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R Donaldson

Publications and source records attributed to R Donaldson.

At least 19 recordsLinked to original sources
PubMed2004

Linkage disequilibrium maps constructed with common SNPs are useful for first-pass disease association screens.

To develop an efficient strategy for mapping genetic factors associated with common diseases, we constructed linkage disequilibrium (LD) maps of human chromosomes 5, 7, 17, and X. These maps consist of common single nucleotide polymorphisms at an average intermarker distance of 100 kb. The genotype data from these markers in a panel of American samples of European descent were analyzed to produce blocks of markers in strong pair-wise LD. Power calculations were used to guide block definitions and predicted that high-level LD maps would be useful in initial genome scans for susceptibility alleles in case-control association studies of complex diseases. As anticipated, LD blocks on the X chromosome were larger and covered more of the chromosome than those found on the autosomes.

Black or African American↗
PubMed2001

Single-nucleotide polymorphisms in the public domain: how useful are they?

There is a concerted effort by a number of public and private groups to identify a large set of human single-nucleotide polymorphisms (SNPs). As of March 2001, 2.84 million SNPs have been deposited in the public database, dbSNP, at the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/SNP/). The 2.84 million SNPs can be grouped into 1.65 million non-redundant SNPs. As part of the International SNP Map Working Group, we recently published a high-density SNP map of the human genome consisting of 1.42 million SNPs (ref. 3). In addition, numerous SNPs are maintained in proprietary databases. Our survey of more than 1,200 SNPs indicates that more than 80% of TSC and Washington University candidate SNPs are polymorphic and that approximately 50% of the candidate SNPs from these two sources are common SNPs (with minor allele frequency of > or =20%) in any given population.

DNA↗
PubMed2001

A method for parallel, automated, thermal cycling of submicroliter samples.

A large fraction of the cost of DNA sequencing and other DNA-analysis processes results from the reagent costs incurred during cycle sequencing or PCR. In particular, the high cost of the enzymes and dyes used in these processes often results in thermal cycling costs exceeding $0.50 per sample. In the case of high-throughput DNA sequencing, this is a significant and unnecessary expense. Improved detection efficiency of new sequencing instrumentation allows the reaction volumes for cycle sequencing to be scaled down to one-tenth of presently used volumes, resulting in at least a 10-fold decrease in the cost of this process. However, commercially available thermal cyclers and automated reaction setup devices have inherent design limitations which make handling volumes of <1 microL extremely difficult. In this paper, we describe a method for thermal cycling aimed at reliable, automated cycling of submicroliter reaction volumes.

Microchemistry↗
PubMed1998

Estrogen receptor alpha is essential for induction of oxytocin receptor by estrogen.

The induction of oxytocin receptor (OTR) synthesis in the periphery and in the brain by estrogen is critical for reproductive success. Oxytocin receptors are involved in the control of parturition, milk ejection, and sexual and maternal behaviors. The discovery of a second estrogen receptor (ERbeta) in the brain and the failure of in vitro transcription studies using OTR promoter constructs to replicate the in vivo transcriptional regulation have raised questions regarding the molecular mechanisms involved in the regulation of the OTR gene by estrogen. Using mice genetically deficient in estrogen receptor alpha (ERalpha), we demonstrate that ERalpha is not necessary for basal OTR synthesis, but is absolutely necessary for the induction of OTR binding in the brain by estrogen.

Animals↗
PubMed1997

Increased frequency of P-glycoprotein gene amplification in colchicine-resistant Rat-1 clones transformed by v-src.

A rat fibroblast cell line (Rat-1) carrying a temperature-sensitive mutation of v-src was used to determine whether inducible cellular transformation altered the ability of cells to amplify the p-glycoprotein gene in response to colchicine selection. Transformed and nontransformed Rat-1 fibroblasts selected under 4 times the LD50 generated the same number of colchicine-resistant colonies. We next examined colchicine-resistant colonies derived from transformed cells and compared them to colchicine-resistant colonies derived from nontransformed cells. When Rat-1 cells were selected at 35 degrees C (transforming temperature), 7 out of 7 clones exhibited a 3- to 5-fold p-glycoprotein gene amplification. These results contrasted to those found at the nontransforming temperature (40 degrees C); none of the 8 colchicine-resistant clones examined had amplified the p-glycoprotein gene. Thus in Rat-1 cells carrying a temperature-sensitive v-src gene, p-glycoprotein gene amplification was observed at a high frequency only in transformed clones selected at the temperature permissive for v-src activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Influence of angiotensin converting enzyme inhibition on exercise performance and clinical symptoms in chronic heart failure: a multicentre, double-blind, placebo-controlled trial.

One hundred and seven patients with chronic heart failure (NYHA class II to IV) stabilized on digitalis and/or diuretics, recruited from 11 centres were randomized into a double-blind, placebo-controlled study to assess the effect of 12 weeks of cilazapril therapy on exercise tolerance and clinical status. Thirty-five patients were randomized to placebo and 72 to cilazapril at a starting dose of 1 mg daily; titration to cilazapril 2.5 mg at week 4 and 5 mg at week 8 (or matching placebo) was carried out in patients who did not improve clinically. Demographic characteristics, including exercise test duration increased from 402 s (+/- 17 SEM) at baseline to 462 s (+/- 19 SEM) at week 12 for the cilazapril group (+15%) and from 405 s (+/- 23 SEM) at baseline to 408 s (+/- 30 SEM) at week 12 in patients on placebo (+1%) (P < 0.001). In the placebo group, patients able to exercise for more than 6 min at baseline showed an increase in exercise duration at week 12 while those able to exercise for up to 6 min at baseline showed a decrease (P = ns). In contrast, cilazapril-treated patients showed an increase in exercise tolerance regardless of baseline exercise test duration; patients with the most impaired exercise tolerance at baseline showed a greater improvement than patients with mildly impaired baseline exercise tolerance (P < 0.05 vs placebo). NYHA class improved by at least one grade in 51% of the cilazapril group vs 32% in the placebo group (P = ns). At the end of the trial, 15% of the patients were non-responders on cilazapril vs 41% on placebo (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Making your own videotapes for patient instruction.

Producing your own videotapes can be both fun and clinically helpful. They are extremely effective for patient instruction and for obtaining informed consent. This article discusses the production, presentation, and effective use of videotapes in office practice.

Humans↗
PubMed1986

Use of monophasic action potential recordings during routine coronary-artery bypass surgery as an index of localised myocardial ischaemia.

In 8 patients undergoing routine coronary-artery bypass surgery, monophasic action potentials (MAPs) were measured by means of a hand-held pressure contact electrode to provide an index of local ischaemic changes. 4 patients received left internal mammary anastomoses (LIMA), and there were a total of 27 saphenous vein grafts (SVG). After completion of all grafts blood-flow to the myocardium was reduced for 90 s by means of different permutations of SVG and LIMA occlusion, either on or off bypass. In all patients MAPs indicated typical ischaemic changes. The high sensitivity of the method enables the study to be completed quickly and without hazard to the patient. The technique provides a new means to assess local ischaemia, the viability of specific areas of myocardium, and the efficiency of individual grafts during surgery.

Action Potentials↗
PubMed1986

The diagnosis of aortic root abscess by cross-sectional echocardiography.

Aortic root abscess is frequently a lethal complication of infective endocarditis. Early diagnosis of this complication is of paramount importance because antibiotic therapy is often ineffective and early surgery is probably the treatment of choice. We have compared the diagnostic accuracy of cross-sectional echocardiography with operative findings in the diagnosis of aortic root abscess. Aortic root abscess was diagnosed in nine of 129 patients with infective endocarditis at the National Heart Hospital between 1983 and 1985. Cross-sectional echocardiography demonstrated the presence and location of the aortic root abscess in eight cases; in the ninth case a small abscess was missed. In two other cases, a large abscess was visualised, but abscesses of between 2 mm and 4 mm were missed; the extent and size of large aortic abscesses tended to be underestimated. Echocardiography should be an integral part of the investigation of patients with aortic valve infective endocarditis.

Abscess↗
PubMed1985

d-Sotalol: a new potent class III anti-arrhythmic agent.

We have compared the effect of a new drug d-sotalol which has minimal beta-blocking action with the parent (beta-blocking) compound dl-sotalol on monophasic action potential (MAP) duration in open-chested dogs. In seven experiments d-sotalol was administered in intravenous bolus doses of 1.5, 3 and 6 mg/kg given at 10 min intervals. In a further seven experiments dl-sotalol was administered using the same dosage regimen. The animals were anaesthetized with chloralose and urethane. Atrioventricular block was created by injection of the bundle of His with 0.1 ml of 40% formalin in order to ensure capture by ventricular pacing. After prior beta-blockade with propranolol (0.25 mg/kg), simultaneous epicardial and endocardial MAP were recorded at paced heart rates of 100 and 150 beats/min after each bolus injection. d-Sotalol and dl-sotalol showed similar prolongation of MAP duration (measured at 90% repolarization) in both endocardial and epicardial recording at both paced heart rates. These results show that the dextro-isomer of sotalol possesses similar class III action to the parent compound and that this action is homogeneous with respect to left ventricular endocardium and epicardium at heart rates of 100 beats/min and 150 beats/min over a wide dose range. d-Sotalol may be a useful anti-arrhythmic agent in man.

Action Potentials↗