showed no substantial deviation from the diagonal. The area under the curve was 0.62, the 95% CI (0.47-0.76) indicating no significant discrimination. Three of 49 fetuses with SpO2 recording during the last 10 minutes were born in clinical depressed status (APGAR < 7). None was indicated by a SpO2 value below 30%. CONCLUSION: Fetal distress and impaired condition of the newborn are not identified or predicted during routine application of SpO2 monitoring in the fetus during labor with adequate safety.

Acidosis↗
PubMed2000

Changes in lymphocyte subsets during pregnancy and post-partum in cases of beginning eclampsia.

AIMS: The goal of the present retrospective study was to examine the peripheral blood lymphocytes for expression of phenotypic and activation markers concerning the development of hypertension in pregnancy. METHODS: 16 women (aged 25-43 years; mean 35.1) developing hypertension in the third trimester (week 25-34) have had blood samples taken in the first (< 14 weeks), the second (week 14-23), the third trimester (week 24-35), in late pregnancy (week 36-termination of pregnancy) and within 1 week post-partum, The control group consisted of 16 age-matched pregnant healthy women, who underwent the same regime. All blood samples were taken in the morning, stored at room temperature and stained within 6 hours and measured within 24 hours. Kruskal-Wallis analysis of variance between both groups was done with multiple comparison according to Dunn. RESULTS: Comparing both groups, the total white cell count was significantly increased in all pregnancies and post-partum. In case of hypertension in pregnancy the cell numbers of suppressor/cytotoxic (CD 8+) and CD 56(+)-activated T cells showed a significant increase in the first trimester (< 14 weeks) [p < 0.05] and decreased thereafter to normal values. In the second trimester (week 14-23) helper/inducer lymphocytes and CD 56+/CD 3+ lymphocytes decreased in case of pre-ecclampsia and cytotoxic lymphocytes elevated [p < 0.05]. In the third trimester (week 24-35) there was no difference in both study groups and in late pregnancy (week 36-termination) there were only small differences without statistical significance. Within 1 week postnatal the value of Il-2 receptor T lymphocytes decreased in the group of pre-eclampsia in comparison to normal pregnancies [p < 0.05]. CONCLUSIONS: Regarding the major changes in activated T cells in both study groups no specific pattern of lymphocyte subsets in case of pre-eclampsia could be found in comparison to healthy pregnant women. Further investigations should focus on functional activation and/or suppression of the cellular immune system. Perhaps this could lead to a screening test for pre-eclampsia in future, which is non-invasive for the patient and economic for our social community because it might reduce medical costs.

Adult↗
PubMed1999

Generation of a large complex antibody library from multiple donors.

We have generated a large complex library of single chain antibodies based on four individual libraries from each of 50 donors. DNA coding for the heavy and light chain variable domains of the IgM and IgG repertoires was amplified by PCR using two different sets of primers. Each individual library was composed of approximately 1-5x10(7) independent clones giving a final combined library of 4x10(9) members. Screening this library by phage display of single chain antibodies with small haptens, peptides and proteins yielded specific antibodies for each class of antigen.

Blood Donors↗
PubMed1999

CSF and serum levels of soluble interleukin-6 receptors (sIL-6R and sgp130), but not of interleukin-6 are altered in multiple sclerosis.

Interleukin-6 (IL-6) has recently been implicated in multiple sclerosis (MS), since IL-6 deficient mice were resistant to a demyelinating form of experimental autoimmune encephalomyelitis and IL-6 expression was upregulated in MS. The cytokine IL-6 and its action mediating soluble receptors (sIL-6R and sgp130) were measured in cerebrospinal fluid (CSF) and serum of 61 MS patients and 39 controls. In the presence of unchanged IL-6 concentrations, sIL-6R and sgp130 serum levels were significantly increased in MS and correlated with disease severity. Furthermore, sgp130 CSF levels were decreased in MS, suggesting a possibly altered IL-6 regulation in the CSF.

Adult↗
PubMed1999

Potential misinterpretation of the case-only study to assess gene-environment interaction.

Novel epidemiologic study designs are often required to assess gene-environment interaction. A design using only cases, without controls, is one of several approaches that have been proposed as more efficient alternatives to the typical random sampling of cases and controls. However, it has not been pointed out that a case-only analysis estimates a different interaction parameter than does a traditional case-control analysis: The latter typically estimates departure from multiplicative population odds or rate ratios, depending on the method of control selection, while the former estimates departure from multiplicative risk ratios if genotype and environmental exposure are not associated in the population. These parameters are approximately equal if the disease risk is small at all levels of the study variables. The authors quantify the impact of allowing for higher disease risk among gene carriers, a relevant situation when the gene under study is highly penetrant. Their findings show that the cross-product ratio computed from case-only data may be substantially smaller than the odds ratio computed from case-control data and may therefore underestimate either the population odds or the rate ratio. Thus, to avoid misinterpretation of interaction parameters estimated from case-only data, the definition of multiplicative interaction should be made explicit.

Case-Control Studies↗
PubMed1999

Apoptosis of a human melanoma cell line specifically induced by membrane-bound single-chain antibodies.

CD28 is a key regulatory molecule in T cell responses. Ag-TCR/CD3 interactions without costimulatory signals provided by the binding of B7 ligands to the CD28R appear to be inadequate for an effective T cell activation. Indeed, the absence of B7 on the tumor cell surface is probably one of the factors contributing to the escape of tumors from immunological control and destruction. Therefore, to increase the immunogenicity of tumor cell vaccines, we have expressed anti-CD3 and anti-CD28 single-chain Abs (scFv) separately on the surface of a human melanoma SkMel63 cell line (HLA-A*0201). A mixture of cells expressing anti-CD3 with cells expressing anti-CD28 resulted in a marked activation of allogeneic human PBL in vitro. The apparent induction of a Th1 differentiation pathway was accompanied by the proliferation of MHC-independent NK cells and MHC-dependent CD8+ T cells. PBL that had been cultured together with transfected SkMel63 tumor cells were able to specifically induce apoptosis in untransfected SkMel63 cells. In contrast, three other tumor cell lines expressing HLA-A*0201, including two melanoma cell lines, showed no significant apoptosis. These results provide valuable information for both adoptive immunotherapy and the generation of autologous tumor vaccines.

Animals↗