John Radcliffe Hospital

About: John Radcliffe Hospital is a healthcare organization based out in Oxford, Oxfordshire, United Kingdom. It is known for research contribution in the topics: Population & Antigen. The organization has 14491 authors who have published 23670 publications receiving 1459015 citations.

Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is peptide-specific

Abstract: The recognition of MHC class I molecules by killer cell immunoglobulin-like receptors (KIR) is central to the control of NK cell function and can also modulate the CTL activation threshold. Among KIR receptors, KIR3DL2 is thought to interact with HLA-A3 and -A11, although direct evidence has been lacking. In this study, we show that HLA-A3 and -A11 tetramers specifically bind to KIR3DL2*001 transfectants and that this recognition is peptide-specific. Single amino acid substitutions in the nonamer peptide underline a critical role for residue 8 in recognition of KIR3DL2. However, the role of this interaction in vivo still remains to be established.

Human Cortical Responses to Water in the Mouth, and the Effects of Thirst

Abstract: In an event-related functional magnetic resonance imaging (fMRI) study in humans it was shown, first, that water produces activations in cortical taste areas (in particular the frontal operculum/anterior insula which is the primate primary taste cortex, and the caudal orbitofrontal/secondary taste cortex) comparable to those produced by the prototypical tastants salt and glucose. Second, the activations in the frontal operculum/anterior insula produced by water when thirsty were still as large after the subjects had consumed water to satiety. Third, in contrast, the responses to water in the caudal orbitofrontal cortex were modulated by the physiological state of the body, in that responses to the oral delivery of water in this region were not found after the subjects had drunk water to satiety. Fourth, further evidence that the reward value or pleasantness of water is represented in the orbitofrontal cortex was that a positive correlation with the subjective ratings of the pleasantness of the water was found with activations in the caudal and anterior orbitofrontal cortex, and also in the anterior cingulate cortex. Fifth, it was found that a region of the middle part of the insula was also activated by water in the mouth, and further, that this activation only occurred when thirsty. Sixth, analyses comparing pre- and postsatiety periods (i.e., when thirsty and when not thirsty) independently of stimulus delivery revealed higher activity levels in the rostral anterior cingulate cortex. The activity of the rostral anterior cingulate cortex thus appears to reflect the thirst level or motivational state of the subjects.

Rapid modulation of GABA concentration in human sensorimotor cortex during motor learning.

Abstract: Movement representations within the human primary motor and somatosensory cortices can be altered by motor learning. Decreases in local GABA concentration and its release may facilitate this plasti...

An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation.

Abstract: The role of allogeneic bone marrow transplantation in lymphoma remains uncertain. We have analyzed 1185 allogeneic transplants for lymphoma reported to the EBMT registry between 1982 and 1998 and compared the results with those of 14687 autologous procedures performed over the same period. Patients receiving allogeneic transplants were subdivided according to histology: low-grade non-Hodgkin's lymphoma (NHL) 231 patients; intermediate-grade NHL 147 patients; high-grade NHL 255 patients; lymphoblastic NHL 314 patients; Burkitt's lymphoma 71 patients; and Hodgkin's disease 167 patients. These patients received allogeneic transplants as their first transplant procedure. Actuarial overall survival (OS) at 4 years from transplantation was: low-grade NHL 51.1%; intermediate-grade NHL 38.3%; high-grade NHL 41.2%; lymphoblastic lymphoma 42.0% years; Burkitt's lymphoma 37.1%; and Hodgkin's disease 24.7% years. These outcomes are relatively poor because of the high procedure-related mortality associated with these procedures, particularly in patients with Hodgkin's disease (51.7% actuarial procedure-related mortality at 4 years). Multivariate analysis showed that for all lymphomas apart from Hodgkin's disease, status at transplantation significantly affected outcome. A matched analysis was performed: for all categories of lymphoma, OS was better for autologous than for allogeneic transplantation. Relapse rate was better in the allogeneic group for low-, intermediate- and high-grade, and lymphoblastic NHL. It was equivalent for Burkitt's lymphoma and worse in the allogeneic group for Hodgkin's disease. Allogeneic transplantation appears to be superior to autologous procedures in terms of producing a lower relapse rate. The toxicity of allogeneic procedures must however be reduced before this translates into an improvement in OS.