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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 559 records · Page 31Linked to original sources
PubMed1988

Relation of noninvasive parameters and pulmonary artery mean pressure in patients with chronic obstructive lung disease.

A series of 31 patients with various degrees of chronic obstructive pulmonary disease (COPD) underwent radionuclide ventriculography with right heart catheterization. The patients were divided into 2 groups on the basis of their reduction in forced expiratory volume in 1 s (FEV1). In patients with FEV1 greater than or equal to 1,300 ml (group 1) the oxygen partial pressure (PaO2) did not significantly change with exercise, while in patients with FEV1 less than or equal to 1,200 ml (group 2) the PaO2 significantly decreased (p less than 0.05) with exercise. The groups were significantly different from each other as to the correlation between hemodynamic and noninvasive parameters. In the resting state, the correlation between pulmonary artery mean pressure (PAP) and both residual volume to total lung capacity (RV/TLC) and PaO2 was close only in group 2. By contrast, the right ventricular end diastolic wall thickness (RWD) correlated closely with PAP in both groups. With exercise close correlations were observed between PAP and the noninvasive parameters: RWD, PaO2 and right ventricular ejection fraction in both groups. Arterial CO2 partial pressure (PaCO2) was only increased (greater than or equal to 45 mm Hg) in group 2. This parameter correlated moderately closely with PAP both in the resting and the exercise state only in group 2. The predictive value of PaCO2 greater than or equal to 45 mm Hg for estimation of PAP greater than 35 mm Hg during exercise was 100%. We conclude that separation of patients with COPD into groups with different impairments of the lung function parameter FEV1 can improve the correlation coefficients between noninvasive and invasive parameters. The exercise values obviously correlate more closely than the resting values. An increased value of echocardiographically determined RWD seems to be a reliable parameter for prediction of PAP.

Adult↗
PubMed1987

Point mutation at the ATP binding site of EGF receptor abolishes protein-tyrosine kinase activity and alters cellular routing.

Cultured NIH 3T3 cells devoid of endogenous EGF receptors were transfected with cDNA constructs encoding either the human EGF receptor or an EGF receptor mutant in which Lys721, a key residue in the ATP binding site, was replaced with an alanine residue. The mutant receptor was properly processed, and it displayed both high- and low-affinity surface binding sites. Unlike the wild-type receptor, the mutant receptor did not possess intrinsic protein-tyrosine kinase activity. The initial rate of EGF internalization was similar for wild-type and mutant EGF receptors. Surprisingly, the mutant receptors were not down regulated, but appeared to recycle in transfected cells. These data suggest that degradation of normal EGF receptors after endocytosis is due to the kinase activity endogenous to this receptor. A single amino acid substitution rendered a "down-regulated" receptor into a receptor that can recycle from cytoplasmic compartment back to the cell surface.

Adenosine Triphosphate↗
PubMed1987

An angiogenic growth factor is expressed in human glioma cells.

Progression to increased malignancy frequently occurs in human brain tumors of glial origin and usually involves neovascularization--a massive proliferation of endothelial cells into the tumor tissue. We have shown previously that subversion of a normal growth factor-related pathway is frequently associated with human gliomas. Here we show that human glioma cell lines express the gene encoding the angiogenic peptide endothelial cell growth factor (ECGF) or acidic fibroblast growth factor (a-FGF) and that an ECGF-like polypeptide is produced by these cells. The glioma-derived growth factor was partially purified from cell extracts by heparin-Sepharose affinity chromatography where it eluted at 1.5 M sodium chloride. On reversed-phase h.p.l.c., growth factor activity for endothelial cells was eluted at the same concentration of acetonitrile as found for bovine brain-ECGF, also a potent mitogen for endothelial cells. Moreover, human glioma cells possess specific cell surface receptors for ECGF and are mitogenically stimulated by exogenous addition of this growth factor. Glioma derived-ECGF may therefore have a dual influence: first, by autocrine growth-stimulation of human gliomas and, second, by paracrine-stimulation of endothelial cell proliferation which results in neovascularization of the tumor tissue.

Cell Line↗
PubMed1987

A mutant epidermal growth factor receptor with defective protein tyrosine kinase is unable to stimulate proto-oncogene expression and DNA synthesis.

Cultured NIH-3T3 cells devoid of endogenous epidermal growth factor (EGF) receptors were transfected with cDNA expression constructs encoding either normal human EGF receptor or a receptor mutated in vitro at Lys-721, a residue that is thought to function as part of the ATP-binding site of the kinase domain. Unlike the wild-type EGF-receptor expressed in these cells, which exhibited EGF-dependent protein tyrosine kinase activity, the mutant receptor lacked protein tyrosine kinase activity and was unable to undergo autophosphorylation and to phosphorylate exogenous substrates. Despite this deficiency, the mutant receptor was normally expressed on the cell surface, and it exhibited both high- and low-affinity binding sites. The addition of EGF to cells expressing wild-type receptors caused the stimulation of various responses, including enhanced expression of proto-oncogenes c-fos and c-myc, morphological changes, and stimulation of DNA synthesis. However, in cells expressing mutant receptors, EGF was unable to stimulate these responses, suggesting that the tyrosine kinase activity is essential for EGF receptor signal transduction.

Adenosine Triphosphate↗
PubMed1987

Proliferation-dependent changes of proteoglycan metabolism in arterial smooth muscle cells.

Cultured arterial smooth muscle cells synthesize and secrete two types of sulfated proteoglycans designated as proteoglycan A and proteoglycan B. Proteoglycan A has been characterized as chondroitin sulfate-rich, whereas proteoglycan B was found to be dermatan sulfate-rich [Schmidt, A. & Buddecke, E. (1985) Eur. J. Biochem. 153, 260-273]. During the logarithmic growth phase, arterial smooth muscle cells incorporated about 3 times more [35S]sulfate into the total proteoglycans secreted into the culture medium than did non-dividing cells. When arterial smooth muscle cells stopped proliferating the ratio of [35S]proteoglycan A/B increased. No differences were detected in the respective molecular and chemical characteristics of purified proteoglycans A and B isolated from both proliferating and non-dividing cells. Regardless of the growth phase proteoglycan A had a molecular mass of about 280 kDa and contained 8-9 chondroitin sulfate-rich side chains. Proteoglycan B had a molecular mass of about 180 kDa and contained 6-7 dermatan sulfate-rich side chains. The [35S]methionine-labelled protein cores of proteoglycan A and B had a molecular mass of about 48 kDa, but were distinguishable by their specific reactions to monospecific antibodies. Proliferating cells endocytosed proteoglycan B at a rate up to 100% higher than that of non-dividing cells. In all growth phases proteoglycan A was endocytosed at a 10-fold lower rate than proteoglycan B.

Animals↗
PubMed1987

Involvement of the 2'-5' A pathway in the augmentation of natural killer activity.

Pretreatment of human large granular lymphocytes (LGL) or unseparated peripheral blood mononuclear cells with interferon (IFN) resulted in a significant augmentation of natural killer (NK) activity. This increase was paralleled by an increase in the 2'-5'A synthetase activity. In order to investigate the possibility that IFN might be inducing augmentation of NK cells via the 2'-5'A pathway, we tested the effects of nonphosphorylated core material [(A2'p)2A] and of the triphosphorylated form of the 2'-5'A [ppp(A2'p)2A]. The core material had no detectable effect on NK activity. In contrast, when experiments were performed with the triphosphorylated form of 2'-5'A, NK activity was stimulated. In order to achieve activation, permeabilization of LGL with calcium chloride was necessary and, under these conditions, a dose-dependent augmentation of NK activity was seen. However, the calcium treatment had considerable toxic effects on basal levels of NK activity. Collectively, these results suggest that IFN may be inducing augmentation of NK activity via the 2'-5'A pathway. Further studies will be necessary to determine the effects of IFN and/or 2'-5'A on subsequent activation steps in the process leading to cytotoxicity by NK cells.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Mapping of proteoglycans in human arterial tissue.

The major families of proteoglycans in human arterial tissue have been localized and characterized by electron microscopy. After staining with the polycationic dye cuprolinic blue in the presence of a critical electrolyte concentration, three differently sized populations of proteoglycan-cuprolinic blue precipitates are found. The precipitates are distinguished of the basis of their morphology, topographical distribution and susceptibility to specific glycosaminoglycan-degrading enzymes. Each type of proteoglycan is preferentially associated with one connective tissue component: (a) a dermatan sulfate proteoglycan interacts with collagenous fibers, (b) a heparan sulfate proteoglycan is associated with elastic fibers and with the exterior surface of the basement membrane-like layer surrounding smooth muscle cells, and (c) a chondroitin sulfate proteoglycan forms aggregates with hyaluronate in the soluble matrix. Information about the pattern of proteoglycans in normal human arterial tissue should constitute a useful basis for evaluating perturbations in proteoglycan distribution in arteriosclerotic plaques.

Adult↗
PubMed1987

Hemopoietic responses in mice injected with purified recombinant murine GM-CSF.

Normal adult BALB/c, C57BL, and C3H/HeJ mice were injected intraperitoneally three times daily for six days with 6-200 ng purified, bacterially synthesized, murine recombinant GM-CSF. Mice injected with 200 ng rGM-CSF developed a twofold increase in blood neutrophils. In the peritoneal cavity, a dose-related rise was observed in macrophages (up to 15-fold), neutrophils (10- to 100-fold) and eosinophils (10- to 100-fold). Peritoneal macrophages exhibited 15-fold increased mitotic activity (to 7.6/10(3) cells) and increased phagocytic activity for antibody-coated erythrocytes. Increased numbers of infiltrating neutrophils and monocytes were observed in the liver and lung. Dose-related rises were observed in spleen weight (up to 50%) and the spleen content of monocytes (twofold) and nonerythroid progenitor cells (up to fourfold). A dose-related fall occurred in total marrow cellularity (40%) and total nonerythroid progenitor cells (37%-66%), but levels of neutrophils and monocytes remained constant. The data indicate that the injection of rGM-CSF to normal mice increases overall numbers of granulocytes and macrophages and the phagocytic activity of macrophages and provides direct evidence for the conclusion that GM-CSF is likely to function in vivo as a regulator of these cell populations.

Animals↗
PubMed1987

Biochemical events during stapling of the proximal tibial epiphyseal plate in pigs.

Epiphyseal stapling is considered a safe, effective method of correcting angular deformities of the knee in growing children. A study of the underlying biochemical events would contribute to a better understanding of the control of longitudinal growth rate in epiphyseal growth plates and of the molecular pathology of exaggerated physiologic bowleg or knock-knee deformities. Blount stainless staples were applied to the medial side of the proximal tibia epiphyseal growth plate of domestic pigs. The resulting biochemical changes were investigated by incubation of the isolated growth plate cartilage under organ culture conditions. On the fourth to the eighth day after stapling, a significant decrease of [14C]glucose uptake and lactate formation and a significantly lower specific radioactivity of the isolated glycosaminoglycans were observed in relation to the controls. During the second to 12th week, the incorporation of [3H]thymidine and the specific radioactivity of the glycosaminoglycans following incubation with [14C]glucose showed statistically significant decreases. The glycosaminoglycan content of the cartilage was not altered, but the chondroitin sulfate/keratan sulfate ratio was lower in the stapled than in the nonstapled areas. In this period, glucose uptake and lactate production were found to be normalized.

Animals↗