Search PubMed⌕ Search

Biomedical subjects

K Saunders

Publications and source records attributed to K Saunders.

69 records · Page 4Linked to original sources

Infectious RNA derived by transcription from cloned cDNA copies of the genomic RNA of an insect virus.

RNA transcripts of cloned cDNA of the genomic RNAs of BBV (black beetle virus) are infectious to cultured cells of Drosophila melanogaster. Individual transcripts had approximately 10% of the infectivity of the corresponding authentic virion RNA. Progeny virus resulting from transcript infection was phenotypically indistinguishable from the progenitor virus used to generate the original cDNA forms as judged by sucrose density gradient sedimentation, specific infectivity, plaque morphology, and serology. Although the transcript RNAs used to produce this virus had 20 nonviral bases headed by a capping group at their 5' termini, these 20 bases were absent in the progeny viral RNAs. The cDNA forms, and therefore the resulting transcript RNAs, should be readily modifiable by the techniques of recombinant DNA technology both for viral studies and for the insertion of foreign genes into the viral genome and thus into the host cytoplasm.

Animals↗

Erythropoiesis in pregnancy.

The reticulocyte count, serum ferritin and serum erythropoietin concentrations were measured during the course of pregnancy in 41 women. A decrease in iron stores early in pregnancy was accompanied by a significant rise in the reticulocyte count until the 28th week. Erythropoietin levels did not rise significantly until the 28th week of pregnancy and had fallen to the post-natal level by 40 weeks. The results are consistent with an increase in erythropoietic activity early in pregnancy which did not appear to depend upon increased plasma erythropoietin levels.

Adult↗

Effect of ileal and intravenous infusions of fat emulsions on feeding and satiety in human volunteers.

The effect of ileal infusion of a lipid emulsion, containing 50% corn oil and 3% albumen, on food intake and satiety was measured in paired experiments carried out in 6 healthy volunteers. Subjects ate for shorter periods of time during ileal infusions of fat emulsion compared with control infusions of albumen and saline (25 +/- 1 vs. 32 +/- 3 min, mean +/- SEM) and consumed a smaller amount of food (670 +/- 23 g vs. 884 +/- 89 g) and energy (1016 +/- 79 kcal vs. 1591 +/- 228 kcal). The quantity of liquid drunk and the rates of eating and drinking were not significantly affected by the infusion of fat emulsion. In a further series of experiments carried out in 5 normal volunteers, ileal infusion of corn oil emulsions delayed gastric emptying compared with ileal infusion of albumen and saline (t1/2 = 203 +/- 48 vs. 68 +/- 12 min, p less than 0.02). The possibility that the observed reductions in food intake were related to the effect of absorbed fat was investigated in 6 healthy volunteers during intravenous infusion of either fat emulsion or isosmotic saline. Food intake was not affected by intravenous infusion of lipid. Our results suggest that lipid may interact with ileal receptors to induce early satiety and reduce the amount of food consumed. The earlier inhibition of food intake during lipid infusion is perhaps best explained by early gastric distention caused by delayed gastric emptying, though the data would not exclude the release of an ileal mechanism, which has a direct action on the satiety centers.

Adolescent↗

Template-dependent RNA polymerase from black beetle virus-infected Drosophila melanogaster cells.

Infection of cultured cells of Drosophila melanogaster with black beetle virus (BBV) induces an RNA polymerase that is bound to cellular particulate material in a complex with a template RNA. We have solubilized the polymerase by treatment of the relevant particulates with detergents such as dodecyl-beta-D-maltoside. The polymerase activity was made dependent upon exogenous RNA by destruction of the endogenous template RNA with micrococcal nuclease. Addition of BBV RNA1 or RNA2 induced synthesis of full-length negative-strand RNA isolated as a double-stranded complex with the added RNA. Newly synthesized plus strands were also detected in the RNA2 complexes. Certain other viral RNAs also induced synthesis of their negative strands.

Animals↗

Multiple sites of recombination within the RNA genome of foot-and-mouth disease virus.

Recombinant foot-and-mouth disease viruses were isolated from cells infected with a mixture of temperature-sensitive (ts) mutants belonging to different subtype strains. In order to select for recombination events in many different regions of the genome, crosses were performed between various pairs of mutants, with ts mutations in different regions of the genome. ts+ progeny were analysed by electrofocusing virus-induced proteins and RNase T1 fingerprinting of their RNA. All but 5 out of 43 independent isolates, from nine crosses, proved to have recombinant RNA genomes. Maps of these genomes, based on a knowledge of the locations of the unique oligonucleotides, were constructed. Most could be interpreted as being the products of single genetic cross-overs, although three recombinants were formed by two cross-overs each. Cross-overs in at least twelve distinct regions of the genome were identified. This evidence of a large number of recombination sites suggests that RNA recombination in picornaviruses is a general, as opposed to a site-specific, phenomenon.

Aphthovirus↗

Recombination and oligonucleotide analysis of guanidine-resistant foot-and-mouth disease virus mutants.

Guanidine resistance (gr) mutations of foot-and-mouth disease virus were mapped by recombining pairs of temperature-sensitive mutants belonging to different subtypes. In each cross, one parent possessed a gr mutation. Recombinants were isolated by selection at the nonpermissive temperature and assayed for the ability to grow in the presence of guanidine. From the progeny of three crosses, four different types of recombinant were distinguished on the basis of protein composition and RNA fingerprint. The sequences of the RNase T1-resistant oligonucleotides were determined and located in the full-length sequence of foot-and-mouth disease virus. The resulting maps show that (i) each recombinant was generated by a single genetic crossover, and (ii) both of the gr mutations studied were located within an internal 2.9-kilobase region which spans the P34 gene. This supports our hypothesis that guanidine inhibits the growth of foot-and-mouth disease virus by acting on nonstructural polypeptide P34. Additional evidence was provided by RNA fingerprinting gr mutants. In two of four cases the gr mutation was associated with a change in an oligonucleotide located near the 3' end of the P34 gene; in one of these the nucleotide substitution was identified.

Aphthovirus↗

Guanidine-resistant mutants of aphthovirus induce the synthesis of an altered nonstructural polypeptide, P34.

Extracts of cells infected with guanidine-resistant mutants of aphthovirus were examined for differences in virus-induced polypeptides by using electrofocusing. Four of 1 independent spontaneous mutants induced the synthesis of an altered nonstructural polypeptide, P34. The precursor of P34, P52, and a previously unmapped polypeptide, P20c, also carried these charge-change mutations. No mutations in other regions of the genome were detected, and the remaining six guanidine-resistant mutants appeared entirely normal by electrofocusing. However, when the P34 of one of the latter mutants was examined by tryptic peptide fingerprinting, it too differed from that of the guanidine-sensitive parent. The frequency of P34 alterations among guanidine-resistant mutants suggests that P34 is functionally involved in the antiviral action of guanidine.

Aphthovirus↗

Effect of mutation on the virulence in mice of a strain of foot-and-mouth disease virus.

Twenty-eight mutations, representing mutation in five different polypeptide-coding regions of the foot-and-mouth disease genome, were examined for their effect on the virulence of the virus for suckling mice. Five types of mutation were examined: temperature-sensitive (ts), electrophoretic (e), co-variant temperature-sensitive and electrophoretic (ts/e), guanidine-resistant (gs+) and putative co-variant guanidine-resistant and electrophoretic (gs+/e). All the ts mutations and three out of the 11 non-ts mutations produced some reductions in virulence. In the majority of cases this reduction in virulence was shown to co-vary with the mutation. No correlation was observed between the site of a mutation or its 'cut-off' temperature and the extent of the reduction in virulence. Studies of the growth in vivo of a small selection of ts mutants suggested that for most mutants their reduced virulence was a trivial effect of their slow growth rate. With one exception they all eventually grew to parental virus levels, the resulting virus being temperature-sensitive and the disease indistinguishable from that caused by the parental virus. The one exception was an avirulent ts mutant which only grew to one-thousandth the titre of the parent virus. This mutant did not cause disease and was therefore considered to be the only avirulent mutant. Its mutation was in the coat protein-coding region of the genome, probably the region coding for VP3.

Animals↗

The platelet count in pregnancy.

The platelet count was measured at approximately monthly intervals during the course of 44 normal pregnancies. There was no evidence of any fall in the platelet count during pregnancy. Any significant change in the platelet count in pregnant women is unlikely to be the result of a normal pregnancy.

Analysis of Variance↗

Long-term follow-up of direct current cardioversion after cardiac surgery with special reference to quinidine.

The results of the long-term follow-up of 119 patients who had DC cardioversion performed are described. All patients had had corrective cardiac surgery for chronic rheumatic valvar heart disease. The poor prognosis for maintenance of sinus rhythm in this type of patient is emphasized. Of the total patients, 83 per cent were converted to sinus rhythm, but relapses were common in those who had atrial fibrillation before operation. Only 40 per cent of such patients maintained sinus rhythm for 2 months, 15 per cent for 1 year, and 9 per cent for 2 years.By contrast, when atrial fibrillation occurred for the first time in the post-operative period, 82 per cent maintained sinus rhythm for 2 years after conversion.Post-operative DC cardioversion is in general not recommended for patients with rheumatic heart disease and atrial fibrillation unless atrial fibrillation occurs for the first time in the post-operative period. A controlled trial of prophylactic quinidine is reported and shows no significant increase in the number of patients remaining in sinus rhythm as compared with a control group not receiving quinidine.

Atrial Fibrillation↗

Intravascular lipoma of the superior vena cava: CT features.

An intrinsic lipoma of the right brachiocephalic vein and superior vena cava is described. This intraluminal tumour expanded the superior vena cava and produced superior mediastinal widening, which was of fatty radiodensity on chest radiography. The CT and venographic findings in this case are described.

Adult↗

Treatment costs, cost offset, and cost-effectiveness of collaborative management of depression.

OBJECTIVE: The report estimates the treatment costs, cost-offset effects, and cost-effectiveness of Collaborative Care of depressive illness in primary care. STUDY DESIGN: Treatment costs, cost-offset effects, and cost-effectiveness were assessed in two randomized, controlled trials. In the first randomized trail (N = 217), consulting psychiatrists provide enhanced management of pharmacotherapy and brief psychoeducational interventions to enhance adherence. In the second randomized trial (N = 153). Collaborative Care was implemented through brief cognitive-behavioral therapy and enhanced patient education. Consulting psychologist provided brief psychotherapy supplemented by educational materials and enhanced pharmacotherapy management. RESULTS: Collaborative Care increased the costs of treating depression largely because of the extra visits required to provide the interventions. There was a modest cost offset due to reduced use of specialty mental health services among Collaborative Care patients, but costs of ambulatory medical care services did not differ significantly between the intervention and control groups. Among patients with major depression there was a modest increase in cost-effectiveness. The cost per patient successfully treated was lower for Collaborative Care than for Usual Care patients. For patients with minor depression. Collaborative Care was more costly and not more cost-effective than Usual Care. CONCLUSIONS: Collaborative Care increased depression treatment costs and improved the cost-effectiveness of treatment for patients with major depression. A cost offset in specialty mental health costs, but not medical care costs, was observed. Collaborative Care may provide a means of increasing the value of treatment services for major depression.

Adult↗