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Biomedical subjects

R Riley

Publications and source records attributed to R Riley.

At least 37 records · Page 2Linked to original sources
PubMed1994

Endogenous superantigens in allogeneic bone marrow transplant recipients rapidly and selectively expand donor T cells which can produce IFN-gamma.

Despite the existence of many non-MHC disparities between MHC matched but non-MHC mismatched donors and recipients, graft-versus-host disease (GVHD) is not clinically apparent following a significant number of allogeneic bone marrow transplants (BMT) in experimental animals. The present studies examined V beta TcR expression and IFN-gamma production by donor T cells in a BMT model involving an MHC matched, allogeneic donor-recipient combination which included a unidirectional superantigen disparity (Mls). B10.D2-->BALB/c, but not BALB/c-->B10.D2 recipients develop GVHD and mortality ensues 8-12 weeks post-transplant. During the first 2 weeks post-transplant of B10.D2-->BALB/c, approximately 50% of all Thy1.2+ spleen and lymph node cells were found to express T cell receptors utilizing V beta 3. A similar rapid and selective expansion of V beta 3+ TcR bearing donor T cells was detected in two other H-2 matched superantigen disparate donor-recipient BMT combinations. An increased percentage of V beta 3+ T cells was noted among both the CD4+ and CD8+ populations. Thus, in these donor/recipient combinations, all TcR families were not equally expanded early following transplant. At 4-10 days post-transplant, IFN-gamma specific mRNA was readily detected in the spleens of B10.D2-->BALB/cBMT recipients containing large numbers of V beta 3+ T cells. Moreover, V beta 3+ donor T cells from these recipients contained IFN-gamma mRNA. Specific stimulation in vitro with immobilized anti-TcR moAbs demonstrated that V beta 3+ T cells secreted a large amount of the total IFN-gamma levels detected. The ability of endogenous superantigens to activate large numbers of T cells which can produce cytokines after BMT indicates that when present, such antigenic differences may contribute to events occurring during initial graft-versus-host reactions. Such antigens could therefore participate in the events influencing whether GVHD develops following BMT between certain donors and recipients.

Animals↗
PubMed1993

Hepatitis B vaccination of high-risk neonates in the South West Region of New South Wales: evaluation of program coverage.

The authors evaluated the high-risk neonate hepatitis B vaccination program in the South West Region of New South Wales. Infants from ethnic groups with a high rate of chronic hepatitis B virus (HBV) infection and infants of HBV carrier mothers were targeted. The program identified 323 infants born between October 1987 and December 1990 who were at high risk of HBV infection, of whom 68.7 per cent were Aboriginal. Overall, 194 infants (60.1 per cent) received three doses of vaccine. Although the number of infants identified increased from 46 in 1988 to 119 in 1990, the proportion fully vaccinated each year did not increase, remaining at around 60 per cent. The authors stress the importance of promoting the program and educating the high-risk groups and health professionals involved, in order to improve vaccination coverage.

Carrier State↗
PubMed1993

Proposal for a composite index of alcohol problems.

This study proposes constructing a composite index to measure the severity of alcohol problems in Canada. Composite summary indicators are used in many areas, particularly in economics where the Consumer Price Index is well known. The composite indexes developed for this analysis were constructed using the index number method. The indexes were based on the statistical series for alcohol consumption, alcohol morbidity, alcohol mortality and alcohol-related traffic offences in the ten provinces and cover the years 1975, 1980, 1985 and 1990. The selected statistical series were compared using both Spearman and the Pearson correlations. In addition, Kendall's coefficient of concordance was used to determine the degree of association among all the statistical series together. The initial results indicated that there were different provincial rankings for each of the four statistical series, demonstrating that in comparing provinces the ranking of the "alcohol problem" depends on the statistical series selected. The construction of a composite index can be an effective strategy for resolving these differences in the rankings. Provincial rankings for the composite indexes on the severity of alcohol problems were fairly consistent for each time period. In terms of general trends among the provinces, Prince Edward Island, Alberta, British Columbia and Saskatchewan had the highest composite indexes; Manitoba, Nova Scotia and Ontario the mid-range; and New Brunswick, Newfoundland and Quebec the lowest.

Accidents, Traffic↗
PubMed1992

The enzymology of doxorubicin quinone reduction in tumour tissue.

We have reported previously that enzymes present in the Sp 107 rat mammary carcinoma catalyse doxorubicin quinone reduction (QR) to 7-deoxyaglycone metabolites in vivo [Willmott and Cummings, Biochem Pharmacol 36: 521-526, 1987]. In order to provide insights into the role of QR in the antitumour mechanism of action of doxorubicin, we have attempted in this work to identify the enzyme(s) responsible. NAD(P)H: (quinone acceptor) oxidoreductase (DT-diaphorase) was the major quinone reductase in the tumour accounting for approximately 70% of all the activity measured in microsomes and cytosols (microsomal activity, 28.4 +/- 4.6 nmol/min/mg; cytosolic activity, 94.3 +/- 11.9 nmol/min/mg). Its presence was confirmed by western blot analysis. Low levels of NADH cytochrome b5 reductase (15.6 +/- 6.3 nmol/min/mg) and NADPH cytochrome P450 reductase (14.5 +/- 4.0 nmol/min/mg) were detectable in microsomes. The presence of the latter was confirmed by western blot analysis. Pretreatment of tumours with doxorubicin (48 hr) at a therapeutic dose decreased the level of activity of all the reductases studied by at least 2-fold (P < 0.01, Student's t-test). Doxorubicin was shown not to be a substrate for purified rat Walker 256 tumour DT-diaphorase with either NADH or NADPH as co-factor and utilizing up to 20,000 units of enzyme/incubation but was confirmed to be a substrate for purified rat liver cytochrome P450 reductase. 7-Deoxyaglycone metabolite formation by purified cytochrome P450 reductase had an absolute requirement for NADPH as co-factor, was inhibited by molecular oxygen and dicoumarol (IC50 approx. 50 microM), and modulated by specific reductase antiserum. Reductive deglycoslation of doxorubicin to 7-deoxyaglycones was localized to the microsomal fraction of the Sp 107 tumour, with negligible activity being found in cytosols (NADH, NADPH and hypoxanthine as co-factors) and mitochondria (NADH and NADPH). The tumour microsomal enzyme had an absolute co-factor requirement for NADPH, was inhibited by oxygen and dicoumarol, and modulated by cytochrome P450 reductase antiserum. These data indicate strongly that NADPH cytochrome P450 reductase is the principal enzyme responsible for catalysing doxorubicin QR in the Sp 107 tumour.

Animals↗