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Biomedical subjects

M Roy

Publications and source records attributed to M Roy.

At least 217 records · Page 12Linked to original sources

Immunohistological analysis of the immune cells in the normal oral mucosa of aging mice.

Normal gingival tissues of BNL mice of different ages were studied, using recently developed immunohistochemical techniques to detect T and B lymphocytes, Langerhans cells and macrophages. The presence of mast cells, plasma cells and neutrophils was also determined. Cell densities were determined in the epithelium and connective tissue of all three areas studied. Their numbers increased significantly with age in the attachment area and in the papillary connective tissue. Langerhans cells (F4/80+) were detected in the epithelium of all three areas examined. Their numbers did not vary significantly with age. The highest concentrations of T lymphocytes and Langerhans cells were observed in the attachment area at all ages. Macrophages (F4/80+) were detected in the connective tissue of all three areas examined. Their numbers increased significantly in the papillary connective tissue of older animals (78 weeks of age). Neither B lymphocytes (RA-2C2+) nor plasma cells were detected in any of the tissue areas examined. The presence of neutrophils in the attachment area increased with age. Mast cells were present in all samples in the more vascularized areas (the papilla and diastema). The results suggest that, throughout the lifespan, T lymphocytes, macrophages, Langerhans cells and mast cells are normal constituents of the oral mucosa of the mouse, while B lymphocytes, plasma cells and, for the most part, neutrophils are absent under normal conditions. Furthermore, the concentrations of T lymphocytes and macrophages increased with age in the areas adjacent to the dentition, possibly as a result of reduced tissue resistance to external antigens.

Aging↗

Atlantoaxial instability in Down syndrome--guidelines for screening and detection.

A community survey was conducted in all adults with Down syndrome living in three health districts to see if there was any correlation between radiological and neurological abnormalities which could indicate the presence of atlantoaxial instability. There was no difference in the proportion of individuals with neurological abnormalities in the group with radiological abnormalities suggestive of atlantoaxial instability (6/14) compared with individuals with normal X-rays (50/123) as determined by the chi square test (0.01463: not significant). The clinical and ethical implications for screening of people with Down syndrome living in the community are discussed in view of these findings.

Adult↗

Selenium and immune cell functions. I. Effect on lymphocyte proliferation and production of interleukin 1 and interleukin 2.

The dietary intake of selenium (Se) has been shown to influence the development and expression of various biologic processes. This study examined the immunologic competence of lymphocytes from C57BL/6J mice maintained for 8 weeks on Se-deficient (0.02 ppm Se), normal (0.20 ppm Se, as sodium selenite), or Se-supplemented (2.00 ppm Se) Torula yeast-based diets. The ability of the cells to recognize alloantigens, to proliferate in response to stimuli, and to produce interleukin 2 (IL-2) was determined. Se deficiency significantly inhibited the ability of the lymphocytes to proliferate in response to allogeneic stimulation in the mixed lymphocyte reaction or to mitogen stimulation by phytohemagglutinin, whereas Se supplementation significantly enhanced both responses. In contrast, the amounts of IL-2 and interleukin 1 (IL-1) produced by lymphocytes and macrophages, respectively, removed from Se-deficient or Se-supplemented animals did not differ significantly from the amounts of IL-2 and IL-1 produced by cells removed from animals maintained on the control diet. These results suggest that the mechanism(s) responsible for the observed effects of Se on lymphocyte proliferation are independent of the levels of IL-2 or IL-1.

Animals↗

Selenium and immune cell functions. II. Effect on lymphocyte-mediated cytotoxicity.

Selenium (Se) is an essential nutritional factor with a chemopreventive potential. This study examined the ability of C57BL/6J mice, maintained for 8 weeks on Se-deficient (0.02 ppm Se), normal (0.20 ppm Se), or Se-supplemented (2.00 ppm Se) Torula yeast-based diets, to generate cytotoxic lymphocytes (CTL) and to destroy tumor cells. CTL were generated in vivo by intraperitoneal immunization with P815 cells and in vitro by allogeneic stimulation of cells from animals maintained on a normal diet in media supplemented with 1 x 10(-9) to 1 x 10(-6) M Se (as selenite). Lymphocytes from animals maintained on the Se-supplemented diet had a greater ability to destroy tumor cells than lymphocytes from animals maintained on the normal diet, whereas Se deficiency reduced the cytotoxicity. The effects on cytotoxicity were accompanied by parallel changes in the levels of lymphotoxin produced. The greatest enhancement of tumor cytodestruction occurred with supplementation of 1 x 10(-7) M Se, whereas with 1 x 10(-6) M there was inhibition of the cytotoxic responses. The stimulatory effect of Se occurred during the phase of CTL generation rather than during the lytic phase of cytotoxicity. These results indicated that Se supplementation enhances CTL generation and the ability of a host to destroy malignant cells, whereas Se deficiency has the opposite effect.

Animals↗

Efficacy and tolerance of sustained-release diltiazem 300 mg and a diuretic in the elderly.

A randomized, double-blind, parallel study has been performed to compare the antihypertensive action and clinical and biological tolerance of monotherapy with two different substances: sustained-release diltiazem 300 mg and a diuretic combining 25 mg of hydrochlorothiazide and 50 mg of triamterene (HCT-T). Antihypertensive treatment was suspended at least 15 days before initiation of a placebo period that lasted 14 days and allowed confirmation of persisting hypertension. Eighty-five patients who were at least 65 years old were included in the study: 42 in the group treated with sustained-release diltiazem 300 mg and 43 in the group treated with a diuretic. All of them presented with mild to moderate arterial hypertension, characterized by supine diastolic blood pressures (supine DBP) of 95-115 mm Hg. Duration of treatment was 3 months. After 1 and 3 months, efficacy and tolerance of the antihypertensive treatment were evaluated. On day 30, a significant decrease (p less than 0.0001) in the main parameter, i.e., supine DBP, as well as other parameters such as standing diastolic blood pressure (standing DBP), supine systolic blood pressure (supine SBP), and standing systolic blood pressure (standing SBP) was observed. Blood pressure was reduced by 18, 16, 28, and 26 mm Hg, respectively, in the sustained-release diltiazem 300 mg group and by 13, 12, 21, and 18 mm Hg, respectively, in the diuretic group. Moreover, on day 90, blood pressure values were maintained in the diuretic-treated group, whereas an additional significant reduction in supine DBP (p less than 0.002) was noted in the sustained-release diltiazem 300 mg-treated group (-4.8 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Environmental factors in the etiology of Parkinson's disease].

We examined the role of the environment in the development of Parkinson's disease (PD). A group of 42 parkinsonians have been compared with a group of 84 matched controls. The epidemiological study (1987-1989) covered the territory of the Community Health Department of Valleyfield, in southern Quebec (Canada). Odds ratio adjusted for age and sex were calculated for seven environmental factors. A decreased risk for PD was associated with residence in rural areas (OR: 0.31; p less than or equal to 0.05) and residence near industry or mining (OR: 0.15; p less than or equal to 0.05). An increased risk for PD seems to be associated with occupational exposure to the three metals Mn, Fe and Al (OR: 2.28; p = 0.07) especially when the duration of exposure is longer than 30 years (OR: 13.64; p less than or equal to 0.05). Other environmental factors not found to be associated with PD were: pesticides manipulation, farm work, industrial work and well water consumption.

Environment↗

Spectroscopic signatures of the T to R conformational transition in the insulin hexamer.

The cobalt(II)-substituted human insulin hexamer has been shown to undergo the phenol-induced T6 to R6 structural transition in solution. The accompanying octahedral to tetrahedral change in ligand field geometry of the cobalt ions results in dramatic changes in the visible region of the electronic spectrum and thus represents a useful spectroscopic method for studying the T to R transition. Changes in the Co2+ spectral envelope show that the aqua ligand associated with each tetrahedral Co2+ center can be replaced by SCN-, CN-, OCN-, N3-, Cl-, and NO2-. 19F NMR experiments show that the binding of m-trifluorocresol stabilizes the R6 state of zinc insulin. The chemical shift and line broadening of the CF3 singlet, which occur due to binding, provide a useful probe of the T6 to R6 transition. Due to the appearance of new resonances in the aromatic region, the 500 MHz 1H NMR spectrum of the phenol-induced R6 hexamer is readily distinguishable from that of the T6 form. 1H NMR studies show that phenol induces the T6 to R6 transition, both in the (GlnB13)6(Zn2+)2 hexamer and in the metal-free GlnB13 species; we conclude that metal binding is not a prerequisite for formation of the R state in this mutant.

Insulin↗

Rabbit blastocoelic fluid regulation of tumor-cell proliferation in vitro.

To determine whether rabbit blastocoelic fluid could inhibit tumor-cell proliferation, day-9 and day-12 embryonic fluids, together with autologous and homologous sera, were collected from pregnant or pseudopregnant rabbits and tested against 13 different cell lines and on human carcinoma cells in primary culture. An inhibitory effect on cell proliferation was observed in the presence of blastocoelic fluids, but not with homologous or heterologous sera. This suppression was higher with samples collected at day 12 than at day 9 of pregnancy. No such inhibition could be detected on one-cell rabbit embryos or on freshly prepared uterine stromal or myometrial cells. In addition, the inhibitory activity on tumor cells was completely reversible upon removal of the fluids. Incorporation of 3H-thymidine, 3H-uridine and 35S-methionine revealed that, in the presence of blastocoelic fluids, both DNA and RNA syntheses were rapidly inhibited. Inhibition of protein synthesis did not occur before 24 hr of treatment. We conclude that rabbit blastocoelic fluid suppresses the proliferation of tumor cells via inhibition of RNA and DNA synthesis by a process which may involve the expression of growth-suppression gene(s).

Animals↗

The site of substrate and fructose 2,6-bisphosphate binding to rabbit liver fructose-1,6-bisphosphatase.

The binding site(s) in rabbit liver fructose-1,6-bisphosphatase for the active site binding ligand, fructose 6-phosphate, and the inhibitor, fructose 2,6-bisphosphate, have been investigated by using nuclear magnetic resonance spectroscopy. The distance from a nitroxide spin label to the bound ligands and the distance from the structural metal site to the bound ligands are about the same within experimental error. These data indicate that the two ligands probably bind at the active site in the rabbit liver enzyme.

Animals↗

L-serine analogues form Schiff base and quinonoidal intermediates with Escherichia coli tryptophan synthase.

Substrate analogues of L-serine have been found that react with the alpha 2 beta 2 complex of Escherichia coli tryptophan synthase. Upon reaction with alpha 2 beta 2, the analogues glycine, L-histidine, L-alanine, and D-histidine form chemical intermediates derived from reaction with enzyme-bound pyridoxal 5'-phosphate with characteristic UV-visible spectral bands. The spectra of the products of the glycine, L-histidine, and L-alanine reactions with alpha 2 beta 2 contain contributions from the external aldimine, the quinonoid species, and other intermediates along the catalytic pathway. Just as previously reported for the reaction of L-serine with beta 2 [Goldberg, M. E., York, S., & Stryer, L. (1968) Biochemistry 7, 3662-3667], the reactions of glycine, L-histidine, and L-alanine with the beta 2 form of tryptophan synthase yield spectra with no contributions from catalytic intermediates beyond the external aldimine. The kinetics of intermediate formation and comparisons of the time courses for the exchange of alpha-1H for solvent 2H catalyzed by alpha 2 beta 2 or beta 2 were found to be consistent with these assignments. Intermediates further along the tryptophan synthase catalytic pathway are stabilized to a greater degree in the alpha 2 beta 2 complex than in the beta 2 species alone. This observation strongly suggests that the association of alpha and beta subunits to form the native alpha 2 beta 2 species lowers the activation energies for the interconversion of the external aldimine with chemical species further along the catalytic path.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Highly sensitive and rapid radioimmunoassay for aldosterone in plasma and cell culture medium.

A radioimmunoassay for aldosterone was developed using a sensitive and specific antibody and 125Iodinated-aldosterone. This assay could be used for direct determination of aldosterone in cell culture medium or after extraction of aldosterone from plasma by solid phase procedure using C18 Sep-pak cartridges. The very low cross-reactivity of the antibody with cortisol and corticosterone (0.005% and 0.04% respectively) would allow the direct determination of aldosterone in cell culture medium without any prior extraction step. Since the incubation is performed at room temperature for 1 h and then, at 4 degrees C for 15 min, the results can be obtained in less than 3 h. The assay was linear from 0.5 fmol/tube to 1500 fmol/tube with an ED50 at 30 fmol/tube. The accuracy of the assay estimated using spiked plasma samples with a known amount of aldosterone give a coefficient of correlation of 0.97 (n = 10) between the aldosterone concentrations found and expected levels. The within-assay variability for plasma aldosterone varied from 4.7 to 11.1% and the between-assay variability ranged from 13.9 to 14.2%. The coefficient of correlation between plasma aldosterone measured by this new assay or by a current assay was 0.8 (n = 43). In summary, the combination of a shortened incubation time with a simple solid phase extraction for aldosterone in serum samples represents the major advantage of the present assay over the current methodology which usually requires a chromatographic separation of the mineralocorticoid prior to radioimmunoassay. Therefore this assay would be useful in experimental studies as well as in clinical laboratory.

Aldosterone↗

Metastatic potential of gastric leiomyosarcoma.

Metastatic and lethal gastric leiomyosarcoma in 12 of 30 surgically treated cases was found most closely correlated with larger size tumors. A highly statistically significant correlation (p less than 0.0001) between tumor diameter and success or failure of surgical extirpation was demonstrated for the total of 241 gastric leiomyosarcomas in the present series and collected from the literature. Six other gross and microscopic attributes analyzed, including mitotic counts, did not provide equally useful prognostic indications. Inadequate sampling may be responsible for lack of correlation between histological criteria and tumor progression.

Humans↗

Lung clearance modeling on the basis of physiological and biological parameters.

To construct models and choose parameters for recommended lung dosimetric models, it is necessary to integrate many sets of experimental data. Information is not always useful, and appropriate quantitative data are often lacking. Therefore, available data from animal experiments and human clinical studies are often used as substitutes; this is the case, for example, for values of mechanical clearance pathways and factors. On the other hand, multiple and diverse data sets can help to evaluate the influence of individual variations, such as sex differences, age, exercise state, waking or sleeping state, and various abnormal conditions, so models will be suitable to describe conditions in a large number of people. When precise values cannot be estimated from existing data, it may be necessary to investigate a particular mechanism, such as material solubilization, by means of in vivo and in vitro techniques. However, it is difficult to extrapolate from such studies to humans. In this paper we discuss construction of an interspecies model of Co3O4 lung clearance from data for several animal species and a few human subjects.

Aerosols↗

Identification of a second "French Canadian" LDL receptor gene deletion and development of a rapid method to detect both deletions.

Hobbs et al. (N. Engl. J. Med. 317: 734-737, 1987) reported a large deletion of approximately 10 kilobases in the 5' portion of the human low-density lipoprotein (LDL) receptor gene. This deletion affects about 60% of familial hypercholesterolemia (FH) heterozygotes in the French Canadian population. We have developed a rapid, convenient method for the detection of the deletion using double digestion with the restriction enzymes XbaI and EcoRV, or triple digestion with XbaI, EcoRV and XmnI, and a 650 bp cDNA probe, radio-labeled using a random oligonucleotide primer technique. Eighty French Canadian FH heterozygotes were screened for the presence of the deletion. Forty-seven (59%) of them were found to carry the 10 kb deletion. Using the same method, we also identified a new mutation which was found in four of the 80 (5%) FH patients. This mutation has been found to be a 5 kb deletion removing exons 2 and 3 of the LDL receptor gene, which correspond to the first two repeats of the LDL receptor binding domain. Cosegregation of the 5 kb deletion and the FH phenotype was observed in one family. Possible structure-function relationship is discussed.

Canada↗

Retinal leakage in retinal vein occlusion: reduction after hyperbaric oxygen.

A 54-year-old woman with a history of bilateral central retinal vein occlusion, probably due to an inflammatory process, developed a hemispheric retinal vein occlusion with cystoid macular edema in her only seeing eye. Five months later, in the absence of improvement in vision and macular edema, she received on two occasions a 2-weekly course of twice daily 100% hyperbaric oxygen. After each course retinal leakage, as assessed by vitreous fluorophotometry, decreased from abnormal to the normal range while visual acuity improved by two lines. The possible implications are discussed.

Female↗