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Biomedical subjects

A Kulkarni

Publications and source records attributed to A Kulkarni.

At least 19 recordsLinked to original sources
PubMed2000

Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation.

We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in alpha-galactosidase A (alpha-gal A) knockout mice, a model of Fabry disease. C57BL/6 mice treated twice daily for 3 days with D-threo-1-ethylendioxyphenyl-2-palmitoylamino-3-pyrrolidi no-propanol (D-t-EtDO-P4) showed a concentration-dependent decrement in glucosylceramide levels in kidney, liver, and spleen. A single intraperitoneal injection of D-t-EtDO-P4 resulted in a 55% reduction in renal glucosylceramide, consistent with rapid renal glucosylceramide metabolism. A concentration-dependent decrement in renal and hepatic globotriaosylceramide levels was observed in alpha-Gal A(-) males treated for 4 weeks with D-t-EtDO-P4. When 8-week-old alpha-Gal A(-) males were treated for 8 weeks with 10 mg/kg twice daily, renal globotriaosylceramide fell to below starting levels, consistent with an alpha-galactosidase A-independent salvage pathway for globotriaosylceramide degradation. Complications observed with another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, including weight loss and acellularity of lymphatic organs, were not observed with D-t-EtDO-P4. These data suggest that Fabry disease may be amenable to substrate deprivation therapy.

1-Deoxynojirimycin↗
PubMed1999

Heterogeneity of coronary heart disease risk factors in Indian, Pakistani, Bangladeshi, and European origin populations: cross sectional study.

OBJECTIVE: To compare coronary risk factors and disease prevalence among Indians, Pakistanis, and Bangladeshis, and in all South Asians (these three groups together) with Europeans. DESIGN: Cross sectional survey. SETTING: Newcastle upon Tyne. PARTICIPANTS: 259 Indian, 305 Pakistani, 120 Bangladeshi, and 825 European men and women aged 25-74 years. MAIN OUTCOME MEASURES: Social and economic circumstances, lifestyle, self reported symptoms and diseases, blood pressure, electrocardiogram, and anthropometric, haematological, and biochemical measurements. RESULTS: There were differences in social and economic circumstances, lifestyles, anthropometric measures and disease both between Indians, Pakistanis, and Bangladeshis and between all South Asians and Europeans. Bangladeshis and Pakistanis were the poorest groups. For most risk factors, the Bangladeshis (particularly men) fared the worst: smoking was most common (57%) in that group, and Bangladeshis had the highest concentrations of triglycerides (2.04 mmol/l) and fasting blood glucose (6.6 mmol/l) and the lowest concentration of high density lipoprotein cholesterol (0.97 mmol/l). Blood pressure, however, was lowest in Bangladeshis. Bangladeshis were the shortest (men 164 cm tall v 170 cm for Indians and 174 cm for Europeans). A higher proportion of Pakistani and Bangladeshi men had diabetes (22.4% and 26.6% respectively) than Indians (15.2%). Comparisons of all South Asians with Europeans hid some important differences, but South Asians were still disadvantaged in a wide range of risk factors. Findings in women were similar. CONCLUSION: Risk of coronary heart disease is not uniform among South Asians, and there are important differences between Indians, Pakistanis, and Bangladeshis for many coronary risk factors. The belief that, except for insulin resistance, South Asians have lower levels of coronary risk factors than Europeans is incorrect, and may have arisen from combining ethnic subgroups and examining a narrow range of factors.

Adult↗
PubMed1999

Sensitivity of human subjects to head-related transfer-function phase spectra.

Head-related transfer functions (HRTFs) for human subjects in anechoic space were modeled with modified phase spectra, including minimum-phase-plus-delay, linear-phase, and reversed-phase-plus-delay functions. The overall (wide-band) interaural time delay (ITD) for the modeled HRTFs was made consistent with that of the empirical HRTFs by setting the position-dependent, frequency-independent delay in the HRTF for the lagging ear. Signal analysis of the minimum-phase-plus-delay reconstructions indicated that model HRTFs deviate from empirical HRTF measurements maximally for contralateral azimuths and low elevations. Subjects assessed the perceptual validity of the model HRTFs in a four-interval, two-alternative, forced-choice discrimination paradigm. Results indicate that monaural discrimination performance of subjects was at chance for all three types of HRTF models. Binaural discrimination performance was at chance for the linear-phase HRTFs, was above chance for some locations for the minimum-phase-plus-delay HRTFs, and was above chance for all tested locations for the reversed-phase-plus-delay HRTFs. An analysis of low-frequency timing information showed that all of these results are consistent with efficient use of interaural time differences in the low-frequency components of the stimulus waveforms. It is concluded that listeners are insensitive to HRTF phase spectra as long as the overall ITD of the low-frequency components does not provide a reliable cue. In particular, the minimum-phase-plus-delay approximation to the HRTF phase spectrum is an adequate approximation as long as the low-frequency ITD is appropriate. These results and conclusions are all limited to the anechoic case when the HRTFs correspond to brief impulse responses limited to a few milliseconds.

Adult↗
PubMed1999

Role of ethamsylate in preventing periventricular-intraventricular hemorrhage in premature infants below 34 weeks of gestation.

OBJECTIVE: To determine the role of ethamsylate in prevention of PVH-IVH in premature infants <34 weeks gestational age. DESIGN: Prospective, randomized, controlled study. METHODS: Infants less than 34 weeks gestational age were included in the trial. Neonates with congenital malformations, family history of bleeding disorders and with Apgar scores <5 at 5 minutes were excluded. Subjects were randomized into two groups--Group A infants received intravenous ethamsylate (12.5 mg/kg) six hourly for four days and Group B infants served as a control group. Regular cranial ultrasounds to detect the presence of PVH-IVH were done between days 3-5, 10-14 and 28-30 of post natal age, and before hospital discharge in all infants and weekly in infants detected to have PVH-IVH on earlier scans. Various antenatal and postnatal factors known to affect the incidence of PVH-IVH were recorded. RESULTS: A total of 192 infants underwent the trial, 93 in Group A and 99 in Group B. Antenatal corticosteroids (1 or 2 doses) were administered to 32 ( 34.4%) and 36 (36.3%) women in Group A and Group B, respectively. None of the mothers received phenobarbitone, vitamin K or indomethacin antenatally and none of the infants received phenobarbitone, vitamin E or indomethacin postnatally during the study period. PVH-IVH was seen in 26 infants in Group A, of which Grade I IVH occurred in 9, Grade II in 14, Grade III in 2 and Grade IV in one infant. Twenty-nine infants had PVH-IVH in Group B of which 11 had Grade I, 15 Grade II and 3 Grade III. None of the differences were statistically significant. CONCLUSION: Postnatal administration of ethamsylate did not decrease the incidence of PVH-IVH in the study infants.

Cerebral Hemorrhage↗
PubMed1998

Phenotypic consequences of transforming growth factor beta1 gene ablation in murine embryonic fibroblasts: autocrine control of cell proliferation and extracellular matrix biosynthesis.

The profound effects of transforming growth factor beta1 (TGF-beta1) on the immune system, cardiogenesis, in yolk sac hematopoeisis and in differentiation of endothelium have been demonstrated by detailed analyses of TGF-beta1 knockout mice during embryogenesis. We have systematically examined the autocrine and paracrine roles of TGF-beta1 in cell proliferation and in its ability to modulate the gene expression of selected components of extracellular matrix (ECM) using embryonic fibroblasts from TGF-beta1 null mice (TGF-beta-1(-/-)). The rates of cell proliferation of embryonic fibroblasts from normal mice (TGF-beta1(+/+)) and TGF-beta1 null mice were compared by cell counting, by 3H thymidine incorporation, and by measuring the fraction of cells in the G1, S, and G2/M phases of the cell cycle by fluorescent activated cell sorting (FACS). Concurrently, the expression of pro-alpha1(I) collagen, fibronectin, and plasminogen activator inhibitor-1 (PAI-1) was also quantified by hybridization of total mRNA from TGF-beta1(+/+) and TGF-beta1(-/-) embryonic fibroblasts. We report that TGF-beta1(-/-) cells proliferated at about twice the rate of TGF-beta1(+/+) cells. Further, TGF-beta1 null fibroblasts accumulated and synthesized lower constitutive levels of pro-alpha1(I) collagen, fibronectin, and PAI-1 mRNA. The quantitative differences in the rates of cell proliferation and ECM gene expression between TGF-beta1(+/-) and TGF-beta1(-/-) cells could be eliminated by treatment of TGF-beta1(+/+) cells with a neutralizing antibody of TGF-beta1. Thus, our results are consistent with the hypothesis that TGF-beta1 acts as a negative autocrine regulator of growth and a positive autocrine regulator of ECM biosynthesis in embryonic fibroblasts.

Animals↗
PubMed1997

Nutritional supplementation of nucleotides restores opioid CNS-mediated phenomena in mice.

Previous experiments have demonstrated that suppression of immune function by either cyclosporin A or by a nucleotide free (NF) diet results in attenuation of morphine withdrawal symptoms in mice suggesting that immune status impacts CNS opioid-related phenomena. The present study elaborates on these initial findings by examining the effects of repletion of the NF diet with nucleotides or their precursors on opiate withdrawal. Female Balb/c mice were divided into six groups: a control group (C) given a standard lab chow diet and five experimental groups each given one of the following diets: a nucleotide free diet (NF); the NF supplemented with 0.25% RNA (NFR 0.25); the NF supplemented with 2.5% RNA (NFR 2.5) the NF supplemented with 0.06% uracil (NFU 0.06); the NF supplemented with 0.6% uracil (NFU 0.6). The mice were made morphine dependent by subcutaneous implantation of morphine pellets. Seventy-two hours after morphine pellet implantation, withdrawal was precipitated with naloxone (2 mg/kg). The mice were then observed and two indicators of withdrawal scored: jumping and diarrhea. The NF, NFR 0.25, NFR 2.5 and NFU 0.06 groups demonstrated significantly attenuation of the withdrawal signs relative to control animals. The NFU 0.6 group, however, had withdrawal scores restored to near control levels for both jumping and diarrhea. This suggests that nucleotides, particularly uracil, may play an important role in the immune-to-brain signaling pathway.

Animals↗
PubMed1997

Nucleoside-nucleotide-free diet suppresses cytokine production and contact sensitivity responses in rats with trinitrobenzene sulphonic acid-induced colitis.

We examined the effects of dietary nucleoside-nucleotide mixture on synthesis of inflammatory cytokines, interleukin-8 and tumor necrosis factor-alpha, in sensitized and nonsensitized colitic rats. Sensitized and nonsensitized colitic rats that were fed a nucleoside-nucleotide mixture had greater colonic weight and macroscopic and microscopic damage scores than nucleoside-nucleotide-free sensitized and nonsensitized colitic rats. Increased colonic tumor necrosis factor-alpha and interleukin-8 concentrations were associated with increased colonic inflammation and ulceration in the nucleoside-nucleotide mixture-fed group. There was also increased ear thickness in the nucleoside-nucleotide mixture-fed sensitized and nonsensitized colitic rats, which correlated highly with increased tumor necrosis factor-alpha and interleukin-8 levels in the ear lobes. Nucleoside-nucleotide-free diets may suppress cytokine secretion, thereby reducing colonic damage and contact sensitivity responses in colitic rats.

Animals↗
PubMed1996

Pseudocysts of pancreas in children.

A total of 7 patients pseudopancreatic cysts was managed in children over a period of 5 years. Trauma was responsible for the development of pseudocyst in one while in rest of the patients no etiologic factor could be identified. All the patients underwent trans-gastric cyctogastrostomy. With a mean follow-up of 30 months, no death and no recurrence was found. It seems that surgical experience of pseudopancreatic cysts in children is similar to that seen in adults.

Child↗
PubMed1996

Pseudocysts of pancreas in children.

A total of 7 patients of pseudopancreatic cysts was managed in children over a period of 5 years Trauma was responsible for the development of pseudocyst in one while in rest of the patients no etiologic factor could be identified. All the patients underwent transgastric cystogastrostomy. With a mean follow-up of 30 months, no death and no recurrence was found. It seems that surgical experience of pseudopancreatic cysts in children is similar to that seen in adults.

Child↗
PubMed1995

Nucleic acids and/or their components: a possible role in immune function.

Dietary sources of nucleic acids and/or their components, have not been considered essential for normal growth and development. However, growing evidence shows that the compounds regulate various steps of the immune system and demonstrate the necessity of the compounds in the response to immunological challenge. The significance of exogenously administered purine or pyrimidine bases, nucleotides, and nucleosides in the immune response is reviewed.

Humans↗
PubMed1995

Coronary angioplasty in unstable angina: contemporary experience.

OBJECTIVE: To evaluate the role of percutaneous transluminal coronary angioplasty (PTCA) in the treatment of patients with unstable angina. DESIGN: Retrospective analysis of administrative records of all acute care hospital discharges at Robert Wood Johnson University Hospital from 1987 to 1993 with International Classification of Diseases, 9th revision, codes for coronary angioplasty and corresponding catheterization laboratory reports. SETTING: Tertiary care teaching hospital. RESULTS: Of 4826 PTCA cases, unstable angina was identified in 780 as the main indication for the procedure. Baseline clinical features of patients with unstable angina were not different from those in patients with stable angina. The overall success rate for PTCA in patients with unstable angina was significantly higher (707 of 780, 91%) than the success rate in patients with stable angina (3466 of 4046, 86%). The major complication rate in unstable angina patients was low (29 of 780, 3.7%) and did not differ from that in stable angina patients (136 of 4046, 3.4%). The success and complication rates in patients with unstable angina were analyzed in terms of time of PTCA, ie, early (less than 48 h from admission) versus late (48 h or more from admission). The procedure was successful in 343 of 380 (90%) patients treated early and 364 of 400 (91%) patients treated late (not significant), and the complication rates were low (12 of 380, 3.2% versus 17 of 400, 4.3%; not significant in both groups). However, length of hospital stay was considerably shorter for patients treated early than for patients treated late (4.5 +/- 3.3 days versus 10.4 +/- 6.6 days, respectively, P < 0.0001). CONCLUSION: Contemporary results of PTCA in patients with unstable angina parallel those reported for stable angina. Thus, PTCA appears to be an effective and safe treatment for unstable angina patients, and treating these patients soon after admission does not appear to affect the success or complication rates.

Angina, Unstable↗
PubMed1994

Platelet-activating factor mediates trinitrobenzene induced colitis.

Platelet-activating factor (PAF) is an endogenous phospholipid which may be an important mediator of shock and inflammation. Recent evidence suggests that PAF plays a role in the development of ischemic colitis and inflammatory bowel disease. Its effects are mediated by second messengers, including the arachidonic acid metabolites. Using an ex vivo isolated left colon rabbit perfusion model, our aims were to determine whether exogenously administered trinitrobenzene sulfonic acid (TNB), which produces experimental colitis, stimulates both PAF and eicosanoid release in the colon, and if so, whether this effect can be blocked by a PAF antagonist. Colonic inflammation was induced by the intracolonic administration of 0.25 ml of 50% ethanol containing 30 mg of TNB. Tissue and perfusate concentrations of the eicosanoids, [prostaglandin E (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2), leukotriene B4 (LTB4)] and the autocoid PAF were measured by ELISA. During TNB infusion there was a significant increase in tissue levels of PAF compared to control colons. Additional studies performed pretreating the colons with the PAF receptor antagonist WEB-2170 prior to TNB infusion blocked PAF release. TNB stimulated release of luminal eicosanoids except LTB4 and suppressed release of tissue prostanoids. Pretreatment with WEB-2170 prior to TNB inhibited luminal eicosanoids, and inhibited PGE2 and prostacyclin, but not TX tissue suppression. Inhibition of TNB-stimulated PAF release by WEB-2170 suggests that PAF may play a role in TNB-induced colitis and this phenomenon may mediate tissue injury.

6-Ketoprostaglandin F1 alpha↗