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Biomedical subjects

V Reddy

Publications and source records attributed to V Reddy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Altered myosin light-chain phosphorylation in resting platelets from premenopausal women with diabetes.

Gender-related differences in the rate of coronary heart disease (CHD) between premenopausal women and men are greatly diminished in women with diabetes mellitus (DM). This may be related, in part, to altered platelet function in premenopausal diabetic women. Hyperglycemia may contribute to increase platelet aggregation through enhancement of oxidative stress, increased nitric oxide (NO) destruction, and increased myosin light-chain (MLC) phosphorylation (MLC-P). Accordingly, we investigated functional and biochemical parameters of platelet function in 32 women (14 premenopausal and postmenopausal controls and 18 age-matched patients with DM); platelet MLC-P and cyclic guanosine monophosphate ([cGMP] reflecting NO) were assessed. Other parameters including age, body mass index (BMI), waist to hip ratio, total cholesterol, and platelet count were not different in the control and diabetic groups. In the premenopausal women, baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP levels were similar in the two groups at baseline (22.7 +/- 3 fmol/mL in controls v 23.1 +/- 3 fmol/mL in diabetic subjects) and 3 minutes after insulin exposure. The platelet content of ascorbic acid (AA), an endogenous antioxidant compound, was elevated in premenopausal women with DM (P = .02) compared with the controls. Despite similar estradiol (beta,E2) levels, platelets of premenopausal women with DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an increase in platelet AA, as this suggests decreased platelet oxidative stress in this patient population. These observations indicate that an altered redox state and associated MLC-P of platelets does not contribute to enhanced platelet aggregation and CHD in premenopausal women with DM.

Adolescent↗
PubMed2001

Utilisation of different phosphorus sources in relation to their fluorine content for broilers and layers.

1. The relative utilisation of different phosphorus sources in relation to their fluorine (F) content was studied in commercial broilers (5 to 40 d) and White Leghorn layers (252 to 364 d). The phosphorus (P) sources tested were bonemeal (BM), low fluorine (LFRP) and high fluorine (HFRP) rock phosphates and a commercial mineral mixture (CMM). The P sources were incorporated in broiler and layer diets by replacing dicalcium phosphate (DCP) on a P basis. 2. The F contents of diets based on BM, LFRP, CMM and HFRP were 53, 365, 622 and 1383 mg/kg in the broiler experiment and 34, 242, 437 and 967 mg/kg in the layer experiment, respectively. F was not detected in DCP based diets. 3. In broilers, body weight gain, food intake, gain: food, P retention and serum inorganic P content on P sources (BM and LFRP) containing F up to 365 mg/kg diet were similar to those on DCP. Body weight gain, food intake, serum calcium and inorganic P contents and retention of P were depressed in groups fed on CMM and HFRP, which may have been due to the toxic effects of F (622 and 1383 mg/kg) present in diets based on these P sources. 4. Bone ash and its P content were not affected by feeding diets containing F up to 1383 mg/kg from various P sources. The amount of F deposited in tibia increased significantly with increases in dietary F concentration. 5. In layers, egg production and food intake were not affected by F up to 437 mg/kg in diets containing BM, LFRP or CMM as the sole source of supplemental P. Egg production and food intake were depressed significantly in layers given the diet containing 967 mg F/kg from HFRP. 6. Egg mass: food, egg weight, shell quality (shell thickness and shell weight) and serum calcium and inorganic P levels were not affected by F up to 967 mg/kg in diets containing different P sources. 7. It may be concluded that the performance of broilers and layers was not affected by feeding various P supplements with dietary levels of F up to 365 and 437 mg/kg, respectively. The reduced performance in broilers and layers observed with some of the P sources may have been due to poor availability of P and/or toxic effects of F (622 and 967 mg/kg, respectively).

Animals↗
PubMed2001

Transgenic overexpression of hepatocyte growth factor in the beta-cell markedly improves islet function and islet transplant outcomes in mice.

Recent advances in human islet transplantation have highlighted the need for expanding the pool of beta-cells available for transplantation. We have developed three transgenic models in which growth factors (hepatocyte growth factor [HGF], placental lactogen, or parathyroid hormone-related protein) have been targeted to the beta-cell using rat insulin promoter (RIP). Each displays an increase in islet size and islet number, and each displays insulin-mediated hypoglycemia. Of these three models, the RIP-HGF mouse displays the least impressive phenotype under basal conditions. In this study, we show that this mild basal phenotype is misleading and that RIP-HGF mice have a unique and salutary phenotype. Compared with normal islets, RIP-HGF islets contain more insulin per beta-cell (50 +/- 5 vs. 78 +/- 9 ng/islet equivalent [IE] in normal vs. RIP-HGF islets, P < 0.025), secrete more insulin in response to glucose in vivo (0.66 +/- 0.06 vs. 0.91 +/- 0.10 ng/ml in normal vs. RIP-HGF mice, P < 0.05) and in vitro (at 22.2 mmol/l glucose: 640 +/- 120.1 vs. 1,615 +/- 196.9 pg. microg protein(-1). 30 min(-1) in normal vs. RIP-HGF islets, P < 0.01), have two- to threefold higher GLUT2 and glucokinase steady-state mRNA levels, take up and metabolize glucose more effectively, and most importantly, function at least twice as effectively after transplantation. These findings indicate that HGF has surprisingly positive effects on beta-cell mitogenesis, glucose sensing, beta-cell markers of differentiation, and transplant survival. It appears to have a unique and unanticipated effective profile as an islet mass- and function-enhancing agent in vivo.

Animals↗
PubMed2001

Sharing laughter: the humour of pre-school children with Down syndrome.

Humour and laughter have often been portrayed as fundamentally cultural and social phenomena. They can be used to tell us about children's ability to engage socially and to understand others, but have rarely been explored for this purpose. The present paper summarises the results of a study of simple forms of humour in children with Down syndrome and with autism, two groups which are reported to differ in their sociality and interpersonal understanding. Sixteen children with Down syndrome and 19 children with autism, matched on non-verbal mental age, participated in a cross-sectional study. Parental reports and video-tapes of naturalistic interaction between parents and children were analysed to show that although there were no overall differences in the presence or frequency of child or parent laughter between the two groups, there were differences in what sorts of events were more likely to prompt child laughter, the extent to which child laughter was shared, and how the children responded to others' laughter. The children with Down syndrome were more likely than the children with autism to laugh at funny faces and socially inappropriate acts and less likely to laugh in strange or inexplicable situations, and more likely to laugh at shared events. They also responded to others' laughter with attention or smiles more, and tried to re-elicit it through acts of clowning. Children with Down syndrome are thus active participants in humour and laughter, sharing it at both an emotional and a cultural level.

Child Behavior↗
PubMed2000

Regulation of elastinolytic cysteine proteinase activity in normal and cathepsin K-deficient human macrophages.

Human macrophages mediate the dissolution of elastic lamina by mobilizing tissue-destructive cysteine proteinases. While macrophage-mediated elastin degradation has been linked to the expression of cathepsins L and S, these cells also express cathepsin K, a new member of the cysteine proteinase family whose elastinolytic potential exceeds that of all known elastases. To determine the relative role of cathepsin K in elastinolysis, monocytes were differentiated under conditions in which they recapitulated a gene expression profile similar to that observed at sites of tissue damage in vivo. After a 12-d culture period, monocyte-derived macrophages (MDMs) expressed cathepsin K in tandem with cathepsins L and S. Though cysteine proteinases are acidophilic and normally confined to the lysosomal network, MDMs secreted cathepsin K extracellularly in concert with cathepsins L and S. Simultaneously, MDMs increased the expression of vacuolar-type H(+)-ATPase components, acidified the pericellular milieu, and maintained extracellular cathepsin K in an active form. MDMs from a cathepsin K-deficient individual, however, retained the ability to express, process, and secrete cathepsins L and S, and displayed normal elastin-degrading activity. Thus, matrix-destructive MDMs exteriorize a complex mix of proteolytic cysteine proteinases, but maintain full elastinolytic potential in the absence of cathepsin K by mobilizing cathepsins L and S.

Cathepsin B↗
PubMed2000

Three-dimensional fold of the human AQP1 water channel determined at 4 A resolution by electron crystallography of two-dimensional crystals embedded in ice.

Here, we present a three-dimensional (3D) density map of deglycosylated, human erythrocyte aquaporin 1 (AQP1) determined at 4 A resolution in plane and approximately 7 A resolution perpendicular to the bilayer. The map was calculated by analyzing images and electron diffraction patterns recorded from tilted (up to 60 degrees ), ice-embedded, frozen-hydrated 2D crystals of AQP1 in lipid bilayer membranes. This map significantly extends the findings related to the folding of the AQP1 polypeptide chain determined by us at a lower, 7 A by approximately 20 A, resolution. The solvent-accessible volume within a monomer has a vestibular architecture, with a narrow, approximately 6.5 A diameter constriction near the center of the bilayer, where the location of the water-selective channel is postulated to exist. The clearly resolved densities for the transmembrane helices display the protrusions expected for bulky side-chains. The density in the interior of the helix barrel (putative NPA box region) is better resolved compared to our previous map, suggesting clearer linkage to some of the helices, and it may harbor short stretches of alpha-helix. At the bilayer extremities, densities for some of the inter-helix hydrophilic loops are visible. Consistent with these observed inter-helix connections, possible models for the threading of the AQP1 polypeptide chain are presented. A preferred model is deduced that agrees with the putative locations of a group of aromatic residues in the amino acid sequence and in the 3D density map.

Aquaporin 1↗
PubMed2000

G-CSF modulates cytokine profile of dendritic cells and decreases acute graft-versus-host disease through effects on the donor rather than the recipient.

Allogeneic peripheral blood stem cell transplantation (PBSCT) is increasingly used instead of bone marrow transplantation, particularly in HLA identical sibling pairs. Despite the presence of significantly increased numbers of T cells in the PBSC graft, acute graft-versus-host disease (GVHD) is not increased. We have investigated whether granulocyte-colony stimulating factor (G-CSF) administration to PBSCT recipients, both with and without donor G-CSF pretreatment, further modulates acute GVHD in a murine model of PBSCT. Recipients of G-CSF mobilized splenocytes showed a significantly improved survival (P<0.001) and a reduction in GVHD score and serum LPS levels compared with control recipients. G-CSF treatment of donors, rather than recipients, had the most significant effect on reducing levels of tumor necrosis factor (TNFalpha) 7 days after transplantation. As a potential mechanism of the reduction in TNFalpha, we demonstrate G-CSF decreased dendritic cells TNFalpha, and interleukin-12 production to lipopolysaccharide. In conclusion, G-CSF modulates GVHD predominantly by its effects on donor cells, reducing the production of TNFalpha. G-CSF treatment of bone marrow transplantation recipients, without pretreatment of the donor, does not have an impact on acute GVHD.

Animals↗
PubMed2000

Fine-needle aspiration of scalp lesions.

A variety of inflammatory and neoplastic scalp lesions are encountered in surgical pathology. However, the literature on fine-needle aspirations (FNAs) of the scalp is exceedingly rare. We report on a series of 70 FNAs involving cutaneous and subcutaneous lesions on the scalp. A total of 70 fine-needle aspirations of cutaneous and subcutaneous scalp lesions was reviewed to identify patterns of metastasis to the scalp and to demonstrate the effectiveness of FNA in diagnosing these lesions. There were 42 male and 28 female patients, ranging in age from 29-91 yr (mean, approximately 61 yr). Sixty-one patients had a previous history of malignancy. Of these aspirates, 59 were neoplastic, consistent with the patient's known primary. One case was an abscess, and the remaining case was unsatisfactorvy for cytologic evaluation. Follow-up biopsy revealed granulomatous inflammation. The most common primary tumor to metastasize to the scalp was lung carcinoma, which was seen in 18 cases, followed by hematopoietic malignancies in 14 cases. Melanoma was identified in 6 cases, head and neck tumors in 5 cases, renal malignancies in 4 cases, gastrointestinal tumors in 3 cases, sarcoma in 3 cases, breast and prostate malignancy in 2 cases each, and an olfactory neuroblastoma and meningioma in 1 case each. The remaining 9 aspirates were from patients who did not have a previous history of malignancy. These included 6 benign aspirates consisting of 3 epidermal inclusion cysts, 2 lipomas, and 1 neurofibroma. Two aspirates were malignant and included 1 primary squamous-cell carcinoma and 1 metastatic adenocarcinoma of unknown origin. The remaining case was unsatisfactory for cytologic evaluation. Follow-up biopsy of this lesion showed noncaseating granulomas. Of the aspirates from patients with a previous history of malignancy, 97% were neoplastic. Lung carcinoma and hematopoietic malignancies were the most common neoplasms that metastasized to the scalp. Since the scalp is a common site for metastasis, awareness of this fact is useful to both oncologists and dermatologists. It must be understood that FNA can provide a rapid and accurate diagnosis in the evaluation of scalp masses.

Adult↗