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Biomedical subjects

G Darby

Publications and source records attributed to G Darby.

At least 55 records · Page 3Linked to original sources
PubMed1980

Isolation and characterization of acyclovir-resistant mutants of herpes simplex virus.

Mutants of HSV which are resistant to acyclovir (acycloguanosine) have been isolated following serial passages of several herpes simplex virus (HSV) strains in the presence of the drug. The majority of the mutants isolated are defective in induction of thymidine kinase (TK) and this is consistent with the observation that independently isolated TK- viruses are naturally resistant to ACV. One mutant is described (SC16 R9C2) which is resistant in biochemically transformed cells which express HSV TK. This suggests that its resistance resides at a level other than TK. It is also resistant to phosphonoacetic acid, suggesting that the DNA polymerase locus may be involved. A further mutant is described [Cl (101) P2C5] which induces normal levels of TK, although the nature of resistance of this virus is not yet elucidated.

Acyclovir↗
PubMed1980

Herpes simplex virus latency: the cellular location of virus in dorsal root ganglia and the fate of the infected cell following virus activation.

Latent infections have been established in cervical dorsal root ganglia of Balb/c mice following peripheral inoculation of ts mutants of HSV-1. Activation of the mutant LS2 at the non-permissive temperature in vitro by culture of excised ganglia, or in vivo by neurosurgery has allowed the unambiguous identification of the neuron as the site of latent infection. Evidence is presented which shows that activation of virus infection in latently infected ganglia by neurosurgery results in a reduction of the number of latent foci in that ganglion. One interpretation of this observation is that the productive infection which follows activation of latent virus in the neuron leads to the destruction of that cell.

Animals↗
PubMed1980

Pathogenicity in mice of strains of herpes simplex virus which are resistant to acyclovir in vitro and in vivo.

Mice infected with three different isolates of herpes simplex virus (HSV) and treated with acyclovir (acycloguanosine; ACV) showed low levels of virus replication during the acute phase of infection. However, virus isolated from such treated mice did not show increased resistance to ACV. In contrast, resistant virus was readily isolated in vitro by passaging HSV in the presence of the drug. The degree of resistance was determined, in part, by the nature of the cells used to test the virus. The majority of ACV-resistant strains induced low or undetectable levels of HSV-specified thymidine kinase (TK), the enzyme responsible for phosphorylating ACV in infected cells. The TK-resistant strains were attenuated when injected into mice as indicated by reductions in virus replication, inflammation, and establishment of latent infections in sensory ganglia. The reduced virulence of the TK- strains was most marked after intracerebral inoculation, where the lethal dose was increased more than 100-fold compared with the parental isolates. However, one mutant is described which induced high levels of TK but was highly resistant to ACV and retained virulence for mice.

Acyclovir↗
PubMed1980

Properties of cells carrying the herpes simplex virus type 2 thymidine kinase gene: mechanisms of reversion to a thymidine kinase-negative phenotype.

We have isolated cells with a thymidine kinase-negative (tk(-)) phenotype from cells which carry the herpes simplex virus type 2 tk gene by selection in 5-bromodeoxyuridine or 9-(2-hydroxyethoxymethyl)guanine. Both selection routines generated revertants with a frequency of 10(-3) to 10(-4), and resistance to either compound conferred simultaneous resistance to the other. tk(-) revertants fell into three classes: (i) cells that arose by deletion of all virus sequences, (ii) cells that had lost the virus tk gene but retained a nonselected virus-specific function and arose by deletion of part of the virus-specific sequence, and (iii) cells that retained the potential to express all of the virus-specific functions of the parental cells and retained all of the virus-specific DNA sequences.

Journal Article↗
PubMed1978

Introduction of the herpes simplex virus thymidine kinase gene into mouse cells using virus DNA or transformed cell DNA.

Cells lacking the enzyme thymidine kinase (LMTK- cells) have been transformed to a kinase-positive phenotype using sheared herpes simplex virus (HSV) DNA, and the enzyme found in these transformed cells is HSV-specific. One of the cell lines is able to complement the functional defect found in two temperature-sensitive mutants of HSV 1, and reversion of the cells to a thymidine kinase-negative phenotype results in the loss of this capability. The HSV thymidine kinase gene can also be introduced into LMTK- cells using DNA extracted from transformed cells, and the high efficiency of this procedure suggests that the state of the virus DNA in transformed cells is different from that of DNA in virus particles.

Cell Line↗
PubMed1978

Bent and broken femoral prostheses following total hip replacement: a case report.

The case of a 56-year-old man with a bent heavy, and a broken standard, Charnley femoral prosthesis, following total hip replacement, is presented. Both of these complications are uncommon, and as far as is known this is the first bent Charnley heavy prosthesis recorded. It is suggested that patients in the younger age group following total hip replacement should not expect to be able to lift excessively heavy weights, or to jump from any height.

Femur↗
PubMed1978

Heat inactivation of vaccinia virus particle-associated functions: properties of heated particles in vivo and in vitro.

The heat inactivation characteristics of several vaccinia virus particle-associated functions known to be involved in the transcription of the genome were examined. All functions were more resistant to heat than infectivity. Noninfectious particles were generated which exhibited significant levels of activity of all enzymes examined, and their properties were investigaed both in vitro and in vivo. RNA was synthesized in vitro by such particles, although transport of the RNA into the surrounding medium was defective. This RNA was larger than that made in normal particles but it was polyadenylated and functioned in vitro as a message coding for normal early proteins. The sequences transcribed were similar to those transcribed in normal particles, and we suggest that the production of abnormally large RNA is due to a defect in transcriptional termination. We could not detect any virus-specific protein or RNA synthesis in cells exposed to these inactivated particles and conclude that the loss of infectivity caused by heating is due to a general decline in the activities of a number of particle functions.

Cell Line↗
PubMed1976

The detection of virus DNA sequences in a herpes type 2 transformed hamster cell line (333-8-9).

Herpes simplex virus type 2 DNA labelled in vitro with 125I has been used as a probe to search for virus DNA sequences in the 333-8-9 line of transformed primary hamster cells and in clines derived from the line. Virus DNA sequences were present when the cells were examined initially but these sequences were lost on subsequent handling. No virus sequences were detected in clones derived from the line. It is suggested that the presence of virus DNA is an unstable characteristic of the cell line and that these sequences may be lost at cell division. The possibility that a small fragment of the genome remains cannot be excluded.

Base Sequence↗