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R W Roberts

Publications and source records attributed to R W Roberts.

18 recordsLinked to original sources

Stability and properties of double and triple helices: dramatic effects of RNA or DNA backbone composition.

Studies of a series of short oligonucleotide double and triple helices containing either all RNA, all DNA, or a mixture of the two show strand-dependent variation in their stability and structure. The variation in stability for both groups falls over a range of greater than 10 kilocalories per mole. In forming the triple helix, RNA is favored on both pyrimidine strands, whereas DNA is favored on the purine strand. In general, relatively unstable duplexes form particularly stable triplexes and vice versa. Structural data indicate that the strands in hybrid helices adopt a conformation that is intermediate between molecules containing all DNA and all RNA. Thus, RNA-DNA hybrids were not forced into the conformation of the RNA (A-form). The provocative stability of the triplex with an RNA third strand+DNA duplex points to novel antisense strategies and opens the possibility of an in vivo role of these structures. Overall, the data emphasize the fundamental role of sugars in determining the properties of nucleic acid complexes.

Base Sequence

Specificity and stringency in DNA triplex formation.

Triple-helix formation can in principle serve as a general method for sequence-specific recognition and physical separation of duplex DNA molecules. Realization of this goal depends on how much the triplex is destabilized by mismatches and other defects (specificity) and on finding conditions in which perfect complexes are stable and defect complexes are not (stringency). We have addressed the question of specificity by determining the difference in free energy between perfect and defect complexes by using UV melting curves and equilibrium competition experiments. We find that third strands that bind with either single-base bulges or single mismatches are destabilized relative to the perfect triplex by 2.5-2.9 and 3.2-4.0 kcal/mol (1 cal = 4.184 J), respectively, essentially equivalent to the corresponding values determined for duplex DNA and RNA. Also, we present a method, referred to as stringency clamping, which maintains specific binding under conditions far from normal stringency. To do this, we provide for the formation of a competing structure involving the third strand with stability between that of the perfect and imperfect complexes; the competitive interaction effectively prevents triplex formation at imperfect sites even far below their melting temperature. We illustrate the phenomenon with three different stringency clamps, two of which compete for the all-pyrimidine third strand through Watson-Crick pairing and one that competes through all-pyrimidine pairing at acidic pH. We demonstrate physical separation of two duplex DNA molecules differing by a single base pair in their target sequence for triple-helix formation.

Base Sequence

EPA in the prevention of restenosis post PTCA.

The effect of fish oil on restenosis was evaluated in patients undergoing coronary balloon angioplasty. In addition to routine pharmacotherapy, subjects were given 2.8 g of eicosapentanoic acid (EPA) daily. Treatment was started within twenty-four hours after successful percutaneous transluminal coronary angioplasty (PTCA). After six months of therapy, participants were subjected to coronary arteriography, exercise scintigraphy, exercise electrocardiography, or clinical evaluation. Follow-up evaluation involved 97 coronary lesions in 85 patients. Partial or significant restenosis occurred in 36.5% of patients and 33% of vessels. The presence of severe stenosis before PTCA, dissection, thrombus, multilesion PTCA, and template bleeding time values were not correlated with restenosis. Dilation of the left anterior descending (LAD) and a residual stenosis greater than or equal to 35% were associated with restenosis. Approximately 20% of the patients related difficulty in taking the fish oil. Furthermore, these results show no advantage over expected restenosis rates.

Angioplasty, Balloon, Coronary

A behavioral perspective on conduct disorders.

THIS paper provides a selective overview of behavioral approaches for conduct-disordered behavior. Although no definitive statement can be made regarding etiology, some empirical support exists for behavioral strategies. Assessment approaches discussed include the behavioral interview, behavioral observations, and behavioral checklists. Decisions regarding types of behavioral interventions to be employed directly follow from assessment data. Assessment information can be formulated in terms of a behavioral excess/skill deficit model. Hence, conduct-disordered behavior can be a function of excessive disruptive behavior and/or a lack of requisite skills necessary to obtain satisfaction. Parental training strategies in contingency management and contingency contracting are discussed regarding behavioral excesses. Relative to skill deficits, contingency procedures along with skills training in communication, problem-solving and self-control are reviewed, using parental training and cognitive-behavioral frameworks. In general, these interventions have empirically demonstrated efficacy. However, future research is required to identify specific factors that account for successful treatment, and attention should be directed toward preventive issues. Important data could be obtained from the identification of high-risk environmental situations. A predictive understanding of high-risk populations could result in the development of early intervention programs, which might to some extent obviate the occurrence of conduct disorders.

Adolescent

Practice location preferences of Alabama medical students.

Factors that help determine physicians' practice locations and specialties were listed by 396 students and 103 medical school faculty members at the University of Alabama School of Medicine. The students preferred practice locations similar in size to their hometowns. Their specialty choices were closely related to both practice location preferences and hometown sizes. However, there was a tendency among the students to prefer a small city (20,000 to 100,000 population) practice location irrespective of their hometown sizes or specialty choices. Factors such as spouse's preference, proximity of relatives, and financial incentives were not related to the students' practice location preferences. Faculty members reported they believed that medical education biases students toward urban and nonprimary care practice, and one-third of them said that they were role models for the students' specialty choices. However, the students said faculty members had little influence on their specialty choices while acknowledging the importance of clinical experiences. In general, Alabama medical students are similar to medical students elsewhere with respect to determinants of practice location preference.

Adult

Cyclophosphamide-induced cardiomyopathy: a report of two cases and review of the English literature.

Fatal cardiomyopathy developed in two patients receiving cyclophosphamide in preparation for bone marrow transplantation. Both patients had normal EKGs prior to receiving cyclophosphamide in total doses of 168 mg/kg (case 1) and 144 mg/kg (case 2) and subsequently developed loss of voltage and ST-T wave changes. One patient (case 1) died of CHF and hypotension while the other patient (case 2) developed tamponade. Prior to this report, the lowest total dose of cyclophosphamide reported to cause fatal cardiomyopathy was 180 mg/kg. In contrast to anthracycline congestive cardiomyopathy, the effects of cyclophosphamide appear to have an acute onset and do not appear to be the cumulative result of drug dosing. Postmortem examination in both patients revealed thickened left ventricles with intramyocardial hemorrhage.

Adolescent