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Biomedical subjects

R Haque

Publications and source records attributed to R Haque.

At least 19 recordsLinked to original sources
PubMed2006

Pregnancy outcomes, infant mortality, and arsenic in drinking water in West Bengal, India.

Between 2001 and 2003, the authors studied pregnancy outcomes and infant mortality among 202 married women in West Bengal, India. Reproductive histories were ascertained using structured interviews. Arsenic exposure during each pregnancy, including all water sources used, was assessed; this involved measurements from 409 wells. Odds ratios for spontaneous abortion, stillbirth, neonatal mortality, and infant mortality were estimated with logistic regression based on the method of generalized estimating equations. Exposure to high concentrations of arsenic (> or =200 microg/liter) during pregnancy was associated with a sixfold increased risk of stillbirth after adjustment for potential confounders (odds ratio (OR) = 6.07, 95% confidence interval (CI): 1.54, 24.0; p = 0.01). Arsenic-related skin lesions were found in 12 women who had a substantially increased risk of stillbirth (OR = 13.1, 95% CI: 3.17, 54.0; p = 0.002). The odds ratio for neonatal death was 2.81 (95% CI: 0.73, 10.8). No association was found between arsenic exposure and spontaneous abortion (OR = 1.01, 95% CI: 0.38, 2.70) or overall infant mortality (OR = 1.33, 95% CI: 0.43, 4.04). This study adds to the limited evidence that exposure to high concentrations of arsenic during pregnancy increases the risk of stillbirth. However, there was no indication of the increased rates of spontaneous abortion and overall infant mortality that have been reported in some studies.

Arsenic Poisoning↗
PubMed2006

Adherence-blocking vaccine for amebiasis.

The Gal/GalNAc lectin is a candidate vaccine antigen for an amebiasis vaccine due to its mediation of parasite adherence to the human intestine, because partial immunity in humans is associated with a mucosal IgA response against it, and because it is effective as a vaccine against amebic colitis in the murine model. The LecA domain of the Gal/GalNAc lectin contains neutralizing antibody epitopes. LecA contains the active site of the lectin (the carbohydrate recognition domain or "CRD") and has been an effective vaccine antigen in animal models of amebic colitis and liver abscess. Research needs include production of the LecA domain of the Gal/GalNAc lectin by a process that can be transferred to cGMP and optimization for immunogenicity, using adjuvants such as alum, MF59 or QS-21 adjuvants. Accomplishing this will enable testing of the ability of LecA immunizations to protect from amebic colitis in humans.

Animals↗
PubMed2006

Occult alveolar haemorrhage in pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension that affects predominantly post-capillary pulmonary vessels. A major concern with PVOD is the poor response to available therapies and the risk of pulmonary oedema with continuous intravenous epoprostenol. The present authors hypothesised that alveolar haemorrhage may be a characteristic feature of pulmonary veno-occlusive disease, as compared with other forms of pulmonary arterial hypertension that predominantly involve pre-capillary pulmonary arteries. This paper reports a series of 19 patients with either PVOD (n = 8) or idiopathic pulmonary arterial hypertension (IPAH; n = 11) who underwent bronchoalveolar lavage. Cytological analyses were performed and differential counts were made on Perls-stained preparations. The Golde score was used to assess alveolar haemorrhage. As compared with IPAH, PVOD was characterised by a higher percentage of haemosiderin-laden macrophages (40+/-37 versus 3+/-6%), resulting in elevated Golde scores (81+/-88 versus 4+/-10). It was concluded that occult alveolar haemorrhage is a common feature of pulmonary veno-occlusive disease. Detecting occult alveolar haemorrhage may be of interest in the diagnostic approach of pulmonary veno-occlusive disease.

Adult↗
PubMed2005

Immuno-epidemiology of Ascaris lumbricoides infection in a high transmission community: antibody responses and their impact on current and future infection intensity.

The role of the humoral immune system in human infection with Ascaris lumbricoides remains unclear. This study documents an epidemiological investigation in a highly endemic community in Vietnam, whereby serum antibody levels were assessed before treatment and after a 6-month reinfection period. These data were examined by correlation with infection status using an age-structured approach in an attempt to help shed light on the role of the humoral immune response. The first part of this study characterized levels of all serum antibody isotypes from the community in response to antigens of both adult and larval A. lumbricoides. Data were assessed in terms of their relation to host age and infection intensity with the aim to provide a broadly detailed account of immune responses to the parasite. In the second part, antibody responses to both life-stages of A. lumbricoides in serum samples collected before anthelmintic chemotherapy were analysed in relation to intensity of re-infection with the parasite 6 months following treatment. The results suggest that antibody responses may not confer protection from current infection or re-infection with A. lumbricoides and may not serve as reliable indicators of future infection intensity. Our results thereby lend support to the theory that immunity to A. lumbricoides may not be based on the humoral immune system.

Adolescent↗
PubMed2005

Molecular cloning, localization and circadian expression of chicken melanopsin (Opn4): differential regulation of expression in pineal and retinal cell types.

The avian retina and pineal gland contain autonomous circadian oscillators and photo-entrainment pathways, but the photopigment(s) that mediate entrainment have not been definitively identified. Melanopsin (Opn4) is a novel opsin involved in entrainment of circadian rhythms in mammals. Here, we report the cDNA cloning of chicken melanopsin and show its expression in retina, brain and pineal gland. Like the melanopsins identified in amphibians and mammals, chicken melanopsin is more similar to the invertebrate retinaldehyde-based photopigments than the retinaldehyde-based photopigments typically found in vertebrates. In retina, melanopsin mRNA is expressed in cells of all retinal layers. In pineal gland, expression was strong throughout the parenchyma of the gland. In brain, expression was observed in a few discrete nuclei, including the lateral septal area and medial preoptic nucleus. The retina and pineal gland showed distinct diurnal expression patterns. In pineal gland, melanopsin mRNA levels were highest at night at Zeitgeber time (ZT) 16. In contrast, transcript levels in the whole retina reached their highest levels in the early morning (ZT 0-4). Further analysis of melanopsin mRNA expression in retinal layers isolated by laser capture microdissection revealed different patterns in different layers. There was diurnal expression in all retinal layers except the ganglion cell layer, where heavy expression was localized to a small number of cells. Expression of melanopsin mRNA peaked during the daytime in the retinal pigment epithelium and inner nuclear layer but, like in the pineal, at night in the photoreceptors. Localization and regulation of melanopsin mRNA in the retina and pineal gland is consistent with the hypothesis that this novel photopigment plays a role in photic regulation of circadian function in these tissues.

Amino Acid Sequence↗
PubMed2005

Application of an improved method for the recombinant k 39 enzyme-linked immunosorbent assay to detect visceral leishmaniasis disease and infection in Bangladesh.

Several serology-based immunoassays are used to diagnose visceral leishmaniasis (VL), a chronic protozoan parasitic disease caused by the Leishmania donovani complex. These tests are primarily designed to diagnose the most severe clinical form of VL, known as kala-azar. However, leishmanial infection is frequently asymptomatic and may manifest only as a positive serologic response or positive leishmanin skin test. We modified a previously described enzyme-linked immunosorbent assay (ELISA) that detects patient antibodies reactive with the recombinant Leishmania protein K39 (rK39) to confirm suspected kala-azar and to detect asymptomatic infection in a community study in Bangladesh. With the inclusion of a standard curve on each ELISA plate, the rK39 ELISA was more repeatable (kappa coefficient of agreement=0.970) and more reliable compared to the original method (kappa=0.587, P<0.001). The cutoff point for a positive antibody response was chosen based on the 99th percentile of the ELISA distribution for the negative-control sera. However, we found that sera from all patients with active kala-azar yielded values more than twice the magnitude of this cutoff. Using receiver-operator characteristic curves, we determined a second cutoff value predictive of kala-azar. Using these criteria, the sensitivity and specificity of the modified ELISA for kala-azar were 97.0% and 98.9%, respectively, for sera from our study population. We hypothesize that individuals with antibody levels greater than the 99th percentile of the negative controls but less than the cutoff point for kala-azar have asymptomatic leishmanial infections.

Animals↗
PubMed2003

Treatment of lentigo maligna with topical imiquimod.

A published case report and anecdotal experience suggested that topical imiquimod is an effective treatment for stage 0 melanoma (lentigo maligna). To gauge the efficacy of this therapy, we undertook a trial of topical imiquimod in 30 subjects with histologically confirmed lentigo maligna. Thirty subjects with lentigo maligna were recruited for an open-labelled efficacy trial with daily topical application of imiquimod 5% cream for 3 months. Study subjects were enrolled from the Dermatology service of the University of Oklahoma, the Oklahoma City Veteran's Administration Hospital Dermatology service and from referrals for the study from other practitioners. In order to determine an initial response rate, a four-quadrant biopsy was carried out on all patients 1 month after cessation of treatment, targeting the most clinically and dermatoscopically suspicious areas. Of 28 evaluable subjects who have completed the 3-month treatment phase, 26 (93%) were complete responders and two were treatment failures at the time of the 4-quadrant biopsy. Over 80% of the 28 subjects that completed treatment have been followed for more than 1 year with no relapses. The results of this study demonstrate that topical imiquimod produces a high complete response rate in lentigo maligna when applied daily for 3 months.

Adjuvants, Immunologic↗
PubMed2003

Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide-induced biochemical toxicity.

Walnut (Juglans regia L.) is extensively used in traditional systems of medicine for treatment of various ailments. It is described as an anticancer, tonic, blood purifier and detoxifier agent. The present study was undertaken to investigate modulatory effects of walnut extract on the toxicity of an anticancer drug, cyclophosphamide (CP) with special reference to protection against disruption of drug metabolizing and antioxidant enzymes. Plant extract+CP group animals showed restoration in the level of cytochrome P450 (CYP) content and in the activities of glutathione S-transferase (GST), glutathione peroxidase (GP) and catalase (CAT) in both liver and kidneys. But plant extract restored the activity of superoxide dismutase (SOD) and the level of reduced glutathione (GSH) in the kidneys only when compared with CP-treated animals. Plant extract treatment alone caused significant reduction in the content of CYP in the kidneys mainly. The extract showed a significant increase in the level of GSH and in the activities of GP in both the tissues and CAT in liver only, whereas no significant change was observed in the activities of GST and SOD. CP treatment resulted in a significant (P < 0.01) increase in the lipid peroxidation (LPO) in the liver and kidneys compared with controls, while the extract+CP treated group showed a significant decrease in the LPO in liver and kidneys when compared with the CP-treated group. The study shows that the use of J. regia extract might be helpful in abrogation of CP toxicity during the chemotherapy.

Animals↗
PubMed2001

Delineation of the minimal catalytic domain of human Galbeta1-3GalNAc alpha2,3-sialyltransferase (hST3Gal I).

The CMP-Neu5Ac:Galbeta1-3GalNAc alpha2,3-sialyltransferase (ST3Gal I, EC 2.4.99.4) is a Golgi membrane-bound type II glycoprotein that catalyses the transfer of sialic acid residues to Galbeta1-3GalNAc disaccharide structures found on O-glycans and glycolipids. In order to gain further insight into the structure/function of this sialyltransferase, we studied protein expression, N-glycan processing and enzymatic activity upon transient expression in the COS-7 cell line of various constructs deleted in the N-terminal portion of the protein sequence. The expressed soluble polypeptides were detected within the cell and in the cell culture media using a specific hST3Gal I monoclonal antibody. The soluble forms of the protein consisting of amino acids 26-340 (hST3-Delta25) and 57-340 (hST3-Delta56) were efficiently secreted and active. In contrast, further deletion of the N-terminal region leading to hST3-Delta76 and hST3-Delta105 gave also rise to various polypeptides that were not active within the transfected cells and not secreted in the cell culture media. The kinetic parameters of the active secreted forms were determined and shown to be in close agreement with those of the recombinant enzyme already described (H. Kitagawa, J.C. Paulson, J. Biol. Chem. 269 (1994)). In addition, the present study demonstrates that the recombinant hST3Gal I polypeptides transiently expressed in COS-7 cells are glycosylated with complex and high mannose type glycans on each of the five potential N-glycosylation sites.

Amino Acid Sequence↗
PubMed2001

Amebiasis and mucosal IgA antibody against the Entamoeba histolytica adherence lectin in Bangladeshi children.

Amebiasis is the third leading parasitic cause of death worldwide, and it is not known whether immunity is acquired from a previous infection. An investigation was done to determine whether protection from intestinal infection correlated with mucosal or systemic antibody responses to the Entamoeba histolytica GalNAc adherence lectin. E. histolytica colonization was present in 0% (0/64) of children with and 13.4% (33/246) of children without stool IgA anti-GalNAc lectin antibodies (P= .001). Children with stool IgA lectin-specific antibodies at the beginning of the study had 64% fewer new E. histolytica infections by 5 months (3/42 IgA(+) vs. 47/227 IgA(-); P= .03). A stool antilectin IgA response was detected near the time of resolution of infection in 67% (12/18) of closely monitored new infections. It was concluded that a mucosal IgA antilectin antibody response is associated with immune protection against E. histolytica colonization. The demonstration of naturally acquired immunity offers hope for a vaccine to prevent amebiasis.

Animals↗
PubMed2001

Regulation of cAMP by light and dopamine receptors is dysfunctional in photoreceptors of dystrophic retinal degeneration slow(rds) mice.

cAMP levels in dark and light were studied in dystrophic retinal degeneration slow(rds) mice, which carry a mutation in the rds/peripherin gene. cAMP levels were measured in vivo, in freshly isolated retinas, and in vitro in the presence of glutamate, which confines light modulation to photoreceptors. Experiments were conducted on young animals, when significant numbers of viable photoreceptor cells are present. In vivo levels of cAMP are higher in illuminated rds/rds retinas than levels measured in normal BALB/c retinas. Light-evoked down-regulation of cAMP levels was observed in vitro in normal photoreceptors. These measurements were made in the presence of the cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine; therefore, they reflect an inhibition of cAMP formation. In contrast, light had no effect on cAMP formation in photoreceptors of mutant mice, measured under identical conditions. Thus, elevated levels of cAMP in rds/rds retinas in vivo result from abnormalities in cAMP synthesis in the mutant photoreceptor cells. In addition to regulation by light, cAMP formation in photoreceptor cells is regulated by dopamine, acting through dopamine D4 receptors. A dopamine D2/D4 receptor agonist, quinpirole, reduced cAMP levels in dark-adapted normal retinas in vitro, but not in rds/rds retinas. Our data indicate that alterations in a signal transduction pathway that leads to inhibition of adenylyl cyclase might underlie the abnormalities in cAMP levels in mutant rds/rds retinas. Heterozygous rds/+ photoreceptors demonstrated a normal pattern of light-evoked and quinpirole-mediated down-regulation of cAMP. Thus, partial expression of the normal phenotype is sufficient to render normal characteristics of cAMP regulation to the photoreceptors of the heterozygous mouse. The data obtained in the present study might be relevant to the understanding of photoreceptor pathology of patients with peripherin/rds mutations.

Adenylyl Cyclases↗
PubMed2001

Entamoeba histolytica: genetic diversity of clinical isolates from Bangladesh as demonstrated by polymorphisms in the serine-rich gene.

The varied organ tropisms and clinical presentations of infection by Entamoeba histolytica have stimulated interest in the role of parasite genetic diversity in virulence. We investigated genetic diversity among 54 E. histolytica isolates from Bangladesh by analyzing polymorphism in the serine-rich gene by nested PCR on DNA extracted from stool and liver aspirate pus. We detected both size and restriction site polymorphisms among the isolates within this endemic area. A combination of the nested PCR results and the AluI digestion of the PCR products examined yielded 25 distinct DNA banding patterns among the 42 stool isolates and an additional 9 distinct patterns among the 12 liver abscess isolates. Approximately half of the isolates had unique polymorphisms. Interestingly, the majority of E. histolytica from the liver had polymorphisms which were not present in intestinal isolates from the same geographic area. These data are consistent with the existence of genetic differences between E. histolytica which cause intestinal and those which cause hepatic disease. We conclude that there is genetic diversity within E. histolytica isolates from an endemic population as reflected in serine-rich E. histolytica protein gene polymorphism. The correlation of genetic differences with the pathogenic potential of E. histolytica strains and the implications of genetic diversity for the immunoprophylaxis of amebiasis require further study.

Amino Acid Sequence↗
PubMed2001

Effect of endosulfan on antioxidants of freshwater fish Channa punctatus Bloch: 1. Protection against lipid peroxidation in liver by copper preexposure.

Effect of a single exposure of endosulfan (5 ppb) on catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), and reduced glutathione (GSH) of liver, kidney, and gill of a freshwater fish (Channa punctatus Bloch) were evaluated after 24 h of treatment. Endosulfan exposure resulted in a significant induction (p < 0.05-0.001) of GPx, GST activity, and GSH levels in all the organs. However, CAT activity was found to be significantly decreased (p < 0.01-0.001). Lipid peroxidation (LPO) values were also determined in liver, kidney, and gill and a significant increase in LPO values (p < 0.05-0.01) was observed in all the organs. We also investigated whether preexposure to low concentration of copper (10 ppb) for 4 weeks has any protective effect against endosulfan-induced oxidative damage. In copper-acclimatized endosulfan-exposed fish, a significant decrease in GPx (p < 0.001), GST (p < 0.05), GSH (p < 0.001) levels, and LPO (p < 0.01) was observed in the liver, whereas CAT activity was increased significantly (p < 0.001). However, kidney and gill did not show any significant alterations in antioxidant levels. The results of this study demonstrate that endosulfan induces peroxidative damage in liver, kidney, and gill in response to which levels of antioxidant were modulated. However, when fish preacclimatized to copper were exposed to endosulfan, protection against oxidative damage was observed only in the liver. It is proposed that measurement of antioxidants in fish tissues may prove to be useful in biomonitoring of exposure to aquatic pollutants.

Animals↗
PubMed2001

Protective effect of Cassia occidentalis L. on cyclophosphamide-induced suppression of humoral immunity in mice.

Cassia occidentalis L. (Kasaundi) is a widely used medicinal plant. Earlier, we have shown that it possesses antimutagenic activity against benzo[a]pyrene (BaP) and cyclophosphamide (CP)-induced mutagenicity in mice. In this study, we investigated if this plant could also provide protection against CP-induced immunosuppression in animal models. Swiss albino male mice were treated per os with the aqueous extract of C. occidentalis (100 mg/kg, body weight (b.w.)) for 14 days. Cyclophosphamide was given intraperitoneally in a single dose of 50 mg/kg b.w. Body weight, relative organ weight, lymphoid organ cellularity, hemagglutination titre (HT), plaque forming cell (PFC) assay and quantitative hemolysis of SRBC (QHS) were studied in these animals. CP, as expected, showed suppressive effects on lymphoid organ weight and cellularity and other parameters of humoral immunity. Plant extract treatment itself produced no toxicity. The administration of plant extract to CP-exposed animals resulted in improved humoral responses. C. occidentalis treatment significantly (P<0.01) enhanced PFC response in CP-treated animals. In QHS assay, also C. occidentalis showed protection in CP-treated animals. Bone marrow cell counts, which were reduced in CP-treated animals, were reversed significantly (p<0.01) to normal levels in CP+ plant extract group animals. In our earlier study, we found that C. occidentalis modulated hepatic drug metabolizing enzymes. It is suggested that by a similar mechanism, it may be influencing the hematotoxic and immunotoxic responses of cyclophosphamide.

Animals↗
PubMed2001

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice.

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs in spite of its toxic side effects including immunotoxicity, hematotoxicity, mutagenicity and a host of others. The present study was undertaken to assess the protective effects of total aqueous extract of a medicinal plant, Indian gooseberry (Emblica officinalis Gaertn.) in mice treated with CP. These protective effects were studied on immunological parameters and kidney and liver antioxidants. Plant extract treatment at a dose of 100 mg/kg body weight per os (p.o.) for 10 days resulted in the modulation of these parameters in normal as well as CP (50 mg/kg)-treated animals. Plant extract in particular was very effective in reducing CP-induced suppression of humoral immunity. Plant extract treatment in normal animals modulated certain antioxidants of kidney and liver. In CP-exposed animals, plant pretreatment provided protection to antioxidants of kidney. Not only were the reduced glutathione levels significantly (p<0.001) increased but plant extract treatment resulted in restoration of antioxidant enzymes in CP-treated animals. It is suggested that E. officinalis or its medicinal preparations may prove to be useful as a component of combination therapy in cancer patients under CP treatment regimen.

Adjuvants, Immunologic↗
PubMed2000

Diurnal metabolism of dopamine in dystrophic retinas of homozygous and heterozygous retinal degeneration slow (rds) mice.

Dopamine metabolism was studied in dystrophic retinal degeneration slow (rds) mice which carry a mutation in the rds/peripherin gene. RDS mutations in humans cause several forms of retinal degeneration. Dopamine synthesis and utilization were analyzed at various time points in the diurnal cycle in homozygous rds/rds retinas which lack photoreceptor outer segments and heterozygous rds/+ retinas which have short malformed outer segments. Homozygous retinas exhibited depressed dopamine synthesis and utilization while the heterozygous retina retained a considerable level of activity which was, nevertheless, significantly lower than that of normal retinas. By one year, heterozygous rds/+ retinas which had lost half of the photoreceptors still maintained significant levels of dopamine metabolism. Normal characteristics of dopamine metabolism such as a spike in dopamine utilization at light onset were observed in mutant retinas. However, light intensity-dependent changes in dopamine utilization were observed in normal but not rds/+ retinas. The findings of this study suggest that human patients with peripherin/rds mutations, or other mutations that result in abnormal outer segments that can still capture light, might maintain light-evoked dopamine metabolism and dopamine-dependent retinal functions during the progression of the disease, proportional to remaining levels of light capture capabilities. However, visual deficits due to reduced light-evoked dopamine metabolism and abnormal patterns of dopamine utilization could be expected in such diseased retinas.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Diurnal metabolism of dopamine in the mouse retina.

Dopamine is an important retinal neurotransmitter and neuromodulator that regulates key diurnal cellular and physiological functions. In the present study we carried out a comprehensive analysis of dopamine metabolism during the light phase of the diurnal cycle and evaluated the presence of diurnal and circadian rhythms of dopaminergic activity in the mouse retina. Steady-state levels of dopamine did not change significantly between the dark phase (night) and the light phase (day) of the diurnal cycle, nor did they change between early and late points in the day. Dopamine synthesis and utilization, however, revealed significant alterations between the night and day and between early and late time points in the day. A spike in synthesis and utilization was measured immediately after light onset at the end of the night. Subsequently, dopamine synthesis and utilization partially declined and remained stable throughout the remainder of the day at a level that was significantly higher than that at night. The burst of dopamine synthesis and utilization at the beginning of the day is entirely light evoked and not driven by a circadian clock. Similarly, there was no circadian rhythm in dopamine synthesis and utilization in mice kept in constant darkness. This daily pattern of dopaminergic activity may impact upon a variety of temporally regulated retinal events. Moreover, these data will provide a basis for evaluating the role of dopamine in retinal pathology in mouse models of retinal degeneration where mutations affect light perception.

3,4-Dihydroxyphenylacetic Acid↗