Biomedical subjects

Balaram Ghosh

Publications and source records attributed to Balaram Ghosh.

35 records · Page 2Linked to original sources

PubMed2005

Th(2) immune response in patients with dengue during defervescence: preliminary evidence.

A shift from a T(H)1 to a T(H)2 immune response has been observed in vitro during dengue virus infection. Estimation of plasma IgE level (n = 28), CD4:CD8 lymphocyte ratio, and the intracellular interferon-gamma (IFN-gamma):interleukin-4 (IL-4) ratio (n = 9) was conducted in patients with various severities of dengue around the time of defervescence. The CD4:CD8 lymphocyte ratio was significantly lower (median = 0.45, interquartile range [IQR] = 0.4-0.47 versus 1.3, 1.0-1.9; P = 0.001), and IgE levels were significantly higher (mean = 300.4, SD = 252.5 versus 143.7, 117.9 IU/mL; P = 0.004) in patients than in healthy controls. The intracellular IFN-gamma:IL-4 ratio was significantly lower in patients compared with controls (0.28, 0.13 versus 0.99, 0.4; P = 0.001). These findings suggest that a T(H)2 immune response occurs in patients with dengue around the time of defervescence.

CD4-CD8 Ratio↗

PubMed2004

Para-Bromophenacyl bromide alleviates airway hyperresponsiveness and modulates cytokines, IgE and eosinophil levels in ovalbumin-sensitized and -challenged mice.

Airway hyperresponsiveness, airway eosinophilia and increased IgE levels in serum are the important characteristic features of asthma. We evaluated the potential of para-Bromophenacyl bromide (PBPB), a known phospholipase A(2) inhibitor, on allergen-induced airway hyperresponsiveness in a mouse model. We sensitized and challenged mice with ovalbumin (OVA) to develop airway hyperresponsiveness as assessed by airway constriction and airway hyperreactivity (AHR) to methacholine (MCh) induced by allergen. The mice were orally treated with PBPB (0.1, 1 and 10 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect on airway constriction and AHR to MCh. Determination of OVA-induced airway constriction and AHR to MCh were performed by measuring specific airway conductance (SGaw) using non-invasive dual-chamber whole body-plethysmography. We observed that PBPB (1 mg/kg) significantly reduced OVA-induced airway constriction and AHR to MCh (p<0.01). PBPB (1 mg/kg) treatment significantly inhibited PLA(2) activity in the BAL fluid. Cytokine analysis of the BAL fluid revealed that PBPB caused an increase in interferon-gamma (IFN-gamma) (p<0.02) and a decrease in interleukin-4 (IL-4) (p<0.05) and interleukin-5 (IL-5) (p<0.05) levels. The OVA-specific serum IgE levels (p<0.01) and the BAL eosinophils (p<0.001) were also reduced significantly. Thus, PBPB is capable of modulating allergen induced cytokine levels and serum IgE levels, and alleviating allergen induced airway hyperresponsiveness and eosinophils in mice. These data suggest that PBPB could be useful in the development of novel agents for the treatment of allergen induced airway hyperresponsiveness.

Acetophenones↗

PubMed2004

Uteroglobin-related protein 1(UGRP1) gene polymorphisms and atopic asthma in the Indian population.

BACKGROUND: The secretory protein, uteroglobin-related protein 1 (UGRP1), is mainly expressed in the lung and trachea and has recently been implicated in asthma. The -112 G to A transition in the promoter was reported to be associated with asthma in the Japanese population. However, this has not been replicated in other studies. The aim of this study was to find the association of UGRP1 gene polymorphisms with atopic asthma in the Indian population using a case-control (NP=165, NC=160) and a family-based (60 trios) design. METHODS: Polymorphisms in the promoter region and the first exon and first intron of the UGRP1 gene were determined by direct sequencing. RESULTS: The previously identified G-112A and C222A polymorphisms were found to be in complete linkage disequilibrium (LD) (D'=1) in our population. However, no new polymorphism has been identified in this region. When G-112A polymorphism was analyzed in the cases and controls, no significant difference was observed either at the allele (p=0.68) or at the genotype (p=0.83) levels. Moreover, in our family-based study, we observed no significant deviation of allelic transmission from random proportions (p=0.41). Similarly, when we analyzed our genotypic results for serum total IgE levels, no significant association was observed, in both case-control as well as family-based designs. CONCLUSIONS: Our results suggest that the G-112A and C222A polymorphisms do not play a significant role in the genetic predisposition of UGRP1 gene in atopic asthma in the Indian population.

Adult↗

PubMed2004

Quantitative structure-activity relationship study using refractotopological state atom index on some neonicotinoid insecticides.

Importance of atom-level topological descriptors like electrotopological state atom (E-state) index in QSAR study is increasing. These descriptors help to relate structure and activity at atomic/fragmental level. In view of the earlier success of E-state index on some azidopyridinyl neonicotinoid insecticides, a relatively new atom-level topological descriptor; refractotopological state atom (R-state) index was used in this work. This was used to identify the important atoms/fragments related to dispersive/van der Waals interactions of neonicotinoids with the nicotinic acetylcholine receptor (nAChR). This study showed the structural requirements for the mammal alpha(4)beta(2) and Drosophila nAChR agonistic activity. It also revealed that substituted imine, nitromethylene at X-position were selective to the insecticidal activity. Azido substitution at pyridine ring of neonicotinoids disfavored the binding with the receptors. This study confirmed the validity of the R-state index as a new tool for quantitative structure-activity relationships. It has the ability to find out the required structural features as well as to predict the activity of the neonicotinoids.

Anabasine↗

PubMed2004

Association of an intragenic microsatellite marker in the CC16 gene with asthma in the Indian population.

The gene for Clara cell secretory protein (CC16) is an ideal candidate for investigating genetic predisposition to asthma because of its role in the airway as an anti-inflammatory molecule, differences in its levels between asthmatics and healthy controls, and its genetic location (11q13). We investigated the association of an SNP (A38G) and an intragenic repeat polymorphism in the CC16 gene with asthma and its associated traits, such as total serum IgE levels, in a case control as well as in a family based study design. A significant association was observed for the microsatellite repeat at the level of alleles and genotypes with asthma (P<0.05) in both the study designs. However, no association was observed for the A38G SNP with asthma. When haplotypes were constructed for these two loci and compared, the haplotype A_18 was found at higher frequency in patients (OR=1.59, 95%CI=1.08, 2.33, P=0.016). Also, in the family based design, a biased transmission was observed for haplotypes from parents to affected offspring (P=0.003). Individually, haplotype A_18 showed preferential transmission (82.6%) to affected offspring (P=0.001), thereby confirming the case-control results. In summary, this is the first study identifying the CC16 gene to be associated with asthma in the Indian population.

Amino Acid Substitution↗

PubMed2004

Suggestive evidence of association of C-159T functional polymorphism of the CD14 gene with atopic asthma in northern and northwestern Indian populations.

CD14 is a lipopolysaccharide receptor known to be an important modulator of Th1-Th2 response during early childhood. Genetic association studies of the CD14 gene with asthma and atopic disorders have shown positive as well as negative results in different ethnic populations. The aim of this study was to test for association of C-159T functional promoter polymorphism with atopic asthma and serum IgE levels in northern and northwestern Indian populations. DNA was assayed for the CD14 C-159T polymorphism in a case-control study involving atopic asthmatics (n=187) and healthy normal controls (n=227), and in a family-based association study of 106 trios. The case-control study showed an association at the genotypic (P=0.0146) as well as the allelic level (P=0.0048). Moreover, we observed a deviation of allelic transmission from random proportions (P=0.024) in the transmission disequilibrium test analysis. When we analyzed our results for serum total IgE levels, against this polymorphism, we observed a difference at the genotypic (P=0.0026) as well as at the allelic level (P=0.0016) in a case-control study, whereas no association in the quantitative transmission disequilibrium test analysis was obtained. These findings provide suggestive evidence of association of the CD14 gene locus with atopic asthma in northern and northwestern Indian populations.

Adult↗

PubMed2004

Association of IL4 gene polymorphisms with asthma in North Indians.

BACKGROUND: Asthma is a complex airway disorder, and a number of genetic loci have been found to be associated with asthma. The 5q31-33 region is one of the most important loci linked to asthma and atopic disorders. However, association studies with candidate genes in this region, such as IL4, were inconclusive, as both positive and negative results were obtained in several populations studied. The aim of our case-control study was to determine the association between IL4 and asthma in North Indians. PATIENTS AND METHODS: Polymorphisms in the promoter and a dinucleotide repeat in the 2nd intron in IL4 were genotyped by sequencing and GeneScan analysis, respectively, in ethnically matched, unrelated patients (n = 171) and controls (n = 128), following the guidelines of the American Thoracic Society. RESULTS: The proximal promoter region of the IL4 gene was found to be invariant. Previously reported polymorphisms, -590 C/T and +33 C/T, were found to be absent in our population. The chi2 test using only large expected cell counts (more than 5% of the sample size) showed a significant association between allele size and disease status (chi2 = 38.08, d.f. = 6, p < 0.05). In addition, a significant difference was observed for the allele and genotype frequencies (p < 0.0005 and p = 0.0009, respectively) in the patient and the control groups using the Fisher-Freeman-Halton test. CONCLUSION: Our studies indicate that the promoter of the IL4 gene is invariant in our population. The case-control studies on the CA repeat polymorphism in the 2nd intron of the IL4 gene have shown interesting results and indicate the need for further family-based studies.

Adult↗

PubMed2004

Signal transducer and activator of transcription 6 haplotypes and asthma in the Indian population.

In this paper, we report for the first time the results of an investigation on the association of signal transducer and activator of transcription 6 (STAT6) with asthma in the Indian population. A novel polymorphic CA-repeat in the proximal promoter region [R1] and a previously identified CA-repeat in the 5'-untranslated region [R3] were genotyped, and haplotypes [R1_R3] were generated using PHASE software. The 16 repeat allele at the R1 locus was positively associated (P = 0.01) with asthma. The 15 and 16 repeat alleles at the R3 locus were positively (P < 10(-4)) and negatively (P < 10(-5)) associated with asthma, respectively. Further, the 17_15 (P = 0.0031) and 16_15 (P = 0.001) haplotypes were found to be positively associated with asthma, whereas 17_14, 24_16, and 23_16 were negatively associated (P < 10(-5)). It appears that the R3 and R1 loci together play a bigger role in asthma than either of them alone, and the R3 locus has a larger effect than the R1 locus. Although alleles at the R1 locus appeared to be associated with total serum immunoglobulin E level, the genotypes showed no association, and the R3 locus showed no effect. As no exonic variants of STAT6 are known as yet, repeat polymorphisms in the regulatory regions and their haplotypes could be important in deciphering the genetic role of STAT6 in asthma and atopy.

Adult↗

PubMed2004

1,4-dihydroxyxanthone modulates the adhesive property of endothelial cells by inhibiting intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin.

Cell adhesion molecules, particularly intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1) and E-selectin, play important roles in the recruitment of leukocytes to the site of inflammation. Blocking the expression of these molecules or preventing their interaction with the receptors has been shown to be important in controlling various inflammatory diseases. These cell adhesion molecules are induced on endothelial cells by various proinflammatory cytokines like IL-1beta and TNF-alpha and also by bacterial LPS. We demonstrate here that 1,4-Dihydroxyxanthone (1,4 DHX) inhibits the expression of cell adhesion molecules, such as ICAM-1, VCAM-1 and E-selectin, on endothelial cells in a concentration and time dependent manner. The inhibition by 1,4 DHX is reversible. On further analysis, our results also show that 1,4 DHX inhibits the adhesion of peripheral neutrophils to the endothelial cell monolayers. 1,4 DHX, therefore, could be used as a novel target for controlling various pathological conditions associated with upregulation of endothelial leukocyte adhesion molecules.

Antineoplastic Agents↗

PubMed2003

Diferuloylmethane inhibits neutrophil infiltration and improves survival of mice in high-dose endotoxin shock.

Gram-negative septic shock is a systemic inflammatory response of the body caused primarily by the cell wall component (lipopolysaccharide) of the gram-negative bacteria. During high-dose endotoxin shock, neutrophils infiltrate and accumulate in the liver, causing hepatocellular injury. Cell adhesion molecules, specifically intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), play an important role in the infiltration of neutrophils in the liver tissue. In this study, we demonstrate that diferuloylmethane exerts protective effect in high-dose endotoxin shock by improving survival and reducing the severity of endotoxin shock symptoms such as lethargy, diarrhea, and watery eyes following a challenge with lipopolysaccharide. We demonstrate here that diferuloylmethane inhibits the transmigration and infiltration of neutrophils from blood vessels to the underlying liver tissue and, hence, inhibits the damage to the tissue. Diferuloylmethane blocks the induced expression of ICAM-1 and VCAM-1 in liver and lungs. Diferuloylmethane, being a natural compound, may have few side effects and may be useful in attenuating multiple organ injury in pathological conditions arising due to excessive infiltration of neutrophils into the tissues.

Animals↗

PubMed2003

Curcumin attenuates allergen-induced airway hyperresponsiveness in sensitized guinea pigs.

Anti-asthmatic property of curcumin (diferuloylmethane), a natural product from the rhizomes of Curcuma longa, has been tested in a guinea pig model of airway hyperresponsiveness. We sensitized guinea pigs with ovalbumin (OVA) to develop certain characteristic features of asthma: allergen induced airway constriction and airway hyperreactivity to histamine. Guinea pigs were treated with curcumin during sensitization (to examine its preventive effect) or after developing impaired airways features (to examine its therapeutic effect). Status of airway constriction and airway hyperreactivity were determined by measuring specific airway conductance (SGaw) using a non-invasive technique, constant-volume body plethysmography. Curcumin (20 mg/kg body weight) treatment significantly inhibits OVA-induced airway constriction (p<0.0399) and airway hyperreactivity (p<0.0043). The results demonstrate that curcumin is effective in improving the impaired airways features in the OVA-sensitized guinea pigs.

Allergens↗

PubMed2003

Genetics of asthma: current research paving the way for development of personalized drugs.

Asthma is a complex genetic disorder involving the interplay between various environmental and genetic factors. In this review, efforts have been made to provide information on the recent advances in these areas and to discuss the future perspective of research in the area of developing personalized drugs using pharmacogenomic approach. Atopic asthma is found to be strongly familial, however the mode of inheritance is controversial. A large number of studies have been carried out and a number of candidate genes have been identified. In addition, a number of chromosomal regions have been identified using genome-wide scans, which might contain important unknown genes. It has been shown in studies carried out in different populations that the genetic predisposition varies with ethnicity. In other words, genes that are associated with asthma in one population may not be associated with asthma in another population. In addition to the involvement of multiple genes, gene-gene interactions play a significant role in asthma. The importance of environmental factors in asthma is beyond doubt. However, it remains controversial whether a cleaner environment or increased pollution is a trigger for asthma. Despite the increasing prevalence of the disorder, only a limited number of therapeutic modalities are available for the treatment. A number of novel therapeutic targets have been identified and drugs are being developed for better efficacy with less side-effects. With the rapid progress in the identification of genes involved in various ethnic populations combined with the availability in future of well-targeted drugs, it will be possible to have appropriate medicine as per the genetic make-up of an individual.

Anti-Asthmatic Agents↗

PubMed2002

Identification of single-nucleotide and repeat polymorphisms in two candidate genes, interleukin 4 receptor (IL4RA) and signal transducer and activator of transcription protein 6 (STAT6), for Th2-mediated diseases.

We report here the identification of 26 single-nucleotide polymorphisms (SNPs) spanning a total of 147 kb in two candidate genes, IL4RA and STAT6, for atopic disorders. Fourteen novel SNPs were found in our population. We also report the identification of three novel polymorphic (CA) repeat regions in these genes. No insertion/deletion polymorphisms in AluY elements were detected. The encoded proteins of these two genes are part of a single signaling pathway, and therefore, functional polymorphisms in these genes could potentially lead to higher risk and susceptibility to atopic disorders. We also examined the allelic frequency and haplotypes of these polymorphisms in a control population. These data will be potentially useful for association studies designed to investigate the role of these genes in atopic disorders such as asthma, eczema, and allergic rhinitis. This is the first report on the polymorphic content of these two genes in the Indian population.

Dinucleotide Repeats↗

PubMed2002

Canscora decussata promotes adhesion of neutrophils to human umbilical vein endothelial cells.

A regulated expression of cell adhesion molecules, such as ICAM-1, VCAM-1 and E-selectin, on endothelial cells is essentially required for immune surveillance. Cell adhesion molecules regulate the extravasation and migration of body's effector cells to the site of immune activation. Failure of expression of cell adhesion molecules leads to various pathological diseases as it impairs the individuals' ability to mount an inflammatory response. Our results demonstrate that an aqueous extract prepared from Canscora decussata (CdAqE), promotes the adhesion of peripheral neutrophils to human umbilical vein endothelial cells. The increased adhesion is as a result of induction of the expression of ICAM-1 and E-selectin on endothelial cells. CdAqE increases the expression of steady state transcript levels of these molecules as determined by RT-PCR. These results have implications for the usage of aqueous preparation of C. decussata for upregulation of cell adhesion molecule expression.

Cell Adhesion↗

PubMed2002

Synthesis, screening and quantitative structure-activity relationship (QSAR) studies of some glutamine analogues for possible anticancer activity.

We described the syntheses, biological activities and QSAR studies of 36 new 5-n-substituted-2-(substituted benzenesulphonyl) glutamines 6-41 with different substitutions. These compounds were designed as structural analogues of most reactive amino acid, 'glutamine' (GLN), especially in the tumor cells. They present the new basic lateral chains at R(5) position as well as different substitutions at 2', 3', 4', and 5' positions on the benzene ring. The synthesized compounds have been tested for antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice using percentage inhibition of tumor weight as inhibitory parameter. In order to elucidate the structural requirements for antitumor activity, quantitative structure-activity relationship (QSAR) studies have been performed using extra thermodynamic model of Hansch. QSAR equations showed that the electronic parameter (sigma) on the aromatic ring system, steric parameter (Es) and to some extent Sterimol length of the substituent (L) on the aliphatic side chain correlate significantly with the antitumor activity. Resonance factor occupies the major electronic contribution on the aromatic ring system to the activity.

Antineoplastic Agents↗

PubMed2002

Xanthones as inhibitors of microsomal lipid peroxidation and TNF-alpha induced ICAM-1 expression on human umbilical vein endothelial cells (HUVECs).

Xanthones bearing different functionalities, namely 1-hydroxyxanthone (1), 3-hydroxyxanthone (2), 1,4-dihydroxyxanthone (3), 2,6-dihydroxyxanthone (4), 1,2-diacetoxyxanthone (5), 2,6-diacetoxyxanthone (6), 3-methoxyxanthone (7), 1,3,7-trimethoxyxanthone (8) and 1,5-dihydroxy-6-methoxyxanthone (9) were synthesised and examined for their effect on nicotinamide adenine dinucleotide phosphate (NADPH)-catalysed liver microsomal lipid peroxidation and on tumour necrosis factor-alpha (TNF-alpha) induced expression of intercellular adhesion moledule-1 (ICAM-1) on endothelial cells, with a view to establish structure-activity relationship. Hydroxy- and acetoxyxanthones showed potent inhibitory effects on NADPH-catalysed lipid peroxidation and TNF-alpha induced expression of ICAM-1 on endothelial cells.

Animals↗

PubMed2002

Association of IFNG gene polymorphism with asthma in the Indian population.

Epidemiologic studies in India show that the prevalence of asthma is increasing, but no genetic studies have been reported on the Indian population thus far. We selected the IFNG locus on 12q21 as a candidate gene for asthma on the basis of its role in pathophysiology and positive linkage demonstrated in other populations. The aim of this study was to investigate association of a CA-repeat marker in this gene with asthma and total serum IgE levels in the North Indian population. The repeat region was PCR-amplified from patients and control subjects and analyzed through use of GeneScan. The distributions of allele sizes were found to be significantly different between patients and control subjects (Kolmogorov-Smirnov test, P < 10(-6)). Alleles 10 and 11 were found to be overrepresented in individuals with asthma, whereas alleles 13 and 15 were less likely in asthmatic individuals. We found that the CA-repeat polymorphism in the IFNG gene was significantly associated with total serum IgE levels (ANOVA, P < 10(-4) for control subjects and P =.0036 for patients). Furthermore, a previously reported promoter polymorphism at the -333 base pair position was not detected in our population. This is the first report on the association of a candidate gene with asthma from the Indian subcontinent.

Adult↗