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Biomedical subjects

M Das

Publications and source records attributed to M Das.

At least 289 records · Page 16Linked to original sources
PubMed1982

Epidermal growth factor action as a model for lymphokine function.

The experimental findings described here represent a general approach toward understanding the mechanism of action of polypeptide hormones and mediators by using epidermal growth factor (EGF) as the model system. A photoaffinity labeling method was used for identifying the cell-surface EGF receptor and for following its dynamic and migratory fate after binding to EGF. A different approach involving receptor insertion revealed that the EGF receptor can be transferred in a biologically active orientation from donor hepatic membranes to recipient receptor-negative mutant cells by a novel mechanism requiring no added fusogenic agent. These studies of the EGF receptor led us to probe into the transduction mechanism that relates hormone-receptor binding to its biological function. EGF-receptor interaction in responsive cells was shown to lead to the intracellular generation of macromolecular protein activators of nuclear DNA replication. These molecular intermediates lead to the generation of an ultimate committed prereplicative state that is an innate characteristic and a global property of the whole cell. These studies of the EGF receptor and EGF-induced internal events serve to illustrate the types of systems that might be explored in future research on lymphokines and other such biologically relevant mediators of mitogenesis.

Animals↗
PubMed1982

Depletion of glutathione content and inhibition of glutathione-S-transferase and aryl hydrocarbon hydroxylase activity of rat brain following exposure to styrene.

Dose dependent effects of styrene on cellular glutathione content and activity of cytosolic glutathione-S-transferase and microsomal aryl hydrocarbon hydroxylase of rat brain was investigated. A significant inhibition of aryl hydrocarbon hydroxylase and glutathione-S-transferase activity followed by depletion of glutathione content, was observed only at higher doses (450 and 900 mg/kg). Results suggest that exposure of styrene to rats can affect the biotransformation capacity of brain dependent on glutathione content and the activities of aryl hydrocarbon hydroxylase and glutathione-S-transferase.

Animals↗
PubMed1981

Initiation of nuclear DNA replication: evidence for formation of committed prereplicative cellular state.

This paper explores the transitional states that bridge the gap between nuclear quiescence and mitogenesis. It presents evidence for the formation of a committed but prereplicative state. Quiescent murine Swiss 3T3 cells were exposed to an external mitogenic stimulant (epidermal growth factor or excess serum) and simultaneously to a synchronizer which inhibits entry into the S phase. Thus, the cells were stimulated to synthesize DNA, but the normal replicative response to this stimulus was blocked. The block to DNA replication was removed at varying times after removal of the stimulant. Experiments were done to monitor the decay of commitment to DNA synthesis after removal of the external stimulant. This decay turned out to be a first-order process. The half-life (time required for loss of the commitment to DNA synthesis in half of the initially sensitized cells) was found to be approximately 5 hr. The same result was found whether total DNA synthesis or individually replicating cells were measured and was independent of the type of external growth stimulant or blocker used. These results point to the existence, on the mitogenic pathway, of a committed but prereplicative state. The committed state appears to represent a unit or global property of the whole cell rather than, for example, a critical concentration of some active inducer molecule because the latter would display multi-hit decay kinetics rather than the single-step lability actually observed.

Animals↗
PubMed1981

Glutathione-S-transferase activity in the brain: species, sex, regional, and age differences.

Glutathione-S-transferase activity in the brain of male mammals (rat and mouse) was found to be relatively lower than in that of females. In contrast, the male aves (pigeon, kite, vulture, and crow) exhibited comparatively higher activity in brain glutathione-S-transferase than the corresponding females. Postnatal development of cytosolic glutathione-S-transferase activity in the rat brain was also investigated. The day-7 rats showed a low activity of 48 nmol/min/mg protein that gradually increased 3.2-fold over the age of 28 days. No striking differences in brain enzyme activities were observed between the 35- and 90-day-old rats. Discrete brain regions of immature rats were found to possess considerable but lower quantities of glutathione-S-transferase activity than those of the adults. The activity increased with the onset of development and attained a steady state after 21 days of age.

Aging↗
PubMed1981

Effect of styrene on hepatic mixed function oxidases, glutathione content and glutathione-s-transferase activity in rats.

Effect of styrene administration (250, 450 and 900 mg/kg orally for 7 consecutive days) on hepatic mixed function oxidase (MFO) enzyme activities, glutathione content and glutathione-S-transferase activity were observed. Activity of aryl hydrocarbon hydroxylase and aniline hydroxylase was significantly enhanced at higher doses of styrene (450 and 900 mg/kg). A significant lowering of glutathione content accompanied with the inhibition of glutathione-S-transferase activity was also noticed at the highest dose of styrene (900 mg/kg).

Aniline Hydroxylase↗
PubMed1981

Induction of an intracellular mitogenic messenger by epidermal growth factor.

This paper explores the pathway from nuclear quiescence to mitogenesis. It describes an in vitro assay for an activator of DNA replication induced by epidermal growth factor (EGF) in responsive cells. Cytoplasmic extracts from EGF-treated 3T3 were found to contain substances that can stimulate DNA synthesis in isolated nuclei from spleen cells of adult frogs. Extracts from untreated resting 3T3 cells lack this activity, and EGF itself is incapable of stimulating, DNA synthesis in these cell-free systems. The extract-induced stimulation of 3H-dTTP incorporation into nuclear DNA is ATP-dependent and requires the presence of the 4 deoxyribonucleoside triphosphates, suggesting the occurrence of replication rather than repair synthesis. This cell-free assay has been used to obtain some initial insights into the mechanism of induction and biochemical characterization of the intermediate in EGF action. Half-maximal induction of the active intracellular substance is achieved at about 0.08nM EGF, a concentration that correlates well with the concentration required for half-maximal mitogenesis. Studies on the biochemical characteristics of this active substance strongly suggest that the activity is associated with a protein. The activity is nondialyzable and sensitive to trypsin and heat. Sucrose-gradient centrifugation of the extract revealed 3 peaks of activity with molecular weights of 46,000, 110,000, and 270,000 daltons (sedimentation coefficients: 3 7S, 6.6S, and 12S, respectively). These results indicate that receptor-EGF interaction at the cell surface leads to the intracellular generation of proteins that are capable of stimulating quiescent nuclei into activity.

Animals↗
PubMed1980

Myoglobinuric acute renal failure in phencyclidine overdose: report of observations in eight cases.

Eight cases of myoglobinuric acute renal failure that developed following exposure to phencyclidine were seen in the emergency department of the Martin Luther King Jr. General Hospital during a period of 36 months. All eight survived with complete recovery of renal function. Dialysis was necessary in three patients. Acute renal failure is an uncommon complication of phencyclidine abuse.

Acute Kidney Injury↗
PubMed1980

Mitogenic hormone-induced intracellular message: assay and partial characterization of an activator of DNA replication induced by epidermal growth factor.

This paper explores the pathway from nuclear quiescence to mitogenesis. It describes an in vitro assay for an activator of DNA replication induced by epidermal growth factor (EGF) in responsive cells. Cytoplasmic extracts from EGF-treated 3T3 cells were found to contain substances that can stimulate DNA synthesis in isolated nuclei from spleen cells of adult frogs. Extracts from untreated resting 3T3 cells lack this activity, and EGF itself is incapable of stimulating DNA synthesis in these cell-free systems. The extract-induced stimulation of incorporation of [3H]dTTP into nuclear DNA is ATP dependent and requires the presence of the four deoxyribonucleoside triphosphates, suggesting the occurrence of replication rather than repair synthesis. This cell-free assay has been used to obtain some initial insights into the mechanism of induction and biochemical characterization of the intermediate in EGF action. Half-maximal induction of the active intracellular substance is achieved at about 0.08 nM EGF, a concentration that correlates well with the concentration required for half-maximal mitogenesis. Studies on the biochemical characteristics of this active substance strongly suggest that the activity is associated with a protein. The activity is nondialyzable and sensitive to trypsin and heat. Sucrose gradient centrifugation of the extract revealed three peaks of activity with molecular weights of 46,000, 110,000, and 270,000 (sedimentation coefficients: 3.7 S, 6.6 S, and 12 S, respectively). These results indicate that receptor-EGF interaction at the cell surface leads to the intracellular generation of protein that are capable of stimulating quiescent nuclei into activity.

Animals↗
PubMed1980

Anti-tremor action of C10Dichol, a peripheral acetylcholine synthesis inhibitor.

1 Anti-tremor action of decamethylene bis-(hydroxyethyl)-dimethylammonium bromide (C10Dichol), a peripheral acetylcholine synthesis inhibitor, was investigated. 2 C10Dichol inhibited tremor induced by oxotremorine, nicotine and physostigmine and afforded partial protection from physostigmine-induced mortality in mice. 3 In non-paralysing doses, C10Dichol antagonized the neuromuscular effects of oxotremorine, nicotine and physostigmine. 4 Prior administration of C10Dichol failed to prevent tremor and neuromuscular paralysis induced by harmine and arecoline. 5 In the absence of any antimuscarinic property of C10Dichol, its neuromuscular effects appeared to be casually related to its anti-tremor action. 6 This study reveals a possibility for the development of peripherally acting anti-Parkinson drugs.

Acetylcholine↗