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D Riley

Publications and source records attributed to D Riley.

At least 73 records · Page 4Linked to original sources

Induction of cell growth regulatory genes by p53.

Transcriptionally regulated growth-response genes play a pivotal role in the determination of the fate of a cell. p53 is known to transcriptionally regulate genes important in regulating cell growth potential. Using differential reverse transcription-PCR analysis of rat embryo fibroblast cells containing a temperature-sensitive p53 allele, we were able to isolate several transcripts up-regulated specifically in cells harboring functional p53 protein. Two of these genes, SM20 and microsomal epoxide hydrolase (mEH), are previously described genes. Two previously uncharacterized cDNAs, cell growth regulatory (CGR) genes CGR11 and CGR19, were isolated. The predicted amino acid sequence of these novel proteins contain known motifs; EF-hand domains (CGR11) and a ring-finger domain (CGR19), suggestive of function. CGR11 and CGR19 appear to be primary response genes expressed to moderate levels in functional p53 cells. Both CGR11 and CGR19 are able to inhibit the growth of several cell lines.

Amino Acid Sequence↗

Protection against lethal simian immunodeficiency virus SIVsmmPBj14 disease by a recombinant Semliki Forest virus gp160 vaccine and by a gp120 subunit vaccine.

Infection of pigtail macaques with SIVsmmPBj14, biological clone 3 (SIV-PBj14-bc13), produces an acute and usually fatal shock-like syndrome 7 to 14 days after infection. We used this simian immunodeficiency virus (SIV) model as a rapid and rigorous challenge to evaluate the efficacy of two SIV Env vaccine strategies. Groups of four pigtail macaques were immunized four times over a 25-week span with either a recombinant Semliki Forest virus expressing the SIV-PBj14 Env gp160 (SFV-SIVgp160) or purified recombinant SIV-PBj14 gp120 (rgp120) in SBN-1 adjuvant. Antibody titers to SIV Env developed in all immunized animals (mean peak titers prior to challenge, 1:1,700 for SFV-SIV gp 160 and 1:10,500 for rgp120), but neither neutralizing antibodies nor SIV-specific T-cell proliferative responses were detectable in any of the vaccinees. All macaques were challenged with a 100% infectious, 75% fatal dose of SIV-PBj14-bc13 at week 26. Three of four control animals died of acute SIV-PBj14 syndrome on days 12 and 13. By contrast, all four SFV-SIVgp160-immunized animals and three of the four rgp120-immunized animals were protected from lethal disease. While all virus-challenged animals became infected, symptoms of the SIV-PBj14 syndrome were more severe in controls than in vaccinees. Mean virus titers in plasma at 13 days postchallenge were approximately 10-fold lower in vaccinated than control animals. However, there was no apparent correlation between survival and levels of peripheral blood mononuclear cell-associated culturable virus, provirus load, or any antiviral immunologic parameter examined. The results indicate that while immunization with SFV-SIVgp160 and rgp120 did not protect against virus infection, these Env vaccines did lower the virus load in plasma and protect against the lethal SIV-PBj14 challenge.

Animals↗

Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson's disease. A high potency effect of clozapine.

The purpose of this study was to determine the plasma level of clozapine and its metabolite, N-desmethylclozapine, in Parkinson's disease patients with L-DOPA-induced psychosis responsive to clozapine. The psychotic symptoms of the three patients studied responded to low doses of clozapine with plasma levels of clozapine between 4.5 and 16.1 ng/ml and N-desmethylclozapine between 2.6 and 6.1 ng/ml, much below the plasma clozapine levels usually found in clozapine-treated refractory schizophrenia or affective disorders (range 100 to 687 ng/ml). Possible mechanisms that may account for clozapine's antipsychotic action in dopaminomimetic-induced psychosis in Parkinson's disease, including serotonin2A (5-HT2A) and dopamine D4 receptor blockade, at plasma levels that would be ineffective in refractory schizophrenia, are discussed. It is suggested that 5-HT2A receptor blockade is the most likely basis for the effectiveness of clozapine in L-DOPA psychosis.

Aged↗

Oncology data management in the UK--BODMA's view. British Oncology Data Managers Association.

Over the past 10 years, the original partnership of clinician and statistician for the running of clinical research projects, especially clinical trials, has come to be supplemented by the data manager and trial coordinator. Increasing numbers of such personnel are now being employed, covering a wide diversity of work areas, including clinical research, medical audit and the cancer registries. The British Oncology Data Managers Association (BODMA) was founded in 1987 and is now in a good position to review the current status of data management in the UK. It is proposed that a national network of data managers and trial coordinators within specialist trials centres, oncology departments and district general hospitals, with a good training programme, plus a recognised career structure, is the way to make the best use of this key resource. BODMA is addressing many of these issues and aims to improve and maintain the quality of data management.

Clinical Trials as Topic↗