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Biomedical subjects

A M Kumar

Publications and source records attributed to A M Kumar.

At least 19 recordsLinked to original sources
PubMed2003

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy.

Cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism. Single nucleotide polymorphisms (SNPs) and haplotypes in the CETP gene were determined in 98 patients with untreated dyslipidemias and analyzed for associations with plasma CETP and plasma lipids before and during statin treatment. Individual CETP SNPs and haplotypes were both significantly associated with CETP enzyme mass and activity. However, only certain CETP haplotypes, but not individual SNPs, significantly predicted the magnitude of change in HDL cholesterol (HDL-C) and triglycerides. After adjusting for covariates and multiple testing, the TTCAAA haplotype showed a gene-dose effect in predicting the HDL-C increase (P=0.03), while the TTCAAAGGG and AAAGGG haplotypes predicted a decrease in triglycerides (P=0.04 both). This is the first study to demonstrate that SNP haplotypes derived from allelic SNP combinations in the CETP gene were more informative than single SNPs in predicting the response to lipid-modifying therapy with statins.

Aged↗
PubMed2001

Haplotype variation and linkage disequilibrium in 313 human genes.

Variation within genes has important implications for all biological traits. We identified 3899 single nucleotide polymorphisms (SNPs) that were present within 313 genes from 82 unrelated individuals of diverse ancestry, and we organized the SNPs into 4304 different haplotypes. Each gene had several variable SNPs and haplotypes that were present in all populations, as well as a number that were population-specific. Pairs of SNPs exhibited variability in the degree of linkage disequilibrium that was a function of their location within a gene, distance from each other, population distribution, and population frequency. Haplotypes generally had more information content (heterozygosity) than did individual SNPs. Our analysis of the pattern of variation strongly supports the recent expansion of the human population.

Alleles↗
PubMed2001

Ventilation/perfusion scintigraphy.

V/Q imaging is often very useful in evaluating patients in whom a PE is suspected. A normal scan result can be used to exclude embolism and a high likelihood ratio scan can be used to make the diagnosis of PE. Most patients with PE do not have high likelihood ratio scans; therefore, it is important to pursue this diagnosis in patients with intermediate likelihood ratio scans and in the appropriate clinical setting for patients with the low likelihood ratio scans. In patients with parenchymal chest x-ray abnormalities who are likely to fall into the intermediate category, it can be more appropriate to use CT angiography instead of V/Q scintigraphy. This strategy probably increases the fraction of scans with high diagnostic utility.

Humans↗
PubMed2001

Regulation of HEMA1 expression by phytochrome and a plastid signal during de-etiolation in Arabidopsis thaliana.

The synthesis of 5-aminolevulinic acid (ALA) is the rate-limiting step for the formation of all plant tetrapyrroles, including chlorophyll and heme, and regulation of ALA synthesis is therefore critical to plant development. Glutamyl-tRNA reductase (GluTR) is the first committed enzyme of this pathway and is encoded by a small family of nuclear HEMA genes. Here, we have used transgenic Arabidopsis (Arabidopsis thaliana L. Col) lines expressing chimeric HEMA1 promoter:gusA fusion genes, combined with RNA gel blot analyses, to characterise the light-mediated regulation of the Arabidopsis HEMA1 gene during de-etiolation. HEMA1 was expressed strongly, but not exclusively, in photosynthetic tissues and was shown to be light regulated at the transcriptional level by the phytochrome family of photoreceptors acting in both the far-red high irradiance and low fluence response modes. The HEMA2 gene, which is expressed only in roots of seedlings, was not light regulated. Analysis of truncated HEMA1 promoter constructs demonstrated that a -199/+252 promoter fragment was sufficient to confer full light-responsiveness to gusA expression. This fragment contained GT-1/I-box and CCA-1 binding sites that are implicated as the light-responsive cis elements. Both the full-length and truncated HEMA1 promoters required the presence of intact chloroplasts for full expression, consistent with previous indications that light and plastid factor signals converge to co-ordinately regulate expression of photosynthesis-related nuclear genes. These results provide the most comprehensive analysis to date of the light-regulation of a tetrapyrrole biosynthetic gene and support a direct link between regulation of HEMA1 transcription and chlorophyll accumulation during seedling de-etiolation.

Aldehyde Oxidoreductases↗
PubMed2001

Cerebrospinal fluid 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in HIV-1 infection.

Reduced level of serotonin (5-hydroxytryptamine, 5-HT) in humans has been associated with a number of mental health and behavioral problems including depression, aggression, violence, sexual dysfunctions, sleep and eating disorders. Even though among HIV-1-infected individuals, prevalence of mental health and behavioral problems are common, their relationship with central nervous system serotonin functions is not clearly understood. This investigation was carried out to study the status of CSF 5-HT in HIV-1+ subjects (n = 21), in the early stage of infection, and HIV-1- control subjects (n = 24). Samples of CSF were obtained by lumbar puncture and were analyzed for 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), using high-performance liquid chromatography equipped with electrochemical detector. Levels of CSF 5-HT were significantly lower in the HIV-1+ group compared to the HIV-1- group. There was no significant difference in the CSF 5-HIAA levels between the two groups. In both groups, however, there was a significant correlation between CSF 5-HT and 5-HIAA. In the HIV-1 + group, although CSF 5-HT level was significantly negatively correlated with serostatus, there was no correlation between either CSF 5-HT or 5-HIAA levels and CD4 cell number or any behavioral measures evaluated in this study, including Beck's Depression Inventory and state/trait anxiety scores. These data suggest that HIV-1 infection affects the CNS 5-HT status with no significant association with measures of depression and anxiety, at least in the early stage of infection.

Adult↗
PubMed2001

Client donation program for acquiring dogs and cats to teach veterinary gross anatomy.

A donor program for procuring dogs and cats to meet the needs of anatomical instruction was initiated six years ago at Tufts University School of Veterinary Medicine. The program was initiated in order to comply with state regulations that preclude the use of shelter animals and to satisfy ethical objections of students and faculty. The donor program has successfully met the animal needs for teaching gross anatomy and, in addition, provides opportunities to integrate clinical perspectives and ethics beginning from the first year of veterinary education.

Anatomy↗
PubMed2000

Nefazodone treatment of adolescent depression: an open-label study of response and biochemistry.

OBJECTIVE: The purpose of this study was to find whether nefazodone, effective in adult depression, might be similarly improve symptoms of adolescent depression. Secondary purpose was to relate platelet serotonin content to response, and to find if nefazodone's effect on platelet content was similar to that of the SSRIs. METHOD: 10 adolescents meeting DSMIV criteria for major depression received up to 400 mg of nefazodone for an eight week period. Response was assessed at baseline, 1, 2, 4, and 8 weeks by BDI and HDRS; platelet serotonin (5HT) content was obtained at baseline and final visit (for two dropouts, this was done at last visit, i.e., week 4). RESULTS: In LOCF analysis, significant improvement was found in both HDRS (20.9 to 8.9, p = .01) and BDI (24.6 to 10.2, p = .01). Eight of nine patients with available data showed increases in platelet 5HT content (.02). In seven patients of eight completers with available data, there was a nonsignificant trend for patients with platelet 5HT baseline greater than 30 ng/10(8) platelets to show a greater change in HDRS than those with a baseline of less than 30 ng/10(8) platelets (p = .07). CONCLUSIONS: Further double-blind study of nefazodone in adolescent depression is indicated; nefazodone appears to increase platelet 5HT content.

Adolescent↗
PubMed2000

Neogenesis of pancreatic endocrine cells in copper-deprived rat models.

Transplantation of progenitor cells for regeneration of islet cells could prove invaluable in the treatment of diabetes mellitus. This study provides evidence that in rats maintained on a copper-deficient diet containing the copper-chelating agent tetraethylenepentamine pentahydrochloride, regeneration of single alpha and beta endocrine cells in the ductules and acinar tissue of the adult rat pancreata occurred. These regenerated cells both in the ductules and acinar tissue stained positive for glucagon and insulin similar to cells within the islets and in addition to being reactive to proliferative cellular nuclear antigen, an intracellular marker of active proliferation. In contrast, the control group pancreata did not show any evidence of islet regeneration, proliferation, or proliferative cellular nuclear antigen reactivity pre- or posttransplantation. Transplantation of digested pancreatic tissues from the copper-deficient group into the spleen of syngeneic diabetic rats reversed diabetes, and this was confirmed histologically by demonstrating cells within ductules that stained positively for insulin. This study concludes that copper deprivation contributes to the neogenesis of pancreatic alpha and beta cells in the ductules and acinar tissue of adult pancreas in rat model and that transplanted stem cells maintain their functional capacity in the recipient after transplantation.

Animals↗
PubMed2000

Antisense HEMA1 RNA expression inhibits heme and chlorophyll biosynthesis in arabidopsis.

5-aminolevulinic acid (ALA) is a precursor in the biosynthesis of tetrapyrroles including chlorophylls and heme. The formation of ALA involves two enzymatic steps which take place in the chloroplast in plants. The first enzyme, glutamyl-tRNA reductase, and the second enzyme, glutamate-1-semialdehyde-2,1-aminomutase, are encoded by the nuclear HEMA and GSA genes, respectively. To assess the significance of the HEMA gene for chlorophyll and heme synthesis, transgenic Arabidopsis plants that expressed antisense HEMA1 mRNA from the constitutive cauliflower mosaic virus 35S promoter were generated. These plants exhibited varying degrees of chlorophyll deficiency, ranging from patchy yellow to total yellow. Analysis indicated that these plants had decreased levels of chlorophyll, non-covalently bound hemes, and ALA; their levels were proportional to the level of glutamyl-tRNA reductase expression and were inversely related to the levels of antisense HEMA transcripts. Plants that lacked chlorophyll failed to survive under normal growth conditions, indicating that HEMA gene expression is essential for growth.

Aldehyde Oxidoreductases↗
PubMed1999

Music therapy increases serum melatonin levels in patients with Alzheimer's disease.

CONTEXT: Music therapy is known to have healing and relaxing effects. Although these effects appear to be mediated by release of neurotransmitters and neurohormones, the specific neurohormonal systems involved have not been fully investigated. OBJECTIVE: To assess the effects of a music therapy intervention on concentrations of melatonin, norepinephrine, epinephrine, serotonin, and prolactin in the blood of a group of patients with Alzheimer's disease. DESIGN: Blood samples were obtained before initiating the therapy, immediately at the end of 4 weeks of music therapy sessions, and at 6 weeks follow-up after cessation of the sessions. SETTING: Miami Veterans Administration Medical Center, Miami, Fla. PATIENTS: 20 male inpatients with Alzheimer's disease. INTERVENTION: 30- to 40-minute morning sessions of music therapy 5 times per week for 4 weeks. MAIN OUTCOME MEASURES: Changes in melatonin, norepinephrine, epinephrine, serotonin, and prolactin following music therapy. RESULTS: Melatonin concentration in serum increased significantly after music therapy and was found to increase further at 6 weeks follow-up. A significant increase was found between baseline values and data recorded after the music therapy sessions as well as at 6 weeks follow-up. Norepinephrine and epinephrine levels increased significantly after 4 weeks of music therapy, but returned to pretherapy levels at 6 weeks follow-up. Serum concentration of prolactin and platelet serotonin levels remained unchanged after 4 weeks of music therapy and at 6 weeks follow-up. CONCLUSION: Increased levels of melatonin following music therapy may have contributed to patients' relaxed and calm mood.

Aged↗
PubMed1998

Cocaine abuse and HIV-1 infection: epidemiology and neuropathogenesis.

The epidemiology of cocaine abuse and potential relationships of cocaine withdrawal to human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) are discussed. Neuroendocrinological changes in HIV-1 infection of the central nervous system (CNS) are discussed with the relevant impact of cocaine abuse. HIV-1 load in the brain tissue of infected substance users is described along with possible associations with neuropathology and HAD. Finally, the molecular epidemiology and sequence heterogeneity of HIV-1 and their implications for neuropathogenesis are summarized. The complex context of addressing cocaine abuse in the setting of HIV-1 infection appears more tractable when decomposed into its components.

AIDS Dementia Complex↗
PubMed1998

Long-term function and survival of elderly donor kidneys transplanted into young adults.

BACKGROUND: Traditionally, elderly donor kidneys have not been widely accepted for transplantation on the assumption of inferior performance. However, the United Network for Organ Sharing reports an increase in the number of elderly donors from less than 2% in 1982 to 24% in 1995. This trend is commensurate with the increase of older dialysis patients and an overall increase in the elderly population in the United States (1). Optimal utilization of these kidneys is essential to overcome the acute organ shortage. METHODS: In this study, we transplanted 25 kidneys from elderly donors (ages 56-72 years) into young adult recipients (ages 20-50 years) (group 1) over a 4-year period. We compared the results with matched recipients of young adult donor kidneys (group 2) with regard to long-term kidney function and graft survival. A pretransplant biopsy of elderly donor kidneys was carried out and a frozen section report was obtained. Only those kidneys showing glomerulosclerosis of less than 20% were accepted for transplantation. All cadaveric kidneys were preserved in University of Wisconsin solution. RESULTS: Pretransplant biopsies of elderly donor kidneys showed structural deficits, which included glomerulosclerosis in 85%, arteriolar and/or mesangial thickening in 75%, and interstitial lymphocyte infiltration in 30%. The mean serum creatinine was 2.4+/-0.74, 2.2+/-0.56, and 2.9+/-0.76 mg/100 ml in group 1 and 1.5+/-0.55, 2.3+/-2.24, and 1.7+/-0.62 in group 2 at 1, 3, and 5 years, respectively. The patient survival was 92%, 92%, and 88% in group 1, and 100%, 100%, and 100% in group 2 at 1, 3, and 5 years, respectively. The graft survival was 80%, 64%, and 56% in group 1 and 100%, 96%, and 88% in group 2 at similar time intervals. The differences in the serum creatinine and graft survival between the two groups were statistically significant (P < 0.05). CONCLUSIONS: Most of the elderly donor kidneys with structural deficits transplanted into young adults provided suboptimal function and inferior long-term graft survival. To maximize the utilization and optimize the survival of elderly donor kidneys, we propose transplantation of these kidneys into age-matched recipients with similar physiological requirements as those of donors, with regard to kidney function.

Adult↗
PubMed1998

Peripheral serotonin levels in women: role of aging and ethnicity.

Serotonin has been implicated to play an important role in regulating emotions and behavior, and it is well accepted that the platelet serotonergic system mirrors the presynaptic central serotonergic system. Since prevalence of psychiatric problems increases with age and women are known to be more vulnerable than men, the present investigation was carried out to study the relationship between serotonin activity and age in women. Levels of serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in platelets and plasma in women (n = 49) aged 40-84 years (30 women aged 40-60 years and 19 women aged 61-84 years). There was a significant age difference between the two groups (mean: 47.6 +/- 5.91 years in the younger and 73.0 +/- 6.83 years in the older women, respectively, p < 0.00001). Platelet 5-HT as well as 5-HIAA levels were significantly higher in older women as compared to those in the younger women (89.41 +/- 21.95 ng/10(8) platelets in younger vs. 112.9 +/- 36.07 in older women, p < 0.02, and 1.20 +/- 1.10 in younger vs. 2.19 +/- 1.88 ng/10(8) platelets in older women, p < 0.05, respectively). Pearson correlation coefficients determined in the combined group (n = 49) showed a significant positive correlation between platelet 5-HT and age (r = 0.31, p < 0.03). Plasma 5-HT levels on the other hand were lower in older women compared to those in the younger women (4.50 +/- 3.20 in younger vs. 1.04 +/- 1.28 ng/ml plasma in older women, p < 0.0001) and a significant negative correlation was observed between plasma 5-HT and age (r = -0.44, p < 0.002). Plasma 5-HIAA concentration did not differ between the two groups. Platelet 5-HT levels in the younger group were independent of ethnicity. Since high serotonin activity has also been associated with psychiatric problems, our results of increased concentration of platelet 5-HT as well as 5-HIAA with age may have implications in predisposing aging women to behavioral/psychiatric problems.

Adult↗
PubMed1998

Differential expression and selective localization of vascular permeability factor/vascular endothelial growth factor in the rat uterus during the estrous cycle.

This study examines the expression of the multi-functional cytokine, vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in the rat uterus during early proestrus, proestrus, estrus and diestrus. Groups of ovariectomized or hypophysectomized rats served as endocrine controls. Expression of VPF/VEGF mRNA was 2-fold greater in uteri during proestrus and estrus than in other phases of the estrous cycle. In situ hybridization techniques indicated that VPF/VEGF mRNA expression was confined to the luminal epithelium during proestrus, but shifted to the stromal compartment during estrus. Ovariectomized, hypophysectomized or diestrus rats exhibited scattered localization of VPF/VEGF mRNA among glandular epithelium and endometrial stromal compartments. Although VPF/VEGF mRNA was expressed throughout the estrous cycle, but in different compartments of the endometrium depending on the stage of the estrous cycle, VPF/VEGF protein expression appears to be restricted to the epithelial compartment during proestrus and estrus. Results indicate that circulating levels of gonadal steroids and LH may be associated with the differential expression of VPF/VEGF mRNA and its translation activity in the endometrium during different stages of the estrous cycle.

Animals↗