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M Das

Publications and source records attributed to M Das.

At least 253 records · Page 14Linked to original sources
PubMed1984

Insertion of EGF receptors into target cells in the absence of fusogenic agents.

Epidermal growth factor (EGF) receptors can be spontaneously and selectively transferred from donor plasma membranes to recipient receptorless fibroblasts in the absence of any added fusogenic agent. Studies on the time and temperature dependence of this transfer indicate that it is due to preferential insertion of the EGF receptor over the other plasma membrane proteins. The inserted receptor is exceptionally stable to dissociation or damage. The number of receptors inserted increased with increasing amounts of donor membranes and then reached a plateau, which also suggests the existence of saturable receptor 'docking' sites in recipient cells. It is interesting that both human and murine receptors are selectively inserted into the mutant mouse cell membrane. This suggests that the parts of the receptor molecule responsible for insertion are similar in murine and human receptors, and that a 'docking' factor present in the mouse recipient cells may accept both human and murine receptors.

Animals↗
PubMed1984

Plasma levels and clinical response during treatment with clomipramine.

The plasma levels of clomipramine (CI) and its major metabolite desmethylclomipramine (DMCI) may be related to clinical response during treatment of depression. Not all workers have been able to demonstrate such a relationship. The many factors which may affect clinical response include sample selection, assessment and its quantification and kinetic factors. A further investigation into the relationship between plasma levels and response was, therefore, carried out taking these into account and attempting to control them. Sixty-two patients with depressive illness were included. The plasma levels of CI + DMCI as measured on the 28th day of treatment were correlated against clinical response at the time. Patients with the highest combined plasma levels showed the best response. Patients with intermediate plasma levels showed more modest response, whilst lowest plasma levels tended to be shown by patients who exhibited an inadequate response or who relapsed during subsequent outpatient follow-up. The threshold value for satisfactory antidepressant effect appeared to be a combined CI + DMCI plasma level of 160-200 mg/ml.

Adult↗
PubMed1984

Interaction of acrylamide with glutathione in rat erythrocytes.

Evidence is presented for an enzyme-catalyzed conjugation of acrylamide (ACR) in rat erythrocytes. Daily exposure of rats to ACR for a period of 7, 14 and 21 days resulted in a time-dependent decrease in glutathione content. In vitro incubation of ACR with rat erythrocytes suspension caused a concentration-dependent decrease in glutathione levels. Red blood cell (RBC) enzyme-catalyzed conjugation of ACR with glutathione increased with protein concentration and was dependent on pH and time of incubation. Glutathione-S-transferase (GST) activity using acrylamide and 1-chloro 2,4-dinitrobenzene (CDNB) as substrates followed the order: liver greater than kidney greater than brain greater than erythrocytes. Glutathione peroxidase activity of RBC's was inhibited by the in vitro addition of ACR to erythrocytes. These results suggest that rat erythrocytes are equipped with the mechanism which can inactivate toxic electrophilic chemicals, such as acrylamide.

Acrylamide↗
PubMed1984

Identification of a 34,000-dalton mitogenic protein associated with plasma membranes from human A431 epidermoid carcinoma cells.

We present evidence for a discrete 34,000-Da polypeptide with mitogenic activity, associated with plasma membranes from human A431 carcinoma cells. Plasma membranes from A431 cells are highly mitogenic for quiescent fibroblasts. A significant fraction of the membrane-associated activity can be released by treatment with a high concentration of salt and is relatively acid stable. Incubation of 125I-labeled salt-extracted proteins with target fibroblasts results in preferential binding of a 34,000-Da protein--i.e., greater than 90% of the cell-bound radioactivity is associated with the 34,000-Da polypeptide. Studies correlating the mitogenic activity with the cell-binding 34,000-Da protein indicate that this protein is the acid-stable, peripherally attached, mitogenically active component of A431 membranes. Available data suggest that this protein may be mitogenically active in the nanomolar concentration range. Some properties of this protein are described.

Acetates↗
PubMed1984

Ellagic acid: a potent naturally occurring inhibitor of benzo[a]pyrene metabolism and its subsequent glucuronidation, sulfation and covalent binding to DNA in cultured BALB/C mouse keratinocytes.

The metabolism of [3H]benzo[a]pyrene (BP) by cultured primary keratinocytes prepared from BALB/C mouse epidermis was found to be largely inhibited by the dietary plant phenol, ellagic acid. Varying concentrations of ellagic acid added to the keratinocyte cultures resulted in a dose-dependent inhibition of the cytochrome P-450-dependent monooxygenases aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin-O-deethylase (ECD). The major organic solvent-extractable metabolites found intracellularly in the cultured cells were trans-7,8-dihydro-7,8-dihydroxybenzo[a]-pyrene (BP-7,8-diol) and 3-hydroxybenzo[a]pyrene (3-OH-BP), although small amounts of 9-hydroxybenzo[a]pyrene, quinones and trans-9,10-dihydro-9,10-dihydroxybenzo[a]-pyrene (BP-9,10-diol) were also present. The major organic solvent-extractable metabolites found in the extracellular culture medium were BP-7,8-diol and BP-9,10-diol, with smaller quantities of unconjugated phenols and quinones. The major intracellular and extracellular water-soluble metabolites of BP were conjugated with glucuronide (primarily 3-OH-BP and several BP-quinones), and to a lesser extent with sulfate (primarily BP-7,8-diol). Both intracellular and extracellular metabolism of organic solvent-extractable and water-soluble conjugates was significantly inhibited by ellagic acid in a dose-dependent manner. The intracellular enzyme-mediated binding of BP to mouse keratinocyte DNA was also largely inhibited in a dose-dependent fashion by ellagic acid. Our results indicate that cultured primary mouse keratinocytes offer a useful model system for studying factors affecting the metabolic activation and detoxification of polycyclic aromatic hydrocarbon carcinogens in the epidermis, and that polyphenolic compounds such as ellagic acid may prove useful in modulating the risk of cutaneous cancer that results from exposure to these environmental chemicals.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1984

Dexamethasone suppression test in acute grief reaction.

The authors report a study on the response to the dexamethasone suppression test of bereaved first-degree relatives. Of the 21 subjects who took part two were non-suppressors (plasma cortisol greater than 138 mmol/l), but their grief scores were no higher than the suppressors. Both subjects showed a suppressor response 3 months later.

Adult↗
PubMed1984

Epidermal benzo[a]pyrene metabolism and DNA-binding in Balb/C mice: inhibition by ellagic acid.

Topical application of ellagic acid, a common plant phenol, to control or to 3-methylcholanthrene (3-MC) pretreated Balb/C mice, resulted in significant inhibition of hepatic and epidermal microsomal aryl hydrogen hydroxylase activity, and of benzo[a]pyrene (BP) binding to epidermal and hepatic DNA in vivo. In vitro addition of ellagic acid (0.25 mM) to epidermal microsomal incubation systems from either control or 3-MC-treated animals resulted in 62-75% inhibition of BP binding to calf thymus DNA. These studies suggest that ellagic acid could prove useful in understanding and/or modulating polyaromatic hydrocarbon carcinogenesis.

Animals↗
PubMed1984

Clotrimazole, an inhibitor of epidermal benzo(a)pyrene metabolism and DNA binding and carcinogenicity of the hydrocarbon.

Clotrimazole, a topically applied imidazole antifungal agent widely used in dermatological practice, was shown to be a potent inhibitor of the epidermal metabolism of benzo(a)pyrene (BP) and its microsomal enzyme-mediated binding both to neonatal rat epidermal DNA in vivo and to calf thymus DNA in vitro. Varying concentrations of clotrimazole added to in vitro incubation systems resulted in a dose-dependent inhibition of cytochrome P-450-dependent microsomal aryl hydrocarbon hydroxylase (AHH) in control animals as well as in animals pretreated with topical application of known inducers of the enzyme. Inhibition of epidermal AHH by topically applied clotrimazole was time and dose dependent. The 50% inhibition of clotrimazole for epidermal AHH ranged from 0.12 to 0.25 microM, which suggests that clotrimazole is among the most potent inhibitors of epidermal AHH yet identified. Clotrimazole was also found to be a potent inhibitor of epoxide hydrolase activity in vitro with a 50% inhibition at 0.1 mM. High-pressure liquid chromatographic analysis of the metabolism of BP in rat epidermal microsomes revealed substantial inhibition of metabolite formation by clotrimazole. This occurred in microsomes prepared from untreated as well as animals pretreated with inducers of the enzyme. Furthermore, a single topical application of clotrimazole resulted in 80 and 30% induction of epidermal and hepatic glutathione S-transferase activity, respectively. Topical application of clotrimazole to the skin of BALB/c mice substantially increased the latent period for the development of skin tumors by 3-methylcholanthrene. These studies indicate that clotrimazole is an extremely potent inhibitor of epidermal BP metabolism and of the DNA-binding of polycyclic aromatic hydrocarbon (PAH) carcinogens, and is an enhancer of enzymes necessary for detoxification of the PAH. Clotrimazole also reduces the formation of carcinogenic and mutagenic metabolites of BP in vitro and in vivo and inhibits induction of skin tumors by the PAH. These data indicate that the imidazole antifungal clotrimazole offers promise as an agent useful for the modulation of PAH cancer risk in the skin.

Animals↗
PubMed1984

Mitogenic activity of the epidermal growth factor receptor after transfer from A431 carcinoma cells to receptor-negative fibroblastic cells.

This paper demonstrates spontaneous transfer of epidermal growth factor (EGF) receptor mitogenicity from human A431 carcinoma cells to receptor negative mouse cells. The fact of transfer was documented by the demonstration in the recipient cell of normal EGF-binding affinity, covalent labeling of transferred receptor by 125I-EGF, and reactivity with specific anti-human receptor antibody. Phosphorylation experiments suggest that in the transferred receptor the protein kinase site tends to face the inside of the cell. The transferred receptor imposed upon the normally unresponsive cells a mitogenic responsiveness to EGF in the nM concentration range, as measured by stimulation of DNA replication. EGF-dependent mitogenesis in the recipient cells was abolished by both anti-EGF antibody and anti-human receptor antibody, indicating that the transferred mitogenicity is both EGF and receptor specific. For NR-6 cells without transplanted receptor, the same antibody had no effect on non-EGF-dependent mitogenesis. Interestingly, although the transferred receptor displayed normal behavior in several respects, it did not mediate rapid internalization and degradation of bound EGF.

Animals↗
PubMed1984

Mechanism of the stimulation of prostaglandin H synthase and prostacyclin synthase by the antithrombotic and antimetastatic agent, nafazatrom.

Nafazatrom, an antithrombotic and antimetastatic agent containing a pyrazolone functionality, is a reducing substrate for the peroxidase activity of prostaglandin H (PGH) synthase. Nafazatrom inhibits the hydroperoxide-dependent oxidation of phenylbutazone, stimulates the reduction of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid, and is oxidized by microsomal or purified enzyme preparations from ram seminal vesicles. Consonant with the effects of other peroxidase-reducing substrates, nafazatrom stimulates the oxygenation of arachidonic acid to prostaglandin endoperoxides by the cyclooxygenase component of PGH synthase. In addition, nafazatrom causes an elevation in the levels of 6-keto-prostaglandin F1 alpha, the non-enzymatic hydrolysis product of prostacyclin (PGI2) biosynthesized from arachidonic acid by ram seminal vesicle microsomes. Elevation of PGI2 biosynthetic capacity by nafazatrom occurs under conditions in which prostaglandin endoperoxide biosynthesis is maximal, suggesting that nafazatrom has a stimulatory effect on the conversion of prostaglandin endoperoxides to PGI2. Nafazatrom has no effect on the ability of ram seminal vesicle microsomes to convert PGH2 to PGI2 but protects microsomal PGI2 synthase from inactivation by 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid. Nafazatrom stimulates PGI2 biosynthesis in ram seminal vesicle microsomes by acting as a substrate for the peroxidase-catalyzed reduction of hydroperoxy fatty acids that are irreversible inactivators of PGI2 synthase. Several other compounds, including dipyridamole and triiodothyronine, exert similar effects. This may contribute to the reported ability of nafazatrom and related compounds to elevate the levels of bioassayable PGI2 in vivo and to the antithrombotic and antimetastatic activities of nafazatrom.

Animals↗
PubMed1984

Trampoline-related quadriplegia: review of the literature and reflections on the American Academy of Pediatrics' position statement.

A review of the world's literature documenting cervical spine injuries has been made in an attempt to determine common factors regarding patient characteristics, environment, injury mechanisms, and pathology. The policy statements and safety guidelines of both the American Academy of Pediatrics and athletic administrative bodies have been reviewed in order to evaluate what effect, if any, these policies and guidelines have had on documented injuries. On the basis of this review, it is believed that the AAP was ill-advised in altering its position on the use of trampolines. The opinion is presented that both the trampoline and minitrampoline are dangerous devices when used in the best of circumstances, and their use has no place in recreational, educational, or competitive gymnastics.

Accidents↗
PubMed1984

Fractures of the base of the fifth metatarsal distal to the tuberosity. Classification and guidelines for non-surgical and surgical management.

Between 1973 and 1982 forty-six fractures of the base of the fifth metatarsal, distal to the tuberosity, were treated and followed for a mean of forty months (range, six to 108 months). Roentgenographic criteria were used to define three types of fractures: acute fractures characterized by a narrow fracture line and absence of intramedullary sclerosis; those with delayed union, with widening of the fracture line and evidence of intramedullary sclerosis; and those with non-union and complete obliteration of the medullary canal by sclerotic bone. Of the twenty-five acute fractures in this series, fifteen were treated with a non-weight-bearing toe-to-knee cast, and fourteen of them healed in a mean of seven weeks. Only four of the other ten, which were treated with various weight-bearing methods, progressed to union. Of the twelve patients with delayed union, one refused treatment, one was treated with a bone graft, and ten were treated initially by immobilization of the limb in a plaster cast and weight-bearing. Of these ten fractures, seven healed in a mean of 15.1 months and three eventually required grafting for non-union. Of the nine non-unions in the series, which were treated primarily with medullary curettage and bone-grafting, eight healed in a mean of three months. In all, twenty fractures were treated surgically with an autogenous corticocancellous graft that was inlaid after thorough curettage and drilling of the sclerotic bone that obliterated the intramedullary cavity. Of these twenty fractures, nineteen progressed to complete healing and one, to asymptomatic non-union.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Fracture of the distal radial epiphysis. Characteristics and surgical treatment of premature, post-traumatic epiphyseal closure.

Wrist deformities developed in ten children secondary to injury of the growth plate and premature closure of the distal radial epiphysis. Premature closure of the growth plate followed epiphyseal compression injuries or repeated forceful attempts at reduction. These injuries should not require repeated reductions in children with epiphyseal remodeling potential of more than two years if the initial reduction achieves apposition of more than 50%. Gross deformity develops if the discrepancy between radial and ulnar lengths is more than 4 mm. Ulnar shortening and correction of the radiocarpal angle, as required, constitute the surgical treatment of choice for growth deformity.

Child↗
PubMed1983

Enhancement of lipid peroxidation in rat liver on acute exposure to styrene and acrylamide a consequence of glutathione depletion.

Lipid peroxidation, glutathione level and activity of glutathione-S-transferase were studied in liver and brain of rats 4 and 3 h after a single i.p. administration of 0, 25, 75, 100 mg/kg acrylamide or 0, 50, 100, 200, 600 mg/kg styrene, respectively. In liver both acrylamide and styrene caused an increase in lipid peroxidation and decrease in glutathione contents and activity of glutathione-S-transferase in a dose dependent manner, while in brain only acrylamide produced a decrease in glutathione content. The decrease in glutathione content was not always associated with increase of lipid peroxidation. The enhancement of lipid peroxidation occurred only when glutathione contents were depleted to certain critical levels. No effect of acrylamide or styrene was seen on lipid peroxidation under in vitro conditions. The addition of glutathione in the incubation mixture significantly inhibited the rate of lipid peroxidation of liver homogenates of acrylamide and styrene treated animals. The results suggest that enhancement of lipid peroxidation in liver on exposure to acrylamide or styrene is a consequence of depletion of glutathione to certain critical levels. The inhibition of glutathione-S-transferase activity by acrylamide and styrene suggests that detoxication of these neurotoxic compounds could be suppressed following acute exposure.

Acrylamide↗