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Neil Graham

Publications and source records attributed to Neil Graham.

5 recordsLinked to original sources
PubMed2006

HIV-1 coreceptor use in triple-class treatment-experienced patients: baseline prevalence, correlates, and relationship to enfuvirtide response.

OBJECTIVE: We wished to assess, in heavily treatment-experienced patients, the prevalence of and baseline characteristics associated with HIV-1 coreceptor use and their relationship to responses to enfuvirtide treatment. METHODS: Samples were obtained from participants in phase 3 studies of enfuvirtide. Multiple logistic regression and analysis of covariance were performed on data for baseline coreceptor use, virological and immunological response, and changes in coreceptor use during treatment. RESULTS: Baseline envelopes were phenotyped for 724 patients; 50% harbored R5 strains, 48% harbored dual/mixed (D/M) strains, and 2% harbored X4 strains. D/M strains were associated with significantly lower CD4(+) cell counts but comparable viral loads, compared with R5 strains (P=.0005). Virological and immunological responses to enfuvirtide-based treatment showed no correlation with baseline coreceptor use. Changes in virus tropism from D/M to R5 strains during treatment were common, particularly in patients who received enfuvirtide (27%, vs. 14% who received no enfuvirtide; P<.05). CONCLUSION: At baseline, D/M strains were associated with lower CD4(+) cell counts but similar viral loads, compared with R5 strains, and were common across CD4(+) cell count strata. The comparable virological and immunological responses and bias toward shifts from D/M to R5 strains in patients who received enfuvirtide support its use in triple-class treatment-experienced patients and its study as a therapeutic partner for coreceptor-binding inhibitors.

Adult↗
PubMed2006

Monoclonal antibody HCV-AbXTL68 in patients undergoing liver transplantation for HCV: results of a phase 2 randomized study.

A randomized, double-blind, dose-escalation study evaluated the safety and efficacy of hepatitis C virus (HCV)-Ab(XTL)68, a neutralizing, high-affinity, fully human, anti-E2 monoclonal antibody, in 24 HCV-positive patients undergoing liver transplantation. HCV-Ab(XTL)68 or placebo was administered at doses from 20-240 mg as 2-4 infusions during the first 24 hours after transplantation, followed by daily infusions for 6 days, weekly infusions for 3 weeks, and either 2 or 4 weekly infusions for 8 weeks. Serum concentrations of total anti-E2 obtained during daily infusions of 120-240 mg HCV-Ab(XTL)68 were 50-200 microg/mL above concentrations in the placebo group. Median serum concentration of HCV RNA dropped below baseline in all groups immediately after transplantation. On day 2, median change from baseline in HCV RNA was -1.8 and -2.4 log in the 120-mg and 240-mg groups, respectively, compared with -1.5 log with placebo. The difference was lost after day 7 when the dosing frequency was reduced. The coincidence of increases in anti-E2 with decreases in HCV RNA concentration indicate that the dose-related changes in HCV RNA concentration were a result of HCV-Ab(XTL)68 administration in the 120- and 240-mg groups. The overall incidence of nonfatal serious adverse events was higher with placebo (60%) vs. all active treatments combined (42%). In conclusion, HCV-Ab(XTL)68 may decrease serum concentrations of HCV RNA in patients after liver transplantation. Studies evaluating more frequent daily dosing at doses >120 mg are necessary to investigate sustained viral suppression in this population.

Adult↗
PubMed2003

Dissecting Arabidopsis lateral root development.

Recent studies in the model plant Arabidopsis provide new insight into the regulation of root architecture, a key determinant of nutrient- and water-use efficiency in crops. Lateral root (LR) primordia originate from a subset of pericycle founder cells. Sophisticated mass-spectroscopy-based techniques have been used to map the sites of biosynthesis of auxin and its distribution in Arabidopsis seedlings, highlighting the importance of the phytohormone during LR initiation and emergence. Key components of the cell cycle and signal-transduction pathway(s) that promote and attenuate auxin-dependent LR initiation have recently been identified. Additional signals, such as abscisic acid and nitrate, also regulate LR emergence, raising intriguing questions about the cross-talk between their transduction pathways.

Arabidopsis↗
PubMedDate not supplied

Auxin cross-talk: integration of signalling pathways to control plant development.

Plants sense and respond to endogenous signals and environmental cues to ensure optimal growth and development. Plant cells must integrate the myriad transduction events into a comprehensive network of signalling pathways and responses. The phytohormone auxin occupies a central place within this transduction network, frequently acting in conjunction with other signals, to co-ordinately regulate cellular processes such as division, elongation and differentiation. As a non-cell autonomous signal, auxin also interacts with other signalling pathways to regulate inter-cellular developmental processes. As part of this especially themed edition of Plant Molecular Biology, we will review examples of 'cross-talk' between auxin and other signalling pathways. Given the current state of knowledge, we have deliberately focused our efforts reviewing auxin interactions with other phytohormone and light signalling pathways. We conclude by discussing how new genomic approaches and the Arabidopsis genome sequence are likely to impact this area of research in the future.

Abscisic Acid↗