scispace - formally typeset
Search or ask a question
Institution

John Radcliffe Hospital

HealthcareOxford, Oxfordshire, United Kingdom
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.


Papers
More filters
Journal ArticleDOI
TL;DR: It is concluded that at least some patients with acquired neuromyotonia have antibodies directed against aminopyridine‐ or α‐dendrotoxin‐sensitive K+ channels in motor and sensory neurons, and they are likely to be implicated in the disease process.
Abstract: Acquired neuromyotonia is characterized by hyperexcitability of motor nerves leading to muscle twitching, cramps, and weakness. The symptoms may improve following plasma exchange, and injection of immunoglobulin G (IgG) from 1 neuromyotonia patient into mice increased the resistance of neuromuscular transmission to d-tubocurarine. Here we examine nerves and muscle in vitro from mice injected with plasma or purified IgG from 6 neuromyotonia patients or pooled control subjects, and cultured dorsal root ganglion cells after treatment with IgG. Three of the patients had antibodies against human voltage-gated potassium channels labeled with 125I-alpha-dendrotoxin. The quantal release of acetylcholine (quantal content) at end-plates in diaphragms from mice treated with neuromyotonia IgG preparations was increased by 21% relative to control values (p = 0.0053). With one IgG preparation, the duration of the superficial peroneal nerve compound action currents was increased by 93%. The dorsal root ganglion cells treated with this IgG showed a marked increase in repetitive firing of action potentials. All effects were similar to those obtained with aminopyridines. We conclude that at least some patients with acquired neuromyotonia have antibodies directed against aminopyridine- or alpha-dendrotoxin-sensitive K+ channels in motor and sensory neurons, and they are likely to be implicated in the disease process.

373 citations

Journal ArticleDOI
TL;DR: The sensitivity and predictive value of islet-cell antibodies for the future onset of insulin-dependent diabetes mellitus (IDDM) were determined in 719 first-degree relatives of IDDM patients, and IDDM developed within follow-up of 7 years.

373 citations

Journal ArticleDOI
TL;DR: The story of how both the physiological basis of the disease and the role of acetylcholine-receptor-specific antibodies were determined is a classic example of the application of basic science to clinical medicine and it has provided a model for defining other antibody-mediated disorders of the peripheral and central nervous systems.
Abstract: Myasthenia gravis is a relatively rare neurological disease that is associated with loss of the acetylcholine receptors that initiate muscle contraction. This results in muscle weakness, which can be life-threatening. The story of how both the physiological basis of the disease and the role of acetylcholine-receptor-specific antibodies were determined is a classic example of the application of basic science to clinical medicine, and it has provided a model for defining other antibody-mediated disorders of the peripheral and central nervous systems.

373 citations

Journal ArticleDOI
TL;DR: The MLST scheme was sufficiently robust to allow direct genotyping of C. difficile in total stool DNA extracts without isolate culture and may prove useful as a rapid genotypes method, potentially benefiting individual patients and informing hospital infection control.
Abstract: A robust high-throughput multilocus sequence typing (MLST) scheme for Clostridium difficile was developed and validated using a diverse collection of 50 reference isolates representing 45 different PCR ribotypes and 102 isolates from recent clinical samples. A total of 49 PCR ribotypes were represented overall. All isolates were typed by MLST and yielded 40 sequence types (STs). A web-accessible database was set up (http://pubmlst.org/cdifficile/) to facilitate the dissemination and comparison of C. difficile MLST genotyping data among laboratories. MLST and PCR ribotyping were similar in discriminatory abilities, having indices of discrimination of 0.90 and 0.92, respectively. Some STs corresponded to a single PCR ribotype (32/40), other STs corresponded to multiple PCR ribotypes (8/40), and, conversely, the PCR ribotype was not always predictive of the ST. The total number of variable nucleotide sites in the concatenated MLST sequences was 103/3,501 (2.9%). Concatenated MLST sequences were used to construct a neighbor-joining tree which identified four phylogenetic groups of STs and one outlier (ST-11; PCR ribotype 078). These groups apparently correlate with clades identified previously by comparative genomics. The MLST scheme was sufficiently robust to allow direct genotyping of C. difficile in total stool DNA extracts without isolate culture. The direct (nonculture) MLST approach may prove useful as a rapid genotyping method, potentially benefiting individual patients and informing hospital infection control.

372 citations

Journal ArticleDOI
TL;DR: The current classification of CFTR mutation classes and resulting CF disease phenotypes are described and complex disease alleles and modifier genes are discussed along with alternative disorders, such as disseminated bronchiectasis and pancreatitis, which are also thought to result from CFTR mutations.
Abstract: Cystic fibrosis is a common autosomal recessive disorder that primarily affects the epithelial cells in the intestine, respiratory system, pancreas, gall bladder and sweat glands. Over one thousand mutations have currently been identified in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that are associated with CF disease. There have been many studies on the correlation of the CFTR genotype and CF disease phenotype; however, this relationship is still not well understood. A connection between CFTR genotype and disease manifested in the pancreas has been well described, but pulmonary disease appears to be highly variable even between individuals with the same genotype. This review describes the current classification of CFTR mutation classes and resulting CF disease phenotypes. Complex disease alleles and modifier genes are discussed along with alternative disorders, such as disseminated bronchiectasis and pancreatitis, which are also thought to result from CFTR mutations.

372 citations


Authors

Showing all 14542 results

NameH-indexPapersCitations
Douglas G. Altman2531001680344
Salim Yusuf2311439252912
David J. Hunter2131836207050
Mark I. McCarthy2001028187898
Stuart H. Orkin186715112182
Richard Peto183683231434
Ralph M. Steinman171453121518
Adrian L. Harris1701084120365
Rory Collins162489193407
Nicholas J. White1611352104539
David W. Johnson1602714140778
David Cella1561258106402
Edmund T. Rolls15361277928
Martin A. Nowak14859194394
Kypros H. Nicolaides147130287091
Network Information
Related Institutions (5)
Leiden University Medical Center
38K papers, 1.6M citations

94% related

Medical Research Council
19.1K papers, 1.4M citations

92% related

Beth Israel Deaconess Medical Center
52.5K papers, 2.9M citations

92% related

Brigham and Women's Hospital
110.5K papers, 6.8M citations

92% related

Baylor College of Medicine
94.8K papers, 5M citations

91% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202311
202252
20211,048
20201,013
2019916
2018773