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Biomedical subjects

R Fridman

Publications and source records attributed to R Fridman.

At least 73 records · Page 4Linked to original sources
PubMed1990

Benzodiazepine dependence: management of discontinuation.

This article discusses the management of benzodiazepine (BZ) withdrawal in patients who are chronically benzodiazepine dependent. Gradual benzodiazepine discontinuation is preferable to abrupt discontinuation, particularly for patients on short half-life benzodiazepines. For a small number of patients, replacement of short half-life with long half-life benzodiazepines may also be helpful. Finally, we present new preliminary data from a controlled, double-blind study that suggest that adjunctive use of such drugs as carbamazepine, imipramine, and buspirone may be helpful in managing gradual benzodiazepine discontinuation. Initiating adjunctive medication prior to, and continuing it during and after benzodiazepine discontinuation led to significantly higher discontinuation success rates for carbamazepine (91%), buspirone (85%), and imipramine (79%) than for placebo (58%) (p less than .05). Careful followup for an extended period of time is needed after benzodiazepine discontinuation because, frequently, emerging psychiatric symptoms may again necessitate psychiatric intervention.

Anti-Anxiety Agents↗
PubMed1990

The role of cell adhesion and migration in the in vitro invasiveness of mouse adrenal carcinoma cells.

Using the Matrigel invasion assay, we have examined the role of cell adhesion and migration in the invasiveness of two cell lines, DM and HSR, derived from the Y1 mouse adrenocortical tumor. The DM cells were metastatic and more invasive (10-fold) than the nonmetastatic HSR cells. The difference in invasiveness could not be ascribed to different levels of secreted type IV collagenolytic activity since HSR cells secreted higher levels of activity. Cells from the metastatic DM line showed greater motility to both laminin and fibronectin when compared to the HSR line. Furthermore, both Matrigel and laminin promoted the attachment and spreading of DM cells but they had little effect on the adhesion of the HSR cells. Electron microscopic examination revealed an increased ruffling of the cell membrane in the metastatic DM line. These studies suggest a role for cell adhesion and migration on the invasion of Matrigel by malignant tumor cells.

Adrenal Gland Neoplasms↗
PubMed1989

Invasive and metastatic potential of a v-Ha-ras-transformed human bronchial epithelial cell line.

The in vivo growth behavior and invasive potential of normal and "immortalized" human bronchial epithelial cells were studied by xenotransplantation procedures, an in vitro assay of invasiveness, and determinations of type IV collagenase activity and mRNA expression. BEAS-2B cells, immortalized after hybrid virus infection (adenovirus 12-simian virus 40), reconstituted a columnar epithelium when xenotransplanted into de-epithelialized rat tracheas transplanted sc into athymic BALB/c mice. A few adenomatous growths could be seen 16 weeks after transplantation. BZR cells, obtained by transfer of the v-Ha-ras oncogene into BEAS-2B cells, were tumorigenic in this xenotransplantation model. BZR-T33 cells, obtained from a tumor produced after injection of BZR cells, were also tumorigenic; however, they exhibited a shorter latent period. When these same cell lines were injected sc and iv into athymic BALB/c mice, BEAS-2B cells were not tumorigenic, and the BZR-T33 cells were more tumorigenic than the BZR cells. The incidence of spontaneous metastases after sc inoculation was zero for BEAS-2B cells, 33% for BZR cells, and 100% for BZR-T33 cells. Similar increasing values that correlated well with the data on in vivo growth were noted in the in vitro invasion assay, the collagenolytic ability, and the mRNA expression of type IV collagenase. Normal human bronchial epithelial cells showed the lowest values in all the assays. These progressive changes occurring in cells derived from the same parental line indicate that the presence of the v-Ha-ras oncogene in immortalized bronchial cells is associated with a full-fledged malignant phenotype, which is further enhanced by in vivo passaging.

Animals↗
PubMed1989

In vitro galactosylation of a 110-kDa glycoprotein by an endogenous cell surface galactosyltransferase correlates with the invasiveness of adrenal carcinoma cells.

We have examined the role of a cell surface galactosyltransferase, laminin, and laminin-binding protein (receptor) in the invasion of clonal derivatives of a murine adrenal carcinoma cell line. Although a 10-fold variation was found in the ability to invade a reconstituted basement membrane matrix, levels of intracellular laminin and the laminin-binding protein were shown to be present and secreted equally in all lines. Of the eight lines tested, seven showed a correlation between invasion and the incorporation of [3H]galactose from UDP-[3H]galactose into a 90- to 110-kDa protein. One noninvasive line (clone HSR), however, retained high galactosyltransferase activity yet could not galactosylate the endogenous 90- to 110-kDa substrate. Interestingly, this clone was unable to attach to laminin. Although high galactosyltransferase activity can be consistent with cells of high invasiveness, our results suggest that the galactosylation status of a 90- to 110-kDa Y1 cell surface glycoprotein is most indicative of invasion potential.

Adrenal Gland Neoplasms↗
PubMed1989

Enhancement of the invasive ability of a transformed human bronchial epithelial cell line by 12-O-tetradecanoyl-phorbol-13-acetate and diacylglycerol.

The effect of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was studied using an immortalized human bronchial epithelial cell line, BEAS-2B, both in vivo and in vitro. The in vivo model consisted of tracheas reconstituted with an epithelium of BEAS-2B cells xenotransplanted into athymic nude mice. Intraluminal TPA treatment caused increased BEAS-2B cell proliferation and downgrowth into the tracheal stroma. In an in vitro invasion assay, TPA enhanced the invasive capacity of BEAS-2B cells 20- to 25-fold. A similar result was observed with diacylglycerol (DAG), an endogenous activator of protein kinase C, and the effects of TPA and DAG were abolished by simultaneous treatment with H-7, a protein kinase C inhibitor. TPA induced type IV collagenolysis, and this effect also was prevented by H-7. These data are consistent with the hypothesis that TPA causes these cells to become invasive by inducing collagenase activity and that this effect is mediated via protein kinase C.

Animals↗
PubMed1987

Soluble antigen induces T lymphocytes to secrete an endoglycosidase that degrades the heparan sulfate moiety of subendothelial extracellular matrix.

The antigen-mediated induction of heparanase, an endoglycosidase capable of degrading heparan sulfate from the subendothelial extracellular matrix (ECM), was investigated in a rat T lymphocyte cell line reactive against the basic protein (BP) of myelin. We found that nonactivated T lymphocytes could be induced to express heparanase activity following exposure to soluble but not to ECM-bound BP. The induction of heparanase was immunologically specific and independent of the presence of syngeneic or allogeneic antigen presenting cells (APC). However, anti-IA antibodies inhibited heparanase expression. Soluble BP induced secretion of heparanase into the culture medium within minutes, despite inhibition of protein synthesis. Cell lysates of T lymphocytes contained heparanase activity. Thus, T lymphocytes secrete a preformed heparanase following exposure to specific antigen.

Animals↗
PubMed1987

Aortic endothelial cells synthesize basic fibroblast growth factor which remains cell associated and platelet-derived growth factor-like protein which is secreted.

Cultured bovine aortic endothelial cells synthesize growth factors which markedly differ in the regulation of their storage and secretion. Endothelial cell lysates, but not conditioned medium, contain a growth factor activity that appears to be basic fibroblast growth factor (FGF) by the following criteria: (1) it elutes from heparin-Sepharose at 1.4-1.6 M NaCl; (2) it is mitogenic for bovine aortic and capillary endothelial cells; (3) it is heat sensitive but stable to dithiothreitol; (4) it has a molecular weight of about 18,000 daltons; and (5) it cross-reacts with antiserum directed against basic FGF. In contrast, endothelial cell conditioned medium, but not lysates, contains a growth factor activity that (1) elutes from heparin-Sepharose at 0.4-0.5 M NaCl; (2) is mitogenic for fibroblasts and vascular smooth muscle cells but not for capillary endothelial cells; (3) is heat stable and dithiothreitol sensitive; and (4) competes with platelet-derived growth factor (PDGF) for binding to fibroblasts. From these criteria, it appears that endothelial cells secrete into the medium growth factors some of which are PDGF-like, but secrete little if any basic FGF. It is suggested that endothelial cell-associated basic FGF acts in an autocrine fashion to stimulate endothelial cell proliferation in response to endothelial cell perturbation or injury. On the other hand, the endothelial cell-secreted growth factors which are smooth muscle cell but not endothelial cell mitogens might exert a paracrine function on neighboring cells of the vessel wall.

Animals↗
PubMed1987

Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix.

Bovine aortic and corneal endothelial cells synthesize a growth factor that remains mostly cell-associated but can also be extracted from the subendothelial extracellular matrix (ECM) deposited by these cells. The endothelial cell-derived growth factors extracted from cell lysates and from the extracellular matrix appear to be structurally related to basic fibroblast growth factor by the criteria that they bind to heparin-Sepharose and are eluted at 1.4-1.6 M NaCl, have a molecular weight of about 18,400, cross-react with anti-basic fibroblast growth factor antibodies when analyzed by electrophoretic blotting and immunoprecipitation, and are potent mitogens for bovine aortic and capillary endothelial cells. It is suggested that endothelium can store growth factors capable of autocrine growth promotion in two ways: by sequestering growth factor within the cell and by incorporating it into the underlying extracellular matrix.

Animals↗
PubMed1986

One-year follow-up of anxious patients treated with diazepam.

A 1-year follow-up was conducted on patients who had participated in a 6-month diazepam maintenance study. Of 180 patients contacted, 131 patients (73%) responded. Observed relapse rate was 63%, and Hopkins Symptom Checklist (HSCL) scores at follow-up were significantly higher for relapsed than for nonrelapsed patients. Two thirds of all relapsed patients sought some kind of medical, social, or psychiatric help, frequently including medication. Patients who were the most improved at the end of the diazepam maintenance trial consistently had the lowest HSCL scores at the time of follow-up. The implication of these findings for the management of chronic anxious patients is discussed.

Adult↗
PubMed1985

The antiproliferative effect of interferon and the mitogenic activity of growth factors are independent cell cycle events. Studies with vascular smooth muscle cells and endothelial cells.

We studied the antagonistic effects of interferon (IFN) and growth factors in G0/G1-arrested normal bovine aortic smooth muscle cells (SMC) which were stimulated by serum, or purified platelet derived growth factor (PDGF), supplemented with plasma-derived serum (PDS). The growth response, measured as [3H]thymidine incorporation into DNA, was dependent on the concentration of the mitogen. Human IFN alpha, recombinant human IFN alpha 2, or a crude bovine-IFN preparation prepared from virus-infected bovine aortic endothelial cells, inhibited SMC growth induced by either serum or PDGF with PDS. The extent of IFN inhibition was inversely related to the concentration of the mitogenic stimulus. We also investigated whether IFN inhibited the early events in G1 phase, stimulated by the competence factor PDGF, or the progression of the cell into the S phase induced by PDS. The results indicated that IFN inhibited these two stages of the G1 phase independently. In addition, we investigated the antiproliferative effect of IFN on bovine aortic endothelial cells (BAEC), which do not respond to PDGF but to the mitogenic activity of fibroblast growth factor (FGF). IFN inhibited the mitogenic activity of FGF in a dose-dependent manner. The results indicate that the anti-proliferative activity of IFN and the mitogenic effects of different growth factors are independent.

Animals↗
PubMed1985

Differential structural requirements for the induction of cell attachment, proliferation and differentiation by the extracellular matrix.

The subendothelial extracellular matrix (ECM) mediates the attachment of both human Ewing's sarcoma and colon carcinoma cells. Attachment and flattening of the sarcoma cells was sensitive to heat treatment but not to periodate oxidation of the ECM, whereas the colon carcinoma cells attached and flattened over heated but not periodate-treated ECM. Such differential sensitivity to heat treatment and periodate oxidation was also observed using purified fibronectin and laminin, respectively, but the inhibition of cell attachment was greater than with a similarly treated ECM. It is therefore conceivable that fibronectin and laminin specifically mediate the attachment and flattening of Ewing's sarcoma and colon carcinoma cells to the ECM, but that other constituents may support this attachment either directly or via interaction and stabilization of adhesive glycoproteins in the ECM. The ECM-mediated morphological differentiation of adult rat oligodendrocytes was sensitive to periodate oxidation to a much higher extent than to heat treatment of the ECM. In contrast, both treatments had only a small effect on the ECM-induced proliferation of vascular endothelial cells. These results indicate that different constituents of the ECM may be held responsible for its effects on different parameters of cell behavior, and that various cell types respond differently to a given modification of the ECM.

Animals↗
PubMed1985

Cell interaction with the extracellular matrices produced by endothelial cells and fibroblasts.

The extracellular matrices (ECM) produced by cultured bovine corneal endothelial cells and chick embryo fibroblasts were compared for their induction of cell attachment, proliferation and differentiation. The corneal endothelial ECM (cECM) induced a comparable and rapid attachment and flattening of both human Ewing's sarcoma and colon carcinoma cells which utilize fibronectin and laminin as adhesive glycoproteins, respectively. In contrast, the ECM produced by fibroblasts (fECM) readily supported the attachment and flattening of Ewing's sarcoma cells but had only a small effect on the carcinoma cells. Vascular endothelial cells were stimulated to proliferate by both types of matrices, but to a lesser extent by the fECM. In contrast, the formation of a closely apposed, non-overlapping and contact-inhibited endothelial cell monolayer was only dictated by the cECM. Vascular endothelial cells cultured on fECM grew on top of each other and incorporated [3H]thymidine even late at confluency. Neurite outgrowth (ciliary ganglion cells) and network formation (adult rat oligodendrocytes) were promoted by both types of matrices but in a more consistent manner with the cECM. It is likely that the small amounts of laminin deposited by chick embryo fibroblasts into their ECM are responsible for its efficient induction of neurite outgrowth and for the limited degree of carcinoma cell attachment and flattening. It is thus demonstrated that differences in chemical composition and supramolecular arrangement between cECM and fECM result not only in differences in the attachment, spreading and proliferative responses of cells but also in the expression of their characteristic morphological appearance and differentiated functions.

Animals↗
PubMed1984

Adult rat oligodendrocytes grown in vitro upon an extracellular matrix have the ability to proliferate.

The use of extracellular matrix (ECM) as a natural substrate for cell culture has markedly improved the growth and morphological differentiation of isolated adult rat oligodendrocytes. ECM-grown oligodendrocytes exhibited cyclic nucleotide phosphodiesterase (CNP)-activity which increased with time in culture and network formation. As much as 50-70% of the cells incorporated [3H]thymidine as visualized by the high labeling index of galactocerebroside (GalC)-positive cells. Chemical and enzymatic modifications of the ECM suggested that laminin in conjunction with other ECM constituents, plays a role in the induction of proliferation and/or differentiation responses in mature oligodendrocytes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1984

Diazepam and desmethyldiazepam plasma concentrations in chronic anxious outpatients.

Within the framework of a large-scale clinical study on the effect of diazepam in chronic anxiety, diazepam (D) and desmethyldiazepam (DD) plasma concentrations were determined frequently. Significant relationships were found between the clinical effect and the plasma concentrations of D and DD, respectively; a curvilinear relationship resulted if the dosage was disregarded, but within the individual dosage groups the relationship was found to be linear. For these computations, the daily diazepam dose was treated as a covariable in a factorial analysis of variance approach. It was found, in addition, that the daily diazepam dose was one of the most significant predictors of the plasma concentration of D or DD, respectively. The steady state plasma concentrations were highest in patients experiencing an exacerbation of their conditions of anxiety if they were returned to placebo after 14 to 22 weeks of diazepam medication. The lowest steady state concentrations were found with those patients who showed withdrawal symptoms under these conditions.

Adult↗
PubMed1984

Interferon enhances prostacyclin production by cultured vascular endothelial cells.

The effects of interferon (IFN) on the arachidonate metabolism and physiological functions of cultured endothelial cells and blood platelets have been examined. Cultured bovine aortic endothelial cells were found to be sensitive to the antiviral and antiproliferative activities of human leukocyte (alpha) IFN and to increase their capacity to synthesize prostacyclin (PGI2) upon exposure to IFN. Several observations indicate that IFN stimulates PGI2 synthesis at the level of the enzymes phospholipase A2 and cyclooxygenase: (a) PGI2 production was dependent upon the supply of exogenous arachidonic acid or the liberation of endogenous cellular arachidonate by ionophore A23187, but was not observed when IFN-treated cells were exposed to the endoperoxide prostaglandin H2. (b) IFN had no effect on the spontaneous release of PGI2 into the culture medium during the incubation period (24-72 h). (c) The stimulatory effect of IFN on PGI2 production was inhibited by both glucocorticoids and indomethacin. The effect of IFN on platelet prostaglandin metabolism was also investigated. Incubation of platelet-rich plasma with IFN had no effect on platelet aggregation and thromboxane A2 production. The biological significance of the findings presented in this paper may be considered in view of the protective role of PGI2 in the vessel wall and the fact that infection with certain viruses induces endothelial damage both in man and experimental animal models.

Animals↗