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Biomedical subjects

V Sullivan

Publications and source records attributed to V Sullivan.

13 recordsLinked to original sources
PubMed1999

Anorexia nervosa: friend or foe?

OBJECTIVE: The aim of this study was to examine anorexics' attitudes towards anorexia nervosa. METHOD: Anorexic patients were asked to write two letters to their anorexia nervosa, one addressing it as a friend and the other addressing it as an enemy. A coding scheme was developed using a "Grounded Theory" methodology to group recurrent themes. The scheme was used independently by three raters: the first author, a rater with extensive experience in eating disorders, and a novice in the field. Use of the coding scheme showed high interrater reliability and comprehensivess. RESULTS: Commonly expressed benefits of anorexia nervosa included feeling looked after or protected, gaining a sense of control, and feeling special. Perceived costs of the disorder included constant thoughts about food, feeling taken over, and the damage done to personal relationships. DISCUSSION: The positive themes found in the letters are important indicators of factors which may maintain anorexia nervosa. The use of the letters to examine these factors has important clinical implications which are outlined.

Adolescent↗
PubMed1998

Expression and characterization of the hepatitis G virus helicase.

The hepatitis G virus (HGV) is a new member of the Flaviviridae family and has a genomic organization similar to that of hepatitis C virus (HCV). Protein sequence motifs are present suggesting that HGV encodes a serine proteinase, an RNA-dependent RNA polymerase and a helicase. We have cloned and expressed the putative helicase of HGV and have shown that it contains a poly (U)-stimulated NTPase activity and is able to function as a DNA helicase. Preliminary characterization of the HGV helicase activity reveals similarities with other members of the Flaviviridae, but especially with HCV, raising the possibility that HGV could be used as a surrogate virus for the development of therapies against HCV.

Adenosine Triphosphatases↗
PubMed1998

Metallocene-catalysed cyclo-olefin copolymers.

Metallocene-catalysed cyclo-olefin copolymers offer medical product designers a substantial range of properties. This article outlines the capabilities of these materials and describes the advances in chemical engineering that allowed their mass production. A range of applications are highlighted.

Alkenes↗
PubMed1993

A point mutation in the human cytomegalovirus DNA polymerase gene confers resistance to ganciclovir and phosphonylmethoxyalkyl derivatives.

Ganciclovir-resistant mutant 759rD100 derived from human cytomegalovirus strain AD169 contains two resistance mutations, one of which is in the UL97 gene and results in decreased ganciclovir phosphorylation in infected cells [V. Sullivan, C. L. Talarico, S. C. Stanat, M. Davis, D. M. Coen, and K. K. Biron, Nature (London) 358:162-164, 1992]. In the present study, we mapped the second mutation to a 4.1-kb DNA fragment containing the DNA polymerase gene and showed that it confers ganciclovir resistance without impairing phosphorylation. Sequence analysis of the 4.1-kb region revealed a single nucleotide change that resulted in a glycine-to-alanine substitution at position 987 within conserved region V of the DNA polymerase. Recombinant viruses constructed to contain the DNA polymerase mutation but not the phosphorylation defect displayed intermediate resistance (4- to 6-fold) to ganciclovir relative to the original mutant 759rD100 (22-fold); the recombinant viruses also displayed resistance to ganciclovir cyclic phosphate (7-fold), 1-(dihydroxy-2-propoxymethyl)-cytosine (12-fold), and the phosphonylmethoxyalkyl derivatives (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (8- to 10-fold). However, the recombinant viruses remained susceptible to certain related compounds. These results imply that the human cytomegalovirus DNA polymerase is a selective target for the antiviral activities of ganciclovir, certain of its derivatives and phosphonomethoxyalkyl derivatives; support a role for region V in substrate recognition; and suggest the possibility of clinical resistance of human cytomegalovirus to these compounds because of polymerase mutations.

Amino Acid Sequence↗
PubMed1992

A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells.

Human cytomegalovirus (HCMV) is a major pathogen in immunosuppressed individuals, including patients with acquired immune deficiency syndrome. The nucleoside analogue ganciclovir (9-(1,3-dihydroxy-2-propoxymethyl)-guanine) is one of the few drugs available to treat HCMV infections, but resistant virus is a growing problem in the clinic and there is a critical need for new drugs. The study of ganciclovir-resistant mutants has indicated that the selective action of ganciclovir depends largely on virus-controlled phosphorylation in HCMV-infected cells. The enzyme(s) responsible have not been identified. Here we report that the HCMV gene UL97, whose predicted product shares regions of homology with protein kinases, guanylyl cyclase and bacterial phosphotransferases, controls phosphorylation of ganciclovir in HCMV-infected cells. A four-amino-acid deletion of UL97 in a conserved region, which in cyclic AMP-dependent protein kinase participates in substrate recognition, causes impaired ganciclovir phosphorylation. The implications of these results for antiviral drug development and drug resistance are discussed.

Amino Acid Sequence↗
PubMed1991

Isolation of foscarnet-resistant human cytomegalovirus patterns of resistance and sensitivity to other antiviral drugs.

Investigations of mutants of human cytomegalovirus (CMV) that are resistant to foscarnet could shed light on mechanisms of selective drug action and features of drug resistance that may be clinically important. Preexisting foscarnet-resistant mutants could not be detected in a stock of wild-type strain AD169 at frequencies greater than 0.0025%. However, foscarnet-resistant mutants could be isolated by passage in increasing drug concentrations. Two independent mutants were shown by plaque reduction and dot-blot hybridization assays to be resistant to phosphonoacetic acid and acyclovir, sensitive to ganciclovir, vidarabine, 2'fluoro-5-iodoarabinosylcytosine, and (S)-1-(3-hydroxy-2- phosphonylmethoxypropyl)cytosine; and hypersensitive to aphidicolin and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)adenine. These results have implications for the mutation frequency of CMV, for the possibility that clinically important foscarnet- and acyclovir-resistant CMV infections could emerge, for possible therapies of drug-resistant virus infections, and for the role of viral DNA polymerase in mechanisms of selective action of anti-CMV drugs.

Antiviral Agents↗
PubMed1991

Induction of protective immunity with antibody to herpes simplex virus type 1 glycoprotein H (gH) and analysis of the immune response to gH expressed in recombinant vaccinia virus.

Passive administration of neutralizing monoclonal antibody (MAb) to glycoprotein H (gH) of herpes simplex virus type 1 (HSV-1) was found to protect mice from an HSV-1 strain SC16 challenge infection. To investigate further the protective potential of gH, recombinant vaccinia viruses were constructed which expressed the HSV-1 gH open reading frame under the control of the vaccinia virus 7.5K early/late promoter or the 4b late promoter. Immunization with recombinant viruses, however, did not induce the production of neutralizing antisera and the mice were not protected from zosteriform spread or the establishment of latent infection following viral challenge. The gH produced by the recombinant vaccinia viruses differed in electrophoretic mobility and antigenicity from authentic HSV-1 gH. Only one of three neutralizing MAbs specific for conformational epitopes on gH was able to immunoprecipitate gH synthesized in recombinant vaccinia virus-infected cells. In addition cell surface expression of gH was not detected in cells infected with the recombinant vaccinia viruses.

Animals↗
PubMed1988

The herpes simplex virus type 1 US7 gene product is a 66K glycoprotein and is a target for complement-dependent virus neutralization.

The US7 open reading frame of herpes simplex virus type 1 (HSV-1), previously identified by nucleotide sequencing, has been expressed in a recombinant vaccinia virus (US7-VAC). Antiserum raised against HSV-1 reacted with a 66K glycoprotein in US7-VAC-infected cells and this polypeptide was present on both nuclear and cell surface membranes. In the presence of tunicamycin the protein was reduced in size to 58K showing it contained N-linked sugar residues. Antisera from animals vaccinated with US7-VAC recognized 66K and 58K polypeptides in HSV-1-infected cells and neutralized HSV-1 infectivity in vitro in the presence of complement.

Antibodies, Monoclonal↗
PubMed1987

Expression and characterization of herpes simplex virus type 1 (HSV-1) glycoprotein G (gG) by recombinant vaccinia virus: neutralization of HSV-1 infectivity with anti-gG antibody.

A recombinant vaccinia virus expressing herpes simplex virus type 1 (HSV-1) glycoprotein G (gG) has been constructed. Cells infected with this recombinant virus (gG-VAC) synthesized glycosylated proteins of 48K, 57K and 61K mol. wt. that were recognized by anti-HSV-1 sera. Rabbits and mice vaccinated with the live recombinant virus produced antibodies that recognized 48K, 57K and 61K mol. wt. proteins in HSV-1-infected cells. The gG polypeptides were present on cytoplasmic and nuclear membranes during infection with both HSV-1 and recombinant vaccinia virus gG-VAC. The 57K and 61K mol. wt. gG polypeptides were present in purified HSV-1 virions and were targets for antibody-mediated complement-dependent virus neutralization.

Antibodies, Viral↗