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Biomedical subjects

M Michaud

Publications and source records attributed to M Michaud.

At least 55 records · Page 3Linked to original sources

Genetic diversity and phylogenetic relationships between birches and alders using ITS, 18S rRNA and rbcL gene sequences.

The Betuleae is one of the two Betulaceae tribes and contains two genera, the actinorhizal genus Alnus and the nonactinorhizal genus Betula. To elucidate the phylogenetic relationships within the tribe and compare the relative amounts of genetic diversity between the genera Alnus and Betula, rbcL and 18S rRNA gene sequences as well as rDNA internal transcribed spacer (ITS1 and ITS2) sequences were obtained and compared. In rbcL and 18S rRNA, several substitutions were detected between Alnus and Betula but no variation was observed within Alnus. Minimal length variation was observed among ITS sequences. The numbers of substitutions per site for ITS were, on average, close to 10 times those estimated for 18S between Alnus and Betula. In ITS, numbers of substitutions were, on average, more than twice as large between genera than within genera. Phylogenies from ITS sequences were estimated using neighbor-joining analysis of substitution rates, maximum likelihood and parsimony methods. Each of the two genera appeared monophyletic, which was supported by high bootstrap estimates. Relationships among the three sections of Betula analyzed were also better resolved than those among the three subgenera of Alnus analyzed. Phylogenies estimated from ITS sequences suggested a relatively recent diversification of each genus, in agreement with fossil data.

DNA, Ribosomal↗

The rbcL gene sequence from chestnut indicates a slow rate of evolution in the Fagaceae.

The nucleotide sequence was obtained for the chloroplast gene coding for the large subunit of the ribulose 1,5-bisphosphate carboxylase (rbcL) of chestnut (Castanea sativa Mill.), a member of the woody family Fagaceae. Amplification primers downstream and upstream the rbcL open reading frame are also described. By comparing with other angiosperm sequences, we show that the rate of evolution of rbcL in the family Fagaceae is much slower than that observed for the families of annuals analyzed.

Base Sequence↗

A controlled study of sustained-release morphine sulfate tablets in chronic pain from advanced cancer.

The purpose of this double-blind crossover study was to determine whether a sustained-release morphine sulfate (SRMS) tablet given orally every 12 hours could adequately replace immediate-release morphine sulfate solution (IRMS) given orally every 4 hours in hospitalized patients with chronic pain from advanced cancer. Of 33 patients entered, 27 completed the study and were included in the efficacy and safety analysis. Patients were initially randomized to receive either 30-mg SRMS tablets every 12 hours or IRMS at the same mg/24 hours dose, every 4 hours. After 2 days, a crossover was performed, and patients received the alternate treatment for 3 days. Pain and side effects were assessed using a standard 100 mm visual analogue scale (VAS). There were no statistically significant differences between the two treatment groups for mean VAS pain scores or scores for sleepiness, nausea, depression, and anxiety. The incidence of breakthrough pain was similar for both treatment groups, as was the incidence of confusion and constipation. The results demonstrated that SRMS is a safe, effective analgesic preparation for patients who require oral opioids for cancer pain. The data also support the conclusion that sustained-release morphine tablets administered every 12 hours can replace an immediate-release morphine solution administered every 4 hours.

Chronic Disease↗

The Ah receptor, cytochrome P450IA1 mRNA induction, and aryl hydrocarbon hydroxylase in a human lymphoblastoid cell line.

The immunosuppressive and carcinogenic effects of aryl hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (MC) on B lymphocytes of adult rodents and the induction of cytochrome P450IA1 and aryl hydrocarbon hydroxylase (AHH) in human mitogen-activated lymphocytes and B-lymphoblastoid cell lines are believed to be mediated by the Ah receptor. However, there has not been a direct demonstration or characterization of the Ah receptor in defined populations of any of these cells. We report here the detection and characterization of an abundant, high-affinity B lymphocyte Ah receptor in the AHH-inducible human B lymphoblastoid cell line BCR-5. Our results represent the first characterization of a human lymphocyte receptor in a well-defined lymphocyte population. Sucrose density gradient analysis of BCR-5 cytosols incubated with [3H]TCDD revealed a characteristic 9 S specific binding peak. The maximum concentration of Ah receptor was about 200 fmol/mg protein. Specific binding to the Ah receptor was also detected with [3H]MC and, to a lesser extent, with [3H]benzo[alpha]pyrene. The apparent binding affinity (Kd) for [3H]TCDD (determined by saturation analyses) was about 5 nM. A specific [3H]TCDD-Ah receptor complex which sedimented at 5 S was extracted from nuclei of BCR-5 cells incubated at 37 degrees with [3H]TCDD. The Ah receptor of BCR-5 cells is thus similar in characteristics to that identified in other cell lines. When BCR-5 cells were exposed in culture for 24 hr to increasing concentrations of benz[alpha]anthracene there was a concentration-dependent increase in induction and a good correlation (r = 0.98) between the level of induced AHH activity and the relative abundance of cytochrome P450IA1 mRNA. The human B lymphoblastoid cell line BCR-5, therefore, has a complete regulatory mechanism for Ah receptor-mediated induction of cytochrome P450IA1 that is essentially the same as that which has been well established in many rodent species. The accessibility of human blood lymphocytes and the ease of establishment of B lymphoblastoid cell lines from any donor provide a source of pure cultures of human B lymphocytes which can be grown continuously in vitro for the study of mechanisms related to Ah receptor-mediated cytochrome P450IA1 induction, immunosuppression and carcinogenesis.

Aryl Hydrocarbon Hydroxylases↗

Multiple sclerosis and HLA class II susceptibility and resistance genes.

Probes to the HLA class II genes DR beta, DQ beta, and DQ alpha were used to study DNA from unrelated Caucasian multiple sclerosis (MS) patients by sequential restriction fragment length polymorphism (RFLP) analysis in Taq 1 restriction enzyme digests. Comparison of 104 patients and 108 controls, who were not matched for DR type, has identified for the first time a linked series of allele-specific RFLPs or allogenotypes which form an extended haplotype that is preferentially associated with MS. These allogenotypes include DRw15 or DR2(15); DQ beta lb, which corresponds at the DNA level to the DQwl(DQw6) serotype; a DQA1 allogenotype termed DQ alpha lb; and a 2.2 kb DX (DQA2) allogenotype termed DX alpha U (DQA2U). The role of HLA class II genes in susceptibility to MS was found to be complex. First, 23 of 104 MS patients showed DR-DQ linkages which were not observed in our control population. We suggest these anomalous associations may be important in the pathogenesis of MS. Second, homozygosity of a 2.0 kb DX (DQA2) gene, termed DX alpha L (DQA2L), showed a strong negative association with MS. DX alpha L (DQA2L) is in strong linkage disequilibrium with DR1, 5(w11) 7, and a subset of DR4, all of which also showed a negative association with MS. Since DX alpha L (DQA2L) does not code for any known product, DR1, 5(11), 4, and 7 become candidates for disease resistance genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic Linkage↗

Multiple sclerosis in French Canadians: evidence for HLA class II susceptibility and resistance genes.

HLA class II DRB1, DQB1 and DQA1 gene probes were used to study DNA from unrelated French Canadian multiple sclerosis (MS) patients and controls by restriction fragment length polymorphism (RFLP) analysis. An MS-associated and linked series of allele-specific RFLPs or allogenotypes was identified among this relatively homogeneous ethnic group; the allogenotypes include DRw15, DQw6 and a DQA1 allogenotype termed DQ alpha 1b. An additional allogenotype which cross-hybridizes with DQA1 and is termed DQA2 upper (DQA2U), was shown not only to be part of the MS-associated extended haplotype, but also to be independently associated with MS in DRw15-negative patients. Conversely a second DQA2 allogenotype, termed DQA2 lower (DQA2L) and a DQB1 allogenotype (DQw7) linked to DQA2L showed negative correlations with MS. It seems likely that the relationship of the HLA class II gene region to MS is complex and that MS susceptibility may reflect interaction between disease susceptibility and resistance genes.

Adult↗

Odontometric variation among American black, European, and Mongoloid populations.

Quantified dental parameters (including root and pulp areas and shape variables) derived from periapical radiographs were used to make comparisons among a sample of American Black (8 males--124 teeth, 9 females--138 teeth), European derivative (31 males--304 teeth, 43 females--497 teeth) and Mongoloid populations (12 males--166 teeth, 19 females--252 teeth). The magnitude of sexual dimorphism within each ethnic stock was also examined. Teeth from American Black males were robust. Sexual dimorphism was unambiguous in all groups although a hierarchical order existed from the highly dichotomous American Black sample to the more homogeneous European sample. The female dental phenotype was down-scaled from their male counterparts, but not gracile in form. Easily obtained area and shape parameters derived from dental radiographs proved useful as discriminators among racial groups and the sexes. The relationships among these data lend further support to the hypothesis of an African origin of modern humans.

Adolescent↗

HLA-DR beta, -DQ alpha, and -DQ beta restriction fragment length polymorphisms in multiple sclerosis.

Restriction fragment length polymorphism (RFLP) studies were performed on DNA from unrelated Caucasian patients with multiple sclerosis (MS) using cDNA probes to the HLA class II genes DR beta, DQ alpha, and DQ beta. In a study of 34 patients and 34 controls who were not matched for DR type, we found that the DQ beta allele-specific RFLP or allogenotype, termed DQ beta lb, which corresponds at the molecular level to the DQwl serotype, is preferentially associated with MS. A significant disease association with DR2 was demonstrated by serology but this was not confirmed using DR2/Dw2-specific RFLPs. We suggest that DQ beta lb is largely responsible for HLA-associated susceptibility to MS and that the apparent MS-DR2 serological association is due to the strong linkage disequilibrium between DR2 and DQ beta lb. Homozygosity of one of the two allelic bands of the DX alpha gene, usually termed the DX alpha lower (DX alpha L) band (which cross-hybridizes with the DQ alpha probe), correlated with reduced susceptibility to MS. Similarly a 5.3 kb band identified by the DQ alpha probe in Mspl digests showed a negative correlation with MS. In an analysis of 27 DR2+ controls and 26 DR2+ patients it was found that these individuals all had DR2/Dw2-specific RFLPs and all had identical DR2/Dw2-associated DQ beta (DQ beta lb) and DQ alpha (DQ alpha lb) allogenotypes. We detected no polymorphisms of DR beta, DQ alpha, or DQ beta genes among the DR2+ MS patients which distinguished them from normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Influence of the pain and symptom control team (PSCT) on the patterns of treatment of pain and other symptoms in a cancer center.

To assess the influence of a pain and symptom control team on the pattern of prescription of pharmacologic and nonpharmacologic treatments for cancer pain, we reviewed the charts of 100 consecutive patients admitted to the Cross Cancer Institute during 1987 and 100 patients admitted during 1984. The average daily dose of parenteral morphine per patient was 44 +/- 26 mg in 1987 versus 34 +/- 38 mg in 1984 (p less than 0.05). In 1987 and 1984, only 31 and 22% of the analgesics were ordered around the clock respectively (P:NS). Approximately half of the patients in 1987 and 1984 were prescribed antiemetics and two-thirds of the patients were prescribed laxatives. Parenteral narcotics were prescribed subcutaneously in 0/52 cases in 1984 versus 21/63 cases in 1987 (33%, p less than 0.01). The pattern of prescription of narcotics by residents changed significantly during the last four weeks of rotation as compared to the first four weeks. We conclude that there have been some changes in the modality of treatment of pain that are probably due to changes in the pattern of prescription by the residents and continued improvement in assessment of pain by nurses. However, in several areas of treatment the impact of a pain and symptom control team remains minimal.

Adult↗

Association between asthenia and nutritional status, lean body mass, anemia, psychological status, and tumor mass in patients with advanced breast cancer.

Sixty-four consecutive patients with advanced breast cancer were included in a study designed to determine the prevalence of asthenia and its association with other clinical features. The Asthenia Score (AS, the average of four tests designed by our group to assess asthenia) was 59 +/- 9 for patients versus 88 +/- 7 for a group of 68 normal controls (p less than 0.001). Twenty-six patients (41%) scored below the tenth percentile of normal controls and were considered asthenics. AS was correlated with depression and the general severity index of the SCL-90 R test. No association was found between AS and nutritional status, lean body mass, tumor mass, anemia, or type of treatment. We conclude that asthenia is a frequent symptom in patients with advanced breast cancer, which, in our series, showed independent correlations only with psychological distress.

Aged↗