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Biomedical subjects

T H Pennington

Publications and source records attributed to T H Pennington.

90 records · Page 5Linked to original sources

Bunyamwera virus-induced polypeptide synthesis.

Bunyamwera virus-induced polypeptide synthesis in BSC-1 cell has been studied using polyacrylamide gel electrophoresis and autoradiography. Four virus-induced polypeptides were identified. Their molecular weights were 200 X 10(6) (L), 128 X 10(6) (G1), 31 X 10(6) (G2), and 23 X 10(6) (N). Pulse-chase experiments, short labeling experiments, and experiments using amino acid analogs failed to show evidence of polypeptides processing by proteolytic cleavage. Analysis of the kinetics of synthesis of these polypeptides showed that a clear division into early and late categories could be made, the onset of synthesis of polypeptide N and L rapidly reached a peak and then declined. Polypeptides G1 and G2 were made for several hours; their rate of synthesis then declined. All four polypeptides then continued to be made in relatively small amounts for many hours.

Arboviruses↗

Events following the infections of enucleate cells with measles virus.

The development of measles virus (Edmonston) and SSPE measles virus (Horta-Barbosa) has been examined in enucleate BSC 1 cells. New antigen synthesis in measles virus infected enucleate cells has been demonstrated by fluorescent antibody, by the formation of extensive syncytia from enucleate cells alone and by analysis of polypeptide formation by polyacrylamide gel electrophoresis. All polypeptides formed in nucleate cells were also present in enucleate cells but the amount synthesized was reduced to around 20% of that in nucleate cells. There was also a significant reduction in the amount of antigen detected by fluorescent antibody in enucleate as compared to nucleate preparations. Examination of RNA synthesis in infected enucleate cells revealed only a marginal increase in acid-insoluble material. Titration of the output of infectious virus from enucleate cells infected at both 37 and 31 degrees C indicated a consistent reduction of almost two log units compared to nucleate cells. That the enucleate cells were capable of replicating input genome at these times was demonstrated by the successful growth of respiratory syncytial virus, both at 37 and 31 degrees C. SSPE measles virus grew to higher yield in nucleate BSC 1 than measles virus but there was again a reduction of more than two log units in enucleate cells. All polypeptides synthesized in SSPE infected nucleate cells were apparent in enucleate cells.

Antigens, Viral↗

Effect of 5-bromodeoxyuridine on vaccinia virus-induced polypeptide synthesis: selective inhibition of the synthesis of some post-replicative polypeptides.

The effect of 5-bromodeoxyuridine (BrdU) on vaccinia virus-induced polypeptide synthesis in BSC-1 cells has been investigated. Most virus-induced pre- and post-replicative polypeptides were synthesized in concentrations of 5-bromodeoxyuridine that inhibited virus growth. The synthesis of a few post-replicative polypeptides, however, was severely inhibited under these conditions; included in this group was the precursor of a major core component, polypeptide P4b. A delay in the switch-off of pre-replicative polypeptide synthesis and in the onset of post-replicative polypeptide synthesis was also observed. The significance of these observations is discussed.

Bromodeoxyuridine↗

Virus development in enucleate cells: echovirus, poliovirus, pseudorabies virus, reovirus, respiratory syncytial virus and Semliki Forest virus.

A group of RNA viruses, echovirus, poliovirus, reovirus, respiratory syncytial virus and Semliki Forest virus have been examined for ability to grow in enucleate African green monkey kidney (BSCi) cells. Semliki Forest virus produced an almost normal yield of virus but poliovirus, echovirus, reovirus and respiratory syncytial virus, although showing clear evidence of virus replication when compared with a nuclear DNA virus (pseudorabies virus) gave much lower yields than those from nucleate cells. Analysis of enucleate cells infected with echovirus and reovirus showed no evidence of a specific block in the synthesis of any virus-specified polypeptide. Infection with vesicular stomatitis virus at intervals after enucleation demonstrated a diminishing ability to support virus growth with increasing time. It is suggested that the yield of virus obtained from an enucleate cell is related to the length of the growth cycle of the virus, the reduced yield obtained with some viruses reflecting the declining ability of the enucleate cell to support virus growth.

Autoradiography↗

Ocular vaccinia.

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Acetazolamide↗

Vaccinia virus replication in enucleate BSC-1 cells: particle production and synthesis of viral DNA and proteins.

The growth of vaccinia virus in monolayers of BSC-1 cells enucleated by centrifugation in the presence of cytochalasin B has been studied. No evidence for the production of infectious virus in these cells was obtained, and the production of virus particles was reduced to 8.3% compared with the yield from cytochalasin-treated, uncentrifuged cells. Virus DNA and early and late polypeptides were synthesized with normal timing in enucleate cells, but in reduced amounts; cleavage of structural polypeptide precursors P4a and Px also occurred in enucleate cells. Factories containing immature virus particles were demonstrated in enucleate cells by electron microscopy; these factories were reduced in number and size compared with those found in cytochalasin-treated, uncentrifuged cells.

Amino Acids↗

Inhibition of poxvirus maturation by rifamycin derivatives and related compounds.

The effect of a number of rifamycin derivatives and related compounds on the reversibility of the rifampin-induced virus maturation block was studied by using BHK-21 cells infected with vaccinia virus. All of the derivatives of 3-formyl rifamycin SV maintained this block, the required concentration varying from 100 to 1,000 mug/ml. These compounds vary only in the nature of the side-chain attached to the 3C atom on the naphthohydroquinone moiety; no obvious correlation between the nature of this side-chain and antiviral activity was found. Streptovaricin complex and tolypomycin R also maintained the maturation block; tolypomycin also produced marked alterations in the appearance of the viroplasm contained in rifampin-induced inclusions and immature virus particles.

Animals↗

Effect of rifamycins and related antibiotics on the deoxyribonucleic acid-dependent ribonucleic acid polymerase of vaccinia virus particles.

A number of compounds related to rifampin which act as expected in the Escherichia coli system have been tested for their ability to inhibit the vaccinia particle deoxyribonucleic acid-dependent ribonucleic acid (RNA) polymerase in vitro. Some compounds are inactive even at concentrations of 500 mug/ml, others are able to produce partial inhibition, and others strongly inhibit the enzyme activity at 150 mug/ml or less. The inhibition, where present, operates immediately but appears to be at least partially reversible. At least one compound which is without effect against bacterial RNA polymerase is a potent inhibitor of the viral RNA polymerase. As the enzyme activity of rifampin-resistant mutants of vaccinia virus is inhibited to the same extent as that of the wild type, the observed in vitro effect on vaccinia virus RNA polymerase is not identical with the in vivo effect specifically directed against a vaccinia-specified protein.

Agar↗

In vitro activities of meropenem and other antimicrobial agents against British meningococcal isolates.

The in vitro activity of meropenem was compared with those of penicillin, ampicillin, cefuroxime, cetriaxone, cefotaxime, rifampicin, chloramphenicol, sulphadiazine and ciprofloxacin against 121 British meningococcal isolates by a microdilution method in Mueller-Hinton broth and by the E test. All meningococcal strains were susceptible to the agents except for ampicillin (88.4%), penicillin (88.4%), sulphadiazine (57.9%) and rifampicin (95%). The emergence of resistance problems among meningococcal isolates stresses the need for their constant monitoring and of the development of new agents. In this study we have shown that meropenem is highly active in vitro against Neisseria meningitidis. Recent studies have indicated that meropenem is highly active clinically and bacteriologically in the treatment of bacterial meningitis. Thus, the potentials of meropenem as meningococcal prophylactic and therapeutic agent needs to be fully evaluated.

Anti-Bacterial Agents↗