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Biomedical subjects

M Roy

Publications and source records attributed to M Roy.

At least 37 records · Page 2Linked to original sources
PubMed1997

The A-kinase anchoring domain of type IIalpha cAMP-dependent protein kinase is highly helical.

Subcellular localization of the type II cAMP-dependent protein kinase is controlled by interaction of the regulatory subunit with A-Kinase Anchoring Proteins (AKAPs). This contribution examines the solution structure of a 44-residue region that is sufficient for high affinity binding to AKAPs. The N-terminal dimerization domain of the type IIalpha regulatory subunit of cAMP-dependent protein kinase was expressed to high levels on minimal media and uniformly isotopically enriched with 15N and 13C nuclei. Sequence-specific backbone and side chain resonance assignments have been made for greater than 95% of the amino acids in the free dimerization domain using high resolution multidimensional heteronuclear NMR techniques. Contrary to the results from secondary structure prediction algorithms, our analysis indicates that the domain is highly helical with a single 3-5-residue sequence involved in a beta-strand. The assignments and secondary structure analysis provide the basis for analyzing the structure and dynamics of the dimerization domain both free and complexed with specific anchoring proteins.

Amino Acid Sequence↗
PubMed1997

MHC-dependent cytolysis of autologous tumor cells by lymphocytes infiltrating urothelial carcinomas.

Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas. Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+ and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens confirmed this observation, and indicated that CD4+ T cells surrounded the tumor islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five short-term carcinoma cell lines established from these urothelial tumors were used as target cells in cytolysis assays in order to investigate the functional anti-tumor activity of autologous TIL. TIL from 4/5 tumors were lytic and 3 TIL lines displayed MHC-class-I-dependent cytotoxicity directed against autologous tumor cells. CD4+ T-cell-depletion experiments performed on TIL line 07 confirmed that CD8+ MHC-class-I-dependent CTL were the predominant effectors. Finally, experiments performed on 6 allogeneic urothelial-cancer cell lines matched for HLA-class-I molecules showed that TIL07 exhibited selective lytic activity toward tumor 07. These data indicate that CD8+ MHC-class-I-dependent CTL present in urothelial carcinomas are functional and may participate in the anti-tumor immune response.

CD3 Complex↗
PubMed1997

Antigen-presenting function of murine gonadal epithelial cell lines.

Murine Leydig (TM3) and Sertoli (TM4) cell lines were studied as nonprofessional antigen-presenting cells using the antigen model of human choriogonadotropin (hCG alpha/beta) and specific T-cell hybridomas. Both cell lines were treated with IFN-gamma to induce I-A(d) and I-E(d) molecules expression. Only the TM3 cell line, which expressed MHC-class II molecules upon IFN-gamma stimulation, was able to uptake, process, and present the human choriogonadotropin beta subunit to related T-cell hybridomas. Interestingly, the TM3 cell line was incapable of presenting the human choriogonadotropin alpha subunit, the presentation of which, by classical APC, is highly efficient. Using T-cell hybridomas directed against the immunogenic regions of hCG alpha/beta previously described in BALB/c mice, we showed that the TM3 cell line generated a narrower peptide repertoire than classical APC (i.e., B cells, macrophages, and dendritic cells). This experimental system suggests that Leydig cells could initiate, in vivo, an autoimmune process directed against gonadal tissues. In particular, such a mechanism has been evoked in experimental autoimmune orchitis.

Animals↗
PubMed1997

Reduced blue cone electroretinogram in cocaine-withdrawn patients.

BACKGROUND: The main reinforcing effect of cocaine is alteration of dopaminergic neurotransmission in the brain reward systems. Since dopamine is found in high concentrations in the retina, we investigated whether cocaine dependence may be associated with abnormalities of the electroretinogram. METHODS: We compared recently withdrawn cocaine-dependent patients (n = 20) with age-, sex-, and race-matched normal subjects (n = 20) for responses of cone photoreceptors to light flashes on full-field electroretinograms. RESULTS: Cocaine-dependent patients had significantly reduced blue cone electroretinogram responses compared with matched normal subjects. CONCLUSIONS: This result suggests that cocaine-withdrawn patients have a dysregulation of blue cone function. The electroretinogram may be useful in future studies of cocaine-dependent patients.

Adult↗
PubMed1997

Impaired color vision in cocaine-withdrawn patients.

BACKGROUND: The main reinforcing effect of cocaine happens by altering dopaminergic neurotransmission in the brain reward systems. Dopamine is found in high concentrations in the retina in which it plays an important role in color vision. Therefore, we investigated whether cocaine-dependent patients might have impaired color vision. METHODS: We compared patients recently withdrawn from cocaine (n = 31) with matched normal controls (n = 31) on 2 color vision tests. RESULTS: Cocaine-withdrawn patients had significantly higher error scores than matched controls on the Farnsworth-Munsell 100-hue and Lanthony desaturated D-15 color vision tests. Also, 23 of the 31 cocaine-withdrawn patients had blue-yellow color vision losses on the Farnsworth-Munsell 100-hue test compared with 3 controls (P < .001, chi 2 test) and 15 had blue-yellow color vision loss on the Lanthony desaturated D-15 test compared with 2 controls (P < .001, chi 2 test). CONCLUSIONS: These significantly higher test error scores and blue-yellow color vision losses suggest that color vision is impaired in cocaine-withdrawn patients. Color vision testing may be useful in future studies of cocaine-dependent patients.

Adult↗
PubMed1997

Increased axon number in the anterior commissure of mice lacking a corpus callosum.

Relatively few behavioral deficits are apparent in subjects with hereditary absence of the corpus callosum (CC). The anterior commissure (AC) has been suggested to provide an extracallosal route for the transfer of interhemispheric information in subjects with this congenital defect. Anterior commissure size, axon number, axon diameter, and neuronal distribution were compared between normal mice and those with complete CC absence. No difference in midsagittal AC area was found between normals and acallosals, nor were differences found in the numbers or diameters of myelinated axons. However, axon counts indicated an 17% increase or about 70,000 more unmyelinated axons in the AC of acallosal mice, and the mean diameter of unmyelinated axons was slightly less than in normal mice (0.24 vs 0.26 microm). This decrease in axon diameter enabled more axons to pass through the AC without increasing its midsagittal area. The topographical distribution of neurons sending axons through the AC, assessed with lipophilic dyes, was qualitatively similar for almost all the known regions of origin of the anterior commissure in normal and acallosal mice. There was a pronounced deficit of AC cells in the anterior piriform cortex of BALB/c mice, but this occurred whether or not the mouse suffered absent CC. Although the increase in AC axon number is far smaller than the number of CC axons that fail to reach the opposite hemisphere, the higher number of axons present in the AC of acallosal mice may contribute to the functional compensation for the loss of the CC.

Agenesis of Corpus Callosum↗
PubMed1997

Propofol or midazolam for sedation and early extubation following cardiac surgery.

PURPOSE: The purpose of this randomized, double-blind study was to evaluate the efficacy of midazolam and propofol for postoperative sedation and early extubation following cardiac surgery. METHODS: ASA physical status II-III patients scheduled to undergo elective first-time cardiac surgery with an ejection fraction > 45% were eligible. All patients received a standardized sufentanil/isoflurane anaesthesia. During cardiopulmonary bypass 100 micrograms.kg-1.min-1 propofol was substituted for isoflurane. Upon arrival in the Intensive Care Unit (ICU), patients were randomized to either 10 micrograms.kg-1.min-1 propofol (n = 21) or 0.25 microgram.kg-1.min-1 midazolam (n = 20). Infusion rates were adjusted to maintain sedation within a predetermined range (Ramsay 2-4). The infusion was terminated after four hours. Patients were weaned from mechanical ventilation and their tracheas extubated when Haemodynamic stability, haemostasis, normothermia and mental orientation were confirmed. Haemodynamic measurements, arterial blood gas tensions and pulmonary function tests were recorded at specified times. RESULTS: There were no differences between the two groups for the time spent at each level of sedation, number of infusion rate adjustments, amount of analgesic and vasoactive drugs, times to awakening and extubation. The costs of propofol were higher than those of midazolam. There were no differences in haemodynamic values, arterial blood gas tensions and pulmonary function. CONCLUSION: We conclude that midazolam and propofol are safe and effective sedative agents permitting early extubation in this selected cardiac patient population but propofol costs were higher.

Adolescent↗
PubMed1997

Epidemic Bacillus endophthalmitis after cataract surgery I: acute presentation and outcome.

OBJECTIVE: The purpose of the study is to report the clinical outcome of acute Bacillus endophthalmitis after cataract surgery. DESIGN: The study design is a cohort study. PARTICIPANTS: Fourteen eyes of 14 patients with epidemic acute postoperative inflammation after exposure to bacteria-contaminated viscoelastic material were studied. INTERVENTION: Three patients with milder clinical presentations were treated without vitrectomy or antibiotics. Eleven patients with more severe infection were treated with vitrectomy as well as intravitreous and topical fortified antibiotics. MAIN OUTCOME MEASURES: Final visual acuities were obtained in all 14 study patients. Results of microbiologic studies of aqueous and vitreous specimens from 11 vitrectomized eyes also were analyzed. RESULTS: One patient with late presentation had severe inflammation and had phthisis bulbi develop with no light perception. The remaining 13 patients had successful resolution of inflammation after treatment by 1 month of follow-up. Twelve of these 13 patients, including 1 nonvitrectomized patient, had final visual acuities of 20/100 or better at 6 months' follow-up. Six patients, including two patients with nonvitrectomized eyes, had outcomes of 20/40 or better visual acuity. Bacillus species were grown from all 11 (100%) vitreous and 7 (88%) of 8 aqueous specimens obtained from vitrectomized patients, as well as from the contaminated viscoelastic material remaining in the operating room. CONCLUSIONS: Postoperative Bacillus endophthalmitis need not result in poor outcome. Results depend on factors including bacterial load, specific bacterial species, timing of treatment, and immune status of the patient.

Acute Disease↗
PubMed1997

Controlled trial of 4-ASA in ulcerative colitis.

A six-week placebo-controlled trial of the efficacy and safety of 6 g per day of 4-aminosalicylic acid (4-ASA) was conducted in 30 subjects with mild to moderately severe ulcerative colitis. Subjects were stratified into groups having distal (< 60 cm) or more extensive (> 60 cm) disease. Diarrhea, bleeding, sigmoidoscopic and biopsy appearance, and physician global assessment were scored to judge efficacy. Safety was evaluated by monitoring untoward symptoms and laboratory values. Median percent improvement was significantly greater (P < 0.05) in the 4-ASA > 60-cm group (42.7%) than in the placebo > 60-cm group (21.2%), but 4-ASA was not better than placebo for the < 60-cm group or the total study group. Severe dyspepsia (one subject), abnormal AST (transient in five, persistent in one) and elevated lipase without pancreatitis (six subjects) were noted. Thus 6 g 4-ASA for six weeks was more effective than placebo in mild to moderate ulcerative colitis extending more than 60 cm above the anus, but not in distal disease, and the drug was generally well tolerated.

Aminosalicylic Acid↗
PubMed1997

Evidence for an obligatory intermediate in the folding of interleukin-1 beta.

The folding of the beta-sheet protein, interleukin-1 beta, was examined at pH 5.0 and 25 degrees C using pulse-labelling hydrogen exchange and electrospray ionization mass spectrometric analysis, as well as stopped-flow circular dichroism and fluorescence spectroscopies. The first detectable event is the formation of a partially folded intermediate in a kinetic step with a relaxation time of 126 +/- 26 ms. There is a lag in native protein production of at least 400 ms. Optical studies indicate that the intermediate is converted to the native species in a reaction with a relaxation time of 43 +/- 5 s. The kinetic rates determined from stopped-flow fluorescence, circular dichroism and pulse-labelling experiments are similar and consistent with a simple sequential model for the folding pathway of interleukin-1 beta at pH 5.0 and 25 degrees C. Taken together, our data provide kinetic evidence that formation of the native state of interleukin-1 beta proceeds through an obligatory intermediate. We explain our results in terms of the classical and new views of protein folding.

Interleukin-1↗
PubMed1997

Geographic distribution of French-Canadian low-density lipoprotein receptor gene mutations in the Province of Quebec.

A total of 35 homozygous and 1320 heterozygous patients with familial hypercholesterolemia (FH) was screened for the presence of six low-density lipoprotein receptor (LDLR) gene mutations previously reported among French-Canadians. The geographic distribution of patients' birthplaces and the relative prevalence of these six mutations in the LDLR gene in the province of Quebec were compared. For this purpose, the 16 administrative regions of the province of Quebec were grouped into seven geographic regions. The relative frequency of the six mutations differed in the seven regions: the > 15 kb deletion (delta > 15 kb) had the highest relative frequency in the Bas St-Laurent/Gaspésie region, and the point mutation in exon 3 had the highest relative frequency in the Saguenay-Lac-St-Jean/Côte-Nord region. In the Montreal area, the delta > 15 kb and the mutation in exon 3 had prevalence rates of 71.2% and 13.0%, respectively, whereas the relative frequencies of the delta > 15 kb and the point mutation in exon 3 in the Quebec city region were 57.5 and 21.8%, respectively. Finally, in Saguenay-Lac-St-Jean/Côte-Nord, the relative frequency of the delta > 15 kb only reached 31.5% and the point mutation in exon 3, 59.2%. Thus, on the north shore of the St. Lawrence River, the prevalence of the delta > 15 kb decreases from west to north-east, whereas the relative frequency of the mutation in exon 3 appears to increase. These observations provide a better characterization of FH among French-Canadians of Quebec, a Canadian province with a high prevalence of this inherited disease.

Exons↗
PubMed1997

Study of myopathies by histological and histochemical methods with special reference to staining for desmin expression.

An attempt was made to study the histological and histochemical changes as well as immunohistochemical changes in desmin expression occurring in four types of clinical myopathies e.g. Chronic ischaemic myopathy due to Buerger's disease (Group I), Carcinomatous myopathy (Group II), Metabolic myopathy (Group III) and Muscular dystrophy (Group IV). The number of cases studied were 16 cases, 15 cases, 4 cases and 5 cases respectively. The study revealed: (i) a combination of normal, degenerated, necrotic and regenerating fibres in different proportions in all the four groups having maximum number of degenerated fibres in Group I and Group IV, relatively more number of regenerating fibres in groups III and absence of necrotic fibres in Group I. (ii) Altered tinctorial property in most of the fibres indicating degenerated and regenerating fibres in all the groups with Masson's trichrome staining against inconstant staining with PTAH appear to be a good indicator for myopathy. (iii) The Desmin expression was week and irregular in most of the cases with most of the fibres probably due to reduction of desmin content probably indicating degenerated fibres, appear to be a good indicator for myopathy. (iv) Chronic ischaemic myopathy showed close resemblance with muscular dystrophy though no typical or distinct distinguishing feature could be identified in these four groups.

Desmin↗
PubMed1996

Friedreich ataxia in Acadian families from eastern Canada: clinical diversity with conserved haplotypes.

The gene for Friedreich ataxia (FRDA), an autosomal-recessive neurodegenerative disease, remains elusive. The current candidate region of about 150 kb lies between loci FR2 and F8101 near the D9S15/D9S5 linkage group at 9q13-21.1. Linkage homogeneity between classical FRDA and a milder, slowly progressive Acadian variant (FRDA-Acad) has been demonstrated. An extended D9S15-D9S5 haplotype (C6) predominates in FRDA-Acad chromosomes from Louisiana. We studied 10 Acadian families from New Brunswick, Canada. In eight families, affected individuals conformed to the clinical description of FRDA-Acad; in one, 2 sibs presented with spastic ataxia (SPA-Acad). In the last family, 2 sibs had FRDA-Acad, and one had SPA-Acad. We found that SPA-Acad is linked to the FRDA gene region. The C6 haplotype and a second major haplotype (B7) were identified. The same ataxia-linked haplotypes segregated with both FRDA-Acad and SPA-Acad in two unrelated families. The parental origins of these haplotypes were different. Our observation of different phenotypes associated with the same combination of haplotypes may point to the influence of the parent of origin on gene expression, indicate the effect of modifier genes, or reflect the presence of different mutations on the same haplotypes. Our findings underline the need to investigate families with autosomal-recessive ataxias for linkage to the FRDA region, despite lack of key diagnostic manifestations such as cardiomyopathy or absent deep-tendon reflexes.

Canada↗