Biomedical subjects

N Saha

Publications and source records attributed to N Saha.

At least 73 records · Page 4Linked to original sources

PubMed1995

Carbohydrate-dependent binding of the cell-free hemagglutinin of Vibrio cholerae to glycoprotein and glycolipid.

The carbohydrate-binding specificity of the cell-free hemagglutinin (HA) of Vibrio cholerae (K.K. Banerjee, A.N. Ghose, K. Datta-Roy, S.C. Pal, and A.C. Ghose, Infect. Immun.58:3698-3705, 1990) was studied by using glycoconjugates with defined sugar sequences. The HA was not inhibited by simple sugars including glucobiose, galabiose, and their N-acetylated derivatives. The hemagglutination of rabbit erythrocytes by the HA was inhibited moderately by fetuin, calf thyroglobulin, and human alpha 1-acid glycoprotein, all of which contain multiple asparagine-linked complex-type oligosaccharide units alone or in combination with serine/threonine-linked oligosaccharide units. The inhibitory potencies of the glycoproteins increased approximately 10-fold following removal of the terminal sialic acid and were completely destroyed by exhausative proteolysis. The HA agglutinated phosphatidylcholine liposomes containing GM1-ganglioside or its asialo-derivative in the presence of Ca2+ ions. The association constants of the complexes of the HA with asialofetuin, asialothyroglobulin, GM1-ganglioside, and asialo-GM1-ganglioside were determined by an enzyme-linked immunosorbent assay-based assay and found to be 1.7 x 10(7) M-1, 1.5 x 10(7) M-1, 1.8 x 10(7) M-1, and 2.4 x 10(7) M-1, respectively. Studies using chemically modified glycoproteins and plant lectins with defined sugar specificity revealed that the HA recognized the terminal beta 1-galactosyl moiety of these glycoconjugates. There was no evidence for the presence of an extended carbohydrate-binding domain in the HA molecule or a preference of the HA for a complex, branched oligosaccharide structure. Similar to the mechanisms proposed for the binding of cholera toxin and Shiga toxin to glycolipids and neoglycoproteins, the strong interaction of V. cholerae cell-free HA with glycoconjugates appeared to be a consequence of multiple weak binding to terminal beta1-galactosyl moieties of the glycoproteins or glycolipids.

Animals↗

PubMed1995

Polynesian genetic affinities with Southeast Asian populations as identified by mtDNA analysis.

Polynesian genetic affinities to populations of Asia were studied using mtDNA markers. A total of 1,037 individuals from 12 populations were screened for a 9-bp deletion in the intergenic region between the COII and tRNA(Lys) genes that approaches fixation in Polynesians. Sequence-specific oligonucleotide probes that identify specific mtDNA control region nucleotide substitutions were used to describe variation in individuals with the 9-bp deletion. The 9-bp deletion was not observed in northern Indians, Bangladeshis, or Pakistanis but was seen at low to moderate frequencies in the nine other Southeast Asian populations. Three substitutions in the control region at positions 16217, 16247, and 16261 have previously been observed at high frequency in Polynesian mtDNAs; this "Polynesian motif" was observed in 20% of east Indonesians with the 9-bp deletion but was observed in only one additional individual. mtDNA types related to the Polynesian motif are highest in frequency in the corridor from Taiwan south through the Philippines and east Indonesia, and the highest diversity for these types is in Taiwan. These results are consistent with linguistic evidence of a Taiwanese origin for the proto-Polynesian expansion, which spread throughout Oceania by way of Indonesia.

Asia, Southeastern↗

PubMed1995

Population genetic study among the Orange Asli (Semai Senoi) of Malaysia: Malayan aborigines.

A population genetic study was undertaken to provide gene frequency data on the additional blood genetic markers in the Semai and to estimate the genetic relations between the Semai and their neighboring and linguistically related populations by genetic distance and principal components analyses. Altogether 10 polymorphic and 7 monomorphic blood genetic markers (plasma proteins and red cell enzymes) were studied in a group of 349 Senoi Semai from 11 aboriginal settlements (villages) in the Pahang State of western Malaysia. Both the red cell glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) loci reveal the presence of polymorphic frequencies of a nondeficient slow allele at the G6PD locus and a fast allele at the PGD locus. The Semai are characterized by high prevalences of ahaptoglobinemia and G6PD deficiency, high frequencies of HP*1, HB*E, RH*R1, ACP*C, GLO1*1, PGM1*2+, and GC*1F and corresponding low frequencies of ABO*A, HbCoSp, HB*B0, TF*D, CHI, and GC*2. Genetic distance analyses by both cluster and principal components models were performed between the Semai and 14 other populations (Malay; Javanese; Khmer; Veddah; Tamils of Malaysia, Sri Lanka, and India; Sinhalese; Oraon; Toda and Irula of India; Chinese; Japanese; Koreans) on the basis of 30 alleles at 7 polymorphic loci. A more detailed analysis using 53 alleles at 13 polymorphic loci with 10 populations was carried out. Both analyses give genetic evidence of a close relationship between the Semai and the Khmer of Cambodia. Furthermore, the Semai are more closely related to the Javanese than to their close neighbors--the Malay, Chinese, and Tamil Indians. There is no evidence for close genetic relationship between the Semai and the Veddah or other Indian tribes. The evidence fits well with the linguistic relationship of the Semai with the Mon-Khmer branch of the Austro-Asiatic language family.

Adolescent↗

PubMed1994

Molecular characterisation of red cell glucose-6-phosphate dehydrogenase deficiency in Singapore Chinese.

Sixty-two G6PD deficient Chinese males have been investigated for the presence of seven mutations of the coding region of the G6PD gene by natural and artificially created amplified restriction sites. The results show that the G to T substitution at nucleotide (nt) 1376 and G to A substitution at nt 1388 represent 24% and 21% of G6PD deficiency, respectively, in the Singapore Chinese; 37% of the sample could not be characterised. The remaining samples were identified as follows: 10% C-->T at nt 563, 5% A-->G at nt 95, and 3% C-->T at nt 1024. The G to A substitution (nt 487) and the substitution A-->G (nt 493) were not present in this sample. None of the subjects with the Mediterranean mutation (563 C-->T) had the silent mutation at 1311 (C-->T). This study confirms the extreme molecular heterogeneity of the G6PD gene in the Chinese.

Base Sequence↗

PubMed1994

Influence of polymorphisms for apolipoprotein B (ins/del, XbaI, EcoRI) and apolipoprotein E on serum lipids and apolipoproteins in a Javanese population.

A total of 231 healthy subjects from a central Javanese population were investigated for the distribution of three apolipoprotein B (apo B) polymorphisms (ins/del, XbaI, and EcoRI), as well as apolipoprotein E (apo E) polymorphism in relation to serum lipid and apolipoprotein concentrations. The frequencies of the rarer alleles (del, 0.09; X+, 0.1; and R-, 0.06) were lower than have been found for some Asian and European populations. Distribution of genotypes was in Hardy-Weinburg equilibrium for all the polymorphisms. A linkage disequilibrium was observed only between the ins/del and XbaI site polymorphisms of apo B (chi 2(4)) = 25.3; P < 0.001) consistent with that observed in some other population studies. No polymorphism of the apo B gene had an association with serum lipid or apolipoprotein concentrations in this population except for XbaI, which appeared to be associated with serum TG (as the log transform: R2 = 8.3; F = 4.8; P < 0.01). The apo E4 allele was found to be associated with significantly higher serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC). Apo E polymorphism explained 5.9% of the sample variance of serum LDLC (F = 5.4; P < 0.01).

Adolescent↗

PubMed1994

Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in Chinese non-smokers.

The influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at -75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high-density lipoprotein cholesterol (HDLC) and apo AI and lower low-density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy-Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24-0.31] than that reported in Caucasians (0.12; 95% CI 0.09-0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non-smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits.

Adenine↗

PubMed1994

Lack of association of the dopamine D3 receptor gene polymorphism (BalI) in Chinese schizophrenic males.

Dopamine receptors have been implicated in the aetiology of schizophrenia and mode of action of antipsychotic drugs. A finding of increased homozygosity at the D3 receptor gene (BalI locus) has recently been reported. We have investigated the distribution of D3 receptor gene polymorphism (BalI) in 137 schizophrenic Chinese males and 125 healthy matched controls. The frequency of the rare allele was 0.30 and 0.31 in the patient and the control series. The distribution of genotypes in the patient series did not deviate significantly from Hardy-Weinberg equilibrium in the present series.

Adult↗

PubMed1994

Interrelationships of serum paraoxonase, serum lipids and apolipoproteins in normal pregnancy. A longitudinal study.

Serum paraoxonase (EC 3.1.1.2) may be implicated in the lipid metabolism. In order to substantiate this view we conducted a longitudinal study of interrelationships of serum paraxonase, lipids and apolipoproteins during pregnancy. Fasting serum levels of paraoxonase, serum lipids (total, HDL and LDL cholesterols, triglycerides) and apolipoproteins (AI, AII and B) were estimated in 91 pregnant women at 28 and 32 weeks of gestation and 6 weeks after delivery, and 40 nonpregnant women. Serum paraoxonase, total HDL and LDL cholesterol levels were significantly higher during pregnancy along with corresponding apolipoprotein (p < 0.001). The most striking increase was seen in serum triglycerides and paraoxonase levels (p < 0.001). Serum paraoxonase levels had a significant correlation with triglycerides (r: 0.45-0.60) and Apo-AII (r: 0.32-0.41) in both pregnant and nonpregnant states (p < 0.001). Moreover, both serum paraoxonase and triglyceride levels at 28 weeks of pregnancy were negatively correlated with birth weight (r: 0.3, p < 0.05), suggesting a possible role of paraoxonase in energy delivery for fetal development derived from maternal hypertriglyceridemia.

Apolipoprotein A-II↗

PubMed1994

Association of factor VII genotype with plasma factor VII activity and antigen levels in healthy Indian adults and interaction with triglycerides.

Plasma factor VII activity (factor VIIc) is one of the independent risk factors for coronary artery disease and is controlled by both genetic and environmental factors. Several studies in healthy Caucasian subjects have revealed an association of a common genetic polymorphism at residue 353 (Arg-->Gln) of the factor VII gene with plasma factor VIIc. We have investigated the influence of this polymorphism (factor VII Arg/Gln353) on fasting plasma factor VIIc and antigen (factor VIIag) levels and its interaction with triglyceride levels in 185 healthy Dravidian Indians of both sexes (128 men, 57 women). The frequency of Gln353 has been found to be significantly higher in Dravidian Indians (0.29; confidence interval, 0.27 to 0.30) than in Caucasians (0.10). The distribution of factor VII Arg/Gln353 genotypes was at Hardy-Weinberg equilibrium. The carriers of the Gln353 allele had significantly lower plasma factor VIIc and factor VIIag in men (P < .05). The factor VII Arg/Gln353 polymorphism explained 13% and 11% of the total variance of plasma factor VIIc and factor VIIag, respectively, in men (P < .001) and 6% and 9% in women (P > .1). The genotype-specific correlation of factor VIIc and factor VIIag with triglyceride levels was stronger in carriers of the Gln353 allele (r = .38 and .41; P < .001) than in Arg353 homozygotes (r = .09 and .27; P = .19 and .005, respectively).

Adult↗

PubMed1993

Endogenous hydroperoxide formation, cell volume and cellular K+ balance in perfused rat liver.

Addition of benzylamine (0.5 mM) to isolated perfused rat liver led to a net release of K+ of 10.5 +/- 0.3 mumol/g, which was accompanied by a decrease in liver mass by 9.3 +/- 0.4% and a decrease of the intracellular water space by 13.7 +/- 0.6%, suggestive of hepatocellular shrinkage. Benzylamine had no effect on the perfusion pressure, and there was a close relationship between benzylamine-induced net K+ release and the accompanying decrease in liver mass. Benzylamine-induced net K+ release was sensitive to inhibition of monoamine oxidase by pargyline and increased with benzylamine flux through monoamine oxidase, suggesting its dependence on intracellular H2O2 formation. In line with this, infusion of H2O2 (but not of benzaldehyde, the other product of benzylamine metabolism) stimulated net K+ release from the liver. However, at a given H2O2 load K+ release was about 2-3-fold higher when H2O2 was generated intracellularly during the oxidation of benzylamine, as compared with exogenously delivered H2O2. Inhibition of catalase by 3-amino-1,2,4-triazole (0.2 mM) significantly increased the benzylamine-induced net K+ release as well as the benzylamine-induced release of GSSG into bile, but had no effect on benzylamine oxidation at monoamine oxidase. In the presence of Ba2+ (1 mM) or in Ca(2+)-free perfusions, the benzylamine-induced net K+ efflux was diminished by 60-70% or about 30%, respectively. This was not explained by the 20-30% decrease in flux through monoamine oxidase observed under these conditions. The results suggest that metabolic generation of H2O2 inside the liver leads to a net K+ efflux and subsequent hepatocellular shrinkage. Net K+ efflux under these conditions is enhanced when catalase is inhibited, suggesting that the rate of both intracellular H2O2 generation and degradation can modulate cellular K+ balance and cellular volume. The data support the idea that oxidative stress may affect hepatocellular functions also by lowering the hepatocellular hydration state.

Animals↗

PubMed1993

A molecular basis for human hypersensitivity to aminoglycoside antibiotics.

We have investigated the distribution of mitochondrial DNA polymorphisms in a rare maternally transmitted genetic trait that causes hypersensitivity to aminoglycoside antibiotics, in the hope that a characterization of its molecular basis might provide a molecular and cellular understanding of aminoglycoside-induced deafness (AGD). Here we report that the frequency of a particular mitochondrial DNA polymorphism, 1555G, is associated nonrandomly with aminoglycoside-induced deafness in two Japanese pedigrees, bringing the frequency of this polymorphism to 5 occurrences in 5 pedigrees of AGD, and in 4 of 78 sporadic cases in which deafness was thought to be the result of aminoglycoside exposure; both frequencies are significantly different from the occurrence of this mutation in the hearing population, which was 0 in 414 individuals surveyed. The 1555G polymorphism occurred in none of 34 aminoglycoside-resistant individuals. We propose a specific molecular mechanism for aminoglycoside hypersensitivity in individuals carrying the 1555G polymorphism, based on the three-dimensional structure of the ribosome, in which the 1555G polymorphism favors aminoglycoside binding sterically, by increasing access to the the ribosome cleft.

Adolescent↗

PubMed1993

Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver.

An increase of the hepatocellular hydratation state, induced by hypotonic exposure, amino acids or tauroursodeoxycholate, was shown to increase within minutes the Vmax of transcellular taurocholate transport and excretion into bile [Häussinger, Hallbrucker, Saha, Lang and Gerok (1992) Biochem. J. 288, 681-689]. This stimulatory effect of cell swelling on taurocholate excretion into bile is abolished in the presence of colchicine (5 microM). On the other hand, colchicine did not affect the stimulatory action of hypotonic cell swelling on 14CO2 production from [1-14C]glycine or [1-14C]glucose. Likewise, volume regulatory K+ fluxes following anisotonic exposure were not influenced in the presence of colchicine. Lumicolchicine (5 microM), a stereoisomer of colchicine without an inhibitory effect on microtubules, did not abolish the stimulation of taurocholate excretion into bile following hypo-osmotic exposure. Hypertonic cell shrinkage decreased taurocholate excretion into bile by about 35%; this effect was fully reversible upon normotonic re-exposure. With colchicine pretreatment, however, the hypertonicity-induced inhibition of taurocholate excretion was blunted and was no longer reversible upon normotonic re-exposure. The results suggest that stimulation of taurocholate excretion into bile in response to cell swelling involves a colchicine-sensitive, probably microtubule-dependent, mechanism, but not the stimulation of other cell-volume-sensitive pathways such as glycine oxidation or the pentose-phosphate shunt. It is hypothesized that the swelling-induced stimulation of taurocholate excretion into bile is due to a microtubule-dependent insertion of bile acid transporter molecules into the canalicular membrane.

Animals↗

PubMed1993

DNA polymorphisms of the apolipoprotein B gene are associated with obesity and serum lipids in healthy Indians in Singapore.

Three DNA polymorphisms (Ins/Del, XbaI and EcoRI) of the apolipoprotein B gene and their influence on body-mass index, serum lipids and apolipoprotein levels were studied in 181 healthy Indians of both sexes (121 males and 60 females), aged between 17 and 71 years. The frequencies of X+ (XbaI) and Del (Ins/Del) of the signal peptide region in Indians were found to be significantly lower (0.17 and 0.11, respectively) compared to the frequencies in Caucasians (0.50 and 0.32, respectively) (P < 0.025). The frequency of E- (EcoRI) was similar to that in Caucasians (0.10 vs 0.15). A highly significant linkage disequilibrium was observed between the XbaI site and Ins/Del polymorphism of the apo B gene in this sample (X2 = 31.9, P < 0.001). The simultaneous presence of Del and X+ allele was significantly associated with higher body mass index (X2 = 11.43, P < 0.005), serum total cholesterol (X2 = 5.11; P < 0.025) and triglyceride (X2 = 6.42; P < 0.025) levels. Mean values of adjusted BMI and serum triglyceride levels were found to be 29.0 +/- 1.92 vs 23.7 +/- 0.67 (P < 0.025) and 278.0 +/- 60.78 vs 140.4 +/- 15.43 mg/dl (P < 0.05), respectively, in subjects with Del and X+ compared to others. The multiple regression tests showed that 3.3 and 5.8% of the total variability of BMI is explained by Ins/Del and XbaI polymorphism, respectively, in this sample (P = 0.06 and 0.02), while 3.8% of serum triglyceride levels was explained by Ins/Del polymorphism of the apo B gene (P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Effects of post-training administration of (-)-baclofen and chlordiazepoxide on memory retention in ICRC Swiss mice: interactions with GABAA and GABAB receptor antagonists.

The effects of post-training administration of chlordiazepoxide and (-)-baclofen on memory retention was studied in ICRC Swiss mice by measuring the retest stepdown latency 24 hr after foot-shock in a passive avoidance task. Chlordiazepoxide 20 mg/kg impaired memory retention and a similar effect was produced by 10 mg/kg of diazepam. The effect of chlordiazepoxide was antagonised when combined with picrotoxin but not by the addition of a specific GABAB antagonist CGP 35348. The effect of chlordiazepoxide on memory retention seems to be mediated by action at the GABAA-benzodiazepine receptor complex. (-) Baclofen, the active isomer of the GABAB agonist enhanced memory in ICRC mice and this effect was antagonised by CGP 35348 at a dose of 10 mg/kg. The inactive isomer of baclofen, (+)-baclofen did not produce any effect. This indicates that GABAB receptors contribute to the effects of (-)-baclofen on memory.

Animals↗

PubMed1993

BRL 38227--a potassium channel opener, antagonizes digoxin-induced convulsions.

Experimental evidence suggests that potassium channel openers play an important role in convulsions. In this study, the anticonvulsant activity of BRL 38227, a new potassium channel opener against digoxin-induced convulsions, is reported. Intraventricular administration of digoxin (7.5 micrograms), included "popcorn-type" convulsions in rats. BRL 38227, injected centrally increased the onset time of convulsions and decreased the mortality rate in a dose-dependent manner. Pretreatment with 4-aminopyridine, a potassium channel blocker antagonized the protective effect of BRL 38227. These findings show the involvement of potassium channels in digoxin-induced convulsions. Further these results indicate that in the future potassium channels might be a target for new anticonvulsant drugs.

4-Aminopyridine↗

PubMed1993

Clinical evaluation of the effect of omeprazole, cimetidine, famotidine and ranitidine on histamine induced cutaneous wheal and flare response.

The effect of H2 receptor antagonists on immediate cutaneous response to allergens remain controversial. In the present study, the effect of 7-day administration of omeprazole, cimetidine, famotidine and ranitidine on histamine induced wheal and flare reaction was evaluated. A single blind randomized parallel group study with within patient comparison of responses was planned in non-ulcer dyspepsia patients eligible to receive H2 antagonists or omeprazole. None of the drugs produced any changes in the area of the wheal in comparison to respective baseline values. The area of flare was decreased by all the drugs and the percentage decrease in this parameter caused by omeprazole, cimetidine, famotidine and ranitidine was 2.4, 12.3, 20.2 and 13.2, respectively. Only famotidine caused a significant decrease in flare area (p < 0.05).

Adult↗

PubMed1993

Apolipoprotein H polymorphism and serum lipoprotein and apolipoprotein levels in two Asian populations.

The apolipoprotein H (apo H) is a constituent of several lipoprotein particles and, therefore, may play an important role in lipid metabolism. In this study, we have investigated the role of common apo H structural polymorphism in determining serum total cholesterol; high-density lipoprotein cholesterol; triglycerides; and apolipoproteins A-I, A-II, and B in 655 Chinese and 126 Dravidian Indians from Singapore. Serum lipoprotein and apolipoprotein levels were adjusted for significant concomitant variables for age and body mass index, and the quantitative mean values between different apo H genotypes were compared by an analysis of covariance. The distributions of serum lipoprotein and apolipoprotein levels were found to be comparable between the three common apo H genotypes in both ethnic groups, indicating that the apo H polymorphism may not play a significant role in lipid metabolism.

Apolipoproteins↗

PubMed1993

Effects of ranitidine alone and in combination with chlorpheniramine on histamine-induced wheal and flare and psychomotor performance.

Some reports suggest that addition of an H2 antagonist increases the efficacy of H1 antagonist but the influence on the side effect profile of antihistamines are largely unknown. The effects of ranitidine, chlorpheniramine, their combination and placebo on histamine induced wheal and flare, psychomotor performance and subjective symptoms were studied in 6 healthy male volunteers in a double blind randomized and cross-over (Latin square) study. Ranitidine significantly reduced the histamine induced wheal at 4 hrs (P < 0.05). Chlorpheniramine and the combination significantly reduced both histamine induced wheal and flare at 2 hrs and at 4 hrs (P < 0.05). Addition of ranitidine reduced the feeling of sleepiness produced by chlorpheniramine, though other subjective symptoms were not affected. None of the treatment schedules produced any consistent change in the psychomotor performance of the volunteers.

Adult↗