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Biomedical subjects

R Roy

Publications and source records attributed to R Roy.

At least 37 records · Page 2Linked to original sources

Beyond intimacy: conceptualizing sex differences in same-sex friendships.

This study was designed to replicate and extend prior findings that same-sex friendships of women and men are equally important but that women's friendships are more intimate. A group of adolescents and a group of adults were asked to complete an anonymous questionnaire regarding the quality of their close friendships, the degree to which they would support a close friend in times of difficulty, and the degree to which they would celebrate with a friend in times of success. Results demonstrated that both females and males saw and spoke with their close friends and were equally willing to confront and trust their close friends. Females, however, reported more desire to spend time with a close friend in times of difficulty and to celebrate with a close friend who had just experienced a positive event. Results are discussed in terms of the differing functions of women's and men's same-sex friendships and women's greater general interest in and attention to transitions in the lives of other individuals.

Adolescent↗

Chondrocyte translocation response to direct current electric fields.

Using a custom galvanotaxis chamber and time-lapse digital video microscopy, we report the novel observation that cultured chondrocytes exhibit cathodal migration when subjected to applied direct current (DC) electric fields as low as 0.8 V/cm. The response was dose-dependent for field strengths greater than 4 V/cm. Cell migration appeared to be an active process with extension of cytoplasmic processes in the direction of movement. In some cells, field application for greater than an hour induced elongation of initially round cells accompanied by perpendicular alignment of the long axis with respect to the applied field. Antagonists of the inositol phospholipid pathway, U-73122 and neomycin, were able to inhibit cathodal migration. Cell migration toward the cathode did not require the presence of serum during field application. However, the directed velocity was nearly threefold greater in studies performed with serum. Studies performed at physiologic temperatures (approximately 37 degrees C) revealed a twofold enhancement in migration speed compared to similar studies at room temperature (approximately 25 degrees C). Findings from the present study may help to elucidate basic mechanisms that mediate chondrocyte migration and substrate attachment. Since chondrocyte migration has been implicated in cartilage healing, the ability to direct chondrocyte movement has the potential to impact strategies for addressing cartilage healing/repair and for development of cartilage substitutes.

Animals↗

A variable speed translating couch technique for total body irradiation.

We have developed a variable speed translating patient couch system for the delivery of total body irradiation (TBI). For a whole body Rando-type phantom, dose variation at mid-plane relative to the prescription point (navel) can be as high as 15% (neck or legs) with a constant velocity. By taking into account variations in body thickness, the intensity modulation radiation therapy, resulting from variable velocities, effectively delivers a uniform dose distribution at mid plane. The couch control user interface, technical aspects and dose planning optimization procedure for determining velocity distribution are described.

Biophysical Phenomena↗

Production and consumption of nitric oxide by three methanotrophic bacteria.

We studied nitrogen oxide production and consumption by methanotrophs Methylobacter luteus (group I), Methylosinus trichosporium OB3b (group II), and an isolate from a hardwood swamp soil, here identified by 16S ribosomal DNA sequencing as Methylobacter sp. strain T20 (group I). All could consume nitric oxide (nitrogen monoxide, NO), and produce small amounts of nitrous oxide (N(2)O). Only Methylobacter strain T20 produced large amounts of NO (>250 parts per million by volume [ppmv] in the headspace) at specific activities of up to 2.0 x 10(-17) mol of NO cell(-1) day(-1), mostly after a culture became O(2) limited. Production of NO by strain T20 occurred mostly in nitrate-containing medium under anaerobic or nearly anaerobic conditions, was inhibited by chlorate, tungstate, and O(2), and required CH(4). Denitrification (methanol-supported N(2)O production from nitrate in the presence of acetylene) could not be detected and thus did not appear to be involved in the production of NO. Furthermore, cd(1) and Cu nitrite reductases, NO reductase, and N(2)O reductase could not be detected by PCR amplification of the nirS, nirK, norB, and nosZ genes, respectively. M. luteus and M. trichosporium produced some NO in ammonium-containing medium under aerobic conditions, likely as a result of methanotrophic nitrification and chemical decomposition of nitrite. For Methylobacter strain T20, arginine did not stimulate NO production under aerobiosis, suggesting that NO synthase was not involved. We conclude that strain T20 causes assimilatory reduction of nitrate to nitrite, which then decomposes chemically to NO. The production of NO by methanotrophs such as Methylobacter strain T20 could be of ecological significance in habitats near aerobic-anaerobic interfaces where fluctuating O(2) and nitrate availability occur.

Genes, rRNA↗

Topoisomerase I associates specifically with simian virus 40 large-T-antigen double hexamer-origin complexes.

Topoisomerase I (topo I) is required for releasing torsional stress during simian virus 40 (SV40) DNA replication. Recently, it has been demonstrated that topo I participates in initiation of replication as well as in elongation. Although T antigen and topo I can bind to one another in vitro, there is no direct evidence that topo I is a component of the replication initiation complex. We demonstrate in this report that topo I associates with T-antigen double hexamers bound to SV40 origin DNA (T(DH)) but not to single hexamers. This association has the same nucleotide and DNA requirements as those for the formation of double hexamers on DNA. Interestingly, topo I prefers to bind to fully formed T(DH) complexes over other oligomerized forms of T antigen associated with the origin. High ratios of topo I to origin DNA destabilize T(DH). The partial unwinding of a small-circular-DNA substrate is dependent on the presence of both T antigen and topo I but is inhibited at high topo I concentrations. Competition experiments with a topo I-binding fragment of T antigen indicate that an interaction between T antigen and topo I occurs during the unwinding reaction. We propose that topo I is recruited to the initiation complex after the assembly of T(DH) and before unwinding to facilitate DNA replication.

Animals↗

Susceptibility to infections and immune status in Inuit infants exposed to organochlorines.

We investigated whether organochlorine exposure is associated with the incidence of infectious diseases in Inuit infants from Nunavik (Arctic Quebec, Canada). We compiled the number of infectious disease episodes during the first year of life for 98 breast-fed and 73 bottle-fed infants. Concentrations of organochlorines were measured in early breast milk samples and used as surrogates to prenatal exposure levels. Immune system parameters were determined in venous blood samples collected from infants at 3, 7, and 12 months of age. Otitis media was the most frequent disease, with 80. 0% of breast-fed and 81.3% of bottle-fed infants experiencing at least one episode during the first year of life. During the second follow-up period, the risk of otitis media increased with prenatal exposure to p,p'-DDE, hexachlorobenzene, and dieldrin. The relative risk (RR) for 4- to 7-month-old infants in the highest tertile of p, p'-DDE exposure as compared to infants in the lowest tertile was 1. 87 [95% confidence interval (CI), 1.07-3.26]. The RR of otitis media over the entire first year of life also increased with prenatal exposure to p,p'-DDE (RR, 1.52; CI, 1.05-2.22) and hexachlorobenzene (RR, 1.49; CI, 1.10-2.03). Furthermore, the RR of recurrent otitis media ( [Greater/equal to] 3 episodes) increased with prenatal exposure to these compounds. No clinically relevant differences were noted between breast-fed and bottle-fed infants with regard to immunologic parameters, and prenatal organochlorine exposure was not associated with immunologic parameters. We conclude that prenatal organochlorine exposure could be a risk factor for acute otitis media in Inuit infants.

Acute Disease↗

Active constrained truncated Newton method for simple-bound optical tomography

In the past, nonlinear unconstrained optimization of the optical imaging problem has focused on Newton-Raphson techniques. Besides requiring expensive computation of the Jacobian, the unconstrained minimization with Tikhonov regularization can pose significant storage problems for large-scale reconstructions, involving a large number of unknowns necessary for realization of optical imaging. We formulate the inverse optical imaging problem as both simple-bound constrained and unconstrained minimization problems in order to illustrate the reduction in computational time and storage associated with constrained image reconstructions. The forward simulator of excitation and generated fluorescence, consisting of the Galerkin finite-element formulation, is used in an inverse algorithm to find the spatial distribution of absorption and lifetime that minimizes the difference between predicted and synthetic frequency-domain measurements. The inverse approach employs the truncated Newton method with trust region and a modification of automatic reverse differentiation to speed the computation of the optimization problem. The reconstruction results confirm that the physically based, constrained minimization with efficient optimization schemes may offer a more logical approach to the large-scale optical imaging problem than unconstrained minimization with regularization.

Journal Article↗

Effects of 2-deoxy-D-glucose on Acanthocheilonema viteae: rodent filariids as studied by multinuclear NMR spectroscopyt.

A well known glucose antimetabolite, 2-deoxy glucose (2DG) widely used in chemotherapy of cancer along with radiation, was evaluated as an antifilarial agent by nuclear magnetic resonance. The uptake and metabolism of 2DG in the experimental filarial infection Acanthocheilonema viteae was studied by in vivo multinuclear NMR. An unusually long retention time of 2DG6P within these parasites was observed on continuous 31P NMR monitoring, along with a decrease in ATP levels. These results led to therapeutic investigation in A. viteae infected host Mastomys coucha. 2DG showed a remarkable adulticidal activity (73.6%) with 50% sterilization of surviving female worms at a dose of 250 mg/kg x 5, p.o. NMR observations and activity profile substantiate the findings of one another, directed towards the hitting of bioenergetic machinery of A. viteae by macrofilaricidal agent (2DG).

Administration, Oral↗

On the application of integer-valued time series models for the analysis of disease incidence.

Statistical time series models are practical tools in public health surveillance. Their capacity to forecast future disease incidence values exemplifies their usefulness. Using these forecasts, one can develop strategies to trigger alerts to public health officials when irregular disease incidence values have occurred. Clearly, the better the forecasting performance of the model class used in the time series analysis, the more realistic are the alerts triggered. The time series analysis of disease incidence values has often entailed the Box and Jenkins model class. However, this class was designed to model real-valued variables whereas disease incidences are integer-valued variables. A new class of time series models, called integer-valued autoregressive models, has been developed and studied over the past decade. The objective of this paper is to introduce this new class of models to the application of time series analysis of infectious disease incidence, and to demonstrate its advantages over the class of real-valued Box and Jenkins models. The paper also presents a bootstrap method developed for the calculation of forecast interval limits.

Communicable Diseases↗

Characterization of intracellular metabolites of axenic amastigotes of Leishmania donovani by 1H NMR spectroscopy.

The intracellular metabolites of long-term in vitro cultured axenic amastigotes of Leishmania donovani (strain Dd8) were determined and compared with those of promastigotes and intracellular amastigotes, employing proton NMR spectroscopy. The presence of two new metabolites, i.e. betaine and beta-hydroxybutyrate were reported. Betaine was detected in all the three stages being highest in the promastigotes while beta-hydroxybutyrate could be detected only in promastigotes and axenic amastigotes. Among other metabolites, succinate and valine were found in higher quantities in intracellular amastigotes and axenic amastigotes than in promastigotes. Acetoacetate was present only in axenic and intracellular amastigotes. The comparative metabolite profile of different parasite forms reveals that axenic amastigotes seem to represent an intermediate stage between promastigotes and intracellular amastigotes in spite of their strong resemblance to intracellular amastigotes in morphology, infectivity, biochemical studies and even in the manifestation of amastigote specific A2 protein.

3-Hydroxybutyric Acid↗

Active-latent glycosylation strategy toward Lewis X pentasaccharide in a form suitable for neoglycoconjugate syntheses.

Glycosylation of 4-nitrophenyl 2-acetamido-6-O-tert-butyldiphenylsilyl-2-deoxy-1-thio-beta-D-gluc opyranoside with phenyl 2,3,4,6-tetra-O-benzoyl-1-thio-beta-D-galactopyranoside in the presence of NIS and TfOH as catalyst gave the lactosamine derivative regiospecifically in high yield. Further 3-O-fucosylation with phenyl 2,3,4-tri-O-benzyl-1-thio-beta-L-fucopyranoside using DMTST as promoter afforded the Lex trisaccharide intermediate. The latent glycosyl donor was transformed into its active form (p-acetamidothiophenyl) by reduction with zinc in acetic acid and N-acetylation. Glycosidation with p-nitrothiophenyl lactoside acceptor in the presence of NIS/TfOH as catalyst gave the Lex pentasaccharide in 71% yield.

Carbohydrate Conformation↗

Formaldehyde ferredoxin oxidoreductase from Pyrococcus furiosus: the 1.85 A resolution crystal structure and its mechanistic implications.

Crystal structures of formaldehyde ferredoxin oxidoreductase (FOR), a tungstopterin-containing protein from the hyperthermophilic archaeon Pyrococcus furiosus, have been determined in the native state and as a complex with the inhibitor glutarate at 1.85 A and 2. 4 A resolution, respectively. The native structure was solved by molecular replacement using the structure of the homologous P. furiosus aldehyde ferredoxin oxidoreductase (AOR) as the initial model. Residues are identified in FOR that may be involved in either the catalytic mechanism or in determining substrate specificity. The binding site on FOR for the physiological electron acceptor, P. furiosus ferredoxin (Fd), has been established from an FOR-Fd cocrystal structure. Based on the arrangement of redox centers in this structure, an electron transfer pathway is proposed that begins at the tungsten center, leads to the (4Fe:4S) cluster of FOR via one of the two pterins that coordinate the tungsten, and ends at the (4Fe:4S) cluster of ferredoxin. This pathway includes two residues that coordinate the (4Fe:4S) clusters, Cys287 of FOR and Asp14 of ferredoxin. Similarities in the active site structures between FOR and the unrelated molybdoenzyme aldehyde oxidoreductase from Desulfovibrio gigas suggest that both enzymes utilize a common mechanism for aldehyde oxidation.

Aldehyde Oxidoreductases↗

Does root glutamine synthetase control plant biomass production in lotus japonicus L.?

To investigate the contribution of root cytosolic glutamine synthetase (GS) activity in plant biomass production, two different approaches were conducted using the model legume Lotus japonicus. In the first series of experiments, it was found that overexpressing GS activity in roots of transgenic plants leads to a decrease in plant biomass production. Using (15)N labelling it was shown that this decrease is likely to be due to a lower nitrate uptake accompanied by a redistribution to the shoots of the newly absorbed nitrogen which cannot be reduced due to the lack of nitrate reductase activity in this organ. In the second series of experiments, the relationship between plant growth and root GS activity was analysed using a series of recombinant inbred lines issued from the crossing of two different Lotus ecotypes, Gifu and Funakura. It was confirmed that a negative relationship exists between root GS expression and plant biomass production in both the two parental lines and their progeny. Statistical analysis allowed it to be estimated that at least 13% of plant growth variation can be accounted for by variation in GS activity.

Journal Article↗

Comparison of healing in fresh and preserved arterial allografts in the dog.

The use of aortic allografts for the management of vascular prosthetic infections has recently been reintroduced. Impressive results have been obtained; however, the possibility of late degeneration remains a major concern. The healing behavior of aortic allografts, either fresh or preserved, in antibiotic-supplemented nutrient medium at 4 degrees C for 1 week and used as thoracic aorta substitutes in dogs was investigated after 6 months of implantation. Four dogs received a fresh aortic allograft from four different donors, and four dogs received a preserved allograft from two different donors. Autografts in two dogs were performed as controls. The in vivo investigation was conducted to describe (1) the histological characteristics of the arterial wall, (2) the macroscopic and thrombogenic aspect of the luminal surface, (3) the integrity of the endothelial lining by scanning electron microscopy, and (4) its biochemical function by prostacyclin (PGI2) and thromboxane A2 (TXA2) secretion. Immune-mediated reactions directed toward the grafts were measured by sequential screening of donor-specific serum antibody development. All donor-recipient pairs of dogs were major histocompatibility complex (MHC)-incompatible according to a mixed lymphocyte reaction (MLR) assay. From the results of this study we concluded that although preserved arterial allografts exhibited similar surface characteristics as those of fresh allografts in terms of re-endothelialization and long-term graft function, an elicited immune response, a degenerative process in the media, and a hyperplasic reaction in the intima could not be prevented using this method of preservation.

Animals↗

Pulmonary autograft: should it be used in young patients with rheumatic disease?

BACKGROUND: Although pulmonary autograft is being increasingly used to replace the diseased aortic valve with excellent long-term results, its use in the population with rheumatic disease still needs careful evaluation. PATIENTS AND METHODS: From October 1993 through March 1998, 102 patients underwent aortic valve replacement with a pulmonary autograft (Ross procedure). The mean age was 27.9 +/- 4.2 years (range, 0.8-56 years). The cause was rheumatic disease in 75 patients (73%), bicuspid aortic valve in 26 patients (26%), and myxomatous aortoarteritis in 1 patient (1%). The root replacement technique was used in all. In addition, 31 patients had 33 associated procedures: mitral valve repair (n = 15 patients), open mitral commissurotomy (n = 15 patients), tricuspid repair (n = 2 patients), and homograft mitral valve replacement (n = 1 patient). RESULTS: Operative mortality was 6.9% (7 patients). Late mortality was 7.8% (8 patients). Follow-up ranged from 1 to 60 months (mean, 25.3 +/- 15.4 months) and was 98% complete. Two patients required reoperation for failed mitral valve repair, and 2 other patients underwent reoperation for failure of both the autograft and mitral valve repair. Echocardiographic assessment showed moderate to severe aortic regurgitation in 13 patients, along with thickening of the autograft. All of these patients had rheumatic disease and were young (<30 years). Ten of these patients had undergone associated mitral valve procedure. Morphologic and histopathologic examination of explanted autografts showed features compatible with rheumatic valvulitis. CONCLUSION: Pulmonary autograft is susceptible to rheumatic involvement. Young age (<30 years) and associated mitral valve disease are significant risk factors for autograft failure in patients with rheumatic disease. Use of pulmonary autograft in this subgroup of patients requires a cautious approach.

Adolescent↗