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Biomedical subjects

D R Harper

Publications and source records attributed to D R Harper.

53 records · Page 3Linked to original sources

Recovery of host cell protein synthesis during infection with a temperature-sensitive mutant of Newcastle disease virus.

When chick embryo fibroblasts infected with high multiplicities of a non-revertible temperature-sensitive (ts) mutant (ts53) of Newcastle disease virus (NDV) at the permissive temperature (34 degrees C) and incubated to allow the appearance of virus-induced proteins were shifted up to and incubated at the non-permissive temperature (42 degrees C), analysis of [3H]leucine-labelled proteins by SDS-PAGE revealed a marked increase in cellular protein synthesis and a decline in viral synthesis, with an eventual return to an apparently uninfected state. Mutant ts53 apparently ceased to suppress cellular protein synthesis, and translation of viral proteins was markedly inhibited. This was not observed in ts+-infected cells, or in ts53-infected cells maintained at the permissive temperature. Recovery from the infected state was inhibited by actinomycin D at any stage, but was not prevented by cycloheximide present immediately before and during temperature shift-up. Mutant ts53 was shown to be RNA- at 42 degrees C, although viral mRNAs synthesized at 34 degrees C are shown to be present throughout host recovery but in an inactive state.

Animals↗

A temperature-sensitive mutant of Newcastle disease virus which is affected in both haemagglutinin-neuraminidase and matrix proteins.

Virions prepared from a non-revertible temperature-sensitive (ts) mutant (ts53) of Newcastle disease virus (NDV) grown in ovo at the permissive temperature (34 degrees C) possessed thermolabile haemagglutination and neuraminidase activities compared with parental (ts+) virions. Purified haemagglutinin-neuraminidase (HN) protein from ts53 virions was also more thermolabile than ts+ HN protein. SDS-PAGE analysis of [3H]leucine pulse- and pulse/chase-labelled NDV proteins synthesized in chick embryo fibroblasts following infection with ts+ and ts53 virus revealed that ts53 matrix (M) protein was unstable and disappeared during chase incubations only at the non-permissive temperature (42 degrees C). The non-revertibility of the ts53 mutant may indicate that it is a double mutant affected in both HN and M genes; alternatively this mutant may only be affected in the HN gene, the close physical association of the thermolabile HN with the M protein during virus maturation resulting in the lack of protection of the M protein from the action of cellular proteases at the non-permissive temperature.

Cycloheximide↗

Disease cost in a surgical ward.

Data relating to the cost of caring for individual patients were collected for all patients in a general surgical ward over a six-month period. From this the cost per patient was calculated for various diseases and was found to be related to duration of stay. Postoperative morbidity was important in determining cost. A system that calculates cost by means of units based on the use of resources rather than by cash cost accounting is probably the most suitable for a clinician who has to monitor resources.

Adult↗

Selective angiography in acute mid-gut ischaemia.

Acute mesenteric ischaemia has a high mortality. Early diagnosis and treatment appropriate to the type and extent of vascular insufficiency are essential. Selective angiography can establish the diagnosis and distinguish patients with acute vascular occlusion who require urgent surgery from those with non-occlusive ischaemia for which early surgery is contraindicated.

Aged↗

Induction of neutralizing antibody and T-cell responses to varicella-zoster virus (VZV) using Ty-virus-like particles carrying fragments of glycoprotein E (gE).

During infection with Varicella-zoster virus (VZV), the envelope proteins are highly immunogenic and glycoprotein E (gE) is one of the most abundant and antigenic. We have previously identified the immunodominant regions of gE and mapped the B-cell epitopes. In this study, we have evaluated the immunogenicity of recombinant hybrid Ty-virus-like particles (VLPs) carrying amino acids (1-134) or (101-161) of gE which contain the immunodominant sequences. VZV-specific antibodies were detected by ELISA in sera from mice and guinea pigs immunized with either gE(1-134)-VLPs or gE (101-161)-VLPs. The dominant B-cell epitopes, mapped by pepscan analysis of the sera, were found in peptides spanning amino acids 41-60, 56-75, 101-120, 116-135, 131-150 and 141-161. These sera also showed neutralizing activity against VZV in vitro. Epitopes recognized by neutralizing MAbs were mapped to both gE sequences (3B3 MAb recognizing amino acids 141-161 and IFB9 MAb recognizing amino acids 71-90). Lymphocyte proliferative responses to VZV were detected in four different mouse strains immunized with either gE(1-134)-VLPs or gE(101-134)-VLPs in alum. All mouse strains immunized with gE(1-134)-VLPs recognized epitopes in amino acids 11-30 and 71-90 and all those immunized with gE(101-161)-VLPs recognized epitopes in amino acids 91-110 and 106-125. These results indicate that VLPs carrying these gE sequences can prime potent humoral and cellular anti-VZV responses in small animals and warrant further investigation as potential vaccine candidates against varicella-zoster infections.

Amino Acid Sequence↗

Plethysmography during aorto-iliac surgery.

Cardiac output, arterial and central venous pressures and calf blood flow were used to monitor patients undergoing abdominal aortic surgery. Measurement of calf blood flow by means of venous occlusion plethysmography showed that measurable blood flow to the legs persisted after clamping of the aorta in patients with occlusive aortoiliac lesions and that the hyperaemic response following release of the clamp was reduced. Arterial hypotension after clamp release was of the same time course as the hyperaemia. Leg blood flow measurement was a valuable monitoring procedure.

Aged↗