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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 19 recordsLinked to original sources
PubMed1992

Sensitization of rat alveolar macrophages to enhanced TNF-alpha release by in vivo treatment with dexamethasone.

Treatment of rats with dexamethasone rapidly induced a marked weight loss which occurred within 3 days and persisted for several weeks. The cachectic state was paralleled by increased serum levels of triglycerides, albumin, and protein and a strong reduction of blood mononuclear leukocytes. In lung sections, an increased number of mononuclear giant cells was found but no bacteria, fungi, or Pneumocystis carinii organisms. Quite strikingly, alveolar macrophages from dexamethasone-treated rats, but not from control animals, were highly sensitive to LPS and released large amounts of TNF-alpha ex vivo. Also under in vivo conditions, high TNF-alpha serum concentrations were found in dexamethasone-treated but not control rats when examined 1 1/2 hr after an intravenous LPS injection. These data suggest that the glucocorticoid-induced cachexia of rats may be linked, at least in part, to readily inducible TNF-alpha release from primed macrophages.

Animals↗
PubMed1992

The antiproliferative activity of arterial heparan sulfate resides in domains enriched with 2-O-sulfated uronic acid residues.

Heparan sulfate isolated from bovine arterial tissue by a multistep purification procedure or from arterial tissue proteoheparan sulfate by beta-elimination exhibits antiproliferative activity toward arterial smooth muscle cells when added to subconfluent cell cultures in a concentration of 50-100 micrograms/ml medium. Enzymatic disintegration of heparan sulfate by heparitinases I and II and isolation of the resulting oligosaccharides indicate that the antiproliferative activity of the heparan sulfate molecule resides in a sulfate-rich octa/decasaccharide domain which is separated by longer sequences of sulfate-free or sulfate-poor N-acetylglucosamine containing disaccharide units. The octa/decasaccharide fraction has a 3-4-fold higher antiproliferative activity than the native heparan sulfate molecule and contains 45% of a disulfated disaccharide which consists of 2-O-sulfated uronic acid and N-sulfated glucosamine (UA(2S)-GlcNS and 12% of a trisulfated disaccharide (UA(2S)-GlcNS(6S). A sulfate-rich hexasaccharide fraction containing 14% of the disulfated disaccharide but 18% of the trisulfated disaccharide has negligible antiproliferative activity. The results indicate the presence of specific structural determinants in the arterial heparan sulfate molecule which may have the function of an endogenous inhibitor of arterial smooth muscle cell growth.

Animals↗
PubMed1992

Melatonin and 6-sulfatoxymelatonin circadian rhythms in serum and urine of primary prostate cancer patients: evidence for reduced pineal activity and relevance of urinary determinations.

The circadian rhythms of melatonin and 6-sulfatoxymelatonin (aMT6s) were analyzed in serum and urine of young men (YM, n = 8), of elderly patients with benign prostatic hyperplasia (BPH, n = 7) and of patients of similar age with primary prostate cancer (PC, n = 9). The data expressed as concentration and in urine also as hourly excreted quantity were analyzed chronobiologically by the single cosinor method and, subsequently submitted to linear regression analyses. Circadian rhythms were detected in all cases except for the excreted quantity of melatonin. The circadian patterns of melatonin and aMT6s in serum were very similar in the different groups and regression analyses showed close correlations between both variables. MESOR and amplitude were significantly depressed in PC (40-60%) as compared to BPH and YM indicating that the depression of serum melatonin in PC is due to a reduced pineal activity and is not caused by an enhanced metabolic degradation in the liver. Acrophases of serum melatonin occurred between 01:34 and 03:26 h and of serum aMT6s between 03:58 and 04:35 h. Circadian rhythms similar to those of serum melatonin and aMT6s were found in urine, particularly for aMT6s excretion as well as melatonin concentration; the determination of both parameters in overnight urine samples closely correlated with the nocturnal peak of circulating melatonin. These results imply that it is feasible to estimate changes in pineal function of prostate cancer patients by means of non-invasive determination using urinary melatonin and aMT6s.

Adult↗
PubMed1992

At least three promoters direct expression of the mouse glucocorticoid receptor gene.

We have characterized the gene for the mouse glucocorticoid receptor. The gene spans approximately 110 kilobases, and glucocorticoid receptor transcripts are assembled from nine exons. Expression of the gene is controlled by at least three promoters, resulting in glucocorticoid receptor transcripts with different 5' nontranslated exons. One promoter is cell-specific, found to be active only in T lymphocytes. The other two promoters are active to various degrees in all cell lines and tissues so far analyzed and are located in a CpG island. The promoter activities are accompanied by DNase I hypersensitivity sites in chromatin. In contrast to a conservation of exon-intron structure, differences in promoter organization suggest a divergence between the evolution of regulatory and coding regions among members of the steroid receptor super-family.

Animals↗
PubMed1992

Massive main pulmonary artery embolism diagnosed with two-dimensional Doppler echocardiography.

This report describes the usefulness of echocardiography in the differential diagnosis of acute cardiovascular events. In a 66-year-old patient with known aortic stenosis and mitral valve prosthesis, who suddenly deteriorated with severe dyspnea, a thrombus within the pulmonary artery could be detected with 2-D echo. Pulsed-wave Doppler disclosed the resulting flow-velocity disturbances.

Aged↗
PubMed1992

Pressure recovery in aortic stenosis: an in vitro study in a pulsatile flow model.

OBJECTIVES: This study was designed to study pressure recovery in various models of aortic valve stenosis by performing hemodynamic measurements under physiologic conditions in a pulsatile aortic flow circuit. The results were used to validate calculations of pressure recovery based on theoretic considerations derived from fluid dynamics. BACKGROUND: Pressure recovery in aortic stenosis has not been systematically analyzed. METHODS: Stenoses varying in size, shape (circular, Y-shaped, slitlike) and inlet configuration (sharp-edged, nozzle-shaped inlet, artificially stenosed bioprostheses) were used. Aortic pressures were measured at multiple sites distal to the stenotic orifice to determine pressure gradients and recovery. RESULTS: With decreasing orifice area (2, 1.5, 1 and 0.5 cm2) pressure recovery increased (5, 7, 10 and 16 mm Hg, respectively) and the index pressure recovery to maximal peak to peak gradient decreased (56%, 37%, 24% and 14%, respectively). For a given orifice size of 0.5 cm2, this index ranged between 12% for a Y-shaped orifice and 15% for a circular orifice with a nozzle (cardiac output 4 liters/min). Increasing the cardiac output increased pressure recovery, whereas the ratio of pressure recovery to maximal pressure gradient remained constant. CONCLUSIONS: The index pressure recovery to transvalvular pressure gradient, which expresses the hemodynamic relevance of pressure recovery, decreases with increasing severity of aortic stenosis but is independent of transvalvular flow. Thus, pressure recovery is of minor importance in severe aortic stenosis but may account for discrepancies between Doppler and manometric gradients observed in patients with mild to moderate aortic stenosis or a prosthetic valve in the aortic position.

Aortic Valve Stenosis↗
PubMed1992

Streptavidin binding to biotinylated lipid layers on solid supports. A neutron reflection and surface plasmon optical study.

Neutron reflection and surface plasmon optical experiments have been performed to evaluate structural data of the interfacial binding reaction between the protein streptavidin and a solid-supported lipid monolayer partly functionalized by biotin moieties. Since both experimental techniques operate in a total internal reflection geometry at a substrate/solution interface, identical sample architectures allow for a direct comparison between the results obtained with these two recently developed methods. It is found that a monomolecular layer of dipalmitoyllecithin doped with 5 mol% of a biotinylated-phosphatidylethanolamine shows a thickness of d1 approximately (3.4 +/- 0.5) nm. Binding of streptavidin to the biotin groups results in an overall layer thickness of d = (5.9 + 0.5) nm that demonstrates the formation of a well-ordered protein monolayer with the (biotin+spacer) units of the functionalized lipids being fully embedded into the binding pocket of the proteins. It is demonstrated by model calculations that a more detailed picture of the internal structure of this supramolecular assembly can only be obtained if one uses deuterated lipid molecules, thus generating a high contrast between individual layers.

Bacterial Proteins↗
PubMed1992

Long-term results after partial and unilateral nephrectomy in childhood.

In a clinical follow-up, 47 patients after unilateral or partial nephrectomy were examined. The average age at operation was 5.8 years (range 3 days-17.1 years), the average follow-up period after surgery was 11.9 years (range 8.2-18.3 years). Main indications for surgery were hydronephrosis (n = 27), other congenital malformations (n = 6) and neoplasia (n = 9). In one patient, we found hypertension, two patients presented with moderately diminished creatinine clearance, two further patients suffered from unilateral hydronephrosis after partial nephrectomy. We found by ultrasonography marked compensatory hypertrophy in cases of solitary kidneys (225.6 +/- 49.3%) as well as contralateral kidneys after partial nephrectomy (158.7 +/- 55.6%).

Adolescent↗
PubMed1992

Excimer laser coronary angioplasty: experience with a prototype multifibre catheter in patients with stable angina pectoris.

Percutaneous excimer laser coronary angioplasty (ELCA) was performed in a first group of 20 patients with stable angina pectoris caused by significant coronary stenosis, and long-term follow-up was evaluated. Prototype 4 to 5.5 French multifibre catheters with 18-20 quartz fibres of 100 microns diameter, concentrically arranged around a central lumen for taking up a guide wire, were coupled to a commercial XeCl excimer laser. Energy was delivered at a wavelength of 308 nm with a pulse duration of 60 or 120 ns. Operating at a repetition rate of 20 Hz, mean energy transmission was 13.4 +/- 6.8 mJ per pulse. In all but one patient the lesion could be passed by the catheter. Percent diameter stenosis decreased from 77.1 +/- 10.8% to 53.1 +/- 11.8% after ELCA. Complications were frequently observed, intracoronary thrombus formation in eight instances, dissection in six patients and spasm in five cases, causing total vessel occlusion in five procedures. All complications could be managed efficaciously by thrombolytic and vasodilating drugs and/or balloon angioplasty. Subsequent PTCA was performed in case of complication or insufficient stenosis reduction after ELCA in 18 patients with adequate results (residual stenosis, 28.5 +/- 10.2%). Long-term follow-up angiography, which could be performed in 16 of 19 laser treatments, demonstrated significant restenosis in only three patients. Our preliminary results suggest that, using ELCA, ablation of atherosclerotic lesions is feasible in most cases. However, compared with PTCA, stenosis reduction is significantly less, and the acute complication rate is much higher. Thus, further improvements of the catheter system are necessary in order to realize the advantages of excimer laser ablation, which can be demonstrated by experimental studies.

Adult↗
PubMed1992

Cloning, sequencing, mapping, and transcriptional analysis of the groESL operon from Bacillus subtilis.

Using a gene probe of the Escherichia coli groEL gene, a 1.8-kb HindIII fragment of chromosomal DNA of Bacillus subtilis was cloned. Upstream sequences were isolated as a 3-kb PstI fragment. Sequencing of 2,525 bp revealed two open reading frames in the order groES groEL. Alignment of the GroES and GroEL proteins with those of eight other eubacteria revealed 50 to 65% and 72 to 84% sequence similarity, respectively. Primer extension studies revealed one potential transcription start site preceding the groESL operon (S) which was activated upon temperature upshift. Northern (RNA) analysis led to the detection of two mRNA species of 2.2 and 1.5 kb. RNA dot blot experiments revealed an at least 10-fold increase in the amount of specific mRNA from 0 to 5 min postinduction, remaining at this high level for 10 min and then decreasing. A 9-bp inverted repeat within the 5' leader region of the mRNA might be involved in regulation of the heat shock response. By using PBS1 transduction, the groESL operon was mapped at about 342 degrees.

Amino Acid Sequence↗
PubMed1992

Sphingolipid long-chain-base auxotrophs of Saccharomyces cerevisiae: genetics, physiology, and a method for their selection.

A selection method for sphingolipid long-chain-base auxotrophs of Saccharomyces cerevisiae was devised after observing that strains that require a long-chain base for growth become denser when starved for this substance. Genetic analysis of over 60 such strains indicated only two complementation classes, lcb1 and lcb2. Mutant strains from each class grew equally well with 3-ketodihydrosphingosine, erythrodihydrosphingosine or threodihydrosphingosine, or phytosphingosine. Since these metabolites represent the first, second, and last components, respectively, of the long-chain-base biosynthetic pathway, it is likely that the LCB1 and LCB2 genes are involved in the first step of long-chain-base synthesis. The results of long-chain-base starvation in the Lcb- strains suggest that one or more sphingolipids have a vital role in S. cerevisiae. Immediate sequelae of long-chain-base starvation were loss of viability, exacerbated in the presence of alpha-cyclodextrin, and loss of phosphoinositol sphingolipid synthesis but not phosphatidylinositol synthesis. Loss of viability with long-chain-base starvation could be prevented by also blocking either protein or nucleic acid synthesis. Without a long-chain-base, cell division, dry mass accumulation, and protein synthesis continued at a diminished rate and were further inhibited by the detergent Tergitol. The cell density increase induced by long-chain-base starvation is thus explained as a differential loss of cell division and mass accumulation. Long-chain-base starvation in Lcb- S. cerevisiae and inositol starvation of Inos- S. cerevisiae share common features: an increase in cell density and a loss of cell viability overcome by blocking macromolecular synthesis.

Cell Division↗
PubMed1992

Tissue polypeptide antigen for monitoring of advanced bladder cancer after MVEC chemotherapy.

58 patients with advanced bladder cancer were treated with MVEC chemotherapy (methotrexate, vinblastine, epirubicin and cisplatinum). 22 patients suffered from locally advanced disease (pT3-4 M0 N0), in 20 patients regional lymph node metastases were found (pT3-4 N1-3 M0). In 16 patients distant metastases were noted (pT1-4 N0-1 M1). In 89% transitional cell and in 11% squamous cell cancer or anaplastic carcinoma was seen. Complete response was noted in 45%, partial response in 23% and no response in 32%. Tissue polypeptide antigen (TPA) was registered before each course of chemotherapy and 3 months after the last application. The sensitivity for (pT3-4 N0 M0) tumors was 90.9%, for (pT3-4 N1-3 M0) 100% and for tumors with distant metastases 100% also, overall 96.6%. No statistically significant different values between each tumor group were found. In 85.7% a concordant reaction of TPA values and clinical status was notable. In conclusion, TPA has been proven as a valuable and a reliable marker for monitoring therapeutic efficacy of chemotherapy for advanced bladder cancer.

Aged↗
PubMed1992

Temporal pattern of pancreatic insulin and C-peptide secretion and of plasma glucose levels after nutritional stimulation.

The dependency of the secretory pattern of insulin and C-peptide on either oral ingestion of the energy substrates glucose and protein or gastric distension was determined in nine healthy male subjects. To analyze secretion dynamics, high frequency blood sampling, computed estimation of individual hormone half-lives, deconvolution of data, and pulse analysis of the deconvoluted data by the Cluster program were used. After stimulation with oral glucose and protein, baseline insulin, C-peptide, and glucose levels increased in parallel, forming two or three large increases (macropulses), with a mean duration of 63.8 min. The frequency of high frequency insulin and C-peptide pulses was unchanged, whereas a significantly increased amplitude formed the basis of insulin/C-peptide macropulses after both oral stimulations. No changes in baseline insulin/C-peptide concentrations or in amplitude or frequency were observed after a challenge with 400 mL H2O (n = 3). Gastric distension with an equal volume of H2O (400 mL) did not influence pancreatic hormone secretion. Insulin and C-peptide secretions were pulsatile, with a frequency of approximately one pulse per 12 min correlated to C-peptide pulses. When calculated by multiple regression analysis glucose, insulin and C-peptide plasma levels increased simultaneously after the challenge with either glucose or protein, suggesting a neuronal or humoral intestinal-pancreatic regulation of pancreatic hormone secretion. These findings suggest that high frequency insulin and C-peptide pulses form the basis of insulin and C-peptide plasma levels after meal stimulation.

Administration, Oral↗
PubMed1992

Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids.

We have identified a novel member of the steroid hormone receptor superfamily by cDNA cloning from a human osteosarcoma SAOS-2/B10 cell library. Sequence analysis predicts a protein of 441 amino acids, which includes the conserved amino acid residues characteristic of the DNA- and ligand-binding domains of nuclear receptors. Amino acid sequence alignment and transcriptional activation experiments revealed that the new protein is closely related to the mouse peroxisome proliferator activated receptor. The overall homology is 62%, and the highest similarity is seen in the DNA- and ligand-binding domains, 86% and 71%, respectively. Northern blot analysis showed that in mature rats, the receptor is highly expressed in heart, kidney, and lung as a transcript of approximately 3500 nucleotides. In human cells, the size of the mRNA is approximately 4000 nucleotides. Transcription assays using hybrid receptors consisting of the ligand-binding domain of the new protein and the DNA-binding domain of the glucocorticoid receptor showed weak stimulation by the peroxisome proliferator activator WY14643, suggesting a relationship to that receptor. Similar stimulation was observed with arachidonic and oleic acid (100-250 microM).

Amino Acid Sequence↗
PubMed1992

[Expression of APO-1, a cell surface molecule mediating apoptosis, during normal B cell ontogeny and in B cell tumors. Co-expression and coregulation of APO-1 and ICAM-1 (CD54) in germinal central cells].

APO-1 is a 48kDa transmembrane glycoprotein and belongs to the NGF/TNF receptor family of surface molecules. Cross-linking of APO-1 induces apoptotic cell death in sensitive cells. Here we show that APO-1 is an activation molecule on B cells. It could be induced/enhanced on dense and buoyant tonsillar B cells, respectively, through surface immunoglobulin cross-linking in combination with interleukin-2 or by interferon-gamma together with tumor necrosis factor-alpha. These conditions also increased the amount of intercellular adhesion molecule-1 (ICAM-1; CD54) on these cells. Epstein-Barr virus transformants of peripheral B cells co-expressed APO-1 and CD54 at very high levels. Immunohistologically, APO-1 was detectable at low levels in a subpopulation of follicular center B blasts and, at higher levels, in sinusoidal B cells. APO-1 was undetectable in follicular mantle B cells and plasma cells. Neoplastic B cell essentially mimicked their reactive counterpart with regard to APO-1 and CD54 expression.

Antibodies, Monoclonal↗
PubMed1992

[Illness concepts of children. Validation of a modified locus of control test in illness and health].

We investigated the health and illness concepts of 53 healthy children aged 8 to 14 years using a modified illness and health locus of control scale (KKG, Lohaus and Schmitt, 1989) with the scales internal, external-p (powerful others) and external-c (chance). A comparison of the results with those on self-esteem (FSK 4-6), anxiety (CMAS-R) and hopelessness (HSC) scales showed a decrease in externality, but not an increase in internality, with increasing age and a correlation between self-confidence and a more internal locus of control. The influence of children's health locus of control on treatment compliance is discussed.

Adolescent↗