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.

HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers.

Abstract: Most HIV-1 transmission is sexual; therefore immune responses in the genital mucosa may be important in mediating protection against HIV infection. This study examined HIV-1-specific mucosal immunoglobulin A (IgA) in a cohort of HIV-1-resistant Kenyan female sex workers. HIV-1-specific immune responses were compared in HIV-1-resistant and HIV-1-infected sex workers and in lower risk uninfected women. Cervical and vaginal samples from each group were tested for HIV-1-specific IgA and IgG by enzyme immunoassay. Systemic T-helper lymphocyte cell responses to HIV-1 envelope peptide epitopes were assayed using an interleukin 2 bioassay. HIV-1 risk-taking behaviors were assessed using standardized questionnaires. HIV-1-specific IgA was present in the genital tract of 16 out of 21 (76%) HIV-1-resistant sex workers 5 out of 19 (26%) infected women and 3 out of 28 (11%) lower-risk women (P < 0.0001). Among lower risk women the presence of HIV-1-specific IgA was associated with HIV-1 risk- taking behavior. Systemic T-helper lymphocyte responses to HIV-1 envelope peptides were present in 11 out of 20 (55%) HIV-1- resistant women 4 out of 18 (22%) infected women and 1 out of 25 (4%) lower-risk women (P < 0.001). T-helper lymphocyte responses did not correlate with the presence of titer of virus-specific mucosal IgA in any study group. HIV-1-specific IgA is present in the genital tract of most HIV-1-resistant Kenyan sex workers and of a minority of lower risk uninfected women where it is associated with risk-taking behavior. These data suggest a role for mucosal HIV-1-specific IgA responses in HIV-1 resistance independent of host cellular responses. (authors)

Evidence for Selective Advantage of Pathogenic FGFR2 Mutations in the Male Germ Line

Abstract: Observed mutation rates in humans appear higher in male than female gametes and often increase with paternal age. This bias, usually attributed to the accumulation of replication errors or inefficient repair processes, has been difficult to study directly. Here, we describe a sensitive method to quantify substitutions at nucleotide 755 of the fibroblast growth factor receptor 2 (FGFR2) gene in sperm. Although substitution levels increase with age, we show that even high levels originate from infrequent mutational events. We propose that these FGFR2 mutations, although harmful to embryonic development, are paradoxically enriched because they confer a selective advantage to the spermatogonial cells in which they arise.

Dynamic Interactions Between Musical, Cardiovascular, and Cerebral Rhythms in Humans

Abstract: Background— Reactions to music are considered subjective, but previous studies suggested that cardiorespiratory variables increase with faster tempo independent of individual preference. We tested whether compositions characterized by variable emphasis could produce parallel instantaneous cardiovascular/respiratory responses and whether these changes mirrored music profiles. Methods and Results— Twenty-four young healthy subjects, 12 musicians (choristers) and 12 nonmusician control subjects, listened (in random order) to music with vocal (Puccini’s “Turandot”) or orchestral (Beethoven’s 9th Symphony adagio) progressive crescendos, more uniform emphasis (Bach cantata), 10-second period (ie, similar to Mayer waves) rhythmic phrases (Giuseppe Verdi’s arias “Va pensiero” and “Libiam nei lieti calici”), or silence while heart rate, respiration, blood pressures, middle cerebral artery flow velocity, and skin vasomotion were recorded. Common responses were recognized by averaging instantaneous cardiorespiratory...

A Regulatory SNP Causes a Human Genetic Disease by Creating a New Transcriptional Promoter

Abstract: We describe a pathogenetic mechanism underlying a variant form of the inherited blood disorder alpha thalassemia. Association studies of affected individuals from Melanesia localized the disease trait to the telomeric region of human chromosome 16, which includes the alpha-globin gene cluster, but no molecular defects were detected by conventional approaches. After resequencing and using a combination of chromatin immunoprecipitation and expression analysis on a tiled oligonucleotide array, we identified a gain-of-function regulatory single-nucleotide polymorphism (rSNP) in a nongenic region between the alpha-globin genes and their upstream regulatory elements. The rSNP creates a new promoterlike element that interferes with normal activation of all downstream alpha-like globin genes. Thus, our work illustrates a strategy for distinguishing between neutral and functionally important rSNPs, and it also identifies a pathogenetic mechanism that could potentially underlie other genetic diseases.