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M C Cohen

Publications and source records attributed to M C Cohen.

At least 55 records · Page 3Linked to original sources
PubMed1993

Regulation of VCAM-1 expression and involvement in cell adhesion to murine microvascular endothelium.

The present studies were undertaken to examine the regulation of murine VCAM-1 expression and the involvement of this molecule in adhesive processes occurring on the surface of microvascular endothelium. Flow cytometric analyses revealed that murine microvascular endothelium (MME) in culture constitutively expresses VCAM-1 and that stimulation of MME by TNF, IL-1, or LPS, but not by PMA or staurosporine, strongly increased the surface expression of this cell adhesion molecule. Stimulation of VCAM-1 expression by TNF may be diminished by ionomycin as well as by inhibitors of protein kinases (H-7 and sangivamycin). However, TGF-beta, which strongly inhibited the adhesiveness of endothelium, had little effect on the expression of VCAM-1. A newly developed adhesion assay, based on the rosette technique, allowed us to distinguish between the adhesive properties of an individual endothelial cell and those of endothelial cell monolayers and demonstrated that inhibition of binding by TGF-beta resulted primarily from its influence on the adhesive properties of individual cells. Studies on the inhibition of cell binding by monoclonal antibodies against mouse VCAM-1 and mouse VLA-4 indicated that VCAM-1 plays a dominant role in mediating the adherence of a variety of cell types, including murine splenocytes and thymocytes, P815 mastocytoma cells, PT 18 mast/basophil cells, human Molt-4 cells, and human eosinophils, to cytokine-activated MME.

Alkaloids↗
PubMed1993

COLO 205 utilizes E-selectin to adhere to human endothelium.

We have demonstrated that pretreatment of human umbilical vein endothelial cells (HUVEC) with tumor necrosis factor-alpha (TNF) or phorbol myristate acetate (PMA) augmented the binding of COLO 205, a human colon carcinoma cell line, in vitro. The increased adherence was both concentration and time dependent with a peak for tumor cell attachment at 4 hr. The increase in binding required both RNA and protein synthesis. This pattern is consistent with increased expression of the adhesion molecule E-selectin (ELAM-1) on the endothelium. Incubation of TNF- or PMA-stimulated HUVEC with BB11, an anti-E-selectin mAb, prior to the addition of COLO 205, led to almost complete inhibition of adherence of the tumor cells. Flow cytometric analysis confirmed that there was expression of E-selectin on HUVEC following both TNF and PMA stimulation.

Antibodies, Monoclonal↗
PubMed1993

Acquired aganglionosis following surgery for Hirschsprung's disease: a report of five cases during a 33-year experience with pull-through procedures.

Acquired Hirschsprung's disease is a rare and controversial form of colonic aganglionosis. Little is known about its aetiology and pathogenesis. We report five cases encountered amongst 173 long-term follow-up patients treated for classical Hirschsprung's disease between 1957 and 1990 at the Red Cross Children's Hospital, Cape Town, and review the current literature. The clinical and pathological findings of the cases have been studied to explore possible aetiological mechanisms. Our cases, like most of those previously reported, developed obstructive symptoms and acquired aganglionosis in pulled-through bowel which had been previously confirmed as ganglionated. Two patients had histological evidence of hyaline fibrosis of blood vessels in the segment of bowel with acquired aganglionosis. Such fibrosis and other features attributable to regional hypoxia were not found in the other three cases. It is suggested that ischaemia with fibrosis may have a pathogenetic role in some, but not all, cases of acquired Hirschsprung's disease. A plea is made for patients developing recurrent symptoms of Hirschsprung's disease, after adequate surgical correction, to be fully studied with repeated sequential biopsies in order to gain a better understanding of the entity.

Child, Preschool↗
PubMed1992

Low density lipoprotein inhibits accumulation of nitrites in murine brain endothelial cell cultures.

Endothelial cells produce nitric oxide which is considered to serve as a major source of endothelial derived relaxing factor activity. It has been demonstrated that activation of mouse brain endothelium by TNF-alpha and IFN-gamma led to accumulation of nitrite which is presumably formed by oxidation of nitric oxide. A number of studies suggest that reactive oxygen species produced by cytokine-activated cells are involved in the conversion of nitric oxide to nitrites and nitrates. We investigated whether low density lipoprotein (LDL), acting as a radical scavenger, is able to inhibit nitrite accumulation in mouse brain endothelial cell cultures and in a cell-free system in which sodium nitroprusside was used as a source of nitric oxide. A comparison of these two models indicates the active involvement of LDL in suppressing nitrite accumulation in murine endothelial cultures.

Animals↗
PubMed1992

Inhibition of basal and tumor necrosis factor-enhanced binding of murine tumor cells to murine endothelium by transforming growth factor-beta 1.

The adherence of cells to microvascular endothelium is important in a number of processes, including inflammatory responses and metastasis. It has been demonstrated that in human models, cytokines such as TNF, IL-1, IFN-gamma increase the adhesiveness of endothelium for cells of the immune and inflammatory system by stimulating the expression of cell adhesion molecules on endothelial cell surfaces. We and others have shown similar cytokine-induced endothelial adhesiveness for tumor cells in murine and human models. In contrast to the effect of those modulators, transforming growth factor-beta (TGF-beta) has been shown to inhibit the binding of human neutrophils and T lymphocytes to human endothelium, although the mechanism of TGF-beta action remains unknown. Little is known about the effect of TGF-beta on tumor cell-endothelial interaction. In the present study, we demonstrate that TGF-beta inhibits basal and TNF-enhanced binding of murine P815 mastocytoma cells to murine microvascular endothelium (MME). The alterations in MME mediated by TGF-beta, also lead to the inhibition of adherence of murine splenocytes, thymocytes, and human lymphoblastoid cells but do not inhibit adherence of murine B16 melanoma cells. The effect of TGF-beta is transient and inhibition of the endothelial adhesive phenotype is strongest 12 to 24 h after addition of the factor to MME. The TGF-beta-mediated inhibition of P815 basal binding to endothelium is dependent on protein synthesis because cycloheximide reverses the TGF-beta effect. TGF-beta does not appear to activate classical signal transduction pathways. Inhibitors of G proteins do not abolish TGF-beta action, protein kinase C and protein kinase A activators elicit an effect opposite to that of the factor, TGF-beta does not increase intracellular cAMP levels, and finally calcium-mobilizing agents do not mimic, but rather inhibit the effect of TGF-beta. However, TGF-beta-mediated inhibition of both basal binding and TNF-enhanced P815 binding to MME is completely abolished in the presence of the protein phosphatase inhibitor okadaic acid which suggests that TGF-beta may elicit its effect by stimulating protein phosphatase activity.

Animals↗
PubMed1992

Primary pulmonary tumors in childhood: a review of 31 years' experience and the literature.

Primary pulmonary tumors are infrequent in childhood, therefore an accurate diagnosis and treatment is often delayed. We review the English language literature and report the clinical and pathological features of eight tumors arising in the lungs of pre-adolescent children, accessioned between 1960 and 1991 in the pathology department of a children's hospital in South Africa. The ratio of pulmonary primary tumors to secondary neoplasms and to non-neoplastic lesions of the lung examined during this period was 1:5:60. Over the last 31 years we received three plasma cell granulomas, two pleuro-pulmonary blastomas, a mucoepidermoid carcinoma, an endobronchial fibrosarcoma, and a hemangioma. All patients presented with cough unresponsive to medical treatment. The incidence and spread of primary lung tumors in children was similar to that reported from other centers. Plasma cell granuloma is the most common primary tumor in the lungs of children. Aggressive behavior is most frequently encountered with pleuro-pulmonary blastoma and rhabdomyosarcoma, and because of their association with cystic lesions careful examination of lungs is required in such cases. Most other malignant neoplasms, such as muco-epidermoid carcinoma and primary fibrosarcoma, are usually of a low grade of malignancy. A decreasing incidence of bronchogenic carcinoma seems to be reported during the first two decades of life.

Adolescent↗
PubMed1991

Studies on the role of protein kinases in the TNF-mediated enhancement of murine tumor cell-endothelial cell interactions.

We have previously demonstrated that the exposure of mouse microvascular endothelium (MME) to tumor necrosis factor-alpha (TNF) led to the increased binding of mouse mastocytoma cells (P815) to endothelial monolayers (Bereta et al., in press). In the current study we examined the possible involvement of protein kinases in TNF signal transduction in the endothelial cells. PKA does not appear to play a role in the potentiation of binding by TNF. We found that the TNF-generated signal is inhibited by H-7 and sangivamycin, but not by staurosporine. TNF did not cause translocation of PKC to the cell membrane and its effect could not be completely mimicked by PMA nor by PMA in the presence of calcium-raising agents. Thus, we concluded that the "classical" PKC pathway is not completely responsible for TNF signalling in this system. We also found that staurosporine itself strongly enhanced adhesion of tumor cells to endothelium, utilizing a mechanism distinct from that of TNF. Although the data provide evidence for the role of kinases in the effect of TNF on binding of tumor cells to MME, this role appears to be a complex one.

Adenylyl Cyclases↗
PubMed1991

Effect of inflammatory cytokines on the adherence of tumor cells to endothelium in a murine model.

We have demonstrated that pretreatment of mouse brain microvascular endothelial cells (MBE) with tumor necrosis factor-alpha (TNF), IL-1, or LPS augmented the binding of P815 mastocytoma cells in vitro. The effect of these agents was dose and time dependent. PMA was able to mimic the influence of these factors to a limited degree. The effect of TNF on endothelium was accompanied by the appearance of changes in the expression of proteins isolated from endothelial cell membranes. The adherence of tumor cells to endothelium was not inhibited by RGD-containing peptides but could be decreased by preincubation of endothelium with high concentrations of FCS. Our data suggest that cytokines regulate the synthesis of endothelial adhesion proteins which may be involved in tumor cell adherence leading to metastasis. These results raise the possibility that cytokines may exert paradoxical effects in vivo, i.e., a cytotoxic effect that reduces tumor mass accompanied by a metastasis-enhancing effect that actually promotes dissemination of the remaining tumor cells. Definition of the molecular events involved in tumor cell-endothelial cell interactions may lead to strategies for minimizing the latter effect in therapeutic settings.

Amino Acid Sequence↗
PubMed1990

Body height change during upright and recumbent posture.

Body height changes are known to occur in response to changes in loads acting along the spine, such as those produced by movement from a recumbent to an upright posture. Lack of previously available data is addressed here by body height measurements closely spaced in time of ten normal subjects during 8 hours upright and 4 hours recumbent, with particular attention paid to the initial changes. Experimental errors are carefully defined and determined. A Kelvin-unit model is fitted to the mean data for each phase and confidence limits provided for the model equation parameters. Rapid height changes are shown to occur: 26% of the 8-hour loss occurred in the first hour upright, and 41% of the 4-hour recovery occurred in the first hour recumbent.

Adult↗
PubMed1989

Survival after myocardial infarction caused by acute left main coronary artery occlusion: case report and review of the literature.

We report a 44-year-old white male presenting with an acute anterior myocardial infarction. Cardiac catheterization at 2 weeks postinfarction revealed total occlusion of the left main coronary artery. There was a normal dominant right coronary artery supplying moderate collaterals to the left coronary system. The patient was managed with conservative therapy and was N.Y.H.A. functional class II on followup 2 years later. A review of the literature relative to myocardial infarction caused by acute left main coronary artery occlusion is presented, and unique features of these cases are described.

Adult↗
PubMed1989

Inhibition of thymocyte mitogenic responses by coculture with thymic epithelial cells.

We have previously reported the isolation and culture of two morphologically distinct types of murine thymic epithelial cells (TECL and TECs) and have studied their capacity to produce soluble factors as well as to bind thymocytes in vitro. In the present study, we examined whether direct interactions of thymic epithelial cells with thymocytes regulate thymocyte function by studying the effect of these thymic epithelial cell lines on thymocyte responses to mitogen. We found that direct contact between thymocytes and epithelial cells markedly suppresses both thymocyte and splenocyte responses to mitogen. This effect is irreversible after a 24-hr incubation on thymic epithelial cells, is not H-2 restricted, and appears to be epithelial cell specific. The inhibitory effect is mediated by a molecule or molecules present constitutively on the plasma membrane of epithelial cells. One mechanism of inhibition involves the generation of suppressor cells on contact of thymocytes with thymic epithelial cells or cell membranes. However, it is also possible that molecules with direct immunosuppressive activity may be present on these cell membranes.

Animals↗
PubMed1989

Attachment of tumor cells to endothelial monolayers: detection of surface molecules involved in cell-cell binding.

Trypsinization of P815 mastocytoma cells interferes with their ability to bind to endothelial monolayers in vitro, suggesting the involvement of proteins in cell-cell binding. Binding is also dependent upon divalent cations. Incubation of tumor cells with tunicamycin, which blocks protein glycosylation, or the monosaccharide N-acetyl-D-glucosamine could also inhibit binding. In addition, antibodies prepared against whole P815 cells had the ability to interfere with tumor cell binding. The protein fragments released from P815 cells by trypsin interfered with the binding of fresh P815 cells to endothelium. Moreover, those fragments as well as CHAPS extracts of tumor cell membranes were able to neutralize the inhibitory effect of an anti-P815 antibody on tumor cell-endothelial cell binding. These observations, taken together, strongly suggest the presence of adhesion molecules on the tumor cell. The anti-P815 antibody preparation could also inhibit endothelial binding of an unrelated tumor. Ehrlich ascites (EA). In addition, membrane preparations of EA could neutralize the antibody's effect on intact P815, and membrane preparations of P815 could neutralize the antibody's effect on EA. These observations suggest that there are common epitopes on these tumor cells and raise the possibility that a variety of tumors may share common mechanisms for attachment to endothelium. This, in turn, raises the possibility that monospecific antibodies against such epitopes might be useful agents for interfering with metastasis in vivo.

Animals↗
PubMed1986

The role of lymphokines in neoplastic disease.

In this brief review, we have focused on studies demonstrating the existence of low-molecular-weight lymphokines that modify a number of tumor cell functions. We have found that lymphokine preparations of human or murine origin contain a protein, TMIF, that can reversibly inhibit the migration of a variety of tumor cells. Both serially passaged animal tumors and spontaneous human neoplasms respond to TMIF. Determination of physicochemical characteristics, including molecular weight, enzyme inactivation, monosaccharide inhibition profile, and noncoordinate production by hybridomas, has led to the conclusion that TMIF is distinct from the lymphokines that inhibit the migration of nonneoplastic cells. TMIF can be detected in vivo and can modify the behavior of tumor cells in vivo. In addition, TMIF-containing preparations can inhibit the binding of tumor cells to endothelial monolayers. Although migration inhibition by TMIF is not associated with cytotoxicity, partially purified TMIF preparations are cytostatic for tumor cells. Cytostasis is not the cause of the observed results in the migration assay, and these properties are therefore functionally distinct. These three activities, appearing within a narrow range of molecular weights, different from those of other known lymphokines, suggest the existence of a distinct class of lymphokine mediators with the common function of influencing functional properties of tumor cells. We propose that these mediators be tentatively defined as neomodulins. Further characterization of this set of lymphocyte-derived effector macromolecules will require thorough exploration of their effects on the various functions listed as tumor cell "job descriptions," demonstration of their in vivo efficacy, and purification of the various factors to homogeneity. The neomodulins are likely to have therapeutic potential, since the tumor cell functions that they regulate are those involved in the expression of malignant potential. In addition, studies are under way to determine whether the in vitro responsiveness of tumor cells to these factors might correlate with their in vivo biologic behavior. Finally, detection of TMIF or related lymphokines in serum or urine from patients with neoplasms could be useful in the detection of cancer and/or monitoring of occult tumor metastases and tumor recurrence.

Animals↗
PubMed1986

The elaboration of a small molecular weight cytostatic factor by lymphoblastoid lines and activated lymphocytes.

In this study, it was observed that the B lymphoid cell line RPMI 8392 produced a tumor cell cytostatic factor that is of lower molecular weight than previously described cytostatic proteins but of greater molecular weight than arachidonate metabolites. This low molecular weight factor was also found to be produced by normal murine lymphocytes upon mitogenic stimulation. Gel filtration chromatography revealed that the molecular weight of this molecule is approximately 6,500 daltons. This is the approximate molecular weight of another tumor cell directed lymphokine which we have previously described, Tumor Migration Inhibition Factor (TMIF). This lymphokine is defined by its ability to inhibit the in vitro migration of a variety of tumor cell types. It was not determined in this study whether or not the proliferation inhibitory activity and the migration inhibitory activity are due to separate molecules. However, experiments presented here demonstrate that these two activities are functionally distinct. In addition, it was found that the cytostatic factor described here, unlike higher molecular weight cytostatic factors, was not associated with cytotoxicity.

Animals↗
PubMed1985

Adherence of tumor cells to endothelial monolayers: inhibition by lymphokines.

Tumor cells can adhere to endothelial cell monolayers in vitro. The kinetics of this reaction are rapid; 50% of maximal binding occurs by 30 min of incubation. In the case of the P815 mastocytoma, the maximal percentage of binding is approximately 70%, suggesting that there are both binding and nonbinding tumor cell populations. Binding is independent of tumor cell dose over a 200-fold range of cell concentrations. Lymphokine-containing preparations were found to markedly suppress the binding of either P815 mastocytoma or Ehrlich ascites cells to endothelium. This effect appeared to be due to both diminished attachment and enhanced dissociation. The activity is found in the same molecular weight range as tumor migration inhibition factor (TMIF), and is not found in preparations lacking TMIF activity. Thus, the factor may prove to be TMIF itself or a lymphokine related to it. Of equal interest is the possibility that it represents a previously undescribed factor.

Animals↗