Search PubMed⌕ Search

Biomedical subjects

T Glaser

Publications and source records attributed to T Glaser.

126 records · Page 7Linked to original sources
PubMed1982

Neuroblastoma X glioma hybrid cells synthesize enkephalin-like opioid peptides.

Partially purified extracts from neuroblastoma X glioma hybrid cells 108CC15 inhibit, like opioids, the prostaglandin E1-evoked formation of cyclic AMP in a dose-dependent manner in the same hybrid cells. The inhibition is prevented by the opioid antagonist naloxone. In addition, the same extract competes with [3H]naloxone and [3H]Leu-enkephalin for binding to opioid receptors of hybrid cell membranes and to a specific antiserum, respectively. The opioid activity in the extracts is destroyed by carboxypeptidase A and leucine aminopeptidase, but not by trypsin. Further purification of the extracts by HPLC, TLC, or high-voltage paper electrophoresis reveals in each case two active fractions which behave like Met- and Leu-enkephalin. The Met-enkephalin-like, but not the Leu-enkephalin-like, fraction is inactivated by treatment with BrCN. Dimethylaminonaphtylsulfonyl (dansyl) derivatives of Met- and Leu-enkephalin correspond to [3H]dansyl derivatives of Met-like substances from hybrid cells. Three to four times as much Met-enkephalin-like as Leu-enkephalin-like material is present in the extract. The overall concentration of opioid peptides in the hybrid cells varies between 0.03 and 1.0 pmol Leu-enkephalin equivalents per mg protein. The amount of opioids in the hybrid cells is strongly dependent on the cell density. The findings suggest that neuroblastoma X glioma hybrid cells contain opioid peptides that are very similar, if not identical, to Met- and Leu-enkephalin. Opioid activity can also be detected in other neuronal cell lines and even in glioma cells.

Alprostadil↗
PubMed1982

Production and regulation of enkephalin-like peptides in neuroblastoma x glioma cells.

Partially purified extracts from neuroblastoma x glioma hybrid cells inhibit via opioid receptors the PGE1-elicited formation of cyclic AMP in the same hybrid cell system. The purification of extracts reveals two active fractions very similar to Met- and Leu-enkephalin by several criteria including treatment with cyanogen bromide. On an average, the intracellular concentration of opioids in hybrid cells is 0.1 pmol per mg protein. The concentration is strongly dependent on the cell density. Furthermore, the content in the hybrids of enkephalin-like peptides is specifically elevated by glucocorticoids.

Cells, Cultured↗
PubMed1981

Ca2+-dependent cross-linking processes in human platelets.

When platelet cytoplasmic Ca2+ is increased by the ionophore A23187 in the presence of the protease inhibitor leupeptin, there is the coincident appearance of a cross-linked polymer and the partial disappearance of monomeric protein and glycoprotein units. In the absence of leupeptin only 30% of the polymer was formed. The disappearance of monomeric protein bands, as detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis, is prevented by histamine, which as a pseudodonor amine is a known inhibitor of transglutaminase-catalyzed cross-linking [14C]Histamine, at a tracer concentration, is incorporated into the polymer as well as into myosin, glycoproteins IIb and III, actin and tropomyosin. The loss of monomeric protein bands is mostly due to their conversion into polymers. Control measurements show that leupeptin effectively inhibited platelet Ca2+-dependent proteases. The cross-linking processes bringing about the observed increase in polymer formation are thus the result of a Ca2+-dependent platelet transglutaminase activity. The latter is located in the platelet cytosol and has been identified as platelet factor XIII on the basis of its specific cross-linking of fibrin. Platelet factor XIII, upon activation, may function physiologically to couple membrane proteins to cytoplasmic structural proteins. Thus, a new concept is proposed for the stabilization of platelet membranes and platelets as they form the hemostatic plug.

Blood Platelets↗
PubMed1981

Dermorphins, opioid peptides from amphibian skin, act on opioid receptors of mouse neuroblastoma x rat glioma hybrid cells.

Dermorphin and its Hyp6 analogue are opiate-like heptapeptides originally discovered in frog skin and characterized by the presence of a D-Ala2 residue in their sequence. They were assayed for their capacity to compete with [3H]Leu-enkephalin for binding to opioid receptors in membranes of neuroblastoma x glioma hybrid cells. In the presence of 7 nM-[3H]Leu-enkephalin, the concentrations at which they caused 50% inhibition of [3H]enkephalin binding (IC50 values) are 0.1 micro M and 0.3 micro M, respectively. In contrast, the synthetic L-Ala2-dermorphin shows very low affinity for the opioid receptors. In addition, like other opioid peptides, dermorphin and hyp6-dermorphin inhibit the elevation by prostaglandin E1 (PGE1) of the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) (IC50 values 0.2 micro M and 0.4 micro M, respectively). The inhibition is prevented by the opiate antagonist naloxone, L-Ala2-dermorphin is at least three orders of magnitude less potent in inhibiting the PGE1-evoked increase in the level of cyclic AMP. The results show that peptides with an amino acid sequence quite different from that of the enkephalins can bind to opioid receptors of the hybrid cells.

Amphibians↗
PubMed1981

Fibronectin in von Willebrand's disease and thrombasthenia: role in platelet aggregation.

Fibronectin is involved in cell-cell and cell-substratum adhesion processes. Since von Willebrand's disease and thrombasthenia are characterized, respectively, by platelet-substratum and platelet-platelet adhesion anomalies, we investigated the state of fibronectin in platelets and plasma of these two disorders as well as the role of plasma fibronectin in platelet aggregation. The levels of platelet and plasma fibronectin in three cases of von Willebrand's disease and in three cases of thrombasthenia did not show statistically significant differences as compared with the normal controls. Immunofluorescent staining intensity and patterns of disease-derived and normal platelets, studied with anti-fibronectin antibodies, were similar. Furthermore, 125I-labeled protein A binds to anti-fibronectin-treated platelets from the two diseases investigated in the same fashion as in normal controls. No role for plasma fibronectin was detected in platelet aggregation induced by ADP, thrombin, collagen, epinephrine, and arachidonic acid. Thus our results do not indicate a direct quantitative role of fibronectin in the adhesion anomalies encountered in these diseases. However, fibronectin may still be important to platelet adhesion and normal hemostasis processes through interactions with the plasma von Willebrand factor and the membrane glycoproteins IIb and III, which have been shown to be deficient in von Willebrand's disease and thrombasthenia, respectively.

Blood Platelets↗
PubMed1975

Fibrin-blood platelet interaction in a contracting clot.

The interaction of fibrin and blood platelets was studied by measuring tension development in clots containing different ratios of these two components. Isometric tension attained a saturation value (MT) when plotted as a function of the concentration of either component at a constant concentration of the other. The value of MT increases linearly with the minimal platelet concentration (Ps) required in order to reach saturation at various different fibrin concentrations. A linear relationship also holds in a plot of Ps versus the logarithm of the corresponding fibrin concentration. When the cylindrical clots contracted isotonically, the velocity, normalized with respect to the momentary length, was found to be constant. This velocity decreased in an hyperbolic manner with increasing fibrin concentration at a constant concentration of blood platelets. The results are interpreted in terms of a three-dimensional network in which the blood platelets serve as contractile cross-bridges connecting fibrin fibres. Tension development is assumed to be accompanied by the reduction of the angle between fibrin fibres. An attempt was made to calculate the isometric tension developed by a platelet.

Blood Coagulation↗
PubMed1975

Effects of ADP and ATP on bovine fibrinogen- and ristocetin-induced platelet aggregation in Glanzmann's thrombasthenia.

With thrombasthenic platelets, aggregation induced by ristocetin (R) and bovine fibrinogen (BF) is reversible, provided ATP is not added to the system. ADP inhibits BF and R induced aggregation, and when added after the onset of aggregation causes rapid disaggregation. ATP prevents these inhibitory and disaggregation effects of ADP. A mechanism is suggested whereby co-operative effects occur between receptors in the membranes of thrombasthenic platelets.

Adenosine Diphosphate↗
PubMedDate not supplied

Regulation of the insulin-like growth factor-I receptor gene by oncogenes and antioncogenes: implications in human cancer.

The insulin-like growth factor-I receptor (IGF-I-R) has a central role in normal cellular proliferation as well as in transformation processes. Transcription of the IGF-I receptor gene is controlled by a number of tumor suppressors, including WT1, p53, and BRCA1. It has been demonstrated that, in their wild-type form, these transcription factors can suppress the activity of the IGF-I-R promoter, with ensuing reduction in the levels of cell-surface IGF binding. On the other hand, a number of oncogenes, including mutant p53 and c-myb, and the fusion protein EWS-WT1 significantly stimulate promoter activity. Interactions between stimulatory and inhibitory transcription factors may determine the level of expression of the IGF-I-R gene and, consequently, the proliferative status of the cell.

Apoptosis↗
PubMedDate not supplied

The beta-subunit of follicle-stimulating hormone is deleted in patients with aniridia and Wilms' tumour, allowing a further definition of the WAGR locus.

One in 10,000 children develops Wilms' tumour, an embryonal malignancy of the kidney. Although most Wilms' tumours are sporadic, a genetic predisposition is associated with aniridia, genito-urinary malformations and mental retardation (the WAGR syndrome). Patients with this syndrome typically exhibit constitutional deletions involving band p13 of one chromosome 11 homologue. It is likely that these deletions overlap a cluster of separate but closely linked genes that control the development of the kidney, iris and urogenital tract (the WAGR complex). A discrete aniridia locus, in particular, has been defined within this chromosomal segment by a reciprocal translocation, transmitted through three generations, which interrupts 11p13. In addition, the specific loss of chromosome 11p alleles in sporadic Wilms' tumours has been demonstrated, suggesting that the WAGR complex includes a recessive oncogene, analogous to the retinoblastoma locus on chromosome 13. In WAGR patients, the inherited 11p deletion is thought to represent the first of two events required for the initiation of a Wilms' tumour, as suggested by Knudson from epidemiological data. We have now isolated the deleted chromosomes 11 from four WAGR patients in hamster-human somatic cell hybrids, and have tested genomic DNA from the hybrids with chromosome 11-specific probes. We show that 4 of 31 markers are deleted in at least one patient, but that of these markers, only the gene encoding the beta-subunit of follicle-stimulating hormone (FSHB) is deleted in all four patients. Our results demonstrate close physical linkage between FSHB and the WAGR locus, suggest a gene order for the four deleted markers and exclude other markers tested from this region. In hybrids prepared from a balanced translocation carrier with familial aniridia, the four markers segregate into proximal and distal groups. The translocation breakpoint, which identifies the position of the aniridia gene on 11p, is immediately proximal to FSHB, in the interval between FSHB and the catalase gene.

Adult↗
PubMedDate not supplied

Flupenthixol decanoate and relapse prevention in alcoholics: results from a placebo-controlled study.

Flupenthixol, with its broad receptor profile, interacts with a variety of dopamine and serotonin binding sites which are important in the neurobiology of alcohol dependence. Its pharmacology, together with encouraging results from both animal studies and clinical trials with cocaine users, led us to postulate that flupenthixol would significantly prevent relapse in detoxified alcohol-dependent individuals. We conducted a prospective, randomized, double-blind, placebo-controlled, multi-centre trial with two parallel groups and appropriate statistical evaluation. Subjects met criteria for moderate to severe alcohol dependence (DSM-III-R), without any concomitant psychiatric disorder. After complete detoxification, 281 women and men received either 10 mg of flupenthixol decanoate or placebo as i.m. injection every second week for 6 months on an out-patient basis, followed by 6 months of follow-up. Efficacy was based on absolute abstinence, with relapse being defined as consumption of any alcohol after inclusion in the study. In contrast to the hypothesis, flupenthixol did not reduce, but was associated with more, relapses. Though well tolerated, relapse rates after 6 months of treatment were 85.2% (flupenthixol) versus 65.5% (placebo), a highly significant difference from the medication. Flupenthixol was also inferior to placebo with regard to other secondary criteria of efficacy (cumulative abstinence duration, relapse rate after 12 months). These results indicate that a 10 mg dose of flupenthixol decanoate does not have a beneficial effect on abstinence maintenance in alcohol-dependent individuals.

Adult↗
PubMedDate not supplied

[The presynaptic metabolic modulation of the impulse-dependent release of 3H-serotonin from rat brain slices by ipsapirone (TVX Q 7821) and other serotonin agonists].

The experiments with thin slices of the cortex and dorsal raphe nucleus of rat midbrain which were incubated with [3H]-hydroxytryptamine ([3H-]HT) have established that serotonin and its agonists inhibit 3H-HT release from the electrically stimulated slices. The serotonin agonists ipsapirone (TVX Q 7821), buspirone, gepirone, and 8-OH-DPAT which mainly stimulate the Type 1A serotonin receptors of somatodendritic synapses inhibit the release of [3H]-HT from the dorsal raphe nucleus slices to a greater extent rather from those of the cortex. On the contrary, the serotonin agonists TFMPP, mCPP, and Ru 24969 which predominantly affect 1B-HT receptors largely inhibit [3H]-HT release from the electrically stimulated cortical slices. Ipsapirone-induced inhibition of the impulse-dependent release of [3H]-HT has been found to be associated with changes in intracellular cAMP levels and protein kinase activity. The nature of serotonin agonist-induced modulation of the impulse-dependent release of [3H]-HT from serotoninergic neurons is discussed in the paper.

Animals↗