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Biomedical subjects

N Roy

Publications and source records attributed to N Roy.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative structure activity relationship of benzoxazinone derivatives as neuropeptide Y Y5 receptor antagonists.

Quantitative structure activity relationship (QSAR) has been established for 30 benzoxazinone derivatives acting as neuropeptide Y Y5 receptor antagonists. The genetic algorithm and multiple linear regression were used to generate the relationship between biological activity and calculated descriptors. Model with good statistical qualities was developed using four descriptors from topological, thermodynamic, spatial and electrotopological class. The validation of the model was done by cross validation, randomization and external test set prediction.

Algorithms↗
PubMed2006

Progenitor cell-based myelination as a model for cell-based therapy of the central nervous system.

Diseases of the brain and spinal cord are especially daunting challenges for cell-based strategies of repair, given the multiplicity of cell types within the adult central nervous system, and the precision with which they must interact in both space and time. Nonetheless, a number of diseases are especially appropriate for cell-based therapy, in particular those in which single phenotypes are lost. Foremost among these are the disorders of myelin, in which oligodendrocytes are the specific and often sole victims of the underlying disease process. These include not only the vascular, traumatic, and inflammatory demyelinations of adulthood, but also the congenital and childhood dysmyelinating syndromes of the pediatric leukodystrophies. These congenital disorders of myelin formation and maintenance may present especially compelling targets for cell-based neurological therapy.

Animals↗
PubMed2006

Sustained release nanoparticulate formulation containing antioxidant-ellagic acid as potential prophylaxis system for oral administration.

The aim of the present work was to develop ellagic acid (EA) loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for oral administration. PLGA nanoparticles were prepared by a method based on the concept of emulsion-diffusion-evaporation by using polyethylene glycol (PEG) 400 as a cosolvent for solubilizing the drug. While developing this method, didodecyldimethylammomium bromide (DMAB) and polyvinyl alcohol (PVA), alone and in combination with chitosan (CS) were employed. DMAB stabilized particles were the smallest of all the formulations with a particle size of 148.5 nm. PVA alone gave particles of 269.7 nm but a blend with CS (80:20) resulted in an increase in particle size (359.6 +/- 23.6 nm). Initial release of EA from nanoparticles in pH 7.4 phosphate buffer was rapid, followed by a slower sustained release. Release rates followed the order PVA > PVA-CS > DMAB. Release rate from the PLGA-DMAB particles was slowest, which is attributed to higher hydrophobicity of DMAB as compared to PVA, preventing diffusion of drug out of polymeric matrix. Insolubility of CS at alkaline pH could have retarded the release in case of PVA-CS system. In situ intestinal permeability study of pure drug and the drug encapsulated in nanoparticles prepared using PVA, PVA-CS blend and DMAB as stabilizer in rats showed 66, 75, 73 and 87% permeation, respectively. EA showed good free radical scavenging effect in a yeast cell culture model as well as in a cell free system.

Animals↗
PubMed2006

Genetic variation of farrowing kinetics traits and their relationships with litter size and perinatal mortality in French Large White sows.

Genetic parameters of litter traits and their relationships with farrowing kinetics traits were estimated in a Large White population to examine the impact of selection for litter size on perinatal mortality and one of its main determinants, farrowing kinetics. Data were collected on 2,947 farrowings from 1,267 sows between 1996 and 2004. Litter traits included the number born in total (NBT), number born alive (NBA), and the number (NSB) and proportion (PSB) of stillborn piglets. Four farrowing kinetics traits were considered: farrowing duration (FD), birth interval (BI = FD/NBT), heterogeneity of birth intervals (SDNB = SD of the number of piglets born each one-half hour), and birth assistance (BA) during the farrowing process. Genetic parameters were estimated using restricted maximum likelihood methodology. All traits were analyzed using a mixed linear animal model including year x month and parity as fixed effects; the additive genetic value of each animal and the sow permanent environment were treated as random effects. To normalize their distribution, kinetics traits were Box-Cox-transformed. Low heritability estimates were obtained for litter size and mortality traits, which was in agreement with literature results (i.e., 0.10 +/- 0.02, 0.08 +/- 0.02, 0.19 +/- 0.02, and 0.14 +/- 0.02 for NBT, NBA, NSB, and PSB, respectively). Heritability values were also low for kinetics traits: 0.10 +/- 0.02, 0.08 +/- 0.02, 0.01 +/- 0.01, and 0.05 +/- 0.03 for FD, BI, SDNB, and BA, respectively. The genetic correlation between NBT and NBA was strongly positive (ra = 0.90). On both phenotypic and genetic scales, NBT was positively associated with stillbirth (ra = 0.45 +/- 0.11, rp = 0.38 for NSB; ra = 0.46 +/- 0.13, rp = 0.17 for PSB). Conversely, NBA had low correlations with SB and PSB. Number born in total was moderately correlated to FD (ra = 0.34 +/- 0.15) and BI (ra = -0.37 +/- 0.15). A stronger relationship was found between NBA and BI (ra = -0.49 +/- 0.13), whereas the relationship with FD was lower (ra = 0.16 +/- 0.17). Moreover, FD was strongly correlated with stillbirth (ra = 0.42 +/- 0.12 with NSB), whereas BI was nearly independent of stillbirth. Contrary to selection on NBT, selection on NBA appears to be a good way to limit the negative side effects on stillbirth. Moreover, selection on NBA would lead to a small increase in FD and a faster and more regular birth process than would be obtained by selecting on NBT.

Animals↗
PubMed2005

Sid4: A secreted vertebrate immunoglobulin protein with roles in zebrafish embryogenesis.

The small members of the immunoglobulin superfamily (IGSF) are a molecularly diverse group of proteins composed solely of immunoglobulin domains. They may be secreted or tethered to the cell mebrane via GPI linkages and are proposed to have important functions in vivo. However, very few small IGSFs have been functionally characterized. During an ongoing in situ hybridization analysis of expressed sequence tags in zebrafish we identified secreted immunoglobulin domain 4 (sid4), a gene encoding a soluble vertebrate protein composed solely of four immunoglobulin domains. Throughout development, sid4 is expressed in regions of the embryo undergoing active cell division and migration. Functional analysis using morpholino antisense oligonucleotides demonstrates that timing of gene expression is normal in morphants, but these embryos are smaller and exhibit defects in epiboly and patterning of axial and prechordal mesoderm. Analyses of chordin, pax2, krox20, and dlx2 expression in morphants demonstrate that early brain patterning is normal but later organization of hindbrain neurons and development of cranial neural crest are perturbed. Levels of apoptosis in morphants were normal prior to 90% epiboly, but were elevated after 10 h post-fertilization (hpf). Apoptosis does not account for early patterning defects of axial mesoderm, but likely contributes to overall reduction in embryo size. Phylogenetic analysis demonstrates that Sid4 is strikingly similar to the fibronectin binding Ig domains of Perlecan/HSPG2. Overall, our data demonstrate a fundamental role for sid4, possibly as a co-factor in extracellular matrix (ECM) interactions, in processes underlying tissue patterning and organogenesis in a vertebrate.

Amino Acid Sequence↗
PubMed2003

Shoulder and elbow function following Marchetti-Vicenzi humeral nail fixation.

Humeral nailing has been associated with reduction of shoulder and elbow function. We present the results of fixation of 15 diaphyseal humeral fractures with Marchetti-Vicenzi nails (B Braun Medical Aesculap). Shoulder and elbow functions were assessed by the Constant shoulder and Mayo elbow scoring systems. The average Constant Shoulder score was good (82.5/100) and the average Mayo Elbow Score was excellent (95.4/100). The indications for surgery included nonunion, pathological fractures and poor fracture position. The mean follow-up was 67 weeks with an average interval to surgery of 19 weeks. The mean time to union was 19 weeks. All the fractures united without any patient requiring any further procedure. There were two postoperative radial nerve palsies and one median nerve palsy, however two patients had complete recovery and one had partial recovery of the radial nerve. There was one deep infection requiring removal of the implant. There were no implant failures. Based on our experience, the Marchetti-Vicenzi humeral nail appears as a relatively safe implant and its use has been associated with preservation of good shoulder and elbow functions.

Adult↗
PubMed2001

An evaluation of the effects of two treatment approaches for teachers with voice disorders: a prospective randomized clinical trial.

Teachers commonly report voice problems and often seek medical assistance for voice-related complaints. Despite the prevalence of voice disorders within this occupation, there are no studies evaluating the effectiveness of treatment programs designed to remedy the voice problems of teachers. To assess the functional effects of two voice therapy approaches, 58 voice-disordered teachers were randomly assigned to 1 of 3 groups: vocal hygiene (VH, n = 20), vocal function exercises (VFE, n = 19), and a nontreatment control group (CON, n = 19). Subjects completed the Voice Handicap Index (VHI)-an instrument designed to appraise the self-perceived psychosocial consequences of voice disorders-before and following a 6-week treatment phase. The VFE and VH subjects also completed a posttreatment questionnaire regarding the perceived benefits of treatment. Only the group who adhered to the VFE regimen reported a significant reduction in mean VHI scores (p <.0002). Furthermore, when compared to the VH group, the exercise group reported more overall voice improvement (p < .05) and greater ease (p < .02) and clarity (p < .01) in their speaking and singing voice after treatment. These findings suggest that the VFE should be considered as a useful alternative or adjunct to vocal hygiene programs in the treatment of voice problems in teachers.

Adult↗
PubMed2001

Protein kinase C regulates transcription of the human guanylate cyclase C gene.

Guanylate cyclase C is the receptor for the bacterial heat-stable enterotoxins and guanylin family of peptides, and mediates its action by elevating intracellular cGMP levels. Potentiation of ligand-stimulated activity of guanylate cyclase C in human colonic T84 cells is observed following activation of protein kinase C as a result of direct phosphorylation of guanylate cyclase C. Here, we show that prolonged exposure of cells to phorbol esters results in a decrease in guanylate cyclase C content in 4beta-phorbol 12-myristate 13-acetate-treated cells, as a consequence of a decrease in guanylate cyclase C mRNA levels. The reduction in guanylate cyclase C mRNA was inhibited when cells were treated with 4beta-phorbol 12-myristate 13-acetate (PMA) in the presence of staurosporine, indicating that a primary phosphorylation event by protein kinase C triggered the reduction in RNA levels. The reduction in guanylate cyclase C mRNA levels was not due to alterations in the half-life of guanylate cyclase C mRNA, but regulation occurred at the level of transcription of guanylate cyclase C mRNA. Expression in T84 cells of a guanylate cyclase C promoter-luciferase reporter plasmid, containing 1973 bp of promoter sequence of the guanylate cyclase C gene, indicated that luciferase activity was reduced markedly on PMA treatment of cells, and the protein kinase C-responsive element was present in a 129-bp region of the promoter, containing a HNF4 binding element. Electrophoretic mobility shift assays using an oligonucleotide corresponding to the HNF4 binding site, indicated a decrease in binding of the factor to its cognate sequence in nuclear extracts prepared from PMA-treated cells. We therefore show for the first time that regulation of guanylate cyclase C activity can be controlled at the transcriptional level by cross-talk with signaling pathways that modulate protein kinase C activity. We also suggest a novel regulation of the HNF4 transcription factor by protein kinase C.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2001

Fibroma induction in rat skin following single or multiple doses of 1.0 GeV/nucleon 56Fe ions from the Brookhaven Alternating Gradient Synchrotron (AGS).

Rat skin was exposed to the plateau region of the 1.0 GeV/nucleon 56Fe beam at the Brookhaven AGS. Rats were irradiated or not with single of split doses of 56Fe or argon; some 56Fe-exposed rats were fed 250 ppm retinyl acetate continuously in the lab chow beginning 1 week before irradiation. All lesions were noted, photographed and identified for eventual histological diagnosis. The preponderance of the tumors so far are fibromas. The data show that single doses of 56Fe ions are 2 or 3 fold more effective than argon in producing tumors at 4.5 Gy but are about equally effective at 3.0 Gy and 9.0 Gy. The presence of 250 ppm retinyl acetate in the lab chow reduced the incidence of tumors by about 50-60% in comparison to groups exposed only to the radiation. These are preliminary findings based on only about one-fourth the eventual number of tumors expected.

Animals↗
PubMed2000

Synthesis of the tetrasaccharide related to the repeating unit of the antigen from Shigella dysenteriae type 5.

Starting from L-rhamnose, D-mannose and 2-amino-2-deoxy-D-glucose hydrochloride, two disaccharide blocks, namely, ethyl 2,4-di-O-benzyl-3-O-[(R)-1-(methoxycarbonyl)ethyl]-alpha-L-rhamnopyranos yl-(1-->3)-2-O-acetyl-4,6-di-O-benzyl-1-thio-alpha-D-mannopyranoside and 2-(trimethylsilyl)ethyl 2-O-acetyl-3,6-di-O-benzyl-alpha-D-mannopyranosyl-(1-->3)-4,6-di-O-benzy l-2-deoxy-2-phthalimido-beta-D-glucopyranoside, were synthesised and then allowed to react in the presence of N-iodosuccinimide and trifluoromethane sulfonic acid to give a tetrasaccharide derivative. This compound was converted into 2-(trimethylsilyl)ethyl 2,4-di-O-benzyl-3-O-[(R)-1-(methoxycarbonyl)ethyl]-alpha-L-rhamno- pyranosyl-(1-->3)-2-O-acetyl-4,6-di-O-benzyl-alpha-D-mannopyranosyl-(1-- >4)-2-O-acetyl-3,6-di-O-benzyl-alpha-D-mannopyranosyl-(1-->3)-2-acetamid o-4,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside, which on hydrogenolysis, afforded the methyl ester 2-(trimethylsilyl)ethyl glycoside of the tetrasaccharide related to the repeating unit of the O-antigen from Shigella dysenteriae type 5.

Antigens, Bacterial↗
PubMed2000

Two paralogs involved in transcriptional silencing that antagonistically control yeast life span.

In the yeast Saccharomyces cerevisiae, one determinant of aging or life span is the accumulation of extrachromosomal copies of rDNA circles in old mother cells [1]. The production of rDNA circles depends upon intrachromosomal recombination within the rDNA tandem array, a process regulated by the protein Sir2 (Sir2p). Together with Sir1p, Sir3p, Sir4p and Orc1p, Sir2p is also involved in transcriptional silencing of genes at the silent mating-type cassettes, in the rDNA array, and at telomeres. Using a 'triple silencer' strain that can monitor an increase or decrease in gene expression at these three loci, we found that deletion of the ZDS1 gene caused an increase in silencing in the rDNA and at a silent mating-type cassette at the expense of telomere silencing. The zds1 deletion also resulted in an increase in life span and a decrease in Sir3p phosphorylation. In contrast, deletion of its paralog ZDS2 caused a decrease in rDNA silencing, a decrease in life span and an increase in Sir3p phosphorylation. As Zds2p, but not Zds1p, had strong two-hybrid interactions with Orc1p and the four Sir proteins, Zds1p might indirectly control Sir3p through a Sir3p kinase.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Organochlorine exposures and breast cancer risk in New York City women.

A hospital-based case-control study of breast cancer risk related to organochlorine (OC) exposure was conducted in a multiethnic setting in New York City. We enrolled 175 breast cancer patients and 355 control patients. The overall racial/ethnic distribution was 57% Caucasian, 21% Hispanic, 22% African-American; cases and controls were frequency-matched by age and race/ethnicity. Tumor markers (estrogen and progesterone receptors, p53, erbB-2) were assessed and organochlorines (DDE, DDT, trans-nonachlor, and higher (HPCB) and lower (LPCB) chlorinated biphenyls) were measured in blood serum. Tumors among minority women were of slightly higher stage than among Caucasians, but tumor markers were similar across the racial/ethnic groups. DDE levels were highest among African-American and Hispanic women; DDT was highest among Hispanics; HPCBs were highest among African-Americans; LPCBs were lowest among Hispanics; and trans-nonachlor was highest among African-Americans. However, OC levels were not associated with risk for breast cancer, nor did OCs differ with respect to tumor stage or tumor markers. Higher DDE levels were associated with increasing body mass index (BMI), but with decreasing level of education, frequency of nulliparity, and frequency of family history of breast cancer. HPCB levels decreased with BMI and were not correlated with breast cancer risk factors. These relationships can be attributed to historical patterns of exposure and to metabolic differences in OCs related to BMI.

Black People↗
PubMed2000

Effect of aluminum on the production of siderophore by Rhizobium sp. (Cicer arietinum).

Rhizobium sp. strain BICC 651 in the presence of 100 microM Al3+ produced a threefold higher level of siderophore than in the control culture under iron limitation during the stationary phase. Al3+ in increasing concentrations resulted in decreased growth, and the effect was alleviated by the addition of iron. Siderophore production decreased gradually in Al3+-treated culture as well as in the control with the addition of increasing concentrations of Fe3+, and at 50 microM Fe3+ the level of siderophore was practically undetectable. The siderophore binds Fe3+ and also Al3+. The outer membrane protein profiles of the bacteria grown in the presence or absence of Al3+ were indistinguishable.

Aluminum Compounds↗
PubMed2000

Congenital Heart Surgery Nomenclature and Database Project: pulmonary atresia--ventricular septal defect.

Pulmonary atresia (PA) and ventricular septal defect (VSD) is a complex and extremely heterogeneous cardiopulmonary malformation that has not been accurately defined, as evidenced by the synonymous use of the term with tetralogy of Fallot with PA. The anatomy and morphology of the pulmonary circulation to a large extent determines the surgical approach and overall outcome, with the intracardiac anatomy playing a secondary role. Based on the characterization of the pulmonary circulation a new classification of PA-VSD is proposed. In type A, there are only native pulmonary arteries (NPA). In type B, pulmonary blood flow is provided by both NPA and by major aortopulmonary collateral arteries [MAPCA(s)]. In type C, there are only MAPCA(s) and no NPA. This new classification is proposed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include all relevant nomenclature categories using synonyms where appropriate. A comprehensive database set is presented which is based on a hierarchical scheme. Data are entered at various levels of complexity and detail which can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented which will allow for data sharing and would lend itself to basic interpretation of trends. Outcome tables relating diagnoses, procedures, and various risk factors are presented.

Databases, Factual↗
PubMed2000

Personality and voice disorders: a multitrait-multidisorder analysis.

To examine whether personality has causal, concomitant, or outcome status in common voice disorders, a vocally normal control group and 4 groups with voice disorders--functional dysphonia (FD), vocal nodules (VN), spasmodic dysphonia (SD), and unilateral vocal fold paralysis (UVFP)--were compared using the Multidimensional Personality Questionnaire (MPQ). Univariate and discriminant analyses confirmed that the FD and VN groups differed significantly from each other, the controls, and the other voice-disordered groups at both a superfactor and lower-trait level of personality description. The FD group was introverted, stress reactive, alienated, and unhappy. The VN group was described as socially dominant, stress reactive, aggressive, and impulsive. Comparisons involving the SD, UVFP, and the control subjects did not identify consistent personality differences. While group trends supported the central tenets of a trait theory outlining the dispositional bases of FD and VN, further research is needed to elucidate the specific causal mechanism(s) in individual cases. The disability hypothesis, which suggests that personality features represent the negative effects of vocal disability, was not strongly supported.

Adult↗
PubMed2000

Vocal violence in actors: an investigation into its acoustic consequences and the effects of hygienic laryngeal release training.

Acoustic analysis techniques were used to investigate the short-term consequences of vocally violent behavior, and to compare voice production before and after training in hygienic laryngeal release (HLR) techniques. Twenty-seven actors ranging in age from 17 to 48 years were audiorecorded before and after multiple productions of 4 vocally violent behaviors: grunting, groaning, sobbing, and shouting. After training in HLR techniques, the experimental protocol was repeated. Audiorecordings of vowels (produced at 3 pitch levels: modal F0, minimum F0, maximum F0) before and after vocal violence, and before and after HLR training, were analyzed using the Multidimensional Voice Program (4305, Kay Elemetrics Corp, Lincoln Park, NJ). After vocal violence, no consistent acoustic changes were detected for voice generated at modal and minimum F0; however, significant increases in both fundamental frequency range and maximum F0 were observed. After training in HLR techniques, acoustic measures sensitive to pitch and amplitude perturbation, and non-harmonic noise, improved across pitch levels. The results also indicated that vocal training does defend the laryngeal system from undesirable changes related to vocally violent maneuvers that might surface at the extremes of an actor's pitch range. Because the HLR technique used in this investigation was multimodal, interesting questions are raised regarding which aspect of training is primarily responsible for the observed effects. Further study is required to identify such factors.

Adolescent↗