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Biomedical subjects

M Rao

Publications and source records attributed to M Rao.

At least 91 records · Page 5Linked to original sources

Estimation of vaccine efficacy in the presence of waning: application to cholera vaccines.

The authors present a nonparametric method for estimating vaccine efficacy as a smooth function of time from vaccine trials. Use of the method requires a minimum of assumptions. Estimation is based on the smoothed case hazard rate ratio comparing the vaccinated with the unvaccinated. The estimation procedure allows investigators to assess time-varying changes in vaccine-induced protection, such as those produced by waning and boosting. The authors use the method to reanalyze data from a vaccine trial of two cholera vaccines in rural Bangladesh. This analysis reveals the differential protection and waning effects for the vaccines as a function of biotype and age.

Adolescent↗

Interactions of chaperone alpha-crystallin with the molten globule state of xylose reductase. Implications for reconstitution of the active enzyme.

alpha-Crystallin is a multimeric protein that has been shown to function as a molecular chaperone. Present investigations were undertaken to understand its mechanism of chaperoning. For this functional in vitro analysis of alpha-crystallin we used xylose reductase (XR) from Neurospora crassa as the model system. Denaturation studies using the structure-perturbing agent guanidinium chloride indicated that XR folds through a partially folded state that resembles the molten globule. Fluorescence and delay experiments revealed that alpha-crystallin interacts with the molten globule state of XR (XR-m) and prevents its aggregation. Cold lability of alpha-crystallin.XR-m interaction was revealed by temperature shift experiments implicating the involvement of hydrophobic interactions in the formation of the complex. Reconstitution of active XR was observed on cooling the alpha-crystallin.XR-m complex to 4 degrees C or on addition of ATP at 37 degrees C. ATP hydrolysis is not a prerequisite for XR release since the nonhydrolyzable analogue 5'-adenylyl imidodiphosphate (AMP-PNP) was capable of reconstitution of active XR. Experimental evidence has been provided for temperature- and ATP-mediated structural changes in the alpha-crystallin.XR-m complex that shed some light on the mechanism of reconstitution of active XR by this chaperone. The relevance of our finding to the role of alpha-crystallin in vivo is discussed.

Aldehyde Reductase↗

Improved morbidity with the use of nasal continuous positive airway pressure in I-cell disease.

Patients with I-cell disease (mucolipidosis II) present with progressive morbidity failure to thrive, cardiomegaly, and recurrent respiratory tract infections leading to progressive deterioration and early death. We evaluated use of nasal continuous positive airway pressure (NCPAP) for 6 months in a 2-year-old girl with I-cell disease, obstructive sleep apnea (OSA), and craniofacial anomalies. We observed a marked decrease in hospitalizations for respiratory problems and a marked improvement in arterial blood gases with the use of NCPAP. In patients with I-cell disease, anatomical defects with superimposed upper respiratory tract infections cause worsening of OSA, and OSA contributes significantly to morbidity. In such patients NCPAP can lessen morbidity and can improve the quality of life.

Carbon Dioxide↗

Ground and surface water developmental toxicity at a municipal landfill: description and weather-related variation.

Contaminated groundwater poses a significant health hazard and may also impact wildlife such as amphibians when it surfaces. Using FETAX (Frog Embryo Teratogenesis Assay-Xenopus), the developmental toxicity of ground and surface water samples near a closed municipal landfill at Norman, OK, were evaluated. The groundwater samples were taken from a network of wells in a shallow, unconfined aquifer downgradient from the landfill. Surface water samples were obtained from a pond and small stream adjacent to the landfill. Surface water samples from a reference site in similar habitat were also analyzed. Groundwater samples were highly toxic in the area near the landfill, indicating a plume of toxicants. Surface water samples from the landfill site demonstrated elevated developmental toxicity. This toxicity was temporally variable and was significantly correlated with weather conditions during the 3 days prior to sampling. Mortality was negatively correlated with cumulative rain and relative humidity. Mortality was positively correlated with solar radiation and net radiation. No significant correlations were observed between mortality and weather parameters for days 4-7 preceding sampling.

Animals↗

Protective effects of cystone, a polyherbal ayurvedic preparation, on cisplatin-induced renal toxicity in rats.

Cystone, a polyherbal ayurvedic preparation, was found to protect rats partially but significantly against cisplatin-induced renal toxicity, when given intraperitonially 1 h before cisplatin. At 500 and 1000 microg/ml, it also inhibited lipid peroxidation induced by cisplatin in renal cortical slices by 62.7 and 71.6%, respectively. The rats pretreated with cystone (1000 mg/kg i.p.) had significantly lower blood urea nitrogen (BUN) and serum creatinine (33.8 and 0.92 mg/dl, respectively) compared to cisplatin alone (51.5 and 1.41 mg/dl, respectively). The control animals had 17.1 and 0.63 mg/dl, respectively. The cystone treated animals lost 5.63 g body weight compared to 12.5 g for cisplatin alone treated animals on day 5. Renal functions like urine to serum creatinine ratio and creatinine clearance showed significant improvement when cystone was given 1 h before cisplatin. However, cystone did not protect increased excretion of urinary protein and decreased WBC count caused by cisplatin. The present study suggests that the cystone protects kidney against cisplatin-induced toxicity and the protection may be mediated through its ability to inhibit lipid peroxidation.

Animals↗

Validation of 24-hour dietary recall: a study in hemodialysis patients.

The 24-hour dietary recall method is frequently used for dietary assessment. However, it is subject to errors by both respondent and observer bias and is largely influenced by the motivation and recall ability of the respondent. The weighment method is regarded as the gold standard for estimating nutrient intake. This study was undertaken to assess the validity of dietary recall in a group of seven maintenance hemodialysis patients, who also had corresponding weighed food records. Actual food consumed and residue were weighed separately. A dietary recall was taken on the next day. Subjects were not allowed to take any food or beverage other than that served during the study period. A good agreement was obtained between dietary recall and the weighed food record (the difference was within 10% of the results of weighment), although there was a consistent underestimate by dietary recall. The results also suggested a training effect since improved recall was noted during the later weeks of the study, although this difference was not statistically significant. Therefore, dietary recall as a method of dietary assessment may be of special value in chronic hemodialysis patients in India, who are usually a motivated and informed group.

Adult↗

Safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli-cholera toxin B subunit vaccine in Egyptian adults.

Enterotoxigenic Escherichia coli (ETEC) is the leading cause of bacterial diarrhea in young children in developing countries. The safety and immunogenicity of a killed, oral ETEC vaccine consisting of whole cells plus recombinantly produced cholera toxin B subunit (rCTB) was evaluated in Egypt, which is endemic for ETEC diarrhea. Seventy-four healthy Egyptian adults (21-45 years old) were randomized and received two doses of the ETEC/rCTB vaccine (E003) or placebo 2 weeks apart. The frequency of adverse events after either dose did not differ by treatment group, and no severe adverse events were reported. After vaccination, peripheral blood IgA B cell responses to CTB (100%) and to vaccine colonization factor antigens CFA/I (94%), CS4 (100%), CS2 (81%), and CS1 (69%) were significantly higher than response rates for the placebo group. These favorable results in Egyptian adults indicate that the ETEC/rCTB vaccine is a promising candidate for evaluation in younger age groups in this setting.

Adult↗

Haemodialysis for end-stage renal disease in Southern India--a perspective from a tertiary referral care centre.

BACKGROUND: There is little information available regarding the practice of haemodialysis, its population characteristics or outcomes in India. These aspects were studied in a cohort of end-stage renal disease (ESRD) patients enrolling in a maintenance haemodialysis (MHD) programme in a tertiary referral centre in S. India, over a 1 year period. RESULTS: A total of 463 ESRD patients enrolled on MHD during the 1 year period. The mean (SD) age was 38.6 (13.9) years. Definitive renal replacement therapy was instituted in 34% of these patients, including renal transplantation in 22.8%. The median duration to transplant was 93 days, and there was a 50% reduction of the original cohort by 1 month. The largest fraction left the programme (59.7%). Renal transplantation as an outcome was determined by a younger age and a planned referral from outside the state of Tamil Nadu; continuation of any form of renal replacement therapy again was more likely in the younger patient who had external financial support. Dialysis therapy was empiric but uniform for all patients, and only 50% of the dialyses delivered a single pool Kt/V > or = 1. The overall mortality was 9.5%, but 58% of the deaths took place within a week of starting dialysis, a quarter being related to severe uraemic complications. CONCLUSIONS: Haemodialysis in India is mainly a short-term measure to support the ESRD patient to transplantation. Economic factors play an important role in outcome, the majority undergoing discharge from the programme. Early mortality is disproportionately high. Subclinical underdialysis is common. The requirement for pre-dialysis care and earlier referral from the community is apparent. Prospective studies to define standards and optimize the practice of dialytic therapy against appropriate short-term outcomes, within prevalent economic frameworks, need to be undertaken.

Adolescent↗

Geriatric nurse practitioners in long-term care: demonstration of effectiveness in managed care.

OBJECTIVE: This study was undertaken to review the impact of utilizing geriatric nurse practitioner/physician (GNP/ MD) teams on cost and utilization for a cohort of Medicare HMO enrollees residing in long-term care facilities. The results would be used by the organization for further development of the GNP Program. DESIGN: A 1-year retrospective data analysis on revenues and cost for 1077 HMO enrollees residing in 45 long term-care facilities. SETTING: Proprietary and not-for-profit, licensed long term care facilities in the HMO's service area of central Massachusetts. Facilities in the study had both skilled (Medicare-certified) and custodial beds. MEASUREMENTS: Data were collected retrospectively on overall cost, revenues, emergency department (ED) transfers, hospital, and subacute days. RESULTS: Of 1077 residents, 414 were cared for by GNP/MD teams compared with 663 by physicians alone. Acute care and ED costs were significantly lower for the GNP/MD-covered patients. There was a gain of $72 per resident per month (PRPM) with the GNP/MD-covered patients compared with a loss of $197 PRPM for physicians alone. There were no significant differences in ancillary services or prescriptions. CONCLUSION: The use of GNPs in collaboration with physicians reduced ED and acute care utilization costs as well as overall costs for a cohort of HMO enrollees in long-term care. This encouraged the HMO to support the concept that all long-term care HMO residents should be covered by GNP/MD teams.

Aged↗

Gastroprotective effect of 1-phenyl-3-(4-hydroxy-3,5-di-tert-butylphenyl)prop-2-en-1-one in rats.

1-Phenyl-3-(4-hydroxy-3,5-di-tert-butylphenyl)prop-2-en-1-one (PHP), an antioxidant, has been studied for gastroprotective activity in-vitro and in-vivo, more specifically for its capacity to inhibit in-vitro iron- and copper-driven oxidant damage at acidic pH values mimicking intragastric conditions in the clinical setting. Our studies showed significant inhibition of both iron- and copper-driven oxidant damage at pH 3.5 and 5.3. Intragastric and intraperitoneal administration of PHP (250 mg kg(-1)) reduced gastric mucosal haemorrhagic lesions in stress-induced and ethanol-induced rat models. The gastroprotective effect of PHP against ethanol was reversed significantly by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis, indicating a possible role of prostaglandins in its gastroprotective effect. Treatment of PHP replenished reduced levels of gastric mucosal non-protein sulphydryls in ethanol-treated rats, suggesting the mediation of its effect through sulphydryls. These results indicate that PHP was active at acidic pH. This is an interesting observation because highly acidic pH is known to be important in the development of gastric ulcers. Our study suggests that PHP might protect gastric mucosa by its capacity to scavenge free radicals.

Animals↗

Protective effects of selenomethionine against cisplatin-induced renal toxicity in mice and rats.

The effect of selenomethionine on the toxicity of cisplatin has been studied in mice and rats. When selenomethionine (0.5-4 mg kg(-1)) was administered intraperitoneally to mice 1 h before intraperitoneal cisplatin (6 mg kg(-1)), the toxicity of cisplatin, as measured by loss of body weight and blood urea nitrogen and serum creatinine levels, was reduced significantly. The protection was dose-dependent but less when given orally. Similar results were obtained with rats. Deterioration of renal function was characterized by reduced creatinine clearance, and increased excretion of urinary protein was significantly reversed. Partial but significant protection was also observed against capsulation-induced reduction of white blood-cell count. Protective properties were further demonstrated by increased survival of mice pretreated with selenomethionine compared with the lethality observed for animals given cisplatin only. These results suggested that selenomethionine protects against cisplatin-induced renal and other toxicity. The study has many clinical implications in cancer chemotherapy and needs further investigation.

Animals↗

Liposomes containing lipid A serve as an adjuvant for induction of antibody and cytotoxic T-cell responses against RTS,S malaria antigen.

Encapsulation of soluble protein antigens in liposomes was previously shown to result in processing of antigen via the major histocompatibility complex class I pathway, as evidenced by costaining of the trans-Golgi region of murine bone marrow-derived macrophages (BMs) by fluorophore-labeled liposomal antigen and by a trans-Golgi-specific fluorescent lipid. Evidence is presented here that free or liposome-encapsulated RTS,S, a particulate malaria antigen consisting of hepatitis B particles coexpressed with epitopes from the Plasmodium falciparum circumsporozoite protein, also was localized in the trans-Golgi after incubation with BMs, suggesting processing by the class I pathway. An in vivo cytotoxic T-lymphocyte (CTL) response was detected, however, only after immunization with RTS,S encapsulated in liposomes containing lipid A and not after immunization with free RTS,S or with RTS,S encapsulated in liposomes lacking lipid A. Therefore, intracellular delivery of antigen containing CTL epitopes to the Golgi of BMs does not necessarily result in a CTL response in vivo unless an additional adjuvant, such as liposomes containing lipid A, is utilized. Encapsulation of RTS,S in liposomes containing monophosphoryl lipid A (MPL) resulted in a dose-dependent enhancement of the NANP-specific immunoglobulin G (IgG) antibody response compared to that of free RTS,S. The IgG1 and IgG2a subclasses predominated after immunization with RTS,S encapsulated in liposomes containing MPL. These results demonstrate that encapsulation of a lipid-containing particulate antigen, such as RTS, S, in liposomes containing lipid A can enhance both humoral and cellular immune responses.

Adjuvants, Immunologic↗

Regulation of apical membrane Na+/H+ exchangers NHE2 and NHE3 in intestinal epithelial cell line C2/bbe.

We examined the regulation of the Na+/H+ exchangers (NHEs) NHE2 and NHE3 by expressing them in human intestinal C2/bbe cells, which spontaneously differentiate and have little basal apical NHE activity. Unidirectional apical membrane 22Na+ influxes were measured in NHE2-transfected (C2N2) and NHE3-transfected (C2N3) cells under basal and stimulated conditions, and their activities were distinguished as the HOE-642-sensitive and -insensitive components of 5-(N,N-dimethyl)amiloride-inhibitable flux. Both C2N2 and C2N3 cells exhibited increased apical membrane NHE activity under non-acid-loaded conditions compared with nontransfected control cells. NHE2 was inhibited by 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate and thapsigargin, was stimulated by serum, and was unaffected by cGMP- and protein kinase C-dependent pathways. In contrast, NHE3 was inhibited by all regulatory pathways examined. Under acid-loaded conditions (which increase apical Na+ influx), NHE2 and NHE3 exhibited similar patterns of regulation, suggesting that the second messenger effects observed were not secondary to effects on cell pH. Thus, in contrast to their expression in nonepithelial cells, NHE2 and NHE3 expressed in an epithelial cell line behave similarly to endogenously expressed intestinal apical membrane NHEs. We conclude that physiological regulation and function of epithelium-specific NHEs are dependent on tissue-specific factors and/or conditional requirements.

Amiloride↗

[Effects of dehydroepiandrosterone sulfate on mimetic aging actions of cerebral cortex of fetal rats in vitro].

The effects of dehydroepiandrosterone sulfate (DHEAS) on mimetic aging action of cultured neurons were studied in two models: the cultured cerebral cortex neurons were exposed to the xanthine oxidase-hypoxanthine(XO-HPX) system; serum free culture of cerebral cortex neurons. The results indicated that when cultured neurons were incubated for 6 h with XO-HPX system or 24 h serum free cultures, LDH release and MDA content increased while the number of surviving neurons decreased. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased and morphological injury developed. DHEAS (25, 50, 100 micrograms.L-1) concentration-dependently increased the number of surviving neurons and the activities of SOD and GSH-Px. It also inhibited the elevation of LDH and MDA induced by free radical and serum free cultures. The results suggest that DHEAS prevent the toxicity of free radical and serum free culture insults by suppressing the generation of lipid peroxide and increasing the activities of antioxidant enzymes.

Aging↗

Abdominal ultra sonographic findings detected in the course of a hepatitis survey in an Egyptian rural area.

The objective of this study was to determine the prevalence of abnormal findings detected by abdominal ultrasonography (US) in an Egyptian rural area. This study was a part of a community based cross sectional survey for virus hepatitis carried out at Kalama village in Nile Delta, 40 kilometers north of Cairo. People above 10 years of age living in a 10% systemic random sample of houses in the village were subjects of this study. A member of the team carried out US examination of the liver, biliary tree, spleen, kidneys, pancreas, para aortic areas and the pelvis. Examination included morphological assessment and organometry. All results are recorded on images by videoprinter. Abnormalities in abdominal US was detected in 34% of examined cases. Abnormal liver impressions were detected in 28.3% of cases. Ascites was detected in 13 cases (1.8%). Diseases of the gall bladder and kidneys were detected in 2.7% and 2.1%, respectively. US diagnosed pregnancy in 5 women, one of them had a blighted ovum. Some of these abnormalities were detected in subjects with no complaint. It is concluded that abdominal US may be a tool for early detection of asymptomatic disease.

Cholecystitis↗

Bronchiectasis in pediatric AIDS.

OBJECTIVES: There are several reports of the pulmonary findings in children with HIV disease; however, the occurrence of bronchiectasis rarely has been noted. We evaluated occurrence of bronchiectasis in a large group of children referred to us with AIDS pneumopathy. METHODS: From January 1984 to April 1996, 203 children with AIDS and respiratory problems were referred to the pediatric pulmonary division at Children's Medical Center of Brooklyn. Medical records for 164 of these children were available and retrospectively reviewed. RESULTS: Uncomplicated pneumonia was present in 75, 24 had recurrent pneumonia, and 18 had unresolved pneumonia; lymphocytic interstitial pneumonitis (LIP) was diagnosed in 47 patients, worsening with time in all patients. Bronchiectasis was observed in 26 patients (26/164, 15.8%), diagnosed by chest radiograph in 26 (26/26, 100%), confirmed by CT scan of chest in 10 (10/26, 38.4%), and by histology in three (3/26, 11.5%). Median age at time of diagnosis of bronchiectasis was 7.5 years (range, 1 to 16 years). Sixteen children with LIP developed bronchiectasis (16/47, 34.0%). Three patients with recurrent pneumonia (3/24, 12.5%) developed bronchiectasis. Five patients with unresolved pneumonia (5/18, 27.7%) developed bronchiectasis. One infant developed bronchiectasis after Pneumocystis carinii pneumonia; another child developed bronchiectasis after P. carinii and Mycobacterium tuberculosis pneumonia. The CD4+ T-cell counts measured within 6 months of diagnosis of bronchiectasis were available in 23/26 patients and, all were < 100 cells per cubic millimeter. CONCLUSION: We conclude, from our experience, that there is a significant occurrence of bronchiectasis in children with AIDS and pulmonary disease, especially in children developing LIP, recurrent pneumonia and unresolved pneumonia, and CD4+ T-cell counts < 100 cells per cubic millimeter.

AIDS-Related Opportunistic Infections↗

Site and significance of cysteine residues in xylose reductase from Neurospora crassa as deduced by fluorescence studies.

Inactivation of xylose reductase (XR) by p-hydroxy-mercury benzoate (PHMB) was found to be biphasic with second-order rate constants of 80 and 6 M-1s-1 for the fast (kf) and slow (ks) phase respectively. Spectroscopic studies indicated that the inactivation was due to modification of one Cys residue per molecule of XR and not due to subsequent disruption of the quaternary structure. The binding of NADPH to XR (Kd 0.9 microM) was depressed on modification of the enzyme by PHMB (Kd 2.3 microM). The dependence of PHMB induced inactivation of XR in the presence of alcohols and varying temperature revealed that the Cys residue is situated in a hydrophobic microenvironment and is not involved in hydrogen bonding. Our present investigation using o-phthalaldehyde (OPTA) as the chemical initiator for fluorescent chemo-affinity labeling and double inhibition studies indicates that Cys residues involved in the reaction with PHMB (SHI) and OPTA (SHII) are distinctly different. Experimental evidence presented here serves to implicate that SHI located in a hydrophobic microenvironment at the high affinity NADPH binding site of XR plays a role in the binding of the coenzyme to XR, whereas SHII serves to maintain the conformation of the active site essential for catalysis by interacting with the NH2 group of an essential lysine residue.

Aldehyde Reductase↗