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Biomedical subjects

R Rao

Publications and source records attributed to R Rao.

At least 91 records · Page 5Linked to original sources
PubMed1998

Inflammatory mechanisms in childhood asthma.

There is now a reasonable body of data that would suggest that the immunopathology of asthma is similar, if not identical, in childhood asthmatics compared with adult asthmatics. Indeed, we now have evidence that much of the immunopathology is established within the airways of asthmatics very early after the onset of symptoms and, given the lack of correlation with duration of symptoms, may even antedate the first manifestations. There are, however, some differences with neutrophil recruitment being somewhat more prominent than has been recorded from adult observations. The utility of any inflammation parameter in identifying the real future asthmatics has yet to be studied in sufficient detail to define sensitivity, specificity and predictive value. Such studies will be an essential prerequisite to establishing very early intervention strategies, particularly if these involve the use of inhaled and/or oral corticosteroid.

Adult↗
PubMed1998

Selenium deficiency in tissue culture: implications for oxidative metabolism.

BACKGROUND: Selenium is located at the catalytic site of the enzyme glutathione peroxidase, and with selenium deficiency the activity of glutathione peroxidase is decreased. Cell culture is an important tool for studying oxidative processes-that is generation and metabolism of oxygen-derived metabolites in the gastrointestinal system. Cell culture is also used to understand the mechanisms of cell injury by oxygen-derived metabolites. METHODS: To assess the importance of the selenium content of cell culture media, Caco-2 cells and the hepatoma-derived cell lines, Hep3B and HepG2, were grown to confluence and placed in media with various concentrations of selenium. After 7 to 14 days, cells were harvested and assayed for glutathione peroxidase, lactate dehydrogenase, and protein content. RESULTS: Cells maintained in media unsupplemented with selenium demonstrated a progressive decrease in glutathione peroxidase activity. Cells maintained in media supplemented with various concentrations of selenium demonstrated a dose-dependent increase in glutathione peroxidase until a plateau was reached. The plateau was reached at approximately 400 times the selenium concentration routinely used in cell culture. In the Caco-2 and hepatoma cells, no toxicity was observed at selenium supplementation five times the lowest concentration needed to reach a plateau. CONCLUSIONS: Cell culture media are routinely deficient in selenium, and cells that are cultured in this medium are deficient in glutathione peroxidase activity. Studies of oxidative metabolism based on cultures deficient in selenium may yield results that could be falsely interpreted. The addition of 1 nM selenium is sufficient for these cell lines to reach a plateau for intracellular glutathione peroxidase activity. These observations may have important ramifications for the study of reactive oxygen metabolite injury in cell culture.

Caco-2 Cells↗
PubMed1998

Pancreatic pseudocyst mimicking idiopathic achalasia.

Pseudoachalasia or secondary achalasia is commonly recognized and sought for in the context of an elderly patient presenting with weight loss and brief duration of symptoms. The majority of cases are caused by adenocarcinomas of the fundus or the cardia. It is accepted by gastroenterologists that endoscopy with "routine retroflexion" and biopsy are necessary in any newly diagnosed case of achalasia. Benign causes of pseudoachalasia are extremely rare in this country. In developing countries and South America, Chagas' Disease may mimic achalasia. Herein, we present a case of secondary achalasia linked to an unrecognized mediastinal pancreatic pseudocyst that resolved with appropriate treatment of the underlying cause.

Deglutition Disorders↗
PubMed1998

The author of Roe.

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Abortion, Induced↗
PubMed1997

Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain: a randomized controlled trial.

CONTEXT: More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units. OBJECTIVE: To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain. DESIGN: Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques. SETTING: A large urban public teaching hospital serving a predominantly African American and Hispanic population. PATIENTS: A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm. MAIN OUTCOME MEASURES: Primary outcomes measured for each subject were LOS and total cost of treatment. RESULTS: The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01). CONCLUSIONS: In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACI.

Adult↗
PubMed1997

Intracellular sequestration of sodium by a novel Na+/H+ exchanger in yeast is enhanced by mutations in the plasma membrane H+-ATPase. Insights into mechanisms of sodium tolerance.

Sodium tolerance in yeast is disrupted by mutations in calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, which is required for modulation of Na+ uptake and efflux mechanisms. Five Na+-tolerant mutants were isolated by selecting for suppressors of calcineurin mutations, and mapped to the PMA1 gene, encoding the plasma membrane H+-ATPase. One mutant, pma1-alpha4, which has the single amino acid change Glu367 --> Lys at a highly conserved site within the catalytic domain of the ATPase, was analyzed in detail to determine the mechanism of Na+ tolerance. After exposure to Na+ in the culture medium, 22Na influx in the pma1 mutant was reduced 2-fold relative to control, consistent with a similar decrease in ATPase activity. Efflux of 22Na from intact cells was relatively unchanged in the pma1 mutant. However, selective permeabilization of the plasma membrane revealed that mutant cells retained up to 80% of intracellular Na+ within a slowly exchanging pool. We show that NHX1, a novel gene homologous to the mammalian NHE family of Na+/H+ exchangers, is required for Na+ sequestration in yeast and contributes to the Na+-tolerant phenotype of pma1-alpha4.

Amino Acid Sequence↗
PubMed1997

PMR1, a Ca2+-ATPase in yeast Golgi, has properties distinct from sarco/endoplasmic reticulum and plasma membrane calcium pumps.

PMR1, a P-type ATPase cloned from the yeast Saccharomyces cerevisiae, was previously localized to the Golgi, and shown to be required for normal secretory processes (Antebi, A., and Fink, G.R. (1992) Mol. Biol. Cell 3, 633-654). We provide biochemical evidence that PMR1 is a Ca2+-transporting ATPase in the Golgi, a hitherto unusual location for a Ca2+ pump. As a starting point for structure-function analysis using a mutagenic approach, we used the strong and inducible heat shock promoter to direct high level expression of PMR1 from a multicopy plasmid. Yeast lysates were separated on sucrose density gradients, and fractions assayed for organellar markers. PMR1 is found in fractions containing the Golgi marker guanosine diphosphatase, and is associated with an ATP-dependent, protonophore-insensitive 45Ca2+ uptake activity. This activity is virtually abolished in the absence of the expression plasmid. Furthermore, replacement of the active site aspartate within the phosphorylation domain had the expected effect of abolishing Ca2+ transport activity entirely. Interestingly, the mutant enzymes (Asp-371 --> Glu and Asp-371 --> Asn) demonstrated proper targeting to the Golgi, unlike analogous mutations in the related yeast H+-ATPase. Detailed characterization of calcium transport by PMR1 showed that sensitivity to inhibitors (vanadate, thapsigargin, and cyclopiazonic acid) and affinity for substrates (MgATP and Ca2+) were different from the previously characterized sarco/endoplasmic reticulum and plasma membrane Ca2+-ATPases. PMR1 therefore represents a new and distinct P-type Ca2+-ATPase. Because close homologs of PMR1 have been cloned from rat and other organisms, we suggest that Ca2+-ATPases in the Golgi will form a discrete subgroup that are important for functioning of the secretory pathway.

Adenosine Triphosphate↗
PubMed1997

Molecular and macromolecular specificity of human plasma phospholipid transfer protein.

Phospholipid transfer protein (PLTP), also known as lipid transfer protein 2 (LTP-2), mediates a transfer of phospholipids between high-density lipoproteins (HDL). The molecular and macromolecular specificities of recombinant human PLTP were studied using a fluorometric assay based on the excimer fluorescence of pyrenyl lipids. To determine lipoprotein specificity of PLTP, donor very low density lipoproteins (VLDL), low-density lipoproteins (LDL), and HDL were labeled with 1-palmitoyl-2-[10-(1-pyrenyl)decanoyl]phosphatidylcholine (PPyDPC) and incubated with unlabeled acceptor VLDL, LDL, and HDL in every pairwise combination. The highest rate of PPyDPC transfer mediated by PLTP occurred between donor HDL and acceptor HDL. Reassembled HDL (rHDL) consisting of 1-palmitoyl-2-oleoylphosphatidylcholine, apolipoprotein A-I, and pyrene lipids (100:1:4) were used to demonstrate that PLTP transfers diacylglyceride > phosphatidic acid > sphingomyelin > phosphatidylcholine (PC) > phosphatidylglycerol > cerobroside > phosphatidylethanolamine. Thus, PLTP transfers a variety of lipids with two carbon chains and a polar head group. Unsaturation of one PC acyl chain greatly increased transfer rate, whereas increasing chain length and exchanging sn-1/sn-2 position had only small effects. The rate of PPyDPC transfer by PLTP decreases with increasing free cholesterol content in rHDL and with decreasing HDL size. In contrast to spontaneous transfer, PLTP mediates the accumulation of PC in small rHDL particles. PLTP may be important in vivo in the recycling of PC from mature HDL to nascent HDL, the latter of which are the initial acceptors of cholesterol from peripheral tissue for reverse cholesterol transport to the liver.

Ca(2+) Mg(2+)-ATPase↗
PubMed1997

Psychiatric disorders in women with bulimia nervosa and their first-degree relatives: effects of comorbid substance dependence.

OBJECTIVE: Women with bulimia nervosa (BN) and comorbid substance dependence often display impulsive behaviors. We assessed Axis I and II psychiatric diagnoses in their first-degree relatives in order to understand the etiological factors that may contribute to this subtype of BN. METHOD: We used contemporary family-epidemiological methodology to compare the lifetime prevalence of psychiatric disorders among 47 women with BN and 44 non-eating-disordered community control women, and their first-degree relatives (177 and 190, respectively). BN probands were stratified by the presence (n = 20) or absence (n = 27) of a lifetime history of alcohol and/or drug dependence. RESULTS: Social phobia, conduct disorder, and clusters B and C personality disorders were significantly more prevalent among BN probands with substance dependence than among BN probands without substance dependence or control women probands. Substance use disorders, social phobia, panic disorder, and cluster B personality disorders were significantly more prevalent among the relatives of BN probands with substance dependence than the relatives of the other two groups. DISCUSSION: Women with BN and substance dependence have problems with social anxiety, antisocial behavior, and a variety of personality disturbances, and come from families where there are problems with substance use disorders, anxiety, impulsivity, and affective instability. These data raise the possibility that a familial vulnerability for impulsivity and affective instability may contribute to the development of substance dependence in a subgroup of women with BN.

Adult↗
PubMed1997

A comparison of subgroups of inpatients with anorexia nervosa.

OBJECTIVE: Classification of subgroups of people with anorexia nervosa has been in flux. It has not been clear whether anorexics who only purge should be grouped with pure restricters or with people who both binge and purge. METHODS: We compared 27 restricting-type anorexics (RAN), 26 bulimic anorexics (BAN), and 34 restricting anorexics with purging behaviors (RAN-P). All subjects were underweight and recently admitted to a hospital. We excluded subjects who had not had a diagnosis of anorexia nervosa for at least 1 year duration. RESULTS: The three groups of subjects had similar scores for Depression and Anxiety on the Beck Depression Inventory, the Spielberger State and Trait Anxiety Inventory, and on the EDI subscales aside from higher scores for BAN subjects on the Bulimia subscale. DISCUSSION: These three subgroups of anorexia nervosa have similar degrees of dysphoric moods and core eating disorder symptoms when underweight and malnourished.

Adult↗
PubMed1997

The association of fetal sex with the rate of cesarean section.

OBJECTIVE: Our purpose was to evaluate the rate of cesarean deliveries according to fetal sex. STUDY DESIGN: We evaluated method of delivery, indication for cesarean section, and infant outcome according to fetal sex in 2439 low-risk nulliparous women in spontaneous labor. Crude odds ratios and 95% confidence intervals were calculated. Confounding was controlled with use of logistic regression. RESULTS: The overall cesarean section rate was 13.2% among 1246 women carrying male fetuses compared with 9.6% among 1193 women carrying female fetuses (odds ratio 1.4, 95% confidence interval 1.1 to 1.8). There was a 30% increase in cesarean sections for failure to progress (odds ratio 1.3, 95% confidence interval 1.0 to 1.8) and a 70% increase in those for fetal distress (odds ratio 1.7, 95% confidence interval 1.0 to 3.0). When adjusted for gestational age and fetal size, male fetal sex no longer predicted the risk of cesarean delivery for failure to progress (adjusted odds ratio 1.04, 95% confidence interval 0.8 to 1.4) but continued to predict the risk of cesarean section for fetal distress (adjusted odds ratio 2.2, 95% confidence interval 1.3 to 4.0). Among infants delivered by cesarean section for fetal distress, males were more than three times as likely than females to have an Apgar score < or = 7 at both 1 and 5 minutes. CONCLUSION: Increased cesarean deliveries for failure to progress among women with male fetuses is related to the larger size of males, whereas the increase for fetal distress is not, and may relate to other developmental differences between male and female fetuses.

Birth Weight↗
PubMed1997

Limited success using the "flare" protocol in poor responders in cycles with low basal follicle-stimulating hormone levels during in vitro fertilization.

OBJECTIVE: To assess an alternate protocol for stimulating poor responders. DESIGN: Prospective clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Eighty poor responders. INTERVENTION(S): Stimulation was withheld until patients fulfilled the following criteria: basal FSH < or = 12 mIU/mL (conversion factor to SI unit, 1.00) with concurrent E2 level < or = 100 pg/mL (conversion factor to SI unit, 3.671), and P level < or = 1.0 ng/mL (conversion factor to SI unit, 3.467). They then started leuprolide acetate on cycle day 2 and a high dose of gonadotropins on cycle day 3. MAIN OUTCOME MEASURE(S): Stimulation response and pregnancy rates (PRs). RESULT(S): Nineteen cycles (23.8%) were canceled because of poor ovarian response. The mean E2 level on day of hCG was 2,578 +/- 1,339 pg/mL (9,464 +/- 4,915 pmol/L) (range, 789 to 5934 pg/mL [2,896 to 21,784 pmol/L]). The number of oocytes retrieved was 10 +/- 6.6 (range, 1 to 37). Nine patients did not have ET (failed fertilization [n = 5], no cleavage of preembryos [n = 3], freeze all [n = 1]). The number of pre-embryos transferred was 3.9 +/- 1.6 (range, 1 to 8). The clinical pregnancy rate was 7 of 61 (11.5%) per retrieval, and 7 of 52 (13.4%) per transfer with an implantation rate of 7 of 201 (3.5%). Three patients miscarried with an ongoing PR of 4 of 61 (6.5%) per retrieval and 4 of 52 (7.6%) per transfer. CONCLUSION(S): Poor responders undergoing controlled ovarian hyperstimulation with the "flare" protocol in cycles with low basal FSH will often show adequate ovarian response and reach oocyte retrieval and ET. The PRs, however, remain low.

Adult↗
PubMed1997

Epidemic of accidental carbon monoxide poisonings caused by snow-obstructed exhaust systems.

We report a case series of accidental carbon monoxide poisonings caused by snow-obstructed automobile exhaust systems. Accumulation of more than 24 inches of snow contributed to the poisoning of 25 patients who were subsequently treated with hyperbaric oxygen therapy. Two illustrative cases are presented in greater detail, illustrating a life-threatening hazard associated with heavy snow accumulations.

Aged↗
PubMed1997

Analysis of DNA ploidy and expression of tumour-associated antigens on human oral carcinomas xenografted in nude mice.

Human squamous cell carcinomas (SCC) of the oral cavity were successfully established as xenografts in nude mice. Tumours with higher malignancy scores and involvement of lymph nodes in patients were more readily accepted as xenografts in nude mice. The xenografted tumours were characterised with respect to morphology, histology, DNA index and expression of tumour-associated antigens (TAA). Flow cytometric analysis of cellular DNA content revealed that many of the xenografts retained the parent tumour DNA pattern while some of the xenografts showed progression to aneuploidy. All the xenografted tumours expressed TAA recognised by monoclonal antibody (MAb) 3F8E3. On Western blotting, MAb 3F8E3 recognised proteins of molecular weight 62-64 kDa on parent and xenografted tumours. In general, the xenografts reflect many of the characteristics of the tumours from which they were derived and may provide a useful model for investigating newer approaches of treatment and diagnosis.

Animals↗