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Biomedical subjects

A Banerjee

Publications and source records attributed to A Banerjee.

At least 487 records · Page 27Linked to original sources

Interaction of colchicine analogues with purified tubulin.

Binding of two colchicine analogues, desacetamidocolchicine and 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone to purified tubulin have been studied. Both analogues bind to tubulin with a significant increase in fluorescence polarization of the drugs in solutions containing tubulin. The Kd for tubulin-drug complexes were found to be 1.25 X 10(-6) M and 1.08 X 10(-6) M for desacetamidocolchicine and 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone, respectively. Scatchard analysis of the fluorescence titration curve of drug tubulin interaction also gives the values of stoichiometry and affinity constant. These were 0.8 and 1.6 X 10(6) M-1 for desacetamidocolchicine, and 0.9 and 0.58 X 10(6) M-1 for 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone.

Animals↗

Charge effect on the colchicine binding-site of tubulin.

Poly(L-lysine) was found to enhance colchicine binding activity of brain tubulin to a several folds. Bases of biological interests that were tested and found to be inactive were spermine, spermidine and even L-lysine. Part of this enhance binding is due to the increase in the affinity of colchicine-tubulin interaction in the presence of poly(L-lysine). Moreover, poly(L-lysine) stabilized the colchicine binding site of tubulin against thermal denaturation.

Animals↗

Patient with 13 chromosome deletion: evidence that the retinoblastoma gene is a recessive cancer gene.

Although a constitutional chromosomal deletion including 13q14 has been found to date in all retinoblastoma patients whose esterase D activity is 50 percent of normal, one female patient has been found who has 50 percent esterase D activity in all normal cells examined but no deletion of 13q14 at the 550-band level. Therefore, she has the smallest constitutional chromosomal deletion within 13q14 that is associated with susceptibility to retinoblastoma. Two stem lines were identified in a retinoblastoma from this patient, and each one had a missing 13 chromosome. No detectable esterase D activity was found in the tumor, indicating that the normal nondeleted 13 chromosome was lost in both stem lines. Thus the data from this patient not only show that there is a total loss of genetic information at the location of the retinoblastoma gene within the tumor, but also imply that recessive genes may play an important role in the development of certain human tumors including retinoblastoma.

Child, Preschool↗

Nonrandom chromosomal changes in untreated retinoblastomas.

The karyotypic patterns of 15 retinoblastomas were examined. Five tumors were found to have two distinct stem lines and, therefore, the chromosomal patterns of 20 tumor cell lines are reported. Three nonrandom chromosomal changes, namely, a loss of a chromosome #13, the presence of an i(6p), or a trisomy of 1q were observed. The potential importance of these chromosomal changes in tumor development is discussed, particularly the loss of a chromosome #13 or the gain of an i(6p). At least one of the three chromosomal changes was found in 75% of the tumor lines analyzed.

Aneuploidy↗

Presence of nonlinear excitations in DNA structure and their relationship to DNA premelting and to drug intercalation.

We propose that collectively localized nonlinear excitations (solitons) exist in DNA structure. These arise as a consequence of an intrinsic nonlinear ribose inversion instability that results in a modulated beta alternation in sugar puckering along the polymer backbone. In their bound state, soliton-antisoliton pairs contain beta premelted core regions capable of undergoing breathing motions that facilitate drug intercalation. We call such bound state structures--beta premeltons. The stability of a beta premelton is expected to reflect the collective properties of extended DNA regions and to be sensitive to temperature, pH, ionic strength and other thermodynamic factors. Its tendency to localize at specific nucleotide base sequences may serve to initiate site-specific DNA premelting and melting. We suggest that beta premeltons provide nucleation centers important for RNA polymerase-promoter recognition. Such nucleation centers could also correspond to nuclease hypersensitive sites.

DNA↗

Activating proteins for ganglioside GM2 degradation by beta-hexosaminidase isoenzymes in tissue extracts from different species.

The existence of activator proteins that stimulate hydrolysis of ganglioside GM2 by beta-hexosaminidase was demonstrated in kidney extracts from four species (rat, mouse, cattle and pig). The extent to which these preparations, as well as their human counterpart, promote ganglioside GM2 catabolism by autologous and heterologous hexosaminidase isoenzymes was compared. It was found that these activators can replace each other functionally, although the animal activator proteins do not cross-react immunochemically with an antiserum against the human protein. All preparations examined catalysed the transfer of ganglioside GM2 between liposomal membranes, indicating that the animal activator proteins act by a mechanism similar to the human GM2 activator.

Animals↗

Comparison of mutagenicity and induction of sister chromatid exchange in Chinese hamster cells exposed to hematoporphyrin derivative photoradiation, ionizing radiation, or ultraviolet radiation.

Cell culture studies have been performed to compare the mutagenic potential and the induction of sister chromatid exchanges for hematoporphyrin derivative photoradiation, ionizing radiation, and UV radiation. The mutation frequency in Chinese hamster ovary cells at the hypoxanthine-guanine phosphoribosyltransferase locus was measured using resistance to 6-thioguanine. Phenotypic expression time prior to mutation selection was also examined. Treatment with either X-rays or UV was effective in producing mutants resistant to 6-thioguanine, but treatment with hematoporphyrin derivative photoradiation (at comparable toxicity levels) did not induce any mutagenic activity above background levels. The hematoporphyrin derivative incubation and photosensitization conditions used in this study did induce sister chromatid exchanges at frequencies comparable to those induced by X-rays but at lower frequencies than for UV treatments.

Animals↗

GABA dehydrogenase activity in rat brain.

The crude mitochondrial fraction of rat brain contains an active dehydrogenase involved in the direct oxidation of gamma-aminobutyric acid. INT (p-iodonitrotetrazolium violet) can serve as an efficient acceptor of electrons in this dehydrogenase reaction. During this oxidation of GABA, ammonia is not produced. In vitro the dehydrogenase activity is inhibited by certain MAO inhibitors. The effects of various inhibitors of GABA-T and GAD were also investigated. The dehydrogenase activity was found to be susceptible to various anti-convulsants and inhibitors of electron transport. The co-factors which may be involved in the transfer of electrons during GABA oxidation in the presence of INT are also discussed.

Animals↗

Interaction of Ni2+ with the tubulin-microtubule system.

In vitro polymerization of purified goat brain tubulin is stimulated at low Ni2+ concentration, whereas at high nickel concentration (greater than 1 . 10(-4)) polymerization is inhibited. Ni2+, over the concentration range of 1 . 10(-4)-1 . 10(-3) M, enhances the rate of colchicine binding to tubulin, although in its presence the colchicine binding site of tubulin is degraded at a much faster rate at 37 degrees C. Finally, incubation of tubulin with Ni2+ at 37 degrees C gradually alters the native conformation of the protein, as revealed by the quenching of intrinsic tryptophan fluorescence.

Animals↗

Effects of sodium valproate and acetazolamide on cerebral respiration.

The effects of sodium valproate and acetazolamide on the oxygen uptake of guinea pig brain cortex slices were investigated. In calcium-free medium, sodium valproate inhibited the oxygen uptake appreciably in the presence of glucose and glutamic acid. Acetazolamide, on the other hand, was more effective in inhibiting oxygen uptake in the presence of glucose than in the presence of glutamic acid. Addition of 0.2 mM CaCl2 in the medium containing 5 mM KCl could appreciably reverse the inhibition of oxygen uptake by acetazolamide in the presence of glucose. The inhibition of oxygen uptake by these drugs in the presence of glucose, however, could be completely reversed by increasing the dose of K+ ions (100 mM) in the medium which had no effect on the inhibition of oxygen uptake in the presence of glutamic acid. When the concentration of Ca2+ ions in the medium was elevated to 0.75 mM, the inhibitory effects of these drugs on the oxygen uptake in the presence of both glucose and glutamic acid could be completely abolished. Sodium valproate also inhibited the endogenous respiration of guinea pig brain cortex slices, whereas acetazolamide was almost without any effect. Increase in the concentration of Ca2+ ions in the medium failed to counteract the inhibition of endogenous respiration of guinea pig brain cortex slices by sodium valproate.

Acetazolamide↗

Effects of L-ascorbic acid supplementation on dieldrin toxicity in rats.

Chronic dieldrin administration to rats (5 mg/kg/day) produced pathological changes in liver and kidney tissues. Dieldrin treated rats showed high levels of liver ascorbic acid and increased activities of inorganic pyrophosphatase in brain and glucose-6-phosphatase in liver. The activities of Mg2+-ATPase in liver and acetylcholinesterase in brain were decreased under toxic doses of dieldrin. L-Ascorbic acid supplements in treated animals could partially prevent the pathological alterations, as observed histologically in liver and kidney tissues. Administration of this vitamin could also prevent alterations in some enzyme activities produced by toxic dieldrin doses.

Animals↗

Blood dehydroascorbic acid and diabetes mellitus in human beings.

Ascorbic acid and dehydroascorbic acid were estimated in the blood of normal healthy subjects and diabetic patients. In normal subjects, blood contained only ascorbic acid while dehydroascorbic acid was practically absent. The ascorbic acid level was low in the blood of diabetic patients but the dehydroascorbic acid content was remarkably high, irrespective of age, sex, history of diabetes, or treatment. About 75% of blood dehydroascorbic acid was present in the erythrocytes: the rest was in plasma. High blood dehydroascorbic acid levels were also found in 90% of the non-diabetic offspring with both parents diabetic, in 24% of the non-diabetic offspring with one parent diabetic, and in 75% of the non-diabetic siblings of diabetic patients. It appears that, in persons having an hereditary predisposition to diabetes, high blood dehydroascorbic acid levels may be used as a marker for early detection of the disease.

Adolescent↗