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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 829 records · Page 46Linked to original sources
PubMedDate not supplied

Differential expression of fragile site Xq27 in cultured fibroblasts from hemizygotes and heterozygotes and its implications for prenatal diagnosis.

Expression of the fragile site Xq27 (fraXq27) was studied in metaphases derived from fibroblasts of 8 hemizygotes and 2 heterozygotes, cultured in 2 different media containing reduced concentrations of folic acid. The proportion of fra(X) (q27)-positive metaphases ranged from 1.0 to 14%, which is considerably lower than in lymphocyte cultures from the same individual, but differed with respect to the culture medium used. Four hemizygotes showed a higher proportion of fra(X)-positive cells in medium 199 than in methotrexate-exposed cultures. No fra(X)-negative cultures were observed when the folic acid inhibitor methotrexate was added to medium 199. Thus, in all 10 individuals carrying the fra(X), the fragile site could be detected in fibroblast cultures. We conclude that the expression of fra(X) (q27) in cultured fibroblasts should be studied using at least 2 types of culture conditions, because familial, i.e. genetic differences may influence the expression of this fragile site in fibroblasts. The implications for prenatal diagnosis are discussed on the basis of investigations in 15 pregnancies at risk for the trait.

Adolescent↗
PubMedDate not supplied

Cholesterol-dependent changes of glycosaminoglycan pattern in human aorta.

Glycosaminoglycans are regular constituents of the arterial wall and essential for its structure and function. The arteriosclerosis-dependent changes of glycosaminoglycans were investigated, the degree of arteriosclerosis was monitored by the cholesterol content of the tissue. Histological characterization was achieved by electron microscopy. Total glycosaminoglycans were isolated from 33 delipidated segments of human aorta thoracica after exhaustive proteolytic digestion, and fractionated into the individual glycosaminoglycans by a multistep purification procedure. Chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), and hyaluronate (HA) were identified and quantified by chemical and enzymatic analysis. The concentration of total and individual glycosaminoglycans, expressed as mg/g delipidated dry weight of tissue, decreased significantly with increasing cholesterol content of tissue (p = 0.0005-0.005). The extent of decrease differed between the individual glycosaminoglycans as indicated by a shift in the CS/DS:HA:HS ratio from 47:32:21 in low cholesterol aortic segments to 59:29:12 in cholesterol-rich specimens. Determination of the relative molecular masses (Mr) revealed 58 kDa for CS/DS and 92 kDa for HS with a (statistically not significant) increase of the molecular mass of CS/DS and a decrease of HS with increasing cholesterol content. The copolymeric CS/DS glycosaminoglycans were disintegrated enzymatically into CS and DS containing fragments. A significantly higher relative DS content (p = 0.01) was found in cholesterol-rich arterial tissue (32.5%) as compared with low cholesterol tissue samples (28.8%). Cell culture experiments revealed that human arterial HS is able to inhibit the proliferation of cultured human arterial smooth muscle cells. The HS concentration required for a 30% inhibition of smooth muscle cell proliferation was in the same order as the tissue concentration of HS. This confirms the function of HS as an endogenous inhibitor of cell division and its impact for the development of atherosclerosis.

Aorta, Thoracic↗
PubMedDate not supplied

Early operation in craniofacial dysostosis.

Craniofacial dysostosis is encountered in different congenital malformations such as Kleeblattschädel deformity, Crouzon's disease, and Apert's, Chotzen's, Pfeiffer's, and Carpenter's syndromes. Premature closure of cranial and facial sutures leads to characteristic disfigurement of the skull with orbital and maxillary hypoplasia. Operative treatment should be performed as early in life as possible to prevent further functional and esthetic deficiencies, and psychosocial problems. Correction is done by an intracranial approach with mobilization, remodeling, and advancement of the deformed skull. Thirty-two children have been operated during the first year of life with a maximum follow-up of 8 years. Most favorable results were obtained in 28 cases. The rate of complications were lower than in a series of children operated on later in life. We advocate that complex 1-stage corrections of craniofacial syndromes may be safely carried out during infancy utilizing modern techniques, expert pediatric anesthesia, and postoperative intensive care.

Child, Preschool↗
PubMedDate not supplied

Functional pulmonary atresia in a newborn with normal intracardiac anatomy.

Functional pulmonary atresia is a relatively rare clinical condition usually associated with Ebstein's malformation, tricuspid valve dysplasia, Uhl's anomaly, or transient myocardial ischemia with severe tricuspid regurgitation. The occurrence of functional pulmonary atresia associated with transient tricuspid regurgitation in a newborn with an anatomically normal heart is even more uncommon. We describe a case in which color Doppler flow mapping played an essential role in diagnosis and follow-up of this clinical condition in a newborn who had normal intracardiac anatomy.

Diagnosis, Differential↗
PubMedDate not supplied

Embolization of iatrogenic vascular injuries of renal transplants: immediate and follow-up results.

PURPOSE: To evaluate the outcome in seven patients in whom iatrogenic vascular complications were treated with catheter embolization. METHODS: Angiography showed an arteriovenous fistula in six of the seven patients, a pseudoaneurysm in three patients, and an arteriocaliceal fistula in three patients. Embolization was performed with GAW coils or microcoils in all cases. In three patients enbucrilate, polyvinyl alcohol, or absorbable gelatin powder was administered as an adjunct to the coils. RESULTS: Angiographic success with total occlusion of the vascular injury was achieved in five of the seven patients and clinical success was achieved in four of seven cases. In two cases, nephrectomy after embolization was necessary because of renal artery occlusion or acute hemorrhage at the renal artery anastomosis, respectively. Infarction of 30%-50% of the renal parenchyma was seen in two cases. CONCLUSION: Angiographically successful embolization is not necessarily associated with clinical success. The complication rate is high.

Adult↗
PubMedDate not supplied

Lovastatin controls signal transduction in vascular smooth muscle cells by modulating phosphorylation levels of mevalonate-independent pathways.

Lovastatin has been proven to effectively lower circulating LDL cholesterol and to exert antiproliferative effects on various cell lines, the latter effect being only incompletely understood. We found that lovastatin modulates the signal transducing phosphorylation cascade in vascular smooth muscle cells in a mevalonate-independent manner. Lovastatin was found to distinctively increase total phosphotyrosine levels in smooth muscle cells, an effect which could not be restored by mevalonate. At a concentration of 5 micromol/L lovastatin had a highly specific effect on the mitogen-activated protein kinase pathway. The expression of p42/44 mitogen-activated protein kinase (MAPK) was clearly reduced, but could be restored by addition of mevalonate, while the phosphorylation of p44 was mildly suppressed and the phosphorylation of p42 MAPK was reduced to non-detectable levels. While the phosphorylation of p44 MAPK could partially be restored by addition of mevalonate, the reduced phosphorylation of p42 MAPK could not be restored by addition of excessive doses of mevalonate or stimulation of the cells with basic fibroblast growth factor. Concurrently the expression of the GTP-binding Ras protein was significantly elevated at 5 and 20 micromol/L lovastatin, this effect being attenuated by addition of mevalonate to cell cultures. The data indicate that lovastatin is capable of modulating cellular signaling independently of the cholesterol synthesis pathway.

Animals↗
PubMedDate not supplied

Functional domains of DnaA proteins.

Functional domains of the initiator protein DnaA of Escherichia coli have been defined. Domain 1, amino acids 1-86, is involved in oligomerization and in interaction with DnaB. Domain 2, aa 87-134, constitutes a flexible loop. Domain 3, aa 135-373, contains the binding site for ATP or ADP, the ATPase function, a second interaction site with DnaB, and is required for local DNA unwinding. Domain 4 is required and sufficient for specific binding to DNA. We show that there are three different types of cooperative interactions during the DNA binding of DnaA proteins from E. coli, Streptomyces lividans, and Thermus thermophilus: i) binding to distant binding sites; ii) binding to closely spaced binding sites; and iii) binding to non-canonical binding sites.

Amino Acid Sequence↗
PubMedDate not supplied

Structural requirements and cell-type specificity for ligand activation of peroxisome proliferator-activated receptors.

The mammalian peroxisome proliferator-activated receptor (PPAR) family consists of three different subtypes, PPARalpha, hNUC1/PPARdelta and PPARgamma. Selective agonists have been identified for PPARalpha and PPARgamma but not for hNUC1, and consequently little is known about the genes that are controlled by this receptor. Using ligand-dependent transcription assays in COS-7 cells, we screened a variety of PPAR activating agents to identify a selective activator of hNUC1. We found that the potent peroxisome proliferator, Wy-14643, and the PPARgamma-selective thiazolidinedione, BRL 49653, were poor activators of hNUC1 (EC50s of > 100 microM). Short chain fatty acids (FAs) appeared more selective for PPARalpha than for hNUC1, whereas the very long chain FA, erucic acid (C22:1) was more selective for hNUC1. Using erucic acid as a probe, we conducted a topological similarity search of the Merck Chemical Collection and identified a fatty acid-like compound, L-631,033 4-(2-acetyl-6-hydroxyundecyl) cinnamic acid, that was a selective activator of hNUC1 (EC50 of 2 microM), but was much less selective for PPARalpha or PPARgamma (EC50s of > 100 microM). Structure-function analysis of PPAR activation by L-631,033 structural analogues showed that receptor selectivity depends on the position of the carboxyl group relative to the phenyl ring on the molecule. Transfection experiments in several cell types: an osteoblastic cell line (MB 1.8), a mouse liver cell line (ML-457), rat aortic smooth muscle cells (RSMCs) and COS-7 cells revealed differences in the activation profile of specific ligands. The most notable differences were observed in RSMCs, where transactivation by L-631,033 and Wy-14643, but not by BRL 49653, was markedly reduced, and in MB 1.8 cells, where oleic acid failed to activate PPARs. These findings identify certain structural features in PPAR-activating agents that modulate PPAR activation, and suggest that as with other nuclear receptors, activation is cell-type specific.

Animals↗