Mutator phenotype induced by aberrant replication

We have identified thermosensitive mutants of five Schizosaccharomyces pombe replication proteins that have a mutator phenotype at their semipermissive temperatures. Allele-specific mutants of DNA polymerase delta (poldelta) and mutants of Polalpha, two Poldelta subunits, and ligase exhibited increased rates of deletion of sequences flanked by short direct repeats. Deletion of rad2(+), which encodes a nuclease involved in processing Okazaki fragments, caused an increased rate of duplication of sequences flanked by short direct repeats. The deletion mutation rates of all the thermosensitive replication mutators decreased in a rad2Delta background, suggesting that deletion formation requires Rad2 function. The duplication mutation rate of rad2Delta was also reduced in a thermosensitive polymerase background, but not in a ligase mutator background, which suggests that formation of duplication mutations requires normal DNA polymerization. Thus, although the deletion and duplication mutator phenotypes are distinct, their mutational mechanisms are interdependent. The deletion and duplication replication mutators all exhibited decreased viability in combination with deletion of a checkpoint Rad protein, Rad26. Interestingly, deletion of Cds1, a protein kinase functioning in a checkpoint Rad-mediated reversible S-phase arrest pathway, decreased the viability and exacerbated the mutation rate only in the thermosensitive deletion replication mutators but had no effect on rad2Delta. These findings suggest that aberrant replication caused by allele-specific mutations of these replication proteins can accumulate potentially mutagenic DNA structures. The checkpoint Rad-mediated pathways monitor and signal the aberrant replication in both the deletion and duplication mutators, while Cds1 mediates recovery from aberrant replication and prevents formation of deletion mutations specifically in the thermosensitive deletion replication mutators.     

Comparison of rest/exercise ECG, thallium-201 scans and radionuclide angiography in patients with suspected coronary artery disease

The results of rest and exercise ECG, 201Tl myocardial perfusion imaging and equilibrium radionuclide angiography were analyzed in 71 consecutive patients referred for diagnosis or evaluation of coronary artery disease (CAD). In 45 patients the diagnosis was established either by catheterization or typical history. In this group the overall sensitivity for rest/exercise ECG was 66%, for 201Tl scans 74%, for both combined 79% and for the ejection fraction response to exercise determined by radionuclide angiography 97%. If only the exercise response was considered, the corresponding sensitivity values were 58% (ECG), 50% (201Tl scans), 71% (ECG + 201Tl) and 97% (radionuclide angiography). The specificity for coronary artery disease was determined to be 71% for ECG, 86% for 201Tl scans and 42% for radionuclide angiography. All patients with false-positive results by radionuclide angiography had cardiomyopathies, thus this test has a high specificity for left ventricular dysfunction rather than for CAD alone. Criteria developed from the analysis of the test results in the 45 patients with definite diagnoses were then applied to the evaluation of 26 additional patients with atypical chest pain. A diagnosis could be made in all but 5 of them and radionuclide angiography was again the single most reliable test. Based on this study a new approach for the noninvasive evaluation of patients with suspected coronary artery disease is proposed.     

Therapeutic effectiveness of bonafton and rimantadine in influenza

The therapeutic effectiveness of bonaphthone and rimantadine was studied by treatment of 439 patients with influenza between 18 and 21 years of age (bonaphthone 94, controls 105, rimantadine 120, controls 120). No therapeutic effectiveness of bonaphthone was established in the study. When rimantadine was given to the patients from the 1st day of the disease, shorter intervals of normalization of the temperature, disappearance of toxicity and catarrhal symptoms were observed than in patients treated with symptomatic drugs. During the period of rimantadine therapy the rate of findings the influenza antigen in smears from the nasal mucosa was lower, but after termination of the course of treatment the antigen was found twice as frequently as in the control group. With the positive therapeutic effect in patients treated with rimantadine, the diagnostic rise of antibody in this group was observed in a lower per cent of cases than in the control group (13 and 20%, respectively). The results of immunofluorescent and serological studies indicate a possible virus reproduction-inhibiting effect of rimantadine. This, however, requires further study. On the basis of the above observations rimantadine may be recommended for treatment of patients with influenza.     

Automatic membrane-filtration system for the "on-demand" supply of large volumes of sterile medium in continuous culture

The construction and use of an automated membrane filtration system is described which produces 300 liters per day of sterile medium over at least four months of continuous fermentation. The capacity of the system is limited only by choice of filter type and has applications in continuous pilot plant work or medium-scale batch fermentation, in the bulk supply of communally used laboratory medium, in supplying banks of small-scale continuous fermentors, and for remote control of medium supply in hazardous fermentations (e.g., methane) with great savings in time and materials. Only two sterile storage jars are needed, irrespective of the total demand for the medium.     

Intestinal nematodes of white-tailed deer in southeastern United States

The small intestine, large intestine, and cecum of 975 white-tailed deer (Odocoileus virginianus) from 83 localities in 13 southeastern states were examined for nematodes. In order of prevalence, the following parasites were found: Capillaria bovis, Eucyathostomum webbi, Monodontus louisianensis, Nematodirus odocoilei, Oesophagostomum venulosum, Trichuris sp, Cooperia punctata, Trichostrongylus longispicularis, Strongyloides sp, Cooperia oncophora, Cooperia spatulata, Cooperia sp, and Trichostrongylus calcaratus. Over one-half of the deer examined were free of intestinal nematodes, and most infected deer harbored few parasites. Of the most prevalent species, C bovis, N odocoilei, O venulosum, and Trichuris sp were widely distributed, whereas M louisianensis and E webbi were restricted in distribution. Severe pathogenicity was associated with only heavy Strongyloides sp infections in 2 penned deer. The findings of this study suggested that white-tailed deer of the Southeast are insignificant in the epizootiology of important intestinal nematodes of domestic livestock.     

Undergraduate training in primary health care: 6 years' experience at the University of Alicante

OBJECTIVE: To assess the opinion of medical students on the teaching offered in the Primary Care context (TOPC). DESIGN: Observational and crossover study. The assessment used an opinion questionnaire. PARTICIPANTS: 296 sixth-year medical students between 1987 and 1992. INTERVENTIONS: The TOPC consisted of four weeks stay in a Health Centre with an eminently practical programme. However this also included hour-long theoretical seminars on the most important Primary Care questions and the student's completion of a research project related to Primary Care. RESULTS: The students expressed satisfaction with the TOPC (average score of 4 out of 5). Moreover this satisfaction increased over the five years (from 3.7 to 4.6, p = 0.0001). They believed the TOPC to be useful (3.6 to 4.7, p = 0.0001) and relevant to their future professional activity (3.1 to 4.6, p = 0.0001). They thought that the tutors were very competent (4 out of 5, with no significant variation) and the Health Centres' teaching facilities suitable (3.8 to 4, with no significant variation). Finally, they considered that TOPC should become a compulsory undergraduate subject (3.9 out of 5). CONCLUSIONS: Medical students give a positive rating to the Primary Care teaching offered and believe it should be integrated into the Medicine syllabus as a compulsory subject.