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C Kirkwood

Publications and source records attributed to C Kirkwood.

7 recordsLinked to original sources
PubMed2001

Report of the Australian Rotavirus Surveillance Program, 2000/2001.

The National Rotavirus Reference Centre together with 15 collaborating laboratories Australia-wide conducted rotavirus surveillance from June 1999. The serotypes of rotaviruses that are responsible for the hospitalisation of children with acute diarrhoea were determined for the period June 2000 to May 2001. We examined 1108 rotavirus specimens using a combination of monoclonal antibody immunoassay, reverse transcription-PCR, and Northern hybridisation. Serotype G1 strains were the most prevalent overall (49.5%), and found in all centres. Serotype G9 rotaviruses, which were first identified in 1997, were second in importance (18.1%). Serotype G2 viruses were next (12.5%), followed by the re-emergence of serotype G4 viruses (9.7%). The findings of this study have implications for vaccine development strategies where protection against serotypes additional to G1-G4 may be required.

Australia↗
PubMed1995

Rotavirus antigenicity is affected by the genetic context and glycosylation of VP7.

Rotavirus variants resistant to neutralization were selected using monoclonal antibodies (N-MAbs) raised to VP7 of rotavirus G types 2, 3, and 6. Their neutralization resistance patterns and deduced VP7 amino acid sequences were obtained. Variants selected by two G2-specific N-MAbs from the homologous parent virus RV-5 showed single amino acid (aa) mutations in the antigenic A region. However, variants selected from reassortant virus RV-5 x SA11 (all genes from SA11 virus except that encoding VP7, which was from RV-5 virus) fell into two neutralization resistance groups. The first group showed identical mutations to the variants selected from RV-5 virus. The second group showed antigenic C region mutations, either alone or in combination with a mutation at aa 69. Variants selected from G3 parent viruses glycosylated at position 238 had a mutation at aa 96 in the A region, otherwise a C-region mutation at 211 was selected. Mutations at amino acid positions 94 or 96 were selected by monoclonal antibodies specific for each of the three serotypes. G3-specific monoclonal antibodies also selected mutations at position 148 and the new position of 264. This latter mutation resulted in substitution of aspartic acid for glycine and was located in a highly conserved and hydrophobic region of VP7. A G2-specific N-MAb selected variants with a mutation at aa 190 producing a new, utilized glycosylation site which we propose to be in new antigenic site E. The positions of mutations in antigenic variants and their antigenicity were determined by parental background genes and VP7 glycosylation.

Amino Acid Sequence↗
PubMed1993

Characteristics and location of cross-reactive and serotype-specific neutralization sites on VP7 of human G type 9 rotaviruses.

The neutralization antigens of human rotavirus VP7 were studied by producing eight neutralizing monoclonal antibodies to G type 9 rotaviruses F45 and WI61 and selecting antigenic variants resistant to neutralization by these monoclonal antibodies. Neutralization resistance patterns and sequence analysis of the antigenic variants indicated the presence of overlapping serotype-specific and serotype cross-reactive epitopes in antigenic region A, and one distinct type-specific epitope. Cross-reactive monoclonal antibodies were more tolerant of amino acid sequence change than type-specific monoclonal antibodies. The existence of a new antigenic region, F, including amino acids 235 to 242 was confirmed. This region contained a cross-reactive epitope not detectable in the presence of glycosylation at amino acid 238. This glycosylation also affected neutralization by a cross-reactive monoclonal antibody directed to antigenic region C. Antigenic regions A, B, C, and F all contain epitopes shared between G types, of which at least two (C and F) are affected by glycosylation.

Animals↗
PubMed1991

Influence of menstrual cycle and gender on alprazolam pharmacokinetics.

The effects of menstrual cycle phases and gender on alprazolam pharmacokinetics were evaluated in normal volunteers. Alprazolam (1 mg) was administered to seven women during the late follicular and luteal phases of the menstrual cycle and to eight men on one occasion. No difference in alprazolam pharmacokinetic parameters was observed during the menstrual cycle phases. Mean alprazolam clearance (+/- SD) was 0.0037 +/- 0.0009 ml/hr during the follicular phase and 0.0036 +/- 0.001 ml/hr during the luteal phase (p greater than 0.05, difference not significant). With use of weight as a covariant, there was no difference in alprazolam pharmacokinetic parameters between women and men. Mean alprazolam clearance (+/- SD) was 0.0036 +/- 0.0009 ml/hr in women compared with 0.0041 +/- 0.0006 ml/hr in men (p greater than 0.05, difference not significant). Although alprazolam metabolism was similar on the 2 days tested, alterations may occur at other times during the menstrual cycle. Further investigation is needed to understand the effects of menstrual cycle phases and gender on drug metabolism.

Adult↗
PubMed1991

Relation of VP7 amino acid sequence to monoclonal antibody neutralization of rotavirus and rotavirus monotype.

The neutralization epitopes of the VP7 of human rotavirus RV-4 were studied by using five neutralizing mouse monoclonal antibodies to select virus variants resistant to neutralization by each of the antibodies. Antibody resistance patterns and sequence analysis of the RV-4 variants revealed that at least four sites on VP7, located at amino acids 94 (region A), 147 to 148 (region B), 213 (region C), and 291, are involved in neutralization of the human G1 rotavirus RV-4. The A-region site elicited antibody cross-reactive between G types and showed species-restricted immunodominance not related to carbohydrate attachment. The monotype 1b rotavirus M37 lacked this site. The B region contained strain-specific and cross-reactive sites, absent in monotype 1c rotaviruses. The C-region site was present in all G1 rotaviruses tested. Monotype 1a rotaviruses contained all these sites of neutralization. Virus monotype and sensitivity to monoclonal antibody neutralization usually related to the presence of a particular amino acid(s) at or next to the positions at which the mutations were selected in the virus variants.

Amino Acid Sequence↗