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Biomedical subjects

A Basu

Publications and source records attributed to A Basu.

At least 235 records · Page 13Linked to original sources
PubMed1987

A genetic study among the Lepchas of the Darjeeling area of eastern India.

A total of 215 Lepchas (75 Buddhists and 140 Christians) living in the Kalimpong subdivision, Darjeeling district, West Bengal, India, were investigated for the distribution of haemoglobin, serum proteins and red cell enzymes. The gene frequencies were as follows: HbE = 0.02; Hp1 = 0.18; TfB = 0.007; TfDChi = 0.005; Gc2 = 0.22; pa = 0.18; pc = 0.03; PGM2(1) = 0.18; PGM6(1) = 0.002; PGDc = 0.17; AK2 = 0.02; GLO1 = 0.21. The most striking features were the complete lack of G6PD deficiency and very high frequency of PGDC. The remaining loci (serum albumin, lactate dehydrogenase, malate dehydrogenase and glucose-6-phosphate dehydrogenase, phosphohexose isomerase and superoxide dismutase) were monomorphic. The gene frequencies were similar in the Buddhist and Christian Lepchas. The observed average heterozygosity (9 loci) was 0.20 in the entire sample.

Acid Phosphatase↗
PubMed1986

Regulation of kinase and intermolecular bonding in intact and truncated epidermal growth factor receptor.

Tyrosine kinase activity of the epidermal growth factor (EGF) receptor can be regulated by its state of association. Studies done with the purified receptor solubilized in Triton X-100 indicate that dimer formation results in negative regulation of kinase, whereas successive binding of EGF and ATP shift the association equilibrium toward the catalytically active monomeric form. The promotion of the monomeric state by ATP can be mimicked by various nonphosphorylating analogs indicating that nucleotide binding rather than autophosphorylation is responsible for stabilizing the monomeric receptor form. Truncated receptor forms, lacking either the external EGF-binding domain or the internal kinase (ATP-binding) domain, are unable to form stable dimers. These results suggest that both intra- and extracellular domains of the receptor act to stabilize the kinase-regulatory dimer.

Adenosine Triphosphate↗
PubMed1986

Sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate as activators of spleen glucocerebrosidase.

Sequential extraction of human spleen membranes with sodium cholate and n-butanol removes endogenous lipids and renders glucocerebrosidase activity dependent upon exogenous acidic lipids (e.g., phosphatidylserine, gangliosides) and a heat-stable activator protein (HSF). In the present report, we show that two previously untested lysosomal acidic lipids, namely sulfogalactocerebroside and bis-(monoacylglyceryl)-phosphate (BMP), also activate normal human glucocerebrosidase. In addition, sulfogalactocerebroside also markedly enhanced the activity of glucocerebrosidase isolated from a patient with type 1 (non-neuronopathic) Gaucher's disease, resulting in a specific activity which was 60-80% that of control glucocerebrosidase. Furthermore, when the sulfolipid was used as the activator, glucocerebrosidase from the type 1 patient was 30 times more active than the corresponding glucocerebrosidase from a person with type 2 (neuronopathic) Gaucher's disease. In contrast, the two BMPs, one rich in C26 saturated fatty acid and another rich in C18 unsaturated fatty acids, were relatively poor activators of both mutant glucocerebrosidases while providing excellent reconstitution of control activity.

Animals↗
PubMed1986

Effects of altitude, ethnicity-religion, geographical distance, and occupation on adult anthropometric characters of eastern Himalayan populations.

With a view to estimating the effect of altitude on body dimensions vis-à-vis ethnicity-religion, geographical distance, and occupation, a comprehensive multivariate statistical analysis was performed on data pertaining to 16 anthropometric characters collected from 1,103 individuals (643 males and 460 females) belonging to two ethnic groups-Sherpa and Lepcha. Samples were drawn from several locations in the eastern Himalayan region-Darjeeling and Kalimpong in West Bengal (India), and Nepal, situated at low (1,000-2,000 meters) and high (above 3,500 meters) altitudes. The individuals sampled practice different occupations and follow different religions. Significant age and sex effects were observed. The data were age-adjusted, and sexes were treated separately. A test of equality of mean vectors indicated heterogeneity among population groups. Almost all characters were found to contribute significantly to the ability to discriminate between the groups. The overall probability of correctly classifying an individual based on body dimensions into the group in which she or he actually belongs was high (between 0.64 and 0.77). Shape and size factors could be identified that explained about 50% of the total variance and yielded a reasonable separation of the groups. Results of four different types of multivariate statistical analyses were in agreement, and showed that altitude is most highly associated with body dimensions.

Adult↗
PubMed1986

Comparison of the ability of phospholipids from rat liver lysosomes to reconstitute glucocerebrosidase.

The in situ lipid activator of rat liver glucocerebrosidase was investigated. Rat liver lysosomes were purified (42.9-fold relative to the crude homogenate) by sequential isopycnic centrifugation in sucrose and metrizamide gradients. Lipids were extracted with chloroform:methanol (2:1) and phospholipids were separated by one-dimensional thin-layer chromatography. The phospholipid content of the lysosome preparation was 0.28 mumol lipid phosphorus/mg protein. Phosphatidylcholine was present as the major nonacidic phospholipid (39.3%). Of the acidic phospholipids, phosphatidylinositol and phosphatidylserine were present in the greatest amounts (12.0 and 19.7%, respectively). The resolved phospholipids were tested separately and in the presence of a heat-stable factor from Gaucher spleen for their ability to reconstitute butanol-delipidated rat liver glucocerebrosidase activity. Alone or in the presence of the heat-stable factor, phosphatidylserine and phosphatidylinositol were the most effective activators of glucocerebrosidase. Bis(monoacylglyceryl) phosphate derived from rat liver tritosomes or rabbit lung macrophages was also effective in reconstituting beta-glucosidase activity.

Animals↗
PubMed1985

Comparison of N-acyl phosphatidylethanolamines with different N-acyl groups as activators of glucocerebrosidase in various forms of Gaucher's disease.

The acidic phospholipid requirement of the predominant particulate beta-glucosidase of mammalian spleen and liver was investigated using a series of N-acyl derivatives of dioleoyl phosphatidylethanolamine (PE). The PE, a neutral phospholipid, was converted to an acidic lipid, (N-acyl)-phosphatidylethanolamine (NAPE) by acylation of the amino group with different fatty acyl chains. Lysosomal beta-glucosidases from rat liver and spleens of controls and patients with various types of Gaucher's disease were solubilized and delipidated by extraction with sodium cholate and 1-butanol. All members of the NAPE series tested were effective activators of the delipidated rat liver beta-glucosidase, and the stimulatory power of the NAPE family increased with increasing chain length of the fatty acid substitution. In contrast, dioleoyl-PE had no effect on beta-glucosidase activity. A heat-stable factor (HSF) purified from the spleen of a patient with Gaucher's disease significantly increased the sensitivity of the rat liver beta-glucosidase to all of the NAPE derivatives. The maximum stimulation achieved in the presence of HSF was independent of N-acyl chain length. Compared to the potent activator, phosphatidylserine (PS), (N-acetyl)-PE and (N-linoleoyl)-PE were half as effective as activators of beta-glucosidase from control human spleen. PS stimulated the beta-glucosidase of type 1 nonneurologic Gaucher's disease, but none of the NAPE compounds activated it. Neither PS nor any of the (N-acyl)-PE compounds could activate a delipidated preparation of beta-glucosidase obtained from the spleen of a neurologic case. These results indicate that although the presence of a net negative charge on a phospholipid confers upon it an ability to reconstitute beta-glucosidase activity to the normal, nonmutant enzyme, it is insufficient to permit differentiation of the various types of Gaucher's disease.

Acylation↗
PubMed1985

Characterization of the activation of rat liver beta-glucosidase by sialosylgangliotetraosylceramide.

We show that sialosylgangliotetraosylceramide (GM1) is a potent activator of delipidated (sodium cholate- and 1-butanol-extracted) lysosomal rat liver glucocerebroside:beta-glucosidase. Stimulation of 4-methylumbelliferyl-beta-D-glucopyranoside hydrolysis by the beta-glucosidase was markedly dependent upon the concentration of GM1 in the assay medium. Estimations of critical micellar concentration (CMC) performed fluorometrically using the dye N-phenylnaphthylamine revealed two CMC values of GM1 above 18 degrees C; the CMC of the primary micelles (3.32 microM) was temperature-independent whereas that of the secondary micelles decreased with decreasing temperature (17.2 and 10.8 microM at 37 and 20 degrees C, respectively). In the temperature range of 18-39 degrees C, beta-glucosidase activity increased sharply when the GM1 concentration was above the CMC of the secondary micelles. Although a heat-stable factor, purified from the spleen of a patient with Gaucher's disease, had a profound effect on the activation of beta-glucosidase by GM1, it decreased the CMC only slightly (14.8 versus 17.2 microM at 37 degrees C). The heat-stable factor (8 micrograms/ml) changed the shape of the activation curve from sigmoidal to hyperbolic, suggesting that the heat-stable factor permits beta-glucosidase to be activated by primary micelles or monomers. The results of gel filtration chromatography and sucrose gradient centrifugation in H2O and D2O revealed that the activation of beta-glucosidase by GM1 was associated with an increase in the size of the enzyme from 45,800 to 178,500 daltons and an increase in the partial specific volume from 0.697 to 0.740 ml/g. The active, reconstituted beta-glucosidase appears to consist of 50% protein and 50% ganglioside (56 molecules/178,500 g). Concentrations of GM1 below the CMC of secondary micelles increased the rate of inactivation of the enzyme by the irreversible inhibitor conduritol B epoxide at 37 degrees C, indicating that GM1 monomers or primary micelles do interact with the enzyme, even though they do not increase the rate of hydrolysis of 4-methylumbelliferyl-beta-D-glucopyranoside by the enzyme.

Animals↗
PubMed1985

Observations on the suramin-mediated inhibition of cellular and viral DNA polymerases.

We have examined the sensitivity of various cellular and viral DNA polymerases to Suramin, an antitrypanosomal drug, which has been reported to exhibit antireverse transcriptase activity. We find that Suramin is a nonspecific inhibitor of all the viral and cellular DNA polymerases, including terminal deoxynucleotidyl transferase, and that the inhibition is most readily reversed by the addition of serum albumin. The drug appears to bind to all the enzyme proteins with no apparent selectivity. Binding of Suramin to enzyme has been found to result in the loss of both substrate and templateprimer binding abilities of various enzymes, confirming the nonspecific nature of protein-Suramin interaction.

DNA Nucleotidylexotransferase↗
PubMed1985

Further studies on the activation of glucocerebrosidase by a heat-stable factor from Gaucher spleen.

Using Sephadex G-75 and DEAE-cellulose column chromatography, an 8270-Da glycopeptide (designated Fragment II) has been isolated from a cyanogen bromide-formic acid digest of a heat-stable factor from Gaucher spleen which activates a lipid-depleted preparation of lysosomal glucocerebrosidase from human liver. Fragment II contains all of the activity present in the native heat-stable factor. Compared with the parent factor, Fragment II contains four fewer cysteine and methionine residues and one less of each of the following: aspartic acid, threonine, serine, valine, isoleucine, and leucine. Nearly all of the monosaccharides present in the parent heat-stable factor can be accounted for in Fragment II, including three glucosamine, three mannose, one sialic acid, and one fucose. By itself, Fragment II has little or no stimulatory activity; its major effect is to markedly increase the sensitivity of glucocerebrosidase to activation by phosphatidylserine. A mixture of 1 microgram phosphatidylserine and 2 micrograms of the cyanogen bromide fragment activates the lipid-depleted preparation of glucocerebrosidase 50% more than 30 micrograms phosphatidylserine alone. Analysis of the Km and Vmax of glucocerebrosidase at various hydrogen ion concentrations revealed that the heat-stable factor and phosphatidylserine together dramatically increase the catalytic efficiency (Vmax/Km) of glucocerebrosidase while making apparent three ionizable groups that participate in the catalysis. Phosphatidylserine alone recruits two ionizable groups, but catalytic efficiency is lower than when heat-stable factor is also present. Heat-stable factor alone has no discernable effect on the ionization of functional groups on the enzyme or on catalytic efficiency. By sucrose density gradient ultracentrifugation, it was shown that preincubation of rat liver glucocerebrosidase with phosphatidylserine and heat-stable factor shifted the enzyme completely from a 56,600-Da form to a 188,100-Da form. The activity of the slower sedimenting form of glucocerebrosidase was totally dependent upon exogenous bile salt activator, whereas the faster sedimenting form exhibited the same activity in the presence or absence of sodium taurocholate. It appears that the heat-stable factor promotes the transfer of phosphatidylserine to glucocerebrosidase, which, in turn, results in an increase in both the catalytic efficiency and size of the enzyme.

Amino Acids↗
PubMed1985

Study of ascorbate status in murine and human leukaemias.

Since mice can synthesize ascorbic acid but man cannot, the ascorbate status in murine and human leukaemia was compared. The decline in plasma ascorbate concentration in both cases indicates that vitamin C deficiency occurs in malignancy. Analysis of tissue ascorbate values in mice also indicated that an enhanced rate of utilization of this vitamin occurs during malignancy, as does an increased rate of excretion, and both events may be responsible for vitamin C deficiency. The hepatic ascorbate values suggest an endeavour by the animals to compensate for the loss through increased synthesis and storage of the vitamin, at least in the early stages of the disease.

Animals↗
PubMed1985

Effects of membrane channel-forming polypeptides on mitochondrial oxidative phosphorylation. A comparison of alamethicin, gramicidin A, melittin and tetraacetyl melittin.

Transmembrane channel-forming polypeptides can function as uncouplers of mitochondrial oxidative phosphorylation. The observed effects are dependent on the phosphate ion (Pi) concentration in the medium. At low Pi (2.5 mM) the order of uncoupling efficiencies is gramicidin A much greater than alamethicin greater than tetraacetyl melittin greater than melittin. The remarkably high activity of gramicidin A suggests insertion of preformed channel dimers into the membrane. It is also suggested that lipid phase association of peptides is necessary in the other cases. At Pi = 100 mM inhibitory effects are observed for alamethicin and tetraacetyl melittin. Less pronounced inhibition is seen for melittin, while no such effect is noted for gramicidin A. The site of inhibition is shown to be complex IV, and the differences in the behavior of the peptides are rationalized in terms of channel structures.

Alamethicin↗