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R Jain

Publications and source records attributed to R Jain.

At least 109 records · Page 6Linked to original sources
PubMed1998

Genomic evidence for two functionally distinct gene classes.

Analyses of complete genomes indicate that a massive prokaryotic gene transfer (or transfers) preceded the formation of the eukaryotic cell. In comparisons of the entire set of Methanococcus jannaschii genes with their orthologs from Escherichia coli, Synechocystis 6803, and the yeast Saccharomyces cerevisiae, it is shown that prokaryotic genomes consist of two different groups of genes. The deeper, diverging informational lineage codes for genes which function in translation, transcription, and replication, and also includes GTPases, vacuolar ATPase homologs, and most tRNA synthetases. The more recently diverging operational lineage codes for amino acid synthesis, the biosynthesis of cofactors, the cell envelope, energy metabolism, intermediary metabolism, fatty acid and phospholipid biosynthesis, nucleotide biosynthesis, and regulatory functions. In eukaryotes, the informational genes are most closely related to those of Methanococcus, whereas the majority of operational genes are most closely related to those of Escherichia, but some are closest to Methanococcus or to Synechocystis.

Genes, Bacterial↗
PubMed1998

Potent antagonists of somatostatin: synthesis and biology.

The search for synthetic analogues of somatostatin (SRIF) which exhibit selective affinities for the five known receptor subtypes (sst1-5) has generated a large number of potent agonist analogues. Many of these agonists display good subtype selectivities and affinities for the subtypes 2, 3, and 5, with very few selective for sst1 or sst4. Until the recent report by Bass and co-workers (Mol. Pharmacol. 1996, 50, 709-715; erratum, Mol. Pharmacol. 1997, 51, 170), no true antagonists had been discovered, let alone any displaying differential receptor subtype selectivity. In this present study, we explore the effect of this putative L5,D6 antagonist motif on various series of somatostatin agonist analogues, both linear and cyclic. It was found that many D5,L6 agonists could be converted into competitive antagonists by applying this motif, the most potent of which was H-Nal-cyclo[DCys-Pal-DTrp-Lys-Val-Cys]-Nal-NH2 (32). This antagonist was selective for hsst2 with an affinity of 75 nM and an IC50 of 15.1 nM against SRIF-14 in a rat in vitro antagonist bioassay. Receptor-selective somatostatin antagonists should provide valuable tools for characterizing the many important physiological functions of this neuropeptide.

Animals↗
PubMed1998

Isolation and analysis of dityrosine from enzyme-catalyzed oxidation of tyrosine and X-irradiated peptide and proteins.

Dityrosine (DT) was isolated in a single-step by reversed-phase HPLC in 25% yield from enzyme-catalyzed oxidation of N-acetyl tyrosine followed by deacetylation. The isolated product was characterized by 1H NMR. A three-step chromatographic procedure was reported to facilitate the preparation of DT from the enzyme-catalyzed oxidation of tyrosine in 26% yield of theoretical maximum. Upon irradiation at 284 nm in acidic and 315 nm alkaline conditions, DT exhibits strong fluorescence at 400 nm-range. However, when excited at 300 nm-range, contribution of similar fluorescence by Trp oxidation and other protein modifications cannot be overruled. In order to identify the formation of DT unequivocally, Tyr was subjected to X-irradiation under nitrogen at pH 4 and labeled with dansyl chloride. HPLC conditions were devised to resolve dansylated DT from dansylated standard amino acids. Radiation-induced DT was identified by cochromatography with a dansylated, authentic sample of DT isolated and characterized from enzyme-catalyzed oxidation of Tyr. The formation of DT in the irradiated samples, determined by the integrated peak area, increased with dose (0-600 Gy). HPLC analysis of dansylated hydrolysate of the major product from an irradiated tripeptide (Tyr Gly Gly) detected Gly and DT (2:0.5). Extension of the model study to irradiated BSA and RNase A also showed DT as the major oxidation product of Tyr under the experimental conditions. Fluorescence signal of dansylated DT was linear from 0.5 pmol to 1.5 nmol (correlation coefficient 0.999, n = 3). The detection limit 0.5 pmol per 5 microliters injection hydrolysate corresponds to one molecule of DT per 300 molecules of BSA (BSA at 1 mg/ml). DT can be used as a marker for assessing oxidative damage of proteins. Most standard amino acid analysis techniques are limited to detect normal residues of proteins. The assay reported in the present study has potential for low-level detection of DT unequivocally and may be useful for monitoring oxidative stress-related physiological and pathological processes.

Chromatography, High Pressure Liquid↗
PubMed1998

Mixed hepatoblastoma diagnosed by fine-needle aspiration biopsy cytology: a case report.

The cytologic features of a case of mixed hepatoblastoma diagnosed by fine-needle aspiration biopsy (FNAB) in a 2 1/2-yr-old child are described. FNAB was carried out on a large, firm mass in the upper abdomen, without any complications. The characteristic cytologic features were clusters of polyhedral cells with mild anisonucleosis, and intracytoplasmic bile pigment. Focal areas of mesenchymal elements were seen. Immature hematopoietic cells were present. FNAB offers a safe and accurate method of diagnosis.

Bile↗
PubMed1998

Stability of a hydrophobic drug in presence of hydrous and anhydrous lactose.

The chemical stability of a hydrophobic Leukotriene receptor antagonist drug was investigated in the presence of lactose (both hydrous and anhydrous) under various humidity and temperature conditions. The effect of wet-granulation and direct-mixing on the stability of the drug was also studied. Mixtures of drug:lactose in the ratio 1:25, 1:50 and 1:100 were prepared and analyzed over a 6 week period after storage at 40, 83 and 97% RH (all at 25 degreesC) and 75% RH at 40 degreesC. The mixtures were subjected to LOD, Karl--Fischer titrimetry, HPLC and DSC analysis to evaluate the amount of moisture pickup, percent potency and presence of drug-moisture-lactose interaction. Mixtures containing lactose anhydrous picked up more moisture and exhibited greater drug degradation than those containing lactose hydrous. Also, mixtures stored under high temperature and humidity condition showed greater moisture uptake than those stored at high humidity alone. Lactose anhydrous becomes hydrated on exposure to high humidity/temperature and storage conditions. The transition state of lactose and not its stable state may be responsible for its greater interaction and subsequent degradation of the drug. Therefore, the normal belief that lactose anhydrous, which has less than 0.5% moisture, should provide greater stability as compared to lactose hydrous, needs to be properly evaluated.

Calorimetry, Differential Scanning↗
PubMed1998

Sequence characteristics of natural populations of tomato spotted wilt tospovirus infecting flue-cured tobacco in Georgia.

Using primers from conserved regions, the nucleocapsid (Nc) gene sequences of naturally occurring tomato spotted wilt tospovirus (TSWV) isolates from flue-cured tobacco (Nicotiana tabacum) grown in several Georgia counties were amplified by immunocapture-reverse transcription-polymerase chain reaction. The resulting amplicons were cloned and sequenced. Sequence analyses showed a high degree of sequence conservation among the Nc genes of the tobacco isolates, and those reported from other parts of the world. However, distinct differences that were unique to these tobacco isolates as well as the previously studied peanut, tomato and pepper isolates from Georgia were present. The Georgia isolates formed a distinct cluster that was clearly resolved from the rest of the TSWV isolates based on sequence phylograms.

Base Sequence↗
PubMed1998

A biomechanical evaluation of different plates for fixation of canine radial osteotomies.

BACKGROUND AND METHODS: The biomechanical properties of plates depend on their geometries and elastic moduli. The low contact-dynamic compression plate (LC-DCP) with relieved undersurfaces is a modification of the dynamic compression plate (DCP). Little attention has been directed toward comparison of the biomechanical properties of the LC-DCP and the DCP. This study compared the stiffness and strength of bone-plate constructs using plates of various designs and materials for fixation of radial osteotomies. In 20 matched pairs of canine radii, midshaft transverse osteotomies were created and fixed with 3.5-mm eight-hole plates on the volar surface. In 10 pairs, stainless-steel LC-DCPs and stainless-steel DCPs were applied. In the other 10 pairs, stainless-steel LC-DCPs and titanium LC-DCPs were placed. Bending and torsional stiffness were determined. The plates were removed, and a 5-mm gap was created at the osteotomy site. The plates were reapplied to the bones with the interfragmental gap. Stiffness and yield point in the anteroposterior direction were determined. RESULTS: In the absence of a bone gap, no statistically significant differences in construct stiffness were seen between the paired groups. In the presence of a gap, the stainless-steel LC-DCP construct was stiffer than the titanium LC-DCP construct (p = 0.02), and the DCP construct was stiffer than the LC-DCP construct (p = 0.002). The yield point of the DCP-bone construct was 59% greater than that of the stainless-steel LC-DCP construct (p = 0.02). However, the yield points of the titanium and stainless-steel LC-DCP-constructs were similar (p = 0.35). CONCLUSION: The similar results between constructs in the absence of a gap indicate that plate design and material properties may be less significant for achieving adequate stability after plate fixation of simple fractures. The use of the stiffer dynamic compression plate may be advantageous when maximum stability is required, such as with comminution or bone loss.

Animals↗
PubMed1998

Inhibition of development of Myxococcus xanthus by eukaryotic protein kinase inhibitors.

Myxococcus xanthus is a social bacterium that lives in the soil and undergoes spectacular development to form multicellular fruiting bodies. It contains a large family of eukaryote-like serine/threonine protein kinases. We found that a number of inhibitors for eukaryotic protein serine, threonine, and tyrosine kinases could inhibit the development and sporulation of M. xanthus to various degrees. These results suggest that serine/threonine and tyrosine phosphorylation may be involved in development of M. xanthus. None of the inhibitors tested had any effect on vegetative growth of M. xanthus. Most of them seemed to act during the early stages of development. However, the expression of a very early development-specific gene, Omega4521, was not significantly affected by the inhibitors. The patterns of protein phosphorylation during development were also not significantly altered by the inhibitors, suggesting that the targets of the inhibitors are minor or unstable phosphoproteins but play key roles in fruiting-body formation in M. xanthus.

Enzyme Inhibitors↗
PubMed1998

Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches.

There has been extensive research on drug delivery by biodegradable polymeric devices since bioresorbable surgical sutures entered the market two decades ago. Among the different classes of biodegradable polymers, the thermoplastic aliphatic poly(esters) such as poly(lactide) (PLA), poly(glycolide) (PGA), and especially the copolymer of lactide and glycolide referred to as poly(lactide-co-glycolide) (PLGA) have generated tremendous interest because of their excellent biocompatibility, biodegradability, and mechanical strength. They are easy to formulate into various devices for carrying a variety of drug classes such as vaccines, peptides, proteins, and micromolecules. Most importantly, they have been approved by the United States Food and Drug Administration (FDA) for drug delivery. This review presents different preparation techniques of various drug-loaded PLGA devices, with special emphasis on preparing microparticles. Certain issues about other related biodegradable polyesters are discussed.

Absorption↗
PubMed1998

Abuse liability of buprenorphine--a study among experienced drug users.

Six male post-detoxified opiate dependent subjects were evaluated for abuse liability of buprenorphine (0.6 mg), morphine (16 mg), pentazocine (30 mg) and distilled water (placebo) intramuscular injection in a single blind cross-over random order. Subjective states, drug discrimination, drug linking, sedation and euphoria were assessed at pre-injection, 30 min and 4 hrs post-injection. Buprenorphine caused significant euphoria and was identified as heroin. On all parameters, buprenorphine resembled morphine rather than pentazocine and placebo. The data suggest that abuse liability of buprenorphine is similar to morphine i.e. moderate rather than low.

Adolescent↗
PubMed1998

Application of fuzzy-classifier system to coronary artery disease and breast cancer.

This paper presents an application of a genetic-algorithm-based representation of fuzzy rules for the classification of coronary artery disease data and breast cancer data. The performance of this fuzzy classifier for classification of coronary artery disease and breast cancer data is evaluated. In this study the concept of fuzzy if-then has been applied of rules proposed by Ishibuchi et al. for a multi dimensional data classification problem which leads to higher classification power. The fitness value of each fuzzy if-then rule was determined by the numbers of correctly and wrongly classified training patterns for that rule. The classification power on real world data for coronary artery disease and breast cancer was thus demonstrated by computer simulations.

Algorithms↗
PubMed1997

Role of the extracellular loops of the thyrotropin-releasing hormone receptor: evidence for an initial interaction with thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH), like most small ligands, appears to bind within the seven transmembrane-spanning helices (TMs) of its G protein-coupled receptor (TRH-R). A role for the extracellular loops (ECLs) of TRH-R has not been established. We substituted residues in the ECLs of TRH-R and show that Tyr-181 is important for high-affinity binding because its substitution leads to a 3700-fold lowering of the estimated affinity compared to wild-type TRH-R. Using TRH analogues, we provide evidence that there is a specific interaction between Tyr-181 in ECL-2 and the pyroGlu moiety of TRH. It was previously suggested that the pyroGlu of TRH may interact with Asn-110 in TM-3 and with Asn-289 in ECL-3; N110A and N289A TRH-Rs exhibit similar apparent affinities that are only 20-30-fold lower than wild-type TRH-R. To better understand these findings, we analyzed a computer-generated model which predicts that the ECLs form an entry channel into the TRH-R TM bundle, that Tyr-181 projects into this channel and that the pyroGlu of TRH cannot simultaneously interact with residues in the TMs and ECLs. Kinetic analysis showed that the association rate of [Ntau-methyl-His]TRH with N289A TRH-R is slower than with wild-type TRH-R and largely accounts for the lower apparent affinity; the association rate with N110A TRH-R is similar to that of wild-type TRH-R. These data are consistent with the idea that there are initial interactions between TRH and the residues of a putative entry channel of TRH-R. We suggest that a role of the ECLs in all G protein-coupled receptors for small ligands may be to initially contact the ligand and allow entry into a TM binding pocket.

Animals↗
PubMed1997

Treatment of rheumatoid arthritis.

The management of rheumatoid arthritis (RA) remains a challenging objective. Recent trends have led to the earlier and more "aggressive" treatment of patients with active disease. This change in outlook is largely the result of the recognition that significant damage can occur fairly soon after the onset of disease. This article reviews the currently available therapies, including a discussion of the benefits and side effects associated with individual agents. In addition, possible approaches to the treatment of RA will be reviewed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Pharmacological investigation of Cassia italica.

In the present study, the ethanolic extract of the whole plant parts (root, stem leaves and pods) of Cassia italica (Mill.) Lam. ex F.W. Ander (Leguminosae) was investigated for bioactivities: namely anti-inflammatory, antipyretic, analgesic and prostaglandin (PG) release by rat peritoneal leucocytes, antineoplastic and antiviral. In rats, the extracts reduced carrageenin-induced paw swelling (100 mg/kg bw-31%) and fever (100 mg/kg bw-37%). The extract showed weak effect on writhing induced by acetic acid. A dose-dependent inhibition of PG release effect was observed using rat peritoneal leucocytes.

Animals↗
PubMed1997

Decreasing blood donor exposure in the neonates by using dedicated donor transfusions.

Critically ill infants receive frequent red cell transfusions for replacement of blood drawn for laboratory analysis and in treatment of symptomatic anemia. Since blood for multiple transfusions on a given day is typically obtained from one fresh RBC unit, each multiply transfused neonate is exposed to many donors increasing the risk of transfusion transmitted disease. We hypothesized that the number of donor exposures per infant would decrease by instituting DDTP and that more infants will be exposed to only a single donor. We started a Dedicated Donor Transfusion Program (DDTP) in our NICU. One unit of red cells is dedicated to each baby for the life of the unit (35 days). We compared the donor exposure in infants for one year, before and after DDTP. The infants were divided into three birth weight groups. Group I were infants < 1000 g; Group II infants were 1000-1500 g; Group III infants were > 1500g. The average number of transfusions per patient decreased significantly from 7.5 +/- 6.0 to 4.7 +/- 4.2 (P < 0.001) in Group I while it remained unchanged in Groups II and III. The Dedicated Donor Transfusion Program significantly reduced the donor exposure in NICU infants. The program also facilitated the reduction of the number of transfusions in the infants under 1000 g.

Blood Donors↗
PubMed1997

Anti-invasive activity of alkaloids and polyphenolics in vitro.

Invasiveness, the ability of certain tumour cells to migrate beyond their natural tissue boundaries, often leads to metastasis, and usually determines the fatal outcome of cancer. The need for anti-invasive agents has led us to search for possibly active compounds among alkaloids and polyphenolics. One hundred compounds were screened in an assay based on the confrontation of invasive human MCF-7/6 mammary carcinoma cells with fragments of normal embryonic chick heart in vitro. Anti-invasive activity was frequently found among chalcones having a prenyl group. Six compounds were found to inhibit invasion when added to the culture medium at concentrations as low as 1 microM. For at least three of them the anti-invasive effect could be associated with a cytotoxic effect on the MCF-7/6 cells, but not on the heart tissue. This selective cytotoxicity was substantiated by different methods, such as histology and growth assays (volume measurements, cell counts, MTT and sulforhodamine B assays). The anti-invasive effects of the compounds could neither be ascribed to induction of apoptosis nor to the promotion of cell-cell adhesion. Our data indicate that among the alkaloids and polyphenolics a number of molecules can inhibit growth and invasion of human mammary cancer cells via selective cytotoxicity.

Alkaloids↗