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R Rao

Publications and source records attributed to R Rao.

At least 145 records · Page 8Linked to original sources
PubMed1995

Interruptions in rheumatology subspecialty care among patients with rheumatoid arthritis.

OBJECTIVE: To identify factors associated with interruptions in care from rheumatologists among patients with rheumatoid arthritis (RA). METHODS: A person-time analysis was used to examine the association of medical insurance status, income, health status, treatment by a primary care physician, and presence of comorbid conditions with interruptions in rheumatology subspecialty care in a cohort of 161 patients with RA followed prospectively for up to 10 years. An interruption was defined as a 6-month period during which a patient was not treated by a rheumatologist. Each patient had at least one interruption. RESULTS: Interruptions in rheumatology care occurred more commonly during periods when patients reported no medical insurance coverage than when they had medical insurance coverage (relative risk, RR = 1.49; 95% confidence interval, CI = 1.05, 2.11). Interruptions in care were more common during intervals in which patients reported at least a 40% improvement in functional disability (RR = 1.30; 95% CI = 1.03, 1.63), but interruptions were not associated with either absolute or relative changes in pain or global arthritis status. Interruptions in rheumatology care also occurred more commonly during periods when patients reported seeing a primary care physician (RR = 2.07; 95% CI = 1.71, 2.50), and when they reported having a comorbid condition (RR = 1.37; 95% CI = 1.06, 1.77). Income was not associated with interruptions in care. CONCLUSION: Lack of medical insurance and short term improvements in functional disability are associated with interruptions in rheumatology care among patients with RA. Patients also appear to substitute primary care for care from rheumatologists. These associations suggest that potential strategies for enhancing continuity in rheumatology care might include the promotion of universal insurance coverage and the development of informational programs for patients.

Adult↗
PubMed1994

Regional variation in expression of acetylcholinesterase mRNA in adult rat brain analyzed by in situ hybridization.

To investigate the molecular basis of regional variation in expression of brain acetylcholinesterase (AChE; EC 3.1.1.7), steady-state levels of AChE activity and mRNA were examined. Relative AChE activity in Triton extracts from six areas of the rat brain varied as follows: cortex < cerebellum < medulla < pons-midbrain < thalamus < striatum. In contralateral samples from the same brains, AChE mRNA was assessed by Northern blotting with random-primed 32P-labeled cDNA. The regional abundance of the major 2.4-kb AChE transcript differed from that of the enzyme activity: cortex < striatum < cerebellum < medulla < thalamus < pons-midbrain. In situ hybridization with a 33P-labeled antisense AChE oligonucleotide provided evidence for high levels of AChE message in cells of the nucleus basalis, nucleus accumbens, neostriatum, substantia nigra, motor nucleus of the facial nerve, and spinal nucleus of the trigeminal nerve. In the caudate-putamen, large, heavily labeled neurons were not numerous, but they were approximately as frequent as the cholinergic interneurons revealed by choline acetyltransferase immunocytochemistry. The relatively low number of these AChE-expressing cells probably explains the relative dearth of AChE mRNA-like material in the neostriatum.

Acetylcholinesterase↗
PubMed1994

Plasmid labeling confirms bacterial translocation in pancreatitis.

To examine whether the gut is a source of infection in acute pancreatitis, bacterial translocation and alterations of intestinal microecology and morphology were studied in 16 dogs. Dogs were colonized with a strain of Escherichia coli (E. coli 6938K) bearing the plasmid pUC4K, which confers kanamycin resistance. In eight dogs (group I), pancreatitis was induced by sodium taurocholate/trypsin injection. Eight other dogs (group II) underwent laparotomy only. The pancreas, mesenteric lymph nodes, peritoneal fluid, liver, and spleen were harvested 7 days later for culturing and histologic analysis. Identification of E. coli 6938K was accomplished by plasmid DNA analysis. Group I dogs had severe pancreatitis and ischemic changes in small bowel mucosa. Group II dogs had no changes. Translocation to the pancreas occurred in five dogs and to mesenteric lymph nodes in six dogs with pancreatitis. No translocation occurred in group II dogs (p < 0.05). In addition to E. coli 6938K, other gram-negative kanamycin-resistant species were isolated, including E. coli (other than 6938K) and Enterobacter cloacae. Enteric origin of these strains was confirmed by antibiography and plasmid DNA analysis. No overgrowth of cecal gram-negative bacteria was found. This study suggests that the gut is a primary source of infection in pancreatitis and that ischemic damage of intestinal mucosa may promote bacterial translocation.

Acute Disease↗
PubMed1994

The clinical challenge of multiple pancreatic pseudocysts.

To evaluate the frequency of multiple pancreatic cysts, the likelihood of preoperative diagnosis, and therapeutic outcome, we retrospectively reviewed the records of 157 patients who underwent operation for pancreatic pseudocysts at 2 institutions between 1970 and 1992. Multiple pseudocysts were found in 29 (18.5%). The 8 women and 21 men ranged in age from 21 to 79 years. The etiology was alcohol abuse in 15 (52%), biliary tract disease in 6 (21%), alcohol abuse and biliary tract disease in 3 (10%), and a variety of other causes in the remaining 5 (17%). There was no difference in age, sex, race, etiology, or presenting signs and symptoms between patients with single pseudocysts and those with multiple cysts. Serum amylase levels were significantly higher in patients with multiple cysts compared to those with single cysts (P < 0.05). Computed tomography accurately demonstrated the extent of disease in 20 of 25 patients (80%), while 1 or more cysts were missed in 5 (20%). The mean number of cysts per patient was 2.7, with a range of 2 to 5. Average pseudocyst diameter was 7.8 cm, with a range from 3 to 20 cm. Multiple internal drainage procedures were performed in 19 patients, a combination of internal and external drainage in 6, external drainage in 1, and resection of multiple cysts in the tail in 2. There was no operative mortality. With a mean follow up of 38.5 months, only 1 recurrent pseudocyst has been found. There were six attempts at percutaneous drainage in six patients. Two of these patients were referred to our institution following failure of percutaneous drainage at other hospitals. Three other patients had residual symptomatic pseudocysts following percutaneous drainage at our hospitals and then underwent multiple internal drainage. The sixth patient refused operative drainage despite the persistence of residual symptomatic pseudocysts after attempted percutaneous drainage. The incidence of multiple pseudocysts (18.5%) is higher than previously reported. There is no difference in the clinical features of patients with single versus multiple pseudocysts. Patients with multiple cysts have higher serum amylase levels. Preoperative computed tomography underestimated the number of cysts in 20% of patients. Careful intraoperative exploration is still needed to avoid missing multiple pseudocysts. Internal drainage is the preferred therapy. A thorough search for multiple cysts at the initial operation should eliminate one potential cause for pseudocyst recurrence.

Adult↗
PubMed1994

Rate of quantal transmitter release at the mammalian rod synapse.

Under scotopic conditions, the mammalian rod encodes either one photon or none within its integration time. Consequently the signal presented to its synaptic terminal is binary. The synapse has a single active zone that releases neurotransmitter quanta tonically in darkness and pauses briefly in response to a rhodopsin isomerization by a photon. We asked: what minimum tonic rate would allow the postsynaptic bipolar cell to distinguish this pause from an extra-long interval between quanta due to the stochastic timing of release? The answer required a model of the circuit that included the rod convergence onto the bipolar cell and the bipolar cell's signal-to-noise ratio. Calculations from the model suggest that tonic release must be at least 40 quanta/s. This tonic rate is much higher than at conventional synapses where reliability is achieved by employing multiple active zones. The rod's synaptic mechanism makes efficient use of space, which in the retina is at a premium.

Animals↗
PubMed1994

Pathophysiological correlates of increased serum tumor necrosis factor in patients with congestive heart failure. Relation to nitric oxide-dependent vasodilation in the forearm circulation.

BACKGROUND: Tumor necrosis factor-alpha (TNF alpha), which we and others have shown to be elevated in patients with severe congestive heart failure (CHF), is involved in the regulation of nitric oxide metabolism. Whether increased concentrations of TNF alpha affect nitric oxide-mediated vasodilation in patients with CHF has not been studied previously. METHODS AND RESULTS: Serum concentrations of TNF alpha, interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined in venous blood (pg/mL) from 17 patients with stable New York Heart Association classes II and III CHF (mean age, 58 +/- 11 years; mean left ventricular ejection fraction, 19.5 +/- 7.3) and 17 age-matched normal subjects with enzyme-linked immunosorbent assays (detection limit of assays, 20 pg/mL). Forearm blood flows were determined with plethysmography (mL/min per 100 mL) in 17 patients and 7 normal subjects in response to brachial artery administration of graded concentrations of acetylcholine (10(-6) mol/L and 10(-5) mol/L) and nitroglycerin (10(-7) mol/L and 10(-6) mol/L). Serum concentrations of TNF alpha were above the detection limits of the assay in 10 of 17 patients with CHF (mean serum concentration, 39.4 +/- 3.8 pg/mL). Forearm blood flow responses to acetylcholine and nitroglycerin were significantly greater in these 10 patients than in the 7 patients without detectable serum TNF alpha and were closely correlated with TNF alpha serum concentrations (r > or = .81, P < .01 and r > or = .65, P < .05 respectively). In 1 of 17 normal subjects, the serum concentration of TNF alpha was just above the detection limit of the assay. Serum concentrations of IL-2 were above the detection limit of the assay in 14 of 17 patients with CHF (mean serum concentration, 112 +/- 19 pg/mL). IL-2 was not detected in the serum of normal subjects. Serum concentrations of IL-1 and IL-6 were below the detection limit of the assays in all patients and normal subjects assayed. CONCLUSIONS: Increased TNF alpha concentrations are closely correlated with forearm blood flow responses to regional administration of acetylcholine and nitroglycerin. The significant correlation between serum concentrations of TNF alpha and forearm blood flow responses to acetylcholine and nitroglycerin suggests that both the inducible and the constitutive forms of nitric oxide synthase are involved in the regulation of peripheral vasomotor tone in patients with CHF.

Adult↗
PubMed1994

Structural features of the yeast plasma-membrane H(+)-ATPase.

The yeast plasma-membrane H(+)-ATPase is a member of the P-family of cation transporters, which share a characteristic membrane topology together with consensus sequences for ATP binding and formation of a beta-aspartyl phosphate reaction intermediate. Although direct knowledge of ATPase structure has been difficult to obtain, several indirect approaches have yielded useful information. This chapter describes new results on the physical interaction between domains of the yeast ATPase and on the role of cysteine residues in structure, function, and biogenesis. A model is proposed based upon these and other recent findings.

Cell Membrane↗
PubMed1994

A new method to obtain a tissue diagnosis of proximal bile duct tumors.

Klatskin tumors often pose a challenge for diagnosis and treatment. Most of these neoplasms are diagnosed clinically because of the difficulty in obtaining tissue that will provide histologic proof of the disease. When a non-operative course is sought, exhaustive attempts should be made to obtain a tissue diagnosis because of the potential for a false-positive clinical diagnosis. We describe a new way to obtain tissue for diagnosis by placing a laparoscopic choledochoscope through a percutaneous transhepatic cholangiogram track, thus allowing the tumor to be directly visualized and biopsied.

Bile Duct Neoplasms↗
PubMed1993

Mutagenesis of conserved residues in the phosphorylation domain of the yeast plasma membrane H(+)-ATPase. Effects on structure and function.

A diagnostic feature of P-ATPases is a phosphorylation motif (DKTGTLT), located in the hydrophilic center of the polypeptide chain, within which the beta-aspartyl-phosphate reaction intermediate is formed. The roles of four invariant residues (Lys379, Thr380, Thr382, and Thr384) in this region of the yeast plasma membrane H(+)-ATPase have been analyzed by site-directed mutagenesis. In addition, a set of six insertion mutants was generated containing a single glycine residue at each of the indicated sites: [sequence: see text] C S D K T GT LT to examine spatial arrangements within this highly conserved domain. In order to minimize toxic effects of the mutations on cell growth, the defective ATPases were expressed behind an inducible heat shock promoter and targeted to an intracellular pool of secretory vesicles, while wild-type ATPase was maintained in the plasma membrane where it is required for viability. Secretory vesicles containing mutant ATPase were isolated as described previously (Nakamoto, R. K., Rao, R., and Slayman, C. W. (1991) J. Biol. Chem. 266, 7940-7949) and assayed for the amount of ATPase polypeptide and for rates of ATP hydrolysis and H+ pumping. All of the insertion mutations led to biosynthetic arrest of the defective enzyme, with no ATPase appearing in the secretory vesicles. Nonconservative amino acid substitutions (Lys-->Gln, Thr-->Ala) inactivated the ATPase, whereas conservative substitutions (Lys-->Arg, Thr-->Ser) retained partial activity which has been characterized in detail. There was little or no change in the Km for ATP or the pH optimum in any of the mutant enzymes. Strikingly, however, all displayed an increase in resistance to vanadate, consistent with the idea that the residues in question contribute to a phosphate/vanadate binding site or that they affect the equilibrium between E1 and E2 conformations of the enzyme.

Adenosine Triphosphate↗
PubMed1993

Enhancing factor protein from mouse small intestines belongs to the phospholipase A2 family.

Enhancing factor (EF), a growth regulatory molecule, isolated from mouse small intestines, has been well characterized in this laboratory. It increases the binding of epidermal growth factor in a unique manner via its own receptor. In the first 20 N-terminal amino acids sequenced, EF showed 50% homology to human Group II phospholipase A2 (PLA2). Here we propose that EF is yet another, unidentified isoform of PLA2 which regulates cell proliferation via modulation of EGF binding. To our knowledge, this is the first report implicating PLA2-II-like molecules in growth regulation.

Amino Acid Sequence↗
PubMed1993

Transcriptional regulation by glucose of the yeast PMA1 gene encoding the plasma membrane H(+)-ATPase.

The yeast plasma membrane H(+)-ATPase generates a membrane electrochemical gradient which is required for the secondary uptake of nutrients. Although the ATPase has previously been shown to be post-translationally regulated in response to the availability of glucose, there has been no evidence to date for transcriptional regulation of the ATPase gene (PMA1). In this work, we have examined the pool of newly synthesized ATPase that accumulates in secretory vesicles en route to the cell surface in the temperature-sensitive secretory mutant sec6-4, and have observed changes in the level of ATPase polypeptide as a function of the glucose concentration in the growth medium. In parallel, there were rapid and reversible changes in the levels of ATPase mRNA. Finally, when cells were grown on a variety of carbon sources, the amount of ATPase polypeptide was proportional to the specific growth rate, suggesting that PMA1 expression is adjusted according to the metabolic state of the cell. These results complement the findings of Capieaux et al. (Capieaux, E., Vignais, M.-L., Sentenac, A. and Goffeau, A. (1989). J. Biol. Chem. 264, 7437-7446), who show that the transcriptional factor TUF/RAP1 binds to upstream activating sequences in the PMA1 gene. Taken together, the results suggest a model in which transcriptional regulation of the ATPase gene by glucose is mediated by TUF/RAP1.

Cell Membrane↗
PubMed1993

alpha-Tocopherol uptake and its influence on cell proliferation and lipid peroxidation in transformed and nontransformed baby hamster kidney cells.

alpha-Tocopherol (alpha-T) uptake and its relationship to cell proliferation and lipid peroxidation was studied in a baby hamster kidney cell line (BHK-21/C13) and its polyoma virus-transformed malignant counterpart (BHK-21/PyY cells). The principal findings were as follows. (i) The level of lipid peroxidation, judged by malondialdehyde (MDA) measurement by HPLC, was higher in the transformed cells than in the nontransformed cells. Oxidative stress by 374 microM Fe3+/10 mM ADP caused a significant increase in the level of MDA of a similar magnitude in both cell types. Addition of 7, 14, and 21 microM alpha-T caused no diminution of the MDA level in the unstressed cells and abolished the rise in MDA seen in the stressed cells. (ii) The endogenous level of alpha-T in the transformed cells was lower than in the nontransformed cells and all the measurable alpha-T in these cells was destroyed by the oxidative stress. Supplementation of the cells with alpha-T caused a rise in the level of alpha-T proportional to the level of inclusion of alpha-T in the medium. (iii) alpha-Tocopheryl quinone in the transformed cells was unaffected by oxidative stress and in the nontransformed cells stress caused a large increase in this metabolite when alpha-T was included at the 21 microM level. (iv) Growth was stimulated by 7 and 14 microM alpha-T but not by the higher level of inclusion in the medium. The growth stimulation was much larger in the transformed cells (163% of growth in the unsupplemented medium) than in the nontransformed cells (120%). (v) These results demonstrate that, in this cell system, the growth-stimulating ability of alpha-T is unrelated to the ability of alpha-T to control lipid peroxidation and that the level of peroxidation is increased in the malignant state.

Adenosine Diphosphate↗
PubMed1993

Phospholipid loss in dying platelets.

The death of a cell results in a large amount of membrane lipid, predominantly phospholipids and cholesterol, that must be eliminated. In this study, we have examined what happens to phospholipids in dying rat platelets. Rat platelets were incubated for up to three days following their activation with thrombin. Platelet death occurred during the first day of incubation. This was indicated by a complete loss of platelet lactate dehydrogenase into the incubation medium. The platelets progressively lost over one-half of their phospholipid content during the three days of incubation. Cholesterol and sphingomyelin (the phospholipid with the highest affinity for cholesterol) were not lost during the same period. Our findings suggest that significant degradation of cellular non-sphingomyelin phospholipid can be triggered by cell death. The preservation of sphingomyelin in dying platelets, may be an adaptive response to maintain cholesterol in a solubilized state within dying cells.

Animals↗
PubMed1993

Surgical therapy in chronic pancreatitis.

Chronic pancreatitis should be treated medically until a surgically correctable complication develops. Incapacitating abdominal pain refractory to medical therapy is the most common indication for operation. Preoperative evaluation of chronic pancreatitis should include a dynamic computed tomography scan to evaluate the pancreas and pancreatic duct. If the pancreatic duct is not seen or is not dilated on computed tomography, an endoscopic retrograde cholangiopancreatogram should be performed. If the pancreatic duct is dilated more than 5 mm, a side-to-side pancreaticojejunostomy should be performed in symptomatic patients. If the pancreatic duct is not dilated and all other causes of pain have been ruled out, a pylorus-preserving Whipple resection or duodenum-preserving pancreatic head resection should be performed. Distal pancreatectomy is reserved for disease isolated to the tail. Total pancreatectomy is used only as a salvage procedure and, whenever possible, should be accompanied by autotransplantation of the residual gland or islet cells.

Chronic Disease↗