Sex and X-chromosome-wide repression in Caenorhabditis elegans.
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Animals↗
Biomedical subjects
B J Meyer
Publications and source records attributed to B J Meyer.
[Anticoagulation and antiaggregation in cardiac patients].
Aspirin treatment for primary prevention is safe and useful at an annual coronary event risk > or = 1.5%. Both aspirin and clopidogrel reduce the rate of cardiovascular events in patients with coronary disease. Clopidogrel in addition to aspirin further reduces cardiovascular events, but is associated with and increased bleeding risk. Recent studies in patients with myocardial infarction suggest that treatment with either coumadin or with coumadin and aspirin are both at least as effective than treatment with aspirin alone. Thromboembolism and bleeding during therapeutic anticoagulation are the major chronic risks for patients with native valvular heart disease and mechanical prosthetic valves. The recommendations for the prevention of thromboembolic events and bleeding complications are discussed and recommended intensity of antithrombotic therapy are outlined. Key points of the guidelines for managing patients with atrial fibrillation are summarised.
Anticoagulants↗
Association of ABO histo-blood group B allele with myocardial infarction.
To investigate a possible association of ABO blood group alleles with myocardial infarction, a case-control study comprising 177 patients (median age 57.0 years; range 32-72 years) and 89 controls was performed. The distributions of the ABO blood-genotype O1, O2, A1, A2 and B alleles were assessed by analysis of genomic DNA, using the sequence-specific primer-polymerase chain reaction (PCR-SSP) technique to investigate exons VI and VII on chromosome 9. The prevalence of the B allele was 2.5 times higher amongst patients with a history of myocardial infarction than amongst controls (16.3 vs. 6.7%; P = 0.034, Fisher's exact test). There was an association between patients carrying the B allele and myocardial infarction, with an odds ratio (OR) of 2.7 (95% confidence interval 1.1-6.8). The B allele remained an independent risk factor for myocardial infarction (P = 0.038) when classical risk factors were adjusted for by unconditional logistic regression. In conclusion, the ABO blood group B allele was found to be an independent risk factor for myocardial infarction.
ABO Blood-Group System↗
Plasma lipid and fibrinogen levels in aerobically trained and untrained postmenopausal women.
AIM: Physically active compared to inactive pre-menopausal women typically possess higher high-density lipoprotein (HDL) cholesterol and reduced plasma fibrinogen levels. The aim of this study was to compare resting blood lipid and fibrinogen levels of aerobically trained and untrained postmenopausal females. METHODS: Subjects were 13 aerobically trained (trained) and 26 untrained postmenopausal females (untrained) all on hormonal replacement therapy. Mean age of trained was 56 years (SD=3.6) and untrained was 58 years (SD=4.1). Testing involved blood sampling after an overnight fast. Plasma blood lipids were assessed through enzymatic methods, whereas plasma fibrinogen was measured through the Clauss method. RESULTS: Trained compared to untrained had significantly greater free fatty acid (51%, p<0.05) and apolipoprotein A levels (24%, p<0.05) and significantly lower fibrinogen (20%, p<0.05). Trained compared to untrained also possessed significantly lower total cholesterol/HDL cholesterol ratio (20%, p<0.05), total cholesterol/apolipoprotein A ratio (19%, p<0.05), apolipoprotein B/apolipoprotein A ratio (35%, p<0.05), and significantly higher HDL cholesterol (22%, p<0.05) although these differences were not significant after adjusting for body mass index (BMI). CONCLUSION: These results show that both a physically active lifestyle and a low BMI contribute to the improved lipid and fibrinogen levels of exercising postmenopausal women.
Fatty Acids, Nonesterified↗
Arenaviruses: genomic RNAs, transcription, and replication.
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Animals↗
[Etiology of acute coronary syndrome--unstable plaque].
Our perception of the mechanisms underlying the acute complications of atherosclerosis has significantly changed in the last decade. Most coronary thromboses result from a rupture or a fissure in the protective fibrous cap of atherosclerotic plaque, but less common from a superficial erosion. The extent of thrombosis is a determinant of the clinical picture of acute coronary syndromes. Until now, we held a high grade stenosis responsible for the vast majority of acute coronary syndromes. However, current findings establish the relevance of qualitative aspects of plaques as important determinants of the vulnerability of plaques, i.e. the risk to cause acute complications. Among morphologic and functional features of plaques, inflammation has emerged as a leading pathophysiologic mechanism. In addition to local effect of inflammation at the level of the unstable plaque itself, systemic factors of the inflammatory response may alter the thrombogenicity of a vulnerable plaque. Knowledge of the role of inflammation helps us to understand the mechanisms by which therapeutic efforts can reduce clinical events. The clinical benefits of dietary modifications, pharmacotherapy with statins, and ACE inhibitors may be due in part to an anti-inflammatory action.
Acute-Phase Proteins↗
Haemochromatosis mutations and ferritin in myocardial infarction: a case-control study.
BACKGROUND: Iron accumulation may contribute to coronary heart disease by catalysing free radical formation and promoting oxidation of low-density lipoprotein cholesterol. Epidemiological studies of iron status and coronary heart disease are conflicting. DESIGN: To test whether genetic haemochromatosis is associated with myocardial infarction, we determined the prevalence of three mutations in the HFE gene (Cys282Tyr, His63Asp and Ser65Cys) in a 2 : 1 case-control study including 177 patients who survived an acute myocardial infarction and 89 controls. Genotypes were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. We also studied the relationship between plasma ferritin and myocardial infarction. RESULTS: The carrier frequencies of these three mutations were not statistically different among patients and controls (Cys282Tyr: 1.4 vs. 10.1%; His63Asp: 26.5 vs. 31.5%; Ser65Cys: 2.8 vs. 1.1%). Mean ferritin levels were elevated among patients (176 +/- 155 microg L(-1)) compared with controls (131 +/- 106 microg L(-1), P = 0.015). Subjects with plasma ferritin concentrations of 300 microg L(-1) or more had a 2.9-fold (95% CI: 1.2-7.3, P = 0.02) unadjusted risk for a myocardial infarction compared with those with normal levels. In a univariate analysis, ferritin was significantly associated with myocardial infarction. Upon multiple regression analysis adjusting for smoking, hypertension, diabetes, body-mass index and total cholesterol, significance was no longer present. CONCLUSIONS: No direct association was found between genetic haemochromatosis and myocardial infarction among Swiss whites. Raised ferritin levels among patients suggest a role of increased iron stores in myocardial infarction, but iron overload was not an independent risk factor for Swiss coronary heart disease patients.
Adult↗
r-Hirudin for percutaneous coronary interventions--time to reconsider?
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Angioplasty, Balloon, Coronary↗
HIM-10 is required for kinetochore structure and function on Caenorhabditis elegans holocentric chromosomes.
Macromolecular structures called kinetochores attach and move chromosomes within the spindle during chromosome segregation. Using electron microscopy, we identified a structure on the holocentric mitotic and meiotic chromosomes of Caenorhabditis elegans that resembles the mammalian kinetochore. This structure faces the poles on mitotic chromosomes but encircles meiotic chromosomes. Worm kinetochores require the evolutionarily conserved HIM-10 protein for their structure and function. HIM-10 localizes to the kinetochores and mediates attachment of chromosomes to the spindle. Depletion of HIM-10 disrupts kinetochore structure, causes a failure of bipolar spindle attachment, and results in chromosome nondisjunction. HIM-10 is related to the Nuf2 kinetochore proteins conserved from yeast to humans. Thus, the extended kinetochores characteristic of C. elegans holocentric chromosomes provide a guide to the structure, molecular architecture, and function of conventional kinetochores.
Animals↗
The effect of bispectral index monitoring on anesthetic use and recovery in children anesthetized with sevoflurane in nitrous oxide.
UNLABELLED: The utility of bispectral index (BIS) monitoring to guide anesthetic administration has been demonstrated in adults. This prospective, randomized observer-blinded study was designed to evaluate the effect of BIS monitoring on anesthetic use and recovery characteristics in pediatric patients. After data collection in 38 historical controls, 202 patients age 0-18 yr were randomized into one of two groups: standard practice (SP) and BIS guided (BIS). Patients age 0-3 yr undergoing inguinal hernia repair (IH) and patients age 3-18 yr undergoing tonsillectomy and/or adenoidectomy (TA) were selected. All patients were anesthetized with sevoflurane in 60% N(2)O/O(2). Hernia patients also received a caudal epidural anesthetic before surgery. In the BIS group, anesthetic delivery was adjusted in an effort to achieve a target BIS of 45-60 during maintenance and 60-70 during the last 15 min of the procedure. BIS was recorded throughout surgery in all patients, but data were unavailable to the anesthesiologist in the SP group. In the TA patients, BIS monitoring was associated with a significant reduction in end-tidal sevoflurane concentration during maintenance (2.4 +/- 0.6%, SP and 1.8 +/- 0.4% BIS, mean +/- SD) and during the last 15 min of the procedure (2.1 +/- 0.7, SP and 1.6 +/- 0.6, BIS). There was a 25%-40% decrease in measured recovery times. In the patients 0-6 mo of age undergoing IH, sevoflurane concentrations during maintenance (2.0 +/- 0.4% SP, 0.9 +/- 0.8 BIS), during the last 15 min (1.6 +/- 0.4% SP, 0.6 +/- 0.6% BIS), and at the end of the procedure (1.1 +/- 0.6% SP, 0.3 +/- 0.3% BIS) were smaller in the BIS group. Emergence and recovery measures were unaffected by BIS titration. In the children 6 mo-3 yr of age, there were no significant differences between the SP and BIS groups in anesthetic use or recovery measures. IMPLICATIONS: Bispectral index monitoring in children results in less anesthetic use and faster recovery than standard practice.
Adenoidectomy↗
Detection of an artifact on lumbar SPECT.
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Artifacts↗
Two subpopulations of intermediate density lipoprotein and their relationship to plasma triglyceride and cholesterol levels.
We observed the appearance of two intermediate density lipoprotein (IDL) subfractions on gradient gel electrophoresis of lipoproteins in the density range 1.006-1.030 g/ml and estimated their approximate concentrations in plasma in subjects with a wide range of lipid levels, from 0.55 to 28.0 mmol/l plasma triglyceride and 3.75-10.0 mmol/l cholesterol. The larger species, IDL-I (31.7 +/- 0.7 nm, mean +/- SD), showed little variation in size in normal and moderate hyperlipidaemic individuals. The estimated concentration of IDL-I was positively related to plasma triglyceride (r = 0.63, P = 0.0004) and low density lipoprotein (LDL) cholesterol (r = 0.68, P = 0.0003). These findings are consistent with the view that IDL-I is a metabolic intermediate between very low density lipoprotein (VLDL) and LDL. The smaller subfraction, IDL-II (25.7 +/- 2.4 nm) was virtually the only true species observed in subjects with plasma triglyceride < 1.0 mmol/l and its estimated concentration fell as plasma triglyceride increased (r = -0.58, P = 0.0002). IDL-II particle size changed in concert with LDL particle size (r = 0.61, P < 0.0001), suggesting that they were influenced by common metabolic factors. These observations provide further support for the hypothesis outlined by Musliner et al. [1] that IDL-I was part of the delipidation chain from VLDL to LDL, whereas IDL-II arose from a separate source, possibly directly released from the liver. Hence the two subpopulations of IDL differ in their relationship to plasma triglyceride and cholesterol levels.
Adult↗
Sex in the wormcounting and compensating X-chromosome dose.
The nematode Caenorhabditis elegans counts its X chromosomes to determine sex and to activate the process of dosage compensation, which ensures that males (XO) and hermaphrodites (XX) express equal levels of most X-chromosome products. The number of X chromosomes is communicated by a set of X-linked genes called X-signal elements, which repress the master sex-determination switch gene xol-1 via two distinct, dose-dependent molecular mechanisms in XX embryos. X-chromosome gene dosage is compensated by a specialized protein complex that includes evolutionarily conserved components of mitotic and meiotic machinery. This complex assembles on both X chromosomes of hermaphrodites to repress transcription by half. The recruitment of chromosome segregation proteins to the new task of regulating X-chromosome-wide gene expression points to the evolutionary origin of nematode dosage compensation.
Animals↗
Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy.
OBJECTIVES: We sought to compare the inhibitory effects of the combination of two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation. BACKGROUND: Enhanced platelet inhibitory effects of clopidogrel by aspirin on platelet aggregation and activation are suggested by experimental studies but have not been shown in humans. METHODS: The effects of clopidogrel 75 mg or aspirin 100 (300) mg on platelet aggregation and activation by flow cytometry after stimulation with various agonists were determined in 30 patients with a past history of myocardial infarction. RESULTS: Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy with aspirin (24.6 +/- 3.3% or 26.6 +/- 2.7% vs. 44.7 +/- 2.9%; p < 0.001). Combined treatment significantly inhibited collagen-induced aggregation compared with aspirin and clopidogrel (16.4 +/- 2.4%, 36.5 +/- 4.2% and 59.3 +/- 5.1%, respectively;, p < 0.001) and resulted in considerable inhibition of aggregation induced by thrombin receptor agonist peptide (TRAP, p < 0.03). Clopidogrel with or without aspirin significantly suppressed expression of platelet activation markers CD 62p, CD 63 and PAC-1 after stimulation with ADP or thrombin (p < 0.001). In addition, the combined treatment was more effective than either agent alone after activation with low dose thrombin (p < 0.05). Both doses of aspirin equally potentiated the platelet inhibitory effects of clopidogrel. CONCLUSIONS In this prospective clinical ex vivo platelet study, clopidogrel was more effective than aspirin in inhibiting ADP-mediated platelet aggregation and activation. Clopidogrel in combination with aspirin showed synergistic inhibitory effects after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.
Adenosine Diphosphate↗
Persistent hantavirus infections: characteristics and mechanisms.
Hantaviruses include serious human pathogens that are maintained in nature in persistently infected rodents and that can also persistently infect cultured mammalian cells, causing little or no cytopathology. The mechanisms of hantavirus persistence are only beginning to be explored. Recent data point to subtle changes in the viral genome that might result in the differential regulation of replication and lead to persistence.
Animals↗
The Caenorhabditis elegans dosage compensation machinery is recruited to X chromosome DNA attached to an autosome.
The dosage compensation machinery of Caenorhabditis elegans is targeted specifically to the X chromosomes of hermaphrodites (XX) to reduce gene expression by half. Many of the trans-acting factors that direct the dosage compensation machinery to X have been identified, but none of the proposed cis-acting X chromosome-recognition elements needed to recruit dosage compensation components have been found. To study X chromosome recognition, we explored whether portions of an X chromosome attached to an autosome are competent to bind the C. elegans dosage compensation complex (DCC). To do so, we devised a three-dimensional in situ approach that allowed us to compare the volume, position, and number of chromosomal and subchromosomal bodies bound by the dosage compensation machinery in wild-type XX nuclei and XX nuclei carrying an X duplication. The dosage compensation complex was found to associate with a duplication of the right 30% of X, but the complex did not spread onto adjacent autosomal sequences. This result indicates that all the information required to specify X chromosome identity resides on the duplication and that the dosage compensation machinery can localize to a site distinct from the full-length hermaphrodite X chromosome. In contrast, smaller duplications of other regions of X appeared to not support localization of the DCC. In a separate effort to identify cis-acting X recognition elements, we used a computational approach to analyze genomic DNA sequences for the presence of short motifs that were abundant and overrepresented on X relative to autosomes. Fourteen families of X-enriched motifs were discovered and mapped onto the X chromosome.
Animals↗
Accumulation of terminally deleted RNAs may play a role in Seoul virus persistence.
Two independent, long-term infections were analyzed to determine whether changes in viral replication could contribute to the establishment and/or maintenance of persistent Seoul virus infections. Infected cell cultures initially contained high levels of infectious virus and intracellular viral RNA that peaked between approximately 7 to 16 days postinfection and then gradually declined until day 26. After day 26, the viral titers and the levels of the small (S), medium (M), and large (L) viral RNAs varied cyclically until the end of the studies. The changes in the concentrations of the RNAs and titer were similar in pattern and appeared to result from changes in the regulation of replication. Neither internal deletions nor an accumulation of nucleotide changes were found in the RNAs. However, fine mapping and sequence analysis revealed short deletions in some of the RNAs in the conserved complementary terminal sequences believed to contain the signals for initiation of replication and transcription. Deletions at the 3' termini of S, M, and L virus-sense RNAs (vRNAs) accumulated during the acute phase of infection just before the time that the viral titer and the concentration of vRNAs and virus complementary-sense RNAs (cRNAs) began to decline. The absence of deletions at the 5' termini of the S, M, and L cRNAs suggests that the 3'-deleted vRNAs may not be replication competent. Thus, as the percentage of 3'-deleted vRNAs increase in the population, they could potentially compete with standard virus and downregulate viral replication. Deletions at the 3' L cRNA and 5' L vRNA termini were also observed, and the proportion of these deleted RNAs varied cyclically during the infections. We propose a model in which terminal nucleotide deletions arise by nuclease activity of the viral polymerase. In addition, we speculate that cleaved terminal fragments might be used as primers during replication, resulting in the repair of some of the deleted RNAs.
Animals↗
Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate.
In many organisms, master control genes coordinately regulate sex-specific aspects of development. SDC-2 was shown to induce hermaphrodite sexual differentiation and activate X chromosome dosage compensation in Caenorhabditis elegans. To control these distinct processes, SDC-2 acts as a strong gene-specific repressor and a weaker chromosome-wide repressor. To initiate hermaphrodite development, SDC-2 associates with the promoter of the male sex-determining gene her-1 to repress its transcription. To activate dosage compensation, SDC-2 triggers assembly of a specialized protein complex exclusively on hermaphrodite X chromosomes to reduce gene expression by half. SDC-2 can localize to X chromosomes without other components of the dosage compensation complex, suggesting that SDC-2 targets dosage compensation machinery to X chromosomes.
Animals↗