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Biomedical subjects

R Ray

Publications and source records attributed to R Ray.

At least 19 recordsLinked to original sources
PubMed2006

Association of OPRM1 A118G variant with the relative reinforcing value of nicotine.

RATIONALE: The endogenous opioid system has been implicated in substance abuse and response to pharmacotherapies for nicotine and alcohol addiction. We examined (1) the association of the functional OPRM1 A118G variant with the relative reinforcing value of nicotine and (2) the main and interacting effects of the mu-opioid receptor antagonist naltrexone on nicotine reinforcement. METHODS: In a within-subject, double-blind human laboratory study, 30 smokers of each OPRM1 genotype (A/A vs. A/G or G/G) participated in two experimental sessions following 4 days of orally administered naltrexone 50 mg or placebo. Participants completed a validated assessment of the relative reinforcing value of nicotine. This cigarette choice paradigm assesses self-administration of 0.6 mg nicotine vs. 0.05 mg (denicotinized) cigarettes after a brief period of nicotine abstinence. RESULTS: The relative reinforcing value of nicotine (number of nicotine cigarette puffs) was predicted by a significant OPRM1 by gender interaction. Among women, the low-activity G allele (A/G and G/G) was associated with a reduced reinforcing value of nicotine; among male smokers, there was no association with genotype. Smokers carrying a G allele were also significantly less likely to differentiate the nicotine vs. denicotinized cigarettes by subjective ratings of satisfaction and strength. No evidence for an effect of naltrexone on nicotine reinforcement was found in the overall sample or in the genotype or gender subgroups. CONCLUSIONS: This study provides initial evidence for an association of the OPRM1 A118G variant with nicotine reinforcement in women.

Adaptation, Psychological↗
PubMed2006

Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p < 0.001). This suggests that use of ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

Animals↗
PubMed2006

A study for evaluation of contaminant transport characteristics through fine-grained soil.

Transport of soluble toxic substances through porous media lead to some significant geoenvironmental problems, for example, leachate migration from municipal and industrial solid waste resulting from unregulated disposal. Advection, dispersion, diffusion, and decay are reported to be the principal mechanisms in such phenomena. Geotechnical properties of the soil also play a significant role in this deterioration. In the present study, laboratory tests were conducted to formulate an appropriate method for assessment of migration of metal ions, such as nickel, through the soil. Relevant kinetic and process parameters, such as aquifer data, surface area, dielectric constant, pH of zero point charge (pHzpc), and permeability were also studied. One-dimensional mathematical modeling was used to describe the dynamics of the process. The present investigation was carried out at an ash pond site of a thermal power plant situated in West Bengal, India.

Environmental Monitoring↗
PubMed2005

Reproductive history, occupational exposures, and thyroid cancer risk among women textile workers in Shanghai, China.

OBJECTIVES: Thyroid cancer risk has been previously associated with increased age at first pregnancy and history of miscarriage. Occupational risk factors for thyroid cancer, with the exception of radioactive iodine, have not been well investigated. We conducted a case-cohort study nested in a cohort of 267,400 female textile workers in Shanghai, China, who had been followed for cancer incidence during 1989-1998. METHODS: The analysis included 130 incident thyroid cases and 3,187 subcohort non-cases. Reproductive history was determined by questionnaire at baseline. Historical exposures were reconstructed from work history and information on factory processes and exposures. Cox proportional hazards analysis was performed to estimate hazard ratios (HR) for reproductive factors and occupational exposures. RESULTS: Associations were observed between thyroid cancer and employment in jobs with 10 or more years of benzene exposure (HR 6.43, 95% CI: 1.08, 38) and formaldehyde exposure (HR 8.33, 95% CI: 1.16, 60). Administration workers also had an increased risk (HR 1.56, 95% CI: 1.08, 2.25). No associations between examined reproductive factors and thyroid cancer were observed in this study. CONCLUSIONS: Despite statistically imprecise risk estimates, the findings suggest potential associations with some occupational chemical exposures in this cohort of textile workers.

Adult↗
PubMed2005

Electrocardiographic and biochemical evidence for the cardioprotective effect of vitamin E in doxorubicin-induced acute cardiotoxicity in rats.

BACKGROUND/AIMS: Cardiotoxicity is a major side effect limiting the use of doxorubicin, a potent chemotherapeutic agent, in the treatment of pediatric neoplastic diseases. The effect of vitamin E in doxorubicin-induced cardiotoxicity in rats has been studied. METHODS: Eighteen Wistar male rats (age 60 - 100 days, weighing 175 - 260 g) were divided into three groups of six: group A (controls); group B (doxorubicin-treated rats); and group C (pretreatment with a high dose of vitamin E followed by doxorubicin treatment). The weights of the rats were measured daily. The rats were sacrificed seven days after the last dose of doxorubicin injection by an overdose of ether. Electrocardiogram (ECG) tracings were recorded before sacrificing the rats. The ECG tracings were then evaluated for rate and rhythm disorders by assessing the PR, ST, and QT intervals. In group B rats ECG tracings were taken three days after the completion of doxorubicin treatment, while in group C rats they were taken at the end of 2 weeks of vitamin E pretreatment and again 3 days after the completion of doxorubicin treatment. Serum levels of creatine phosphokinase (CPK-MB), lactic dehydrogenase (LDH), and serum glutamic oxaloacetic transaminase (SGOT) were assessed from an intracardiac blood sample taken at the time of sacrificing the rat. RESULTS: Mean weight ranged from 205 - 226 g. Mean total dose of doxorubicin in groups B and C ranged from 36 - 38 mg. The PR intervals in the three groups were recorded as 0.006, 0.070, 0.057 s for groups A, B, and C, respectively (p = 0.0024) and the QT interval as 0.023, 0.120, 0.088 s in groups A, B, and C, respectively (p = 0.00089). The ST elevation due to doxorubicin toxicity was significantly reversed by vitamin E treatment. The difference in the levels of CPK-MB and LDH between the three groups was found to be statistically significant. Serum SGOT levels also varied between the three groups but were not statistically significant. CONCLUSION: Vitamin E pretreatment prevented the PR, QT, and ST segment changes caused by doxorubicin. Vitamin E treatment helped to decrease the levels of CPK-MB and LDH that were increased due to myocardial damage caused by the doxorubicin. There is sufficient evidence to believe that vitamin E protects the rat myocardium from doxorubicin-induced damage.

Animals↗
PubMed2005

Thrombotic thrombocytopenic purpura associated with Human Immunodeficiency Virus infection.

Thrombotic thrombocytopenic purpura (TTP) belongs to the group of diseases called Thrombotic microangiopathies (TMA). While several triggering conditions are known, often none is apparent in the individual case. We report a patient presenting with TTP that was associated with a Human Immunodeficiency Virus (HIV) infection, with its consequent diagnostic, therapeutic and prognostic implications. Further, our case had individual clinical features that were of interest within the TTP-HIV subgroup.

Adult↗
PubMed2002

Ketamine dependence.

Ketamine hydrochloride is a safe and rapid-acting non-opioid, lipid soluble anaesthetic with a short elimination half-life that is used for medical and veterinary purposes. It produces a state of "dissociative anaesthesia", probably from action on N-methyl-D-aspartate (NMDA) receptors. The psychotropic effects of ketamine range from dissociation and depersonalization to psychotic experiences and include a sensation of feeling light, body distortion, absence of time sense, novel experiences of cosmic oneness and out-of-body experiences. Abuse of ketamine has been reported, the typical abuser being an individual who uses multiple drugs and has some contact with medical agencies. This case demonstrates the effects of large doses of ketamine in a person with polysubstance abuse. The case also highlights development of significant tolerance to ketamine without prominent withdrawal symptoms. Caution in use of ketamine is reiterated in light of its abuse liability.

Adult↗
PubMed2002

Experimental studies on synergism between aminoglycosides and the antimicrobial antiinflammatory agent diclofenac sodium.

The antiinflammatory agent diclofenac sodium (Dc) exhibited remarkable antibacterial effects both in vitro and in vivo. Fifteen different bacteria sensitive to Dc as well as to a number of common antibiotics were tested for synergistic effects in vitro. Disc diffusion test with Dc and aminoglycosides assessed by stringent computation showed clear-cut synergism. Synergism between Dc and streptomycin (Sm) was found to be statistically significant (p < or = 0.01) when compared with their individual effects. By the checkerboard assessment procedure, the fractional inhibitory concentration (FIC) index of this combination was found to be 0.49, confirming synergism. The mouse protective capacity of this combination was then evaluated in vivo against S. typhimurium as the virulent infecting bacterium, and the size of bacterial load determined from infected autopsied animals. Statistical analysis by Student's 't' test suggested this drug combination is highly synergistic; synergism was also noted between Dc and other aminoglycosides.

Aminoglycosides↗
PubMed2002

Colour Doppler and grey scale ultrasound features of HIV-related vascular aneurysms.

Atypical aneurysms of large elastic arteries owing to human immunodeficiency virus (HIV) vasculopathy are a well described complication of acquired immunodeficiency syndrome (AIDS). However, there are no reports describing the ultrasound features of these lesions. We performed a retrospective review of ultrasound images of 12 patients presenting with 39 HIV-related aneurysms over a 2 year period. Of these there were a total of 12 patients with symptomatic lesions comprising the superficial femoral artery (n=5), the origin of the internal carotid artery (n=3), the popliteal artery (n=2), the common femoral artery (n=1) and the common iliac artery (n=1). The remainder were asymptomatic and were demonstrated radiologically. The ultrasound features of large symptomatic HIV-related femoral and carotid aneurysms were typical of pseudoaneurysms with a defect or "blow-out" in the vessel wall and turbulent pulsatile flow. Of note was the presence of marked thickening of the vessel adjacent to the aneurysm and hyperechoic "spotting" of the arterial wall. These ultrasound features described may be unique to HIV vasculopathy.

Adult↗
PubMed2002

Giant cell arteritis--a rare cause of fever of unknown origin in India.

Giant cell arteritis (GCA) is a systemic large vessel vasculitis. Awareness of various manifestations of GCA is essential for early recognition and prompt treatment so as to prevent complications like blindness. GCA is one of the relatively common causes of fever of unknown origin (FUO) in the elderly in USA and Europe. However, no such cases have been reported from India. A case of GCA presenting as FUO is reported and the literature reviewed.

Fever↗
PubMed2002

Potentiality of a new compound for in vitro differentiation between halophilic and non-halophilic vibrios.

Sensitivity of 21 halophilic vibrios and 16 clinical isolates of non-halophilic vibrios was determined against a new possible antivibrio agent, a pyrimidine analogue, 4, 6-dimethylpyrimidine -2-thiol (4,6-DMPT). It appeared to be a vibriocidal agent, having a mean MIC and MBC of 32 microg/ml for halophilic strains and 64 microg/ml for non-halophilic strains and an LD50 of 300 mg/Kg body weight of mice. Thus, 4,6-DMPT may help an in vitro distinction between halophilic and non-halophilic vibrios. Sensitivity of these strains was also studied with respect to pteridine, crystal violet and Tween 80 hydrolysis as further markers distinguishing between these 2 groups which could also be differentiated by their growth on TCBS or/and CLED media.

Animals↗
PubMed2001

Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).

Steroid hormones are central regulators of a variety of biological processes. According to the free hormone hypothesis, steroids enter target cells by passive diffusion. However, recently we demonstrated that 25(OH) vitamin D(3) complexed to its plasma carrier, the vitamin D-binding protein, enters renal proximal tubules by receptor-mediated endocytosis. Knockout mice lacking the endocytic receptor megalin lose 25(OH) vitamin D(3) in the urine and develop bone disease. Here, we report that cubilin, a membrane-associated protein colocalizing with megalin, facilitates the endocytic process by sequestering steroid-carrier complexes on the cellular surface before megalin-mediated internalization of the cubilin-bound ligand. Dogs with an inherited disorder affecting cubilin biosynthesis exhibit abnormal vitamin D metabolism. Similarly, human patients with mutations causing cubilin dysfunction exhibit urinary excretion of 25(OH) vitamin D(3). This observation identifies spontaneous mutations in an endocytic receptor pathway affecting cellular uptake and metabolism of a steroid hormone.

Animals↗
PubMed2001

Elevated levels of high-mobility-group chromosomal proteins, HMGA1, in murine skin carcinoma.

The high-mobility-group, HMGA1 (formerly HMGI(Y)) chromosomal proteins are known to be involved in gene regulation and their high expression is associated with neoplastic transformation of cells and metastatic tumor progression. Here, we present our results on the expression of HMGA1 in murine skin carcinoma as detected by acid-urea electrophoresis, reverse-phase high-performance liquid chromatography and Western blot. The enhanced expression of HMGA1 proteins directly correlates with the extent of cellular atypia and neoplastic changes noticed in the histopathology of tumor and suggest a potential use of these proteins as marker for determining the grade of skin tumor.

Acetic Acid↗
PubMed2001

Hepatitis C virus core protein modulates the interferon-induced transacting factors of Jak/Stat signaling pathway but does not affect the activation of downstream IRF-1 or 561 gene.

Hepatitis C virus (HCV) has a propensity to cause chronic infection, with a low proportion of patients exhibiting a sustained response to interferon-alpha (IFNalpha) therapy. An earlier report suggested that HCV inhibits IFNalpha-induced signal transduction through the Jak/Stat pathway by preventing the formation of the transacting factor ISGF3 complex, although the effect on downstream pathway and the specific viral protein responsible for inhibition of IFNalpha-mediated signal transduction were not elucidated. HCV core protein displays a number of intriguing functional properties and has been implicated in virus-mediated pathogenesis. In this study, we have analyzed the effect of core protein upon IFNalpha- or IFNgamma-induced regulation of the Jak/Stat signaling pathway. HCV core protein expression exhibited a reduced Stat1 expression in IFN-treated mammalian cells. A gel retardation assay suggested a reduced level of formation of the transacting factors, GAF and ISGF3, in IFN-treated cells. Further studies from protein expression and RNase protection assay revealed that the reduced level of GAF or ISGF3 formation could be attributed to modulation of Stat1 protein expression, an important player for innate immunity in host defense mechanism. However, these modulatory effects did not interfere with the activation of the downstream effector genes, IRF-1 and 561, in IFN-treated cells. Stable transfectants of cells after introduction of a plasmid DNA encoding both the structural and the nonstructural proteins of HCV also exhibited a similar effect. Taken together, these results suggest that although expression of the core protein alone or with other HCV proteins modulate transacting factors of Jak/Stat signaling pathway, expression of the downstream effector genes IRF-1 and 561 remains unaffected upon IFN treatment and may contribute to host defense mechanism.

DNA-Binding Proteins↗
PubMed2001

Hepatitis C virus core protein: intriguing properties and functional relevance.

Hepatitis C virus (HCV) often causes a prolonged and persistent infection, and an association between hepatocellular carcinoma (HCC) and HCV infection has been noted. The pathogenesis of liver damage is at least in part related to virus-mediated factors. Understanding the molecular basis of pathogenesis is a major challenge in gaining insight into HCV-associated disease progression. Recent experimental evidence using HCV cloned genomic regions suggests that the core protein has numerous functional activities. These include its likely role in encapsidation of viral RNA, a regulatory effect on cellular and unrelated viral promoters, interactions with a number of cellular proteins, an modulatory role in programmed cell death or apoptosis under certain conditions, involvement in cell growth promotion and immortalization, induction of HCC in transgenic mice, and a possible immunoregulatory role. These intriguing properties suggest that the core protein, in concert with cellular factors, may contribute to pathogenesis during persistent HCV infection.

Animals↗
PubMed2001

Serum induction of the fibroblast growth factor-binding protein (FGF-BP) is mediated through ERK and p38 MAP kinase activation and C/EBP-regulated transcription.

The fibroblast growth factor-binding protein (FGF-BP) modulates FGF activity through binding and release from the extracellular matrix. Consequently, the expression of FGF-BP in certain tumor types is a rate-limiting regulator of FGF-mediated angiogenesis. FGF-BP is upregulated in squamous cell carcinoma by treatment with mitogens such as EGF or TPA. In this study, we investigated the regulation of FGF-BP gene expression by serum. Treatment of serum-starved ME-180 cells with fetal bovine serum (FBS) resulted in a rapid increase in steady-state levels of FGF-BP mRNA and in the rate of FGF-BP gene transcription. Serum induction of FGF-BP mRNA was not mediated through EGF receptor activation but was dependent on PKC, as well as ERK kinase (MEK) and p38 MAP kinase activation. Promoter analysis showed that C/EBP is the main promoter element required for the serum response. Unlike EGF-activation of FGF-BP, transcriptional induction by serum is not significantly regulated through the AP-1 or E-box sites in the promoter. These results illustrate differences between the mechanism of induction in response to serum and EGF.

Blood Physiological Phenomena↗
PubMed2001

Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity.

Vitamin D-binding protein (DBP) is a multi-functional serum protein that is converted to vitamin D-binding protein-macrophage activating factor (DBP-maf) by post-translational modification. DBP-maf is a new cytokine that mediates bone resorption by activating osteoclasts, which are responsible for resorption of bone. Defective osteoclast activation leads to disorders like osteopetrosis, characterized by excessive accumulation of bone mass. Previous studies demonstrated that two nonallelic mutations in the rat with osteopetrosis have independent defects in the cascade involved in the conversion of DBP to DBP-maf. The skeletal defects associated with osteopetrosis are corrected in these mutants with in vivo DBP-maf treatment. This study evaluates the effects of various forms of DBP-maf (native, recombinant, and 25-hydroxyvitamin D(3) bound) on osteoclast function in vitro in order to determine some of the structural requirements of this protein that relate to bone resorbing activities. Osteoclast activity was determined by evaluating pit formation using osteoclasts, isolated from the long bones of newborn rats, incubated on calcium phosphate coated, thin film, Ostologic MultiTest Slides. Incubation of osteoclasts with ex vivo generated native DBP-maf resulted in a dose dependent, statistically significant, activation of the osteoclasts. The activation was similar whether or not the vitamin D binding site of the DBP-maf was occupied. The level of activity in response to DBP-maf was greater than that elicited by optimal doses of other known stimulators (PTH and 1,25(OH(2)D(3)) of osteoclast function. Furthermore, another potent macrophage activating factor, interferon--gamma, had no effect on osteoclast activity. The activated form of a full length recombinant DBP, expressed in E. coli showed no activity in the in vitro assay. Contrary to this finding, baculovirus-expressed recombinant DBP-maf demonstrated significant osteoclast activating activity. The normal conversion of DBP to DBP-maf requires the selective removal of galactose and sialic acid from the third domain of the protein. Hence, the differential effects of the two recombinant forms of DBP-maf is most likely related to glycosylation; E. coli expressed recombinant DBP is non-glycosylated, whereas the baculovirus expressed form is glycosylated. These data support the essential role of glycosylation for the osteoclast activating property of DBP-maf.

Amino Acid Sequence↗