PubMed Health⌕ Search

Biomedical subjects

R Roberts

Publications and source records attributed to R Roberts.

At least 73 records · Page 4Linked to original sources
PubMed2001

Modification of a rapid method for the identification of gene-specific polymorphisms in Cryptosporidium parvum and its application to clinical and epidemiological investigations.

The application of genotyping to clinical isolates of Cryptosporidium has increased significantly our knowledge and understanding of the distribution and epidemiology of this parasite. However, some methods can be laborious and demand specialist technical expertise. PCR-restriction fragment length polymorphism (RFLP) techniques represent a more rapid and simple method of genotyping to support epidemiological and clinical investigations than conventional DNA analytical techniques. We describe a nested PCR-RFLP technique that identifies polymorphisms in the C. parvum thrombospondin-related adhesive protein gene locus; this method offers a sensitive and specific tool for the confirmation and investigation of disease associated with C. parvum. The potential of this enhanced method is demonstrated by its application to the confirmation and epidemiological investigation of an outbreak of cryptosporidiosis associated with a school visit to an open farm.

Adult↗
PubMed2001

Dynamic cerebral autoregulation is preserved in neurally mediated syncope.

To test whether cerebral autoregulation is impaired in patients with neurally mediated syncope (NMS), we evaluated 15 normal subjects and 37 patients with recurrent NMS. Blood pressure (BP), heart rate, and cerebral blood velocity (CBV) (transcranial Doppler) were recorded at rest and during 80 degrees head-up tilt (HUT). Static cerebral autoregulation as assessed from the change in cerebrovascular resistance during HUT was the same in NMS and controls. Properties of dynamic cerebral autoregulation were inferred from transfer gain, coherence, and phase of the relationship between BP and CBV estimated from filtered data segments (0.02-0.8 Hz). During the 3 min preceding syncope, dynamic cerebral autoregulation of subjects with NMS did not differ from that of controls nor did it change over the course of HUT in patients with NMS or in control subjects. Dynamic cerebral autoregulation was also unaffected by the degree of orthostatic intolerance as inferred from latency to onset of syncope. We conclude that cerebral autoregulation in patients with recurrent syncope does not differ from that of normal control subjects.

Adult↗
PubMed2001

Depression and substance use in minority middle-school students.

OBJECTIVES: This study investigated the association between depression and substance use in a sample of middle-school students. METHODS: The 5721 students (59%-63% Hispanic) completed self-report items on depressive symptoms, recent smoking and binge drinking, and lifetime use of marijuana, cocaine, and inhalants. RESULTS: Symptoms of depression were strongly and positively related to substance use. For every type of use, a stepwise increase was seen between the percentage of students with low symptom frequency and the percentage of students with more symptoms. A sizable number of users reported symptoms indicating major depression. Depression scores showed few clinically meaningful differences among demographic subgroups. Substance use scores, in contrast, showed meaningful intergroup differences for racial/ethnic group and other demographic variables. CONCLUSIONS: Depressive symptoms and substance use were associated in a sample of middle-school students who were largely non-White and predominantly Hispanic. Greater understanding of the nature of this association is needed; this understanding should be used to design prevention programs, and prevention programs should be introduced at least in the middle-school years.

Achievement↗
PubMed2001

Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study.

To determine whether fibrinolytic testing predicts recurrent venous thrombosis, we have performed a prospective cohort study in which 303 patients with a first episode of venous thromboembolism underwent comprehensive fibrinolytic testing while receiving oral anticoagulants, and after anticoagulants had been discontinued. They were then followed for up to 3 years for recurrent venous thrombosis. No systematic differences in the levels or activity of type 1 plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or euglobulin clot lysis times were detected between patients who did, or did not, suffer recurrent thrombosis. There were also no differences in these variables when patients whose initial thrombosis was idiopathic were compared to patients whose thrombosis occurred in the setting of a known thrombotic risk factor. Based on these results, neither measuring fibrinolytic parameters in patients with venous thromboembolism, nor modification of treatment based on the results of such testing, are justified. Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence.

Anticoagulants↗
PubMed2000

Identification and characterization of a novel gene (C4orf5) located on human chromosome 4q with specific expression in cardiac and skeletal muscle.

The loci of several genes responsible for arrhythmogenic right ventricular dysplasia (ARVD) have been mapped. Since ARVD involves the right ventricle, we sought candidate genes preferentially expressed in the right ventricle utilizing differential display polymerase chain reaction (PCR) on mRNA from the chambers of an adult human heart. PCR products were cloned, sequenced, and used to screen an adult heart cDNA library. A novel 1.3-kb cDNA (HGMW-approved symbol C4orf5) with an open reading frame of 795 bp was identified. A probe designed from the 3' untranslated region of the 1.3-kb cDNA was hybridized to the 1.3-kb transcript and an alternatively spliced 2.5-kb transcript in the heart and skeletal muscle RNA lanes on a multitissue Northern blot. Analysis of a 39-kb partial genomic sequence identified three intronic splice sites in the 1.3-kb transcript. The gene was mapped to human chromosome 4q26-q27. Computer-based analysis indicated that this gene is novel with no known function.

Adolescent↗
PubMed2000

Human protein tyrosine phosphatase-like gene: expression profile, genomic structure, and mutation analysis in families with ARVD.

The mouse protein tyrosine phosphatase-like gene (Ptpla) was recently cloned and data suggested that it plays a role in myogenesis and cardiogenesis. The human homologue (PTPLA) was mapped to chromosome 10p13-14, a region where we have mapped a locus responsible for arrhythmogenic right ventricular dysplasia (ARVD). As a positional candidate gene, we characterized PTPLA by determining its tissue expression, its genomic structure, and we also screened for mutations in the ARVD patients. Northern analysis demonstrated PTPLA is preferentially expressed in both adult and fetal heart. A much lower expression was detected in skeletal and smooth muscle tissues. Virtually no expression was observed in other tissues. The protein-encoding sequences of PTPLA consist of seven exons. A sequence variation (Lys64Gln) was found in all the affecteds in a large ARVD family. However, the same variant was also detected in normal control subjects (three alleles/100 chromosomes). Thus, the variant (Lys64Gln) is not responsible for ARVD in our family and is a benign polymorphism. Nevertheless, its tissue-specific expression in the developing and adult heart suggest PTPLA has a role in regulating cardiac development, differentiation, or other cellular events. The genomic structure and intragenic polymorphism of PTPLA should be useful for further clinical and genetic studies such as gene targeting of PTPLA.

Arrhythmogenic Right Ventricular Dysplasia↗
PubMed2000

Tissue Doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is diagnosed clinically by the presence of left ventricular hypertrophy (LVH). However, LVH is absent in a significant number of genotype-positive patients. Because myocyte dysfunction and disarray are the primary abnormalities in HCM, we reasoned that tissue Doppler imaging could identify contraction and relaxation abnormalities, irrespective of hypertrophy, in a transgenic rabbit model of human HCM. METHODS AND RESULTS: M-mode, 2D, Doppler echocardiography and tissue Doppler imaging were performed in nontransgenic (n=24), wild-type beta-myosin heavy chain-arginine(403) (n=14), and mutant beta-myosin heavy chain-glutamic acid(403) (n=24) transgenic rabbits. Mean septal thicknesses were 2.0+/-0.3, 2.0+/-0.25, and 2.75+/-0.3 mm in the 3 groups, respectively (P:=0.001). LVH was absent in 9 of the 24 mutant rabbits. Left ventricular dimensions, systolic function, heart rate, mitral inflow velocities, and time intervals were similar in the groups. However, the difference between atrial reversal and transmitral A wave duration was increased in the mutant rabbits (P:<0.001). More importantly, systolic and early diastolic tissue Doppler velocities were significantly lower in all mutant rabbits (7.45+/-2.2 versus 10.8+/-2.3 cm/s in nontransgenic and 9. 0+/-0.76 cm/s in wild-type; P:<0.001), including the 9 without LVH. A systolic velocity <8.5 cm/s had an 86% sensitivity and 100% specificity in identifying the mutant transgenic rabbits. CONCLUSIONS: Myocardial contraction and relaxation were reduced in the mutant beta-myosin heavy chain-glutamic acid(403) transgenic rabbit model of human HCM, irrespective of the presence or absence of LVH. In addition, tissue Doppler imaging is more sensitive than conventional echocardiography for HCM screening.

Analysis of Variance↗
PubMed2000

Molecular cloning, expression analysis, and chromosome mapping of WDR6, a novel human WD-repeat gene.

The WD-repeat proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as signal transduction, transcription, and proliferation. Here we report on the cloning and characterization of a novel human WD-repeat gene, WDR6, which encodes a protein of 1121 amino acids and contains 11 WD-repeat units. WDR6 is unique since its 11 WD repeats are clustered into two distinct groups separated by a putative transmembrane domain. The WDR6 gene was mapped to chromosome 15q21 by fluorescence in situ hybridization. Northern analysis demonstrated that WDR6 is ubiquitously expressed in human adult and fetal tissues. WDR6 is not homologous to any previously identified human WD-repeat genes including WDR1 through WDR5. However, it was found to have significant sequence similarity with Arabidopsis thaliana hypothetical protein T7B11.12, yeast putative elongation factor G, and probable membrane protein YPL183c. All of them have been defined as WD-repeat proteins. Therefore, WDR6 is a novel protein and probably belongs to a highly conserved subfamily of WD-repeat proteins in which T7B11.12 and YPL183c are its distantly related members.

Amino Acid Sequence↗
PubMed2000

Identification of patients most likely to benefit from implantable cardioverter-defibrillator therapy: the Canadian Implantable Defibrillator Study.

BACKGROUND: Patients with resuscitated ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation) benefit from implantable cardioverter-defibrillators (ICDs) compared with medical therapy. We hypothesized that the patients who benefit most from an ICD are those at greatest risk of death. METHODS AND RESULTS: In the Canadian Implantable Defibrillator Study (CIDS), 659 patients with resuscitated ventricular tachyarrhythmias were randomly assigned to receive an ICD or amiodarone and were then followed for a mean of 3 years. There were 98 and 83 deaths in the amiodarone and ICD groups, respectively. We used multivariate Cox analysis to assess the impact of baseline parameters on the mortality in the amiodarone group. Reduced left ventricular ejection fraction, advanced age, and poor NYHA status identified high-risk patients (P=0.0001 to 0.0009). Quartiles of risk were constructed, and the mortality reduction associated with ICD treatment in each quartile was assessed. There was a significant interaction between risk quartile and the ICD treatment effect (P=0.011). In the highest risk quartile, there was a 50% relative risk reduction (95% CI 21% to 68%) of death in the ICD group, whereas in the 3 lower quartiles, there was no benefit. Patients who are most likely to benefit from an ICD can be identified with a simple risk score (>/=2 of the following factors: age >/=70 years, left ventricular ejection fraction </=35%, and NYHA class III or IV). Thirteen of 15 deaths that were prevented by the ICD occurred in patients with >/=2 risk factors. CONCLUSIONS: In CIDS, patients at highest risk of death benefited most from ICD therapy. These can be identified easily on the basis of age, poor ventricular function, and poor functional status.

Aged↗
PubMed2000

Severity of coronary artery calcification by electron beam computed tomography predicts silent myocardial ischemia.

BACKGROUND: Detection of subclinical coronary artery disease (CAD) before the development of life-threatening cardiac complications has great potential clinical relevance. Electron beam computed tomography (EBCT) is currently the only noninvasive test that can detect CAD in all stages of its development and thus has the potential to be an excellent screening technique for identifying asymptomatic subjects with underlying myocardial ischemia. METHODS AND RESULTS: Over 2.5 years, we prospectively studied 3895 generally asymptomatic subjects with EBCT, 411 of whom had stress myocardial perfusion tomography (SPECT) within a close (median, 17 days) time period. SPECT and exercise treadmill results were compared with the coronary artery calcium score (CACS) as assessed by EBCT. The total CACS identified a population at high risk for having myocardial ischemia by SPECT although only a minority of subjects (22%) with an abnormal EBCT had an abnormal SPECT. No subject with CACS <10 had an abnormal SPECT compared with 2.6% of those with scores from 11 to 100, 11.3% of those with scores from 101 to 399, and 46% of those with scores >/=400 (P<0.0001). CACS predicted an abnormal SPECT regardless of subject age or sex. CONCLUSIONS: CACS identifies a high-risk group of asymptomatic subjects who have clinically important silent myocardial ischemia. Our results support the role of EBCT as the initial screening tool for identifying individuals at various stages of CAD development for whom therapeutic decision making may differ considerably.

Adult↗
PubMed2000

Factors predictive of bone mineral density in eating-disordered women: a longitudinal study.

OBJECTIVE: Osteoporosis in eating-disordered women is well established, but factors predictive of this condition have proved elusive. The roles of behavioral factors, weight, menstrual status, and the degree of bone mineral density change over the clinical course of the eating disorder were investigated METHOD: A cohort of 56 eating-disordered women was subjected to bone mineral density measurement at Scan 1 and were followed up between 9 and 51 months later for repeat measurement (n = 10) at Scan 2. RESULTS: High levels of reduced bone mineral density were observed. Total duration of amenorrhea, body mass index, frequency of vomiting, and cigarette and alcohol consumption accounted for 40% of the variance in spinal bone mineral density measurement at Scan 1. No significant changes in bone mineral density were observed at Scan 2 despite increases in body mass index. DISCUSSION: The results suggest that increases in weight appear not to be sufficient to increase bone mineral density.

Absorptiometry, Photon↗
PubMed2000

Genetic aspects of arrhythmias.

Advances in the treatment and prevention of heart disease have led to consistently declining morbidity and mortality rates over the past 30 years. Despite these advances, therapy remains largely palliative. The development of curative therapies is limited by our lack of knowledge of the basic mechanisms of disease. In the next decade, we will probably change many of these current approaches from treating the crisis to preventing the disease. Molecular biology and genetics have elucidated several basic pathways. It is hoped that targeted therapies will prevent or arrest many of these cardiac diseases, in particular, arrhythmias and sudden death. With the discovery of the genes causing familial diseases like long QT, hypertrophic cardiomyopathy, and Brugada syndrome, we have identified several substrates responsible for triggering malignant arrhythmias.

Adolescent↗
PubMed2000

Rapid and comprehensive determination of cytochrome P450 CYP2D6 poor metabolizer genotypes by multiplex polymerase chain reaction.

The liver enzyme cytochrome P450 CYP2D6 (debrisoquine 4-hydroxylase) metabolizes numerous drugs, including many antidepressants, neuroleptics, antiarrhythmics, and antihypertensive agents. Variability in the gene that encodes this enzyme is an important factor underlying variable drug treatment responses. Some 5-10% of Caucasians lack functional CYP2D6, and the genetic basis of most of these "poor metabolizer" alleles is now well defined. As the CYP2D6 status of a patient can have profound effects on response to drug treatment, it is important to devise methods that permit rapid and economical determination of CYP2D6 genotype. We have developed a robust polymerase chain reaction method that simultaneously identifies the variants CYP2D6 *3, *4, *6, *8, *11, *12, *14, *15, *19, and *20. This constitutes most of the poor metabolizer alleles described in Caucasian and Asian populations. Separate PCR reactions or Southern blots are required for *7, the *5 deletion, and the hybrid alleles *13 and *16. The multiplex assay was validated on 100 individuals previously genotyped by specific polymerase chain reaction-restriction fragment length polymorphism analysis, and proved 100% accurate in this sample. The assay performed consistently with Taq DNA polymerases from various suppliers, within a broad range of temperatures and MgCl(2) concentrations, and using genomic DNA prepared by a range of methods including extraction from dried blood spots on card. This multiplexed, amplification refractory mutation system (ARMS) method is reliable, rapid, relatively cheap, amenable to automation, and offers the advantages of minimal sample handling with no requirement for restriction enzymes as in earlier CYP2D6 assays.

Alleles↗