Biomedical subjects
Publications and source records attributed to R Dodd.
A new DRB1 allele has been identified during routine HLA-DRB1 generic typing with sequence specific oligonucleotides. The new allele was confirmed by PCR-restriction fragment length polymorphism analysis and subsequently sequenced. This showed the novel allele, named HLA-DRB1*1207, was similar in sequence to DRB1*12011, except for codon 69 of exon 2.
This paper describes six new alleles; A*0240, A*2614, B*3924, B*4425, Cw*0807 and Cw*12023, which were discovered during routine genotyping with sequence specific oligonucleotides (SSO's). Five of the new alleles have changes in residues which belong to the antigen binding site of the HLA protein. These new variants may have altered antigen binding properties and may cause differential immunological responses that could affect transplantation outcome1.
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The host and viral factors that underlie infection with HIV-1 vary considerably with some individuals progressing to AIDS within 3 to 5 years after infection, whereas others remain clinically asymptomatic for over 10 years. Host factors that may contribute to disease progression include HLA and allelic variants of the chemokine receptors CCR5 and CCR2, which have been shown to influence both long-term survival and rapid progression. In this study, we have examined the contribution of HLA and polymorphisms in CCR5 and CCR2 to long-term survival in transfusion-acquired HIV-1-infected individuals. We have found a higher number of HLA-A32 and -A25 alleles but a lower number of the HLA-B8 allele in the study group compared with the frequencies seen in the HIV-1-negative Australian caucasian population. However, there was no apparent contribution by allelic variants of CCR5 and CCR2 to long-term survival and the combined influence of HLA and CCR polymorphisms could not be evaluated in this relatively small (n = 20) group of study subjects. The results of this work support a role for HLA in long-term nonprogression though the presence in the Sydney Blood bank Cohort of nef-defective HIV-1 may confound associations between certain HLA alleles and long-term survival in the face of infection with HIV-1.
This paper describes eight new alleles (B*0807, B*0809, B*1551, B*3529, B*3532, B*4025, B*5304 and B*5508) that have been found by routine HLA-B genotyping with sequence-specific oligonucleotides (SSOs). All of the new alleles have variations which cause changes in residues that occur within antigen binding pockets and T-cell recognition sites of the antigen. The new polymorphisms within these new alleles may affect the nature and specificity of peptide binding and cause differential T-cell activation, which may have an affect in transplantation.
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Novel sulfonamide matrix metalloproteinase inhibitors of general formula (9) were synthesised by a route involving a stereoselective conjugate addition reaction. Enzyme selectivity was found to be dependant on the nature of the sulfonamide substituents. Compounds (9f, 9q) are potent selective collagenase inhibitors with good oral bioavailability.
Data from 3156 voluntary blood donors in Victoria, Australia, who were repeatedly reactive on anti-HCV screening test were analysed. It showed that between 1990 and 1997, 0.97% of routine blood donors were anti-HCV repeat reactive. Sixty-four (64) donors tested positive for HCV RNA. They were more likely to be male, had a mean age of 32.7 +/- 10.9 years and a mean serum ALT level of 70.9 +/- 46.5 i.u.L-1: the latter value being significantly different from donors with biological false reactivity (P < 0.0001). Among HCV antibody-positive donors there was a significantly increased rate of prior injecting drug use (34 vs. 1%), transfusion (25 vs. 10%) and tattooing (31 vs. 7%) than among donors with biological false reactivity (all P < 0.0001). The association of these risk factors is stronger with positivity for both immunoblot and HCV RNA than immunoblot alone. The data suggest that efforts should be made to increase the efficacy of donor questioning about prior drug use.
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Expression of G protein-regulated phospholipase C (PLC) beta 4 in the retina, lateral geniculate nucleus, and superior colliculus implies that PLC beta 4 may play a role in the mammalian visual process. A mouse line that lacks PLC beta 4 was generated and the physiological significance of PLC beta 4 in murine visual function was investigated. Behavioral tests using a shuttle box demonstrated that the mice lacking PLC beta 4 were impaired in their visual processing abilities, whereas they showed no deficit in their auditory abilities. In addition, the PLC beta 4-null mice showed 4-fold reduction in the maximal amplitude of the rod a- and b-wave components of their electroretinograms relative to their littermate controls. However, recording from single rod photoreceptors did not reveal any significant differences between the PLC beta 4-null and wild-type littermates, nor were there any apparent differences in retinas examined with light microscopy. While the behavioral and electroretinographic results indicate that PLC beta 4 plays a significant role in mammalian visual signal processing, isolated rod recording shows little or no apparent deficit, suggesting that the effect of PLC beta 4 deficiency on the rod signaling pathway occurs at some stage after the initial phototransduction cascade and may require cell-cell interactions between rods and other retinal cells.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: For persons newly infected with the human immunodeficiency virus type 1 (HIV-1), the time from the onset of infectivity to the development of detectable HIV-1 antibody is unknown. Persons who donate blood during this period account for nearly all instances of HIV-1 transmission from HIV-1 antibody-screened blood transfusions. STUDY DESIGN AND METHODS: To estimate the window period from infectivity to HIV-1 antibody positivity, 701 HIV-1-seropositive blood donors who made a previous seronegative donation at 40 United States blood centers were studied. The HIV-1 antibody status was determined for at least one recipient of blood from the seronegative donation preceding the seropositive donation made by 182 of the 701 donors. RESULTS: There were 39 seropositive recipients of blood from these 182 donors. Three donors were excluded from further analysis because the seropositive recipients of their blood had other HIV-1 risk factors or had HIV-1 infection before transfusion. The final study population comprised the remaining 179 donors, of whom 36 (20%) transmitted HIV-1 infection to recipients. When the interval between the seropositive donation and the preceding seronegative donation was less than 180 days, 46 percent of the donors transmitted HIV-1. In contrast, when that interval exceeded 540 days, only 2 percent transmitted HIV-1. A mathematical model was developed to explain the relationship between the probability that the previous seronegative donation occurred during the donor's window period of infectiousness, and hence transmitted HIV-1, as a function of both the window period and the duration between the seropositive and previous seronegative donations. This model indicated that the transmission data were most consistent with an average window period of 45 days. Assuming a log-normal window period distribution, it was estimated with 95 percent certainty that at least 90 percent of persons had a window period of less than 141 days. CONCLUSION: The window period averages 45 days, with few, if any, donors remaining infectious and seronegative for longer than 6 months.
Interpretation of in vitro experiments using Yersinia enterocolitica in blood components requires information on factors affecting the organism's survival. Several factors were found to influence the survival of Y. enterocolitica (serotype O:8) in blood components. A 20-minute room-temperature incubation with plasma-containing components resulted in approximately 2 log10 inactivation. Inactivation could be prevented by preincubation treatment of the plasma at 55 degrees C for 1 hour, which suggests the involvement of heat-labile plasma factors. No antibacterial activity was observed in washed red cells during the 20-minute room-temperature incubation. However, Y. enterocolitica colony-forming units declined by up to 2 log10 in washed red cells during the first days of 4 degrees C storage. Use of a white cell-reduction filter on freshly inoculated samples removed approximately 1 log10 of the organism regardless of whether bacteria were suspended in saline or washed red cells. Thus, bacterial levels may be affected by plasma, cellular components, and white cell-reduction filters. However, caution should be exercised in interpreting in vitro spiking studies designed to investigate the potential benefits of white cell reduction to eliminate the growth of Y. enterocolitica because of potential differences between naturally infected and experimentally inoculated blood.