Biomedical subjects
Publications and source records attributed to R Roy.
Water-soluble alpha-galactosyl-chitosan conjugates were prepared by reductive amination of p-formylphenyl beta-melibioside on chitosan in good yield. Strong binding with phytohemagglutinin was demonstrated using Griffonia simplicifolia.
Water-soluble T-antigen containing glycopolymers [Gal beta(1,3)-GalNAc alpha) having a high degree of lipophilicity were synthesized from poly[N-(acryloxy)succinimide] (6-10) by amidation with an amine-ending T-antigen derivative (3) and various amines of increasing alkyl chain length (ammonia and methyl-, ethyl-, and propylamine). The enhanced lipophilicity was demonstrated by a solid-phase microtiter plate assay (ELISA) with mouse monoclonal antibody FAA-J11 (IgG3) and by a core 2-beta(1,6)-N-acetylglucoaminyltransferase using tritium-(3H-) labeled UDP-GlcNAc substrate. The new materials were thus useful in solid-phase high-throughput screening for drug discovery.
Membranes made from 4 commercial poly(carbonate urethanes): Carbothane (CB), Chronoflex (CF), Corethane 80A (CT80), and Corethane 55D (CT55), and from 2 poly(ether urethanes): Tecoflex (TF) and Tecothane (TT) were prepared by solution casting and sterilized by either ethylene oxide (EO) or gamma radiation. Their biocompatibility was evaluated in vitro in terms of proliferation, cell viability, and adhesion characteristics of human umbilical veins (HUVEC), monocytes (THP-1), and skin fibroblasts, and by measuring complement activation through the generation of the C3a complex. Their hemocompatibility was determined by measuring the level of radiolabeled platelet, neutrophil, and fibrin adhesion in an ex vivo arteriovenous circuit study in piglets as well as via an in vitro hemolysis test. The results of this study showed no endothelial cell proliferation on any of the materials. The cell viability study revealed that the CB, CF, and TF membranes sterilized by EO maintained the highest percentage of monocyte viability after 72 h of incubation (>70%) while none of the gamma-sterilized membranes displayed any cell viability. The fibroblast adhesion and C3a generation assays revealed that none of the materials supported any cell adhesion or activated complement, regardless of the sterilization method. The hemolysis test also confirmed that the 4 poly(carbonate urethanes) were hemolytic while none of the poly(ether urethanes) were. Finally, the ex vivo study revealed that significantly more platelets adhered to the CB and CT55 membranes while the levels of neutrophil and fibrin deposition were observed to be similar for all 6 materials. In conclusion, the study identified the CF and TF membranes as having superior biocompatibility and hemocompatibility compared to the other polyurethanes.
OBJECTIVE: Results of mitral valve replacement with a mitral homograft were evaluated at 5 years to assess the suitability of the procedure. METHODS: Thirty-seven patients (25 male subjects) aged 10 to 49 years (mean, 32 +/- 10 years) with rheumatic mitral valve disease underwent total (n = 35) or partial (n = 2) mitral valve replacement with a fresh antibiotic-preserved (n = 23) or cryopreserved (n = 14) mitral homograft. The predominant lesion was mitral stenosis (n = 30). RESULTS: There were 5 early deaths. Operative survivors were followed up for 1 to 60 months (mean, 26.6 +/- 12 months). Among these, 21 patients had severe mitral regurgitation during the follow-up period; 3 died and 8 underwent reoperation. The homograft failure rate was not affected by preoperative physiologic lesion (stenosis vs regurgitation, P =.4), type of homograft (antibiotic-preserved vs cryopreserved homograft, P =.9), papillary muscle pretreatment (yes vs no, P =.9), or addition of posterior collar annuloplasty (yes vs no, P =.2). Among the remaining patients, 5 had moderate mitral regurgitation, 4 had either trivial or mild mitral regurgitation, and 2 were lost to follow-up. Study of the explanted mitral homografts (n = 8) revealed that disruption of one of the donor papillary muscles was responsible for early failures (n = 2), whereas cuspal and chordal degeneration was responsible for late failures (n = 6). Microscopically, the explanted valve lacked any viable cellular elements, and there was no evidence of immunologic injury to the homografts. CONCLUSION: The mitral homograft did not fulfill our expectations as a suitable substitute for the diseased mitral valve.
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.
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.
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.
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.
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.
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.
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.
OBJECTIVES: High-altitude pulmonary edema (HAPE) afflicts certain individuals after a rapid gain in elevation. Those susceptible demonstrate an exaggerated hypoxic pulmonary vasoconstrictive response. This causes pulmonary hypertension, which may disrupt vascular integrity. This experiment was designed to test whether inhaled nitric oxide would affect development of HAPE in a rat model. METHODS: Subjects were exposed in a hypobaric chamber to a simulated altitude of 6200 m (barometric pressure = 380 mm Hg, fraction of inspired oxygen = 0.19) for 24 hours. Control animals (n = 48) spontaneously breathed a mixture of 90% room air and 10% nitrogen, whereas the nitric oxide group (n = 48) received a similar mixture containing 83 ppm nitric oxide. Postmortem examination of lungs was performed for light microscopy, total hemoglobin, and gravimetric estimates of water content. RESULTS: Mortality was 39.5% (n = 19) in control animals and 6.2% (n = 3) in the nitric oxide group (P < .001). Both groups significantly increased their lung weight-body weight ratio. Percentage of lung water was similar in both groups despite increases in lung weight, which is consistent with the protein-rich edema characteristic of HAPE. Light microscopic examination of survivors' lungs in both groups revealed scattered alveolar hemorrhage. No significant cellular inflammatory response was present. CONCLUSIONS: We conclude that inhaled nitric oxide improves survival in the rat model of HAPE.
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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).
OBJECTIVES: The present study was done to observe the insulin secretory response in healthy adult offspring of normotensive and hypertensive parents as the etiology of essential hypertension is largely treated as unknown. METHODS: The insulin secretary response was observed in 20 healthy adult offspring of normotensive parents (Group I) and 25 healthy adult offspring of hypertensive parents (Group II). The mean serum insulin levels were assessed at fasting, 30, 60, 90 and 120 minutes after 75 grams of oral glucose load in both groups. RESULTS: The mean serum insulin levels in fasting state was higher in group II (32.40 +/- 18.59) than group I (17.90 +/- 11.98) (p < 0.01). After 30 minutes mean serum insulin levels were higher in group II than group I (88.00 +/- 56.04, 40.5 +/- 15.15 respectively, p < 0.001). There was no statistically significant difference after 60, 90 and 120 minutes of oral glucose load (p > 0.05). CONCLUSIONS: Our observations suggest that the insulin secretory response in fasting and 30 minutes after oral glucose load was earliest metabolic abnormality in subjects at high risk for developing hypertension i.e. offspring of hypertensive parents.
Tuberculosis (TB) of liver is rare but may have a variety of presenting features similar to other more common conditions. A case of tuberculosis liver abscess with right sided pleural effusion is reported.
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.
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