High-energy photons from expanding quark-gluon plasma and hot hadronic matter.
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Journal Article↗
Biomedical subjects
S Chakrabarty
Publications and source records attributed to S Chakrabarty.
Regulation of human colon-carcinoma cell adhesion to extracellular matrix by transforming growth factor beta 1.
The regulatory effect of transforming growth factor beta 1 (TGF-beta 1) on the adhesion of human colon-carcinoma cells to the extracellular matrix (ECM) was investigated. ECMs used in this study included tissue-culture wells coated with fibronectin, laminin, collagen and BSA, as well as plastic wells. Three phenotypically different human colon-carcinoma cell lines (Moser, HCT116, and KM12SM) were used. The Moser cell line is moderately differentiated and, in terms of the diversity of responses elicited by TGF-beta 1, is the human colon-carcinoma cell line most responsive to TGF-beta 1 as reported to date. By comparison, the undifferentiated HCT116 and the highly metastatic KM12SM cells are unresponsive to this growth factor. We showed that TGF-beta 1 regulated the adhesion responses of all 3 cell lines. However, the response profiles as well as the endogenous adhesive properties of each cell line were quite different from those of the others. Endogenous Arg-Gly-Asp(RGD)-related receptors were present on the HCT116 but not on the other cells. The observed regulatory effect of TGF-beta 1 was contingent on the cell line, the type of ECM, and the growth-factor treatment protocol used. When cells were treated with TGF-beta 1 for 16 hr prior to exposure to ECM in a 4-hr adhesion assay, a significant increase in adhesion to fibronectin and collagen was observed for the Moser cells. For the identical experimental protocol, the KM12SM cells responded by increasing adhesion to fibronectin, while the HCT116 cells responded by decreasing adhesion to collagen. Kinetic analyses of TGF-beta 1 treatment showed that increased adhesion response to laminin was induced in the Moser cells after 2 hr of growth-factor treatment. This response declined rapidly upon further exposure of the cells to TGF-beta 1. Simultaneous exposure of cells to both TGF-beta 1 and ECM negated the adhesion responses described above. The up-modulation of adhesion to fibronectin, laminin and collagen by TGF-beta 1 was mediated through RGD-related integrin receptors. RGD-containing peptides effectively blocked the enhanced adhesion responses induced by TGF-beta 1.
Amino Acid Sequence↗
Response of FR3T3 cells transformed by Ha-ras oncogene and epidermal growth factor gene to differentiation induction by N,N-dimethylformamide.
Treatment of chemically transformed fibroblasts with N,N-dimethylformamide (DMF) results in the restoration of a nontransformed phenotype. In an attempt to identify more precisely the mechanisms by which DMF reverses the transformed phenotype, the effects of DMF on fibroblasts which were transformed by a single gene--specifically a synthetic epidermal growth factor (EGF) gene or the Ha-ras oncogene--were examined. The constitutive expression of either the Ha-ras oncogene or the EGF gene in FR3T3 fibroblasts resulted in cellular transformation. The effect of the differentiation-inducing agent DMF on several properties of these transformed cell lines was examined. The EGF-transfected cells were much more responsive to DMF than the ras-transfected cells. DMF treatment of the EGF-transfected cells resulted in the inhibition of anchorage-independent growth, the restoration of a normal cellular morphology and growth rate in monolayer culture, and the down-regulation of the proliferation-associated nucleolar protein B23. DMF treatment had a much slighter effect on growth of the ras-transfected cells in monolayer culture or under anchorage-independent growth conditions. The high proliferation rate of the ras-3 cells was associated with elevated expression of protein B23. The 19-3 cells, but not the ras-3 cells, expressed cell-surface fibronectin. Treatment of the ras-3 cells with DMF did not restore fibronectin expression. The binding of EGF was increased 3-fold in the EGF-transfected cells and decreased 20-fold in ras-transfected cells, but in neither case did DMF alter EGF binding. DMF treatment increased the secretion of EGF in the 2 transfected lines as well as in control cells. These results suggest that the aberrant-growth control in the EGF-transfected cells, but not in the ras-transfected cells, could be modulated by DMF and that the aberrant-growth control mechanisms were different in these 2 cell types.
Animals↗
Role of protein kinase C in transforming growth factor-beta 1 induction of carcinoembryonic antigen in human colon carcinoma cells.
Transforming growth factor-beta 1 (TGF-beta 1) regulates the expression of the carcinoembryonic antigen (CEA) gene family in the human colon carcinoma cell line Moser. The mechanisms through which it acts, however, are unknown. In this communication, several lines of evidence are presented to show that the induction of CEA expression and secretion (collectively called CEA responses) by TGF-beta 1 is associated with protein kinase C (PKC) pathway of signal transduction. Treatment of intact cells with the PKC-specific inhibitor calphostin C down-modulated cellular PKC phosphotransferase activity and blocked the induction of the CEA responses by TGF-beta 1. Depletion of PKC by treatment of intact cells with phorbol ester also blocked the action of TGF-beta 1. The induction of the CEA responses by TGF-beta 1 was also blocked by the protein kinase inhibitor 1-(isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), which also inhibited cellular PKC activity. However, TGF-beta 1 did induce the CEA responses in intact cells treated with the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), the calmodulin-dependent phosphodiesterase inhibitor calmidazolium, the diacylglycerol kinase inhibitor R59 022, and the G-protein inhibitors cholera toxin and pertussis toxin. Treatment of intact cells with TGF-beta 1 induced a rapid and transient increase in PKC phosphotransferase activity. TGF-beta 1, however, was unable to induce PKC enzymatic activity in cells pretreated with calphostin C. Therefore, it is concluded that TGF-beta 1 regulates the CEA responses through a signal transducing pathway associated with PKC.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Protective role of ascorbic acid against lipid peroxidation and myocardial injury.
Ascorbic acid (AH2) is a potential scavenger of superoxide radical and singlet oxygen. In the guinea pig, marginal AH2 deficiency results in intracellular oxidative damage in the cardiac tissue as evidenced by lipid peroxidation, formation of fluorescent pigment and loss of structural integrity of the microsomal membranes. The oxidative damage does not occur due to lack of enzymatic scavengers of reactive oxygen species such as superoxide dismutase, catalase and glutathione peroxidase. Also, glutathione transferase activity is not decreased in AH2 deficiency. Lipid peroxidation, fluorescent pigment formation and protein modification disappear after AH2 therapy. These results, if extra-polated to human beings, would indicate that chronic subclinical AH2 deficiency may result in progressive oxidative damage which in the long run may lead to permanent degenerative diseases in the heart.
Animals↗
Effects of cicletanine on haemodynamics, arrhythmias and extent of necrosis during coronary ligation in rabbits.
1. The effects of cicletanine on arrhythmias, haemodynamics and extent of necrosis during myocardial ischaemia were investigated in rabbits subjected to coronary ligation. 2. Cicletanine increased cardiac output prior to coronary occlusion (P < 0.01) but had no other significant haemodynamic effects at this time and did not significantly alter heart rate, blood pressure or cardiac output during 30 min of ischaemia or 30 min of reperfusion. 3. Ventricular fibrillation and mortality were greater in control (65% and 60% respectively) than treated animals (15.4% and 15.4%, P < 0.01). 4. The extent of myocardial necrosis expressed as a percentage of the area at risk was also reduced by cicletanine from 61 +/- 8% in controls to 37 +/- 6% (P < 0.05). 5. These findings indicate that cicletanine attenuates arrhythmias and preserves myocardium in the early phase of ischaemia and this effect appears to be independent of an established antihypertensive action.
Animals↗
Effects of the PAF antagonists BN50726 and BN50739 on arrhythmogenesis and extent of necrosis during myocardial ischaemia/reperfusion in rabbits.
1. The effects of two novel platelet activating factor (PAF) antagonists BN50726 and BN50739 on arrhythmias, haemodynamics and extent of necrosis during myocardial ischaemia and reperfusion were investigated in anaesthetized rabbits subjected to coronary artery ligation. 2. BN50739 reduced heart rate prior to coronary artery occlusion (P < 0.005) but had no other significant haemodynamic effects at this time. BN50739 and BN50726 did not significantly alter heart rate or blood pressure during 30 min of ischaemia or 30 min of reperfusion, compared to control hearts. 3. BN50739 and BN50726 had no effect on the incidence of arrhythmias during ischaemia. BN50726 significantly reduced the incidence of reperfusion ventricular fibrillation compared to controls (0% v 40%, P < 0.05), and improved survival (80% v 39%, P < 0.05). Similar trends were observed with BN50739. 4. BN50726 reduced the extent of necrosis compared to control hearts (18 +/- 2% v 30 +/- 3%, P < 0.01). A similar trend was observed with BN50739. 5. These results demonstrate that PAF antagonism with BN50726 attenuates reperfusion-induced arrhythmias and preserves myocardium in the early phase of ischaemia, independently of haemodynamic effects.
Animals↗
Production of fibronectin by human tumor cells and interaction with exogenous fibronectin: comparison of cell lines obtained from colon adenocarcinomas and squamous carcinomas of the upper aerodigestive tract.
Cell lines derived from 13 different human colon adenocarcinomas were examined for production of fibronectin by ELISA and for cell-surface expression of fibronectin by indirect immunofluorescence. Two squamous epithelial cell lines obtained from tumors of the upper aerodigestive tract were used as controls. None of the 13 colon carcinoma lines produced detectable amounts of fibronectin or showed detectable cell-surface staining with anti-fibronectin. The 2 squamous epithelial cell lines, in contrast, produced large amounts of fibronectin which could be detected in the culture medium and bound to the substratum. The squamous carcinoma cells also stained brightly when examined in the viable state by immunofluorescence with anti-fibronectin. In addition to being studied for fibronectin production, each cell line was also examined for the ability to interact with exogenous fibronectin in an adhesion assay. None of the colon carcinoma cells were adherent to fibronectin-coated culture dishes while the 2 squamous carcinoma cells rapidly attached and spread on this substratum. These data suggest that cell lines derived from adenocarcinomas of the colon are deficient in production of fibronectin and in their ability to interact with exogenous fibronectin. In their degree of deficiency, the colon carcinoma cells are significantly different from several different types of human tumor cell. The failure of the colon carcinoma cells to synthesize detectable amounts of fibronectin endogenously or to interact with exogenous fibronectin may explain, in part, the low degree of adhesive interaction which these cells have for their substratum. This, in turn, may influence the in vitro and in vivo properties of colon carcinoma cells.
Adenocarcinoma↗
Equation of state of strange quark matter and strange star.
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Journal Article↗
Growth modulation by epidermal growth factor (EGF) in human colonic carcinoma cells: constitutive expression of the human EGF gene.
The functional role of epidermal growth factor (EGF) in epithelium-derived human colonic carcinoma cells was investigated by transfection with plasmid pUCDS3, which contained synthetic human EGF encoding sequences, into two human colonic carcinoma cell types with dissimilar phenotypic properties: the moderately differentiated and growth factor-responsive Moser and the highly metastatic KM12SM cells. The Moser cells exhibited a proliferative response to treatment with exogenous EGF, while the KM12SM cells did not. The constitutive expression of the human EGF gene in these colonic carcinoma cell types resulted in elevated expression of EGF mRNA, with concurrent production and secretion of a large amount of EGF, and downmodulation of transforming growth factor-alpha (TGF-alpha) secretion. Growth stimulation and down-modulation of both high and low affinity EGF receptors were observed in the EGF-transfected Moser clones. Results of experiments using anti-EGF and anti-EGF-receptor antibody to block the proliferation of EGF-transfected Moser clones suggested that autocrine stimulatory mechanisms involving both EGF and TGF-alpha were operative in these cells. By comparison, a growth-inhibitory effect, with no apparent EGF receptor modulation, was observed in the EGF-transfected KM12SM clones. Both the parental and EGF-transfected KM12SM clones possessed fewer EGF receptors than the Moser cells, and anti-EGF or anti-EGF-receptor antibody did not affect the cells' growth properties. These results suggested that the mechanisms of growth inhibition in the EGF-transfected KM12SM clones were non-autocrine or intracellular in nature. Thus, constitutive expression of the human EGF gene in two phenotypically different, epithelium-derived human colonic carcinoma cells resulted in divergent altered growth characteristics.
Cell Division↗
Arrhythmias, haemodynamic changes and extent of myocardial damage during coronary ligation in rabbits anaesthetized with halothane, alpha chloralose or pentobarbitone.
We investigated the incidence of ventricular arrhythmias, extent of myocardial infarction and alteration in haemodynamic parameters during 30 minutes of coronary arterial occlusion in rabbits anaesthetized with halothane, alpha chloralose and pentobarbitone. Ventricular tachycardia and fibrillation occurred in 10 of 15 given halothane and in 11 of 15 animals given alpha chloralose while of 15 animals given pentobarbitone, 5 developed tachycardia and 8 had fibrillation. Following ligation, blood pressure promptly fell in each group to 71-76% of control values at 1 minute and remained low throughout the occlusion period. This was most marked in the group receiving halothane which had significantly lower pressures at 30 minutes than those anaesthetized with alpha chloralose or pentobarbitone (P less than 0.01 in each case). Those receiving halothane also recovered less on reperfusion. Heart rate remained stable with pentobarbitone anaesthesia during coronary occlusion and reperfusion, but promptly declined in the first minute of occlusion in the groups given halothane and alpha-chloralose and then remained low throughout occlusion, especially in the group given alpha-chloralose (P less than 0.001 vs pentobarbitone and P less than 0.01 vs halothane). The extent of myocardial damage was measured from nitroblue tetrazolium-stained sections and expressed as a percentage of the zone at risk, which was obtained in five hearts following 90 minutes coronary ligation. Values were 44.0% with pentobarbitone, 54.0% with alpha chloralose (P less than 0.01 vs pentobarbitone) and 62.1% with halothane (P less than 0.001 vs pentobarbitone). Thus, the choice of anaesthetic employed during experimental myocardial ischaemia may have significant effects on the incidence of ventricular tachycardia, haemodynamic changes and extent of necrosis observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Contribution of platelets and platelet-activating factor (PAF) to the arrhythmogenic, haemodynamic and necrotic effects of acute myocardial ischaemia.
The effects of alterations in platelet activity on arrhythmias, haemodynamics and extent of necrosis during coronary ligation for 30 min were assessed in rabbits. Reduction of platelet counts to less than 1% of control by intravenous injection of platelet antiserum (1 ml kg-1 i.v.) reduced the volume of necrosed tissue from 23 +/- 2% to 15 +/- 1%, P less than 0.01 (expressed as % of total LV) and attenuated the hypotensive effect of ischaemia. Pretreatment with the platelet activating factor (PAF) antagonist BN 52021 also attenuated the hypotension and necrosis caused by coronary ligation 23 +/- 2% vs 14 +/- 1%, P less than 0.01. Pretreatment with the thromboxane antagonist CGS 13080 attenuated the hypotensive response to ischaemia but had only a very small effect on the area of necrosis. Administration of PAF at 10 min following coronary ligation markedly increased the volume of necrosed tissue 36 +/- 2%, P less than 0.01 and caused VF and haemodynamic collapse in 10 out of 12 animals. Pretreatment with platelet antiserum or the PAF antagonist BN 52021 reversed this effect of PAF. Pretreatment with CGS 13080 attenuated the marked hypotensive effect of PAF but failed to reverse its necrotic or arrhythmogenic effects. These findings indicate that platelet activation contributes to the necrosis and hypotension following coronary ligation and that platelet-activating factor may contribute to this. The ameliorating effects of platelet antiserum or BN 52021 support the concept that inhibition of platelet activity may have a useful role in the treatment of acute myocardial infarction.
Animals↗
Modulation of differentiation and proliferation in human colon carcinoma cells by transforming growth factor beta 1 and beta 2.
We have previously characterized the diversity of cellular responses to transforming growth factor (TGF)-beta 1 from human colon carcinoma cells. We now show that morphological alteration and part of the growth-inhibitory responses elicited by growth factor (GF) are associated with the secondary effect of the induction of synthesis of extracellular matrix (ECM) glycoproteins. Specifically, morphological alteration is associated with the ECM glycoprotein laminin, and growth inhibition is associated with both laminin and fibronectin. Both TGF-beta 1 and TGF-beta 2 down-modulate the expression of nucleolar protein B23 (also known as numatrin or nucleophosmin, a positive regulator of cell proliferation). With one exception, the biological effects of both TGF-beta 1 and TGF-beta 2 on these human colon carcinoma cell lines are identical. Both GFs up-modulate the expression of carcinoembryonic antigen (CEA) and CEA-related gene products. However, some of these products are differentially regulated by TGF-beta 1 and TGF-beta 2. The differences in the profile of the induction of these CEA and CEA-related gene products, in the responsive cells, functionally distinguish TGF-beta 1 from TGF-beta 2. Finally, we identified and characterized some of the cellular proteins, the expression of which is up-modulated by GF. These proteins are epithelium-associated, differentiation-related cytokeratins. Both TGF-beta 1 and TGF-beta 2 up-modulate expression of the acidic and basic subtypes of human keratins in the responsive human colon carcinoma cells. Both the responsive and unresponsive cells, however, possess receptors for GFs.
Carcinoembryonic Antigen↗
Modulation of fibronectin synthesis and fibronectin binding during transformation and differentiation of mouse AKR fibroblasts.
In previous studies it was shown that transformation of AKR fibroblasts with 3-methylcholanthrene was associated with a loss of surface fibronectin and that induction of differentiation of the transformed cells with N,N-dimethylformamide (DMF) was associated with reacquisition of surface fibronectin (Chakrabarty et al., J. Cell. Physiol. 133:415, 1987). It is shown in the present study that changes in surface fibronectin reflect altered fibronectin synthesis and altered fibronectin binding. Both the nontransformed cells (AKR-2B) and their transformed counterparts (AKR-MCA) bound 125I-fibronectin in a receptor-like fashion, but the AKR-MCA cells had only 20% of the receptors found on the AKR-2B cells. Whole cell extracts prepared from the AKR-2B cells and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions were examined for 125I-fibronectin binding. Under these conditions, the majority of binding occurred to moieties with molecular weights of 180 kD, 150 kD, and 97 kD. Binding to similar moieties on the AKR-MCA cells was virtually absent but occurred rapidly after treatment with DMF. The appearance of these moieties paralleled the acquisition of 125I-fibronectin binding activity by whole cells. Antibodies to the fibronectin receptor isolated from human placenta reacted with the DMF-sensitive moieties in immunoblot assays. Both the appearance of the fibronectin binding moieties and the acquisition of 125I-fibronectin binding activity by whole cells occurred within 6 hr of DMF treatment and increased over the subsequent 4 day period. The time course of these events paralleled closely the time course for induction of fibronectin biosynthesis by DMF. These changes in fibronectin binding and fibronectin production were associated with alterations in cell-substrate adhesion. The AKR-2B cells rapidly attached and spread on bovine serum albumin-coated dishes and on fibronectin-coated dishes, whereas the AKR-MCA cells were less adhesive on both substrates. Capacity to attach and spread was regained concomitantly with the induction of fibronectin binding and fibronectin production. Adhesion on both substrates was partially inhibited by antibodies to the fibronectin receptor and by RGDS. These studies suggest that fibronectin production and fibronectin binding are coregulated in AKR fibroblasts and that they function together to bring about changes in cell-substrate adhesion.
Animals↗
A curative operation for extra-articular ankylosis of knee.
For the extra-articular ankylosis of knee a new surgical operation has been described, which is a simple technique by which the adhesion of the quadriceps femoris is released from the shaft of femur (corrective release operation). Operative result in 5 cases has been also described. All these patients showed satisfactory improvement of the flexion movement of the knee following this surgical procedure.
Adult↗
Induction of carcinoembryonic antigen and its crossreactive gene products in human colonic adenomas and carcinomas by transforming growth factor-beta.
The inducing effect of transforming growth factor-beta (TGF-B) on carcinoembryonic antigen (CEA) secretion and the cellular expression of CEA and CEA crossreactive glycoproteins (CEA-GLY) was examined from a panel of human colonic cell lines with different phenotypic classification. This panel included carcinomas with dissimilar differentiation characteristics and metastatic behavior, and premalignant adenomas derived from colonic polyps. A great degree of heterogeneity was observed in the endogenous levels of CEA secretion and the cellular expression of CEA and CEA-GLY species. The response profiles of the different cell lines to TGF-B treatment were also found to be heterogenous. However, TGF-B was able to induce CEA secretion and up-modulated the cellular expression of CEA and CEA-GLY from a majority of the cells tested. More importantly, TGF-B was able to exert these effects on carcinoma cells that secrete or express minimal or nondetectable amounts of these glycoproteins. These biologic modifying effects of TGF-B may have potential in augmenting the efficacy of CEA as a colon cancer marker, and in antibody-directed radioimaging and therapeutics. Further investigation in vivo in an experimental animal model system is warranted.
Adenoma↗
Fibronectin/laminin and their receptors in aberrant growth control in FR3T3 cells transformed by Ha-ras oncogene and epidermal growth factor gene.
FR3T3 cells transfected with either the Ha-ras oncogene or the epidermal-growth-factor (EGF) gene demonstrate the transformed phenotype as indicated by in vitro and in vivo criteria. We have examined non-transformed FR3T3 cells as well as Ha-ras-oncogene-transformed and EGF-gene-transformed cells for expression of cell surface fibronectin and cell surface laminin. Fibronectin was absent from the surface of the Ha-ras-oncogene-transformed cells but present on both the EGF-gene-transformed cells and the non-transformed FR3T3 cells. Laminin was present on the cell surface in all 3 lines. The lack of surface fibronectin on the Ha-ras-oncogene-transformed cells was associated with reduced fibronectin production as indicated by immunoblotting of whole cell extracts and by ELISA. Concomitantly, there was a significant reduction of fibronectin binding by the Ha-ras-oncogene-transformed cells was compared to their EGF-gene-transformed and non-transformed counterparts. The Ha-ras-oncogene-transformed cells demonstrated reduced cell-substrate adhesiveness relative to the other two cell lines, as indicated by rates of attachment and spreading on plastic culture dishes in the presence of bovine serum albumin. They also demonstrated reduced adhesiveness in response to fibronectin but not laminin. Taken together, our results suggest that aberrant expression of fibronectin/fibronectin receptors is associated with Ha-ras-oncogene-induced transformation. In contrast, transformation by the EGF gene does not appear to involve aberrant expression of fibronectin/fibronectin receptors.
Animals↗
Fibrin solubilizing properties of certain anionic and cationic detergents.
The fibrinolytic (fibrin dissolving) properties of several anionic, cationic, nonionic and zwitterionic detergents were assessed in an in vitro fibrin agarose assay. Of the 4 anionic detergents tested, only sodium dodecyl sulfate (SDS) was found to be fibrinolytic. SDS was fibrinolytic either in the absence or presence of factor XIII. Four other cationic detergents were found to possess similar fibrinolytic properties. These cationic detergents were cetyltrimethylammonium bromide (CTAB), mix alkyltrimethyl ammonium bromide (MTAB), hexadecyltrimethylammonium bromide (HTAB) and cetylpyridium chloride (CPC). The nonionic (digitonin, triton X-100/tween 20) and zeitterionic (CHAPS, zeittergent 3-08) detergents were not fibrinolytic. Detergents mediated fibrinolysis, unlike that of tissue type plasminogen activator and urokinase, was independent of the presence of plasminogen. Non-detergents such as polyethylene glycol and highly charged compounds such as poly-1-lysine and poly-1-glutamic acid were not fibrinolytic. Fibrinolytic activity was observed for SDS and the cationic detergents at concentrations ranging from 0.1-10 percent. The effects of these fibrinolytic detergents (SDS, CTAB, MTAB, HTAB and CPC) on clot formation and on pre-formed clots were then assessed, using freshly drawn human venous blood. Incorporation of these detergents into blood inhibited the formation of clots in a concentration dependent manner. The detergents were also able to dissolve pre-formed clots in a similar fashion. SDS was found to be most potent in these properties.
Blood Coagulation↗