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Biomedical subjects

R Reddy

Publications and source records attributed to R Reddy.

At least 127 records · Page 7Linked to original sources
PubMed1996

17O-decoupled 1H detection using a double-tuned coil.

17O-decoupled proton MR spectroscopy imaging with a double-tuned radiofrequency (RF) coil at 2 T was used to detect and quantify H2 17O in tissue containing various concentrations of 17O-enriched water in 5% gelatin. The pulse sequence used in these experiments consisted of a conventional proton spin-echo sequence with RF irradiation at the 17O resonance frequency applied between the proton 90 degrees pulse and the signal acquisition window. The double-tuned coil provided several advantages over systems using separate RF coils for 17O decoupling and proton excitation/detection, including ensuring that the same (or similar) sample volumes are excited and decoupled and permitting accurate calibration of the 17O decoupling pulse amplitude. The efficiency of 17O decoupling as a function of decoupling RF amplitude, decoupling duration, and decoupling resonance offset was investigated. Finally, the specific absorption rate of the 17O decoupled pulse sequence was investigated and found to lie within federal guidelines at 1.5 T.

Hydrogen↗
PubMed1996

Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease.

To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Protein engineering studies of A-chain loop 47-56 of Escherichia coli heat-labile enterotoxin point to a prominent role of this loop for cytotoxicity.

Heat-labile enterotoxin (LT), produced by enterotoxigenic Escherichia coli, is a close relative of cholera toxin (CT). These two toxins share approximately 80% sequence identity, and consists of one 240-residue A chain and five 103-residue B subunits. The B pentamer is responsible for GM1 receptor recognition, whereas the A subunit carries out an ADP-ribosylation of an arginine residue in the G protein, Gs alpha, in the epithelial target cell. This paper explores the importance of specific amino acids in loop 47-56 of the A subunit. This loop was observed to be highly mobile in the inactive R7K mutant of the A subunit. The position of the loop in wild-type protein is such that it might require considerable reorganization during substrate binding and is likely to have a crucial role in substrate binding. Five single-site substitutions have been made in the LT-A subunit 47-56 loop to investigate its possible role in the enzymatic activity and toxicity of LT and CT. The wild-type residues Thr-50 and Val-53 were replaced either by a glycine or by a proline. The glycine substitutions were intended to increase the mobility of this active-site loop, and the proline substitutions were intended to decrease the mobility of this same loop by restricting the accessible conformational space. Under the hypothesis that mobility of the loop is important for catalysis, the glycine-substitution mutants T50G and V53G would be expected to exhibit activity equal to or greater than that of the wild-type A subunit, while the proline substitution mutants T50P and T53P would be less active. Cytotoxicity assays showed, however, that all four of these mutants were considerably less active than wild-type LT. These results lend support for assignment of a prominent role to loop 47-56 in catalysis by LT and CT.

Animals↗
PubMed1996

Culture of Helicobacter pylori: effect of preimmersion of biopsy forceps in formalin.

BACKGROUND: Treatment of antibiotic-resistant Helicobacter pylori should be based on bacterial sensitivity testing that requires the ability to isolate the bacterium from gastric mucosal biopsies. The aim of this study was to determine whether the yield for detecting H. pylori infection by culture is reduced by immersion of biopsy forceps in formalin prior to obtaining the specimen. MATERIALS AND METHODS: Gastric antral mucosal biopsies (100 specimens) from 50 patients were obtained for culture of H. pylori. An antral biopsy was taken for culture, and with the same forceps a biopsy was taken for histological examination. The biopsy specimen was removed by shaking, whereas the forceps was immersed in 10% buffered formalin for the histological investigation. The forceps was then used without rinsing to obtain a second specimen for culture from an area adjacent to the first site. H. pylori status was determined by histological assessment with the Genta stain and a rapid urease test. RESULTS: Fifty patients with H. pylori infection documented by histological inquiry and positive rapid urease testing entered the study; 29 had duodenal ulcers, 5 had gastric ulcers, 1 had mucosal associated lymphoid tissue (MALT) lymphoma, and 15 were without ulcer disease. The results of culture both before and after immersion in formalin were identical. One patient had both cultures negative; the sensitivity of culture for detection of H. pylori infection was 98% (95% confidence interval = 93%-100%). CONCLUSION: Preimmersion of biopsy forceps in formalin does not adversely affect the ability to culture H. pylori.

Bacteriological Techniques↗
PubMed1996

Is antrum or corpus the best site for culture of Helicobacter pylori?

BACKGROUND: Isolating Helicobacter pylori on culture media and performing antibiotic susceptibility testing is potentially the most useful tool for guiding antibiotic therapy, especially when antimicrobial resistance is suspected. The aim of this study was to determine whether the yield of H. pylori culture was related to the site from which the gastric specimen was obtained either before or after therapy. METHODS: Gastric mucosal biopsies from the antrum and the corpus of the stomach were cultured. H. pylori status was determined by histological assessment using the Genta stain. RESULTS: Fifty-two patients with documented H. pylori infection were studied: Twenty-three were tested before antibiotic therapy and 29 after therapy had failed. In 47 patients (90%), both antral and corpus culture specimens were positive. In 5 patients (10%), only one site was positive, with three false-negative antral and two false negative corpus cultures. The overall sensitivity of culture in detecting H. pylori infection was 95% (95% confidence interval = 89-98%) and was not significantly different for the antrum or corpus, either before or after therapy. CONCLUSION: Culture of gastric biopsies from either the antrum or the corpus has an excellent diagnostic yield even in patients who failed antimicrobial therapy.

Anti-Bacterial Agents↗
PubMed1996

Direct activity of recombinant human lactoferrin against Helicobacter pylori.

We report the activity of recombinant human lactoferrin against Helicobacter pylori. Lactoferrin exerted a time- and dose-dependent action against 8 of the 13 clinical isolates of H. pylori tested in vitro. These results highlight a potential therapeutic use for lactoferrin against H.pylori infection.

Anti-Bacterial Agents↗
PubMed1996

Bronchodilatation and the inspiratory flow volume curve.

The inspiratory flow volume curve is included in the spirometric tracing provided by most pulmonary function laboratories and is useful in assessing upper airway abnormalities. We analyzed the changes in peak inspiratory flow (PIF), forced inspiratory flow at 50% (FIF50), and forced inspiratory vital capacity (FIVC) that occur with bronchodilator challenge testing (3 puffs of a beta-agonist by metered-dose inhaler without a spacer device) in 145 consecutive patients. Fifty-five patients responded to bronchodilators with either a 12% or 200-mL change in FEV1 or FVC. All of these subjects produced forced expiratory maneuvers that fulfilled American Thoracic Society criteria or acceptability. The FIVC was the only inspiratory parameter that consistently showed a similar correlation to the bronchodilator responsiveness demonstrated by the FEV1 or FVC. With the reduction in air trapping, a 12% or 200-mL change in the FIVC is additional confirmatory evidence of bronchodilator responsiveness.

Adrenergic beta-Agonists↗
PubMed1996

Localization of modified nucleotides in Schizosaccharomyces pombe spliceosomal small nuclear RNAs: modified nucleotides are clustered in functionally important regions.

The specific and dynamic RNA:RNA interactions between pre-mRNA and small nuclear RNAs (snRNAs), especially U2, U5, and U6 snRNAs, form the catalytic core and are at the heart of the spliceosome formation. The functionally important regions in the snRNAs correspond to the highly modified regions in snRNAs from human, rat, and plant cells. To better understand the importance of the modifications of snRNAs, we identified and localized the modified nucleotides in the five spliceosomal snRNAs of Schizosaccharomyces pombe cells. Twenty-two modified nucleotides, including base methylations, 2'-O-methylations, and pseudouridines, were found in the five spliceosomal snRNAs. The conservation of modified nucleotides between human and S. pombe snRNAs is striking. In addition, most of the modified nucleotides are in or around positions that form hydrogen bonds with the pre-mRNA or with other snRNAs. The results are consistent with the suggestion that modified nucleotides are clustered around functionally important regions of the spliceosomal snRNAs. These data provide the basis for further functional studies on posttranscriptional modifications in spliceosomal snRNAs.

Base Sequence↗
PubMed1996

Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole.

BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo. One opinion is that H. pylori "migrates" from the antrum to the corpus in response to omeprazole therapy. METHODS: To determine whether H. pylori migrates in response to omeprazole, we assessed the presence of H. pylori in the antrum and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and histological examination of antral biopsies (Genta stain) were performed before patients received omeprazole, at the end of therapy, and 4-6 wk later. The end points were presence or absence of H. pylori and the number of H. pylori colonies per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and corpus at entry and 4-6 wk after ending therapy. Three general patterns were prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%), antrum-negative and corpus-positive (24%), both antrum- and corpus-negative (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation of the number of colonies per biopsy in those who remained H. pylori-positive in both the antrum and corpus throughout showed that the number of H. pylori decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/- 51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus, respectively, and tended to return to pre-therapy levels 4-6 wk later. The number of H. pylori in the corpus also decreased in the antrum-negative and corpus-positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p < 0.05). In most of the patients studied, the number of H. pylori in the corpus was less posttreatment than it was pretreatment. The decrease in H. pylori load was also reflected in the development of false-negative urea breath tests. CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the corpus; migration from the antrum to the corpus in response to omeprazole is a myth.

Anti-Ulcer Agents↗
PubMed1995

Accurate and efficient N-6-adenosine methylation in spliceosomal U6 small nuclear RNA by HeLa cell extract in vitro.

Human U6 small nuclear RNA (U6 snRNA), an abundant snRNA required for splicing of pre-mRNAs, contains several post-transcriptional modifications including a single m6A (N-6-methyladenosine) at position 43. This A-43 residue is critical for the function of U6 snRNA in splicing of pre-mRNAs. Yeast and plant U6 snRNAs also contain m6A in the corresponding position showing that this modification is evolutionarily conserved. In this study, we show that upon incubation of an unmodified U6 RNA with HeLa cell extract, A-43 residue in human U6 snRNA was rapidly converted to m6A-43. This conversion was detectable as early as 3 min after incubation and was nearly complete in 60 min; no other A residue in U6 snRNA was converted to m6A. Deletion studies showed that the stem-loop structure near the 5' end of U6 snRNA is dispensable for m6A formation; however, the integrity of the 3' stem-loop was necessary for efficient m6A formation. These data show that a short stretch of primary sequence flanking the methylation site is not sufficient for U6 m6A methyltransferase recognition and the enzyme probably recognizes secondary and/or tertiary structural features in U6 snRNA. The enzyme that catalyzes m6A formation in U6 snRNA appears to be distinct from the prolactin mRNA methyltransferase which is also present in HeLa nuclear extracts.

Adenosine↗
PubMed1995

Voltage-sensitive adenylyl cyclase activity in cultured neurons. A calcium-independent phenomenon.

Catalytic subunits of mammalian adenylyl cyclases have been proposed to contain 12 transmembrane domains, a property shared with some voltage-sensitive ion channels. Here we report that adenylyl cyclase activity in cerebellar neurons is synergistically stimulated by depolarizing agents and beta-adrenergic receptor activation. This phenomenon is Ca(2+)-independent and not attributable to Ca(2+)-stimulated adenylyl cyclase activity. Cholera toxin and forskolin also synergistically stimulate adenylyl cyclase activity in combination with depolarizing agents. We hypothesize that conformational changes in the catalytic subunit of the enzymes caused by changes in the membrane potential may enhance stimulation of adenylyl cyclases by the guanylyl nucleotide stimulatory protein. This novel mechanism for regulation of adenylyl cyclases generates robust cAMP signals that may contribute to various neuromodulatory events including some forms of neuroplasticity.

Adenylyl Cyclases↗
PubMed1995

Detection of residual quadrupolar interaction in human skeletal muscle and brain in vivo via multiple quantum filtered sodium NMR spectra.

Using sodium multiple quantum filtered methods, we have, for the first time, demonstrated the presence of residual quadrupolar interaction in human skeletal muscle and brain in vivo. Surface coils were used in both skeletal muscle and brain studies on healthy human volunteers. Theoretical analysis shows that even with arbitrary flip angles the double quantum filter retains filtering capability; it passes even rank two quantum coherence more efficiently than odd rank two quantum coherence. Multiple quantum filtered spectra were obtained from the gastrocnemius muscle in the leg and from the parietal lobe region of the brain. In double quantum filtered spectra, we observed different proportions of narrow and broad components with preparation time, while the line shape of triple quantum filtered spectra remained similar to the one observed in isotropic environment. These results suggest that, in human skeletal muscle and brain, sodium ions are bound to some ordered structures.

Female↗
PubMed1995

Nutritional support in the management of external pancreatic fistulas.

A prospective analysis of 20 patients with external pancreatic fistulas was undertaken over a 5-year period to evaluate the response of pancreatic fistulas to non-operative management. In 90% of patients fistula followed external trauma to the pancreas. There were 18 males and 2 females and the average age was 30.3 years. Fifteen patients were given enteral nutrition alone and 5 received total parenteral nutrition; 2 of these received somatostatin as well. All the fistulas healed spontaneously within 7-80 days, with no deaths. We conclude that if the patient's condition is stable external pancreatic fistulas can be managed safely and effectively by non-operative means. Nutritional support, especially via the enteral route if possible, is beneficial.

Adolescent↗
PubMed1995

A distributed, scalable, community care network architecture for wide-area electronic patient records: modeling and simulation.

Principal systems issues relative to computerizing patient medical records that are yet to be addressed in the scientific literature include (1) the characteristics of networks, i.e. bandwidth and capacity, and their impact on the performance of the system, (2) the architecture and the underlying algorithm of the system, (3) the location and migration of medical records, (4) scalability of the system, and (5) the nature of the performance variation under heavy and light use of the network. Key parameters that affect performance include the number of patients, doctors, frequency of patient visits, and the number of electronic queries and record entries initiated during a patient-doctor interaction episode. This paper presents AMPReD, a Distributed, Scalable, Community Care Network Architecture that aims to provide Real-Time Access to Geographically-Dispersed Patient Medical Records. The AMPReD model includes stationary hospitals and medical clinics, mobile clinics, migrating doctors as well as patients, the communications network, and the patient medical record database. AMPReD's goals include (1) the accurate modeling of the propagation of medical records and (2) providing real-time access to patient medical records from anywhere in the system. To achieve these goals, an asynchronous, distributed algorithm must be developed that achieves concurrent access of multiple, autonomous databases. AMPReD is modeled and simulated for a representative community care network on a network of workstations configured as a loosely-coupled parallel processor, for different parametric combinations of number of doctors, patients, and number of queries or record entries generated corresponding to every patient-doctor interaction episode. AMPReD defines and obtains key performance measures including the idle times of the doctors, patient waiting times, the access times of queries as functions of their sizes, and the growth of the databases. In addition, AMPReD also measures the deviation of the actual time required for a patient-doctor interaction episode from the scheduled interaction interval, as a function of the network load. For the representative system selected, performance measures indicate that the network, utilizing 1/2T1 links, and the database system poses no bottleneck to the system even where the number of doctors and patients within a 30 minute interval are chosen at 192 and 200 respectively. A T1 is a standard, digital, transmission link that is rated at 1.44Mbits/sec.

Algorithms↗