Search PubMed⌕ Search

Biomedical subjects

D Cavanagh

Publications and source records attributed to D Cavanagh.

At least 217 records · Page 12Linked to original sources

Coronavirus IBV: structural characterization of the spike protein.

The spike protein (S; surface projection) of avian infectious bronchitis virus (IBV) strain M41 comprises two glycopolypeptides, S1 (mol. wt. 90 X 10(3] and S2 (mol. wt. 84 X 10(3], in equimolar proportions. The apparent mol. wt. of S was calculated as 354 (+/- 17) X 10(3) following co-sedimentation with catalase in sucrose gradients. Incubation of radiolabelled IBV with urea resulted in the removal of most S1, but none of S2, from the virus particle. A similar result was obtained using low concentrations of SDS, although some nucleocapsid, but not matrix, protein was also released. 2% SDS alone was as effective as 2% SDS plus 2% 2-mercaptoethanol for the separation of S1 and S2 prior to SDS-polyacrylamide gel electrophoresis. Dithiothreitol did not remove S from virions but did decrease the buoyant density of the virus from 1.18 g/ml to 1.16 g/ml, and changed the configuration of S. It is concluded that IBV S protein is an oligomer comprising two copies of each of S1 and S2, although the possibility that there are three copies of each glycopolypeptide cannot be discounted. S is attached to the membrane by S2, while S1 has little or no contact with the membrane and may form the major part of the bulbous end of S. Interpeptide disulphide bonds do not occur in S, and the association of S1 and S2 is weak.

Centrifugation, Density Gradient↗

Coronavirus IBV glycopolypeptides: size of their polypeptide moieties and nature of their oligosaccharides.

Analysis of differentially radiolabelled avian infectious bronchitis virus (IBV) indicated that the matrix (M) polypeptides of mol. wt. 23 X 10(3) (23K), 26K, 28K, 30K and 34K (M23 to M34) which have been shown to give the same peptide maps, differed in their degree of glycosylation; M23 was not glycosylated while glycosylation increased with increasing mol. wt. from M26 to M34. Both glucosamine and mannose were components of M26 to M34 but [3H]fucose appeared to be associated mainly with M34. Endo-beta-N-acetylglucosaminidase H removed oligosaccharides from M28 and M30 but not M26 and M34, to give a polypeptide of 23K. The surface projection glycopolypeptides S1 (90K) and S2 (84K) incorporated 3H-labelled glucosamine and mannose but not fucose and had oligosaccharides removed by endoglycosidase H. The mol. wt. of the resultant polypeptides varied among experiments; the lowest mol. wt. observed were 64K and 61K. These results indicate (i) that the polypeptide moieties of the S polypeptides are approximately 64K and 61K, and 23K for the M polypeptide, (ii) that the oligosaccharides of the S and M polypeptides are of the high-mannose type and are linked to the polypeptides by N-glycosidic linkages, and (iii) that the M glycoprotein of IBV differs from that of murine coronaviruses and bovine coronavirus L9 which have O-linked oligosaccharides.

Coronaviridae↗

Coronavirus IBV: further evidence that the surface projections are associated with two glycopolypeptides.

The surface projections (peplomers) of avian infectious bronchitis virus (IBV) strain M41 have been separated from the nucleocapsid (N) and matrix (M) proteins by sedimentation in a sucrose gradient after virus disruption by the non-ionic detergent Nonidet P40. The peplomers comprised two glycopolypeptides of mol. wt. 90 X 10(3) (90K; S1) and 84K (S2), shown by analysis of differentially radiolabelled virus to be present in equimolar proportions. Polypeptides of 75K and 110K, which were detected by Coomassie Brilliant Blue staining in similar amounts to S1 and S2 in some unlabelled virus preparations, were absent from peplomer preparations and are probably host cell polypeptides. The S1:S2:N:M polypeptide molar ratio for IBV-M41 was approximately 1:1:6:15.

Centrifugation, Density Gradient↗

Glandular intraepithelial neoplasia (GIN)--a unifying concept of the precursors of endometrial adenocarcinoma.

There is considerable variation and a good deal of confusion surrounding definitions and nomenclature for premalignant lesions of the endometrium. A unifying concept, based on the model of cervical intraepithelial neoplasia, is proposed to provide a uniform, practical basis for the diagnosis and management of the precursors of endometrial cancer. Lesions would be classified as glandular epithelial neoplasia (GIN) Grades, 1, 2 and 3. Illustrated examples, and comparisons with other classifications are provided.

Adenocarcinoma↗

Coronaviridae.

The family Coronaviridae comprises a monogeneric group of 11 viruses which infect vertebrates. The main characteristics of the member viruses are: (i) Morphological: Enveloped pleomorphic particles typically 100 nm in diameter (range 60-220 nm), bearing about 20 nm long club-shaped surface projections. (ii) Structural: A single-stranded infectious molecule of genomic RNA of about (5-7) X 10(6) molecular weight. A phosphorylated nucleocapsid protein [mol. wt. (50-60) X 10(3)] complexed with the genome as a helical ribonucleoprotein; a surface (peplomer) protein, associated with one or two glycosylated polypeptides [mol. wt. (90-180) X 10(3)]; a transmembrane (matrix) protein, associated with one polypeptide which may be glycosylated to different degrees [mol. wt. (20-35) X 10(3)]. (iii) Replicative: Production in infected cells of multiple 3' coterminal subgenomic mRNAs extending for different lengths in the 5' direction. Virions bud intracytoplasmically. (iv) Antigenic: 3 major antigens, each corresponding to one class of virion protein. (v) Biological: Predominantly restricted to infection of natural vertebrate hosts by horizontal transmission via the fecal/oral route. Responsible main for respiratory and gastrointestinal disorders.

Antigens, Viral↗

Abdominal wound closure using a nonabsorbable single-layer technique.

A continuous 1-layer abdominal closure using number 2 polypropylene was employed in 200 unselected consecutive patients. All the patients had lower midline incisions and were high-risk, and the majority (82%) had some form of gynecologic malignancy. A significant number had received preoperative radiotherapy (22.5%), another 18% were obese (over 90 kg), and 15% had undergone bowel surgery. The complete evisceration rate in the series was 0. A total of 17 (8.5%) wound infections occurred and 10 (5%) postoperative ventral hernias were seen over a 2-year period. Five of these were incisional and 5 were paraincisional; 1 of each required surgical repair. The method is simple, time-saving, and successful; it carries a low complication rate for patients at high risk for postoperative evisceration.

Abdomen↗

Endotoxic shock in the primate: some effects of dopamine administration.

The circulatory effects of dopamine (3,4-dihydroxyphenylethylamine) in baboons with endotoxic shock were studied. A beneficial effect was seen in all cardiovascular parameters studied. Cardiac output was better maintained, and this was primarily due to an increase in the stroke volume. The renal artery flow was improved with a decrease in the renal resistance in the dopamine-treated group when compared with the group receiving endotoxin alone. Arterial pH and PO2 did not show significant changes. A rise in blood lactic acid level and a decrease in arterial PCO2 were consistent findings whether or not the animals received dopamine. This study supports the view that dopamine improves the cardiovascular status of the subhuman primate in endotoxic shock and has implications with regard to the patient with endotoxic shock.

Animals↗

Septic shock and the obstetrician/gynecologist.

Septic shock continues to be a serious problem with a mortality ranging from 11% to 82%, depending upon the cause, the time of diagnosis, and the type of treatment. The condition is seen in pregnant patients with postabortal or postpartal endometritis, chorioamnionitis, and pyelonephritis. In gynecology patients it is seen after severe pelvic infection and in immunosuppressed patients with gynecologic cancer. Prompt diagnosis, adequate monitoring and vigorous treatment are essential if deaths are to be reduced. Over the period July 1, 1959, to June 30, 1981, 91 patients were treated for septic shock with a mortality of 18%. Although medical treatment is important, the most important aspect of treatment for most patients is removal of the septic focus.

Abortion, Septic↗

Endotoxic shock in the primate: effects of aspirin and dipyridamole administration.

A primate model was utilized to study the cardiovascular and coagulation effects of endotoxic shock. The therapeutic effectiveness of drugs such as aspirin and dipyridamole, which diminish platelet aggregation and adherence, were evaluated. From the data, it appears that the kidney is a target organ in endotoxic shock, at least when a bolus injection of endotoxin is administered. The precipitate falls in the renal artery flow (p less than 0.01) and platelet count (p less than 0.01), which occur 3 minutes after the intravenous injection of endotoxin, can be prevented in part by pretreatment with aspirin (40 mg/kg of body weight). The changes in the coagulation profile were of less magnitude, and the fibrin degradation products appeared late in the group pretreated with aspirin as compared to the other groups. The combination of dipyridamole and aspirin was not as effective as aspirin alone in achieving the apparently protective effect. The study suggests that the administration of aspirin to patients with gram-negative infections may be beneficial.

Animals↗

Structural polypeptides of coronavirus IBV.

Avian infectious bronchitis virus (IBV) was grown and radiolabelled with 35S-methionine, 3H-leucine and 3H-glucosamine in de-embryonated chicken eggs. Approximately 12 different polypeptides were clearly detected by SDS-polyacrylamide gel electrophoresis of virus preparations. Growth of IBV in chorioallantoic membrane cells labelled with 35S-methionine indicated that most of these polypeptides, and additional ones, some of which were glycosylated, were host components. Five polypeptides appeared to be virus-coded, with apparent mol. wt. of 94 x 10(3), 84 x 10(3), 54 x 10(3), 30 x 10(3) and 28 x 10(3). Four of these, p94, p84, p30 and p28, were glycosylated. The virion spikes appeared to be composed of p94 and p84, while p30 and p28 were partially embedded in the virion membrane. By analogy with other reports, p54 is the nucleocapsid polypeptide.

Animals↗

Differential distribution of virus and histological damage in the lower respiratory tract of ferrets infected with influenza viruses of differing virulence.

The distribution of four strains of influenza virus [A/PR/8/34 (H0N1) and clone 64d (attenuated for ferrets) and clones 64c and 7a (virulent for ferrets) of the recombinant virus A/PR/8/34--A/England/939/69 (H3N2)] in the lower respiratory tract (trachea, bronchi and the hilar, intermediate and outer alveolar zones of the lung) of ferrets was monitored daily for 4 days after intranasal inoculation. On day 1, some animals had high virus titres in all the tissues but in other animals virus was undetectable, irrespective of the virus strain. Two days after inoculation increase of virus contents of all tissues tended to be restricted. On days 3 and 4, the virulent clones (64c and 7a), in contrast to the attenuated strains (A/PR/8/34 and clone 64d), consistently infected the lower respiratory tissues. However, for all infected animals the virus contents of the hilar zones of the lungs were higher than those in the intermediate zones, while the alveolar zones were relatively free from virus. Quantitative estimations of the mild histological damage occurring in the lower respiratory tract 3 to 6 days after inoculation also indicated that bronchial and bronchiolar tissue were more susceptible to influenza virus than alveolar tissue and that clones 64c and 7a produced more damage than the other two strains. In agreement with the relative viral contents of clones 64c and 7a in the bronchi and in the hilar and intermediate zones of the lung, clone 64c produced more damage than clone 7a in the bronchi and less in the bronchioles of the lung parenchyma.

Animals↗