tbuckley/cabot-search huggingface dataset:
Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis.
Authors: M J Walsh, J M Murray
Journal: Journal of Clinical Investigation (1998)

Multiple sclerosis (MS) is characterized by intra-blood-brain barrier immunoglobulin synthesis that persists lifelong. Subcellular fractionation and two-dimensional electrophoresis were used in conjunction with immune precipitation and immunoblotting to identify antigenic determinants for this immunoglobulin. We report that 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a protein associated with oligodendrocyte/myelin membranes, also present in lymphocytes and retina, is one major target for the humoral response. Antibodies to CNP are detected in sera of 74% of MS patients. The antibodies are IgM and are present in serum in high titer as well as in cerebrospinal fluid. The antibody response is temporally persistent, consistent with systemic immune activation and persistent antigenic stimulation. Moreover, CNP is isolated as an immune complex from MS brain. CNP is expressed as two isoforms, with CNPII identical to CNPI but with a 20-amino acid extension at the amino terminus of CNPII; however, the antibody response is exclusively restricted to CNPI. In contrast, both isoforms bind the C3 complement, providing a plausible mechanism in MS central nervous system (CNS) for opsonization of myelin membrane CNP, mediated via the C3 receptor, and phagocytosis of CNP-Ig immune complexes, mediated by membrane Ig Fc receptors of macrophages and CNS microglia.
HPV16 E2 Is an Immediate Early Marker of Viral Infection, Preceding E7 Expression in Precursor Structures of Cervical Carcinoma
Authors: Yuezhen Xue, Sophie Bellanger, Wenying Zhang, Diana Lim, Jeffrey Low, Declan Lunny, Françoise Thierry
Journal: Cancer Research (2010)

The viral E2 gene product plays a crucial role in the human papillomavirus (HPV) vegetative cycle by regulating both transcription and replication of the viral genome. E2 is a transcriptional repressor of the E6 and E7 viral oncogenes for HPV types 16 and 18, which are involved in cervical cancers. Using new polyclonal antibodies against the HPV16 E2 protein, we showed that E2 is expressed at various precursor stages of cervical carcinoma by immunohistochemistry on paraffin-embedded clinical samples. E2 was found to be highly expressed in the nuclei and cytoplasm of cells forming the intermediate and upper layers of cervical intraepithelial neoplasia (CIN). We could show that the expressions of E2 and p16(INK4a) (surrogate marker for oncogenic E7 expression) were exclusive in most of the cases, thus implying that E2 is not expressed together with high levels of E7. Moreover, we found that E2 is expressed in a subset of columnar cells adjacent to the CIN. We could show that expression of E2 is topologically distinct from the proliferation markers p63 and Ki67, whereas it coincides with the expression of cytokeratin K13, a marker of squamous cell differentiation. Expression of E2 also topologically coincides with episomal amplification of viral genomes in the upper layers of CIN1. These in vivo data thus validate previous assumptions of the crucial role of E2 in the early steps of HPV infection and of its negative link with expression of the viral E6 and E7 oncogenes.
Relapse of duodenal ulcer: does it matter which drug is used in initial treatment?
Authors: J P Miller, E B Faragher
Journal: BMJ (1986)

diRelapse of duodenal ulcer: does it matter which drug is used in initial treatment?Duodenal ulcers recur within a year in 80-90% of patients treated initially with H2 antagonists,'-' and evidence now exists that relapse rates may be lower after treatment with other ulcer healing drugs.Moshal postulated in 1978 that relapse rates might be lower after treatment with tripotassium di-citrato bismuthate (Moshal MG, Sixth World Congress of Gastroenterology, Madrid, 1978), and in a double blind prospective study we showed that this was indeed so.9 McLean and others'" have concluded that this may also be true for other ulcer healing drugs, including antacids," anticholinergics,'2 antacid and anticholinergic combinations,'3 carbenoxolone,'4 1 ' sucralfate,'6 and trithiozine. 17 18vidence for a reduction in relapse rate relative to cimetidine is not, however, strong for most of these agents individually.The studies have often been small, and the differences have also been small, either failing to reach significance or doing so only transiently.For example, Hansky and others claimed no significance for the difference in relapse rates that they observed in a small study of antacids against cimetidine," and larger studies have found no difference.'920The strength of the argument of McLean and others'0 is, however, that when an appreciable difference in relapse rates is observed it is consistently in favour of the comparative agent and to the detriment of cimetidine.Only in the case of tri-potassium di-citrato bismuthate is there sufficient evidence for a single drug that the effect is real.Although our initial study was not immediately con- firmed,2' four subsequent trials22-29 have shown lower relapse rates after tri-potassium di-citrato bismuthate than after an H2 antagonist.The more recent ofthese studies23125 strengthen the case made by McLean and others and extend it to include ranitidine, which is followed by a similar relapse rate to cimetidine.The consistency of the results leaves little doubt that the phenomenon is genuine, and in a further trial recurrence rates were similar in patients maintained on cimetidine and those given only a short course of tripotassium di-citrato bismuthate to induce healing.26Combining results from the six studies showed that 85% of patients treated with H2 antagonists relapse within a year compared with 59% of those treated with tri-potassium di- citrato bismuthate.9 2-Combining data from clinical trials is unreliable, but this is the best available quantitative estimate of the difference between the treatments.Because duodenal ulceration is so common even a difference of about 25% has
Taking the direct route to make open access even easier
Authors: S. Bloom
Journal: Journal of Clinical Investigation (2005)

Chaisson: We hope the first study will show that moxifloxacin speeds up the sterilization time in sputum samples from TB patients, and then we hope to show that a regimen given for four months is as effective as one given for six months.We will also continue to look at the other drugs in the pipeline and make adjustments to the regimens as the trials proceed.JCI: What do you consider to be your greatest scientific achievement?Chaisson: I have made some contributions that have been worthwhile, I hope.Early on, I was able to show the importance of the interaction of TB and HIV in San Francisco.Over the past few years we have built on this work and explored the public health dimensions of TB and HIV, developing new models of TB control in the era of HIV.I was able to show that supervised treatment for TB improved survival and led to reduced incidence in Baltimore.And back when I was largely focused on HIV, my colleague Richard Moore and I pioneered the use of HIV clinical cohorts, which has led to numerous important observations on the natural history and treatment outcomes of HIV infection and played a critical role in developing treatment guidelines globally.JCI: What about your greatest accomplishment in life outside of science?Chaisson: My greatest non-work-related accomplishment is having a wonderful family, for which I can only take a small amount of credit.I was lucky enough to marry a wonderful woman, Judy Harding, and we have two teenage daughters who give us nothing but joy.JCI: In addition to the moxifloxacin study, you also direct the Consortium to Respond Effectively to the AIDS/TB Epidemic (CREATE), an international effort to treat and control the spread of tuberculosis in countries hit hardest by the two epidemics.What has been your most interesting experience in that realm?Chaisson: The work I am doing on CREATE has drawn the attention and support of some very important people, not the least of whom are Nelson Mandela and Desmond Tutu.Mr. Mandela attended the launch of CREATE in Bangkok last year, and gave one of the most important TB advocacy speeches in history.Archbishop Tutu attended our last investigators' meeting in Cape Town in September and gave the most moving speech I have heard in years.
STAT3 and NF-kB Regulate S100A7 Expression in Human Bronchial Epithelial Cells
Authors: K.E. Hulse, R. Singh, K. Chaung, J. Norton, K. Harris, D. Conley, R. Chandra, R. Kern, A. Peters, L. Grammer, B. Tan, R. Carter, S. Seshadri, L. Suh, A. Kato, R. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2012)
Diarrhoeal diseases still kill more than 1.5m children under 5 each year
Authors: Peter Moszynski
Journal: BMJ (2007)

An orthotopic liver transplantation (OLT) is of a proven benefit in an acute liver failure (ALF). Heparin-induced thrombocytopenia (HIT) is strongly associated with thromboembolic complications. We present the case of a 56-year-old patient who underwent an OLT owing to an ALF of unknown aetiology. HIT type II with consecutive hepatic and portal vein thrombosis caused progressive graft failure. Total hepatectomy and porto-caval shunt were performed to reduce the toxic effects of liver cell necrosis such as multiorgan failure involving the respiratory, renal and cardiovascular systems. A suitable liver graft was allocated after an anhepatic bridging period of 56 h. Specific complications due to end-stage liver failure—such as acidosis, coagulopathy, decrease of vascular resistance, cerebral oedema, myocardial infarction and right heart failure—were treated. Following a re-OLT, the patient made a complete recovery. We present a rare case of HIT-associated early liver graft failure followed by a prolonged anhepatic phase and finally a successful re-OLT.
Murine V lambda x and V lambda x-containing antibodies bind human myelin basic protein.
Authors: F S Galin, C C Maier, S R Zhou, J N Whitaker, J E Blalock
Journal: Journal of Clinical Investigation (1996)

Myelin basic protein (MBP) is highly immunogenic and a known autoantigen capable of inducing experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis. We have previously described a murine monoclonal antibody (mAb), F28C4, directed against the encephalitogenic MBP peptide acetyl (Ac) 1-9, which contains a V lambda x light chain. Considering the rarity of V lambda x usage, we determined whether other Abs having V lambda x light chains shared similar antigen (Ag) specificity. We screened a panel of V lambda x-containing monoclonal and polyclonal Abs, of unknown specificity for reactivity with MBP. All such Ab, but not heavy chain isotype matched controls, bound MBP but were not polyreactive with other potential self Ags. The binding of a recombinant form of V lambda x alone to MBP demonstrated the important contribution of the V lambda x light chain to the reaction. With the exception of mAb F28C4 which recognizes MBP Ac1-9, the epitope specificity of all other V lambda x-bearing Abs was localized to MBP residues 25-34. These results demonstrate a unique association between V lambda x expression and MBP reactivity. Given that V lambda x shares sequence homology with T cell receptors (TCR) from encephalitogenic T lymphocytes, these results imply a potential role for V lambda x in the pathogenesis of EAE.
Back to the future; or forward to the past?
Authors: F T de Dombal
Journal: Gut (1987)

Back to the future; or forward to the past?Technological progress has been defined as sitting in the middle of a traffic jam whilst the in-car stereo system plays Born Free; a facile comment which encapsulates the concept that each step along the road towards the high-tech society brings not only benefits but also problems.Information technology in clinical medicine is a good example of this process.In theory, information technology opens to the gastroenterologist a brave new world of enhanced awareness, increased efficiency, and golden opportunity.In practice many systems promise the moon, cost the earth, and achieve nothing.This has, until recently, partly been the fault of computer people.The image of the wild eyed unkempt incomprehensible computer enthusiast defending his jargon with almost the same determination as the clinician, was often true in the 60s.Irreparable harm in many instances resulted from the impact of such individuals on unprepared clinicians -even while other professions were dealing effectively with the challenge of information technology.In recent years, most information technology workers have observed a profound change in clinicians' attitudes.Whereas 20 years ago clinicians were deeply mistrustful, nowadays many perceive the computer to be a
Comparison of Bilateral Internal Thoracic Artery Revascularization Using In Situ or Y Graft Configurations
Authors: David Glineur, Claude Hanet, Alain Poncelet, William D'hoore, Jean-Christophe Funken, Jean Rubay, Joelle Kefer, Parla Astarci, Valerie Lacroix, Robert Verhelst, Pierre Yves Etienne, Philippe Noirhomme, Gebrine El Khoury
Journal: Circulation (2008)

Background— Bilateral internal thoracic arteries (BITA) demonstrated superiority over other grafts to the left coronary system in terms of patency and survival benefit. Several BITA configurations are proposed for left-sided myocardial revascularization, but the ideal BITA assemblage is still unidentified. Methods and Results— From 03/2003 to 08/2006, 1297 consecutive patients underwent isolated bypass surgery in our institution. 481 patients met the inclusion criteria for randomization, and 304 (64%) were randomized. Patients were allocated to BITA in situ grafting (n=147) or Y configuration (n=152) then evaluated for clinical, functional, and angiographic outcome after 6 months and 3 years. Patient telephone interviews were conducted every 3 months and a stress test performed twice yearly under the referring cardiologist’s supervision. Angiographic follow-up was performed 6 months after surgery. The primary and secondary end points were, respectively, major adverse cerebrocardiovascular events (MACCE) and the proportion of ITA grafts that were completely occluded at follow-up angiography. More arterial anastomoses were performed in patients randomized to the Y than the in situ configuration (3.2 versus 2.4; P &lt;0.001). No significant difference between the 2 groups in terms of hospital mortality or morbidity was found. At follow-up, there was no significant difference in any MACCE rate between the 2 groups. 450 out of 464 anastomosis (97%) in the BITA Y group and 287 of 295 (97%) in the BITA in situ group were controlled patent ( P =0.99). Conclusion— Excellent patency rates were achieved using both BITA configurations with no significant differences in terms of MACCE up to 19 months postoperatively, but longer-term results remain to be established.
Myonecrosis and Myofibrosis as Complications of Sickle Cell Anemia
Authors: Joanne Valeriano-Marcet, Leslie Dubin Kerr
Journal: Annals of Internal Medicine (1991)

Painful crises in sickle cell anemia are associated with infarction and subsequent fibrosis of many different organs. Myonecrosis secondary to muscle infarction during a crisis and subsequent fibrosis are often not recognized as complications of sickle cell anemia. We describe four patients, all of whom had recurrent episodes of symmetric proximal muscle pain and swelling as prominent features of their crises. Muscle biopsies showed acute myonecrosis with a minimal inflammatory reaction as well as myofibrosis with abundant collagen deposition. Chronic sequelae consisted of muscle induration, atrophy, and contractures.
Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data
Authors: Lesley A. Stewart, Mike Clarke, Maroeska Rovers, Richard D. Riley, Mark Simmonds, Gavin Stewart, Jayne F. Tierney
Journal: JAMA (2015)

<h3>Importance</h3> Systematic reviews and meta-analyses of individual participant data (IPD) aim to collect, check, and reanalyze individual-level data from all studies addressing a particular research question and are therefore considered a gold standard approach to evidence synthesis. They are likely to be used with increasing frequency as current initiatives to share clinical trial data gain momentum and may be particularly important in reviewing controversial therapeutic areas. <h3>Objective</h3> To develop PRISMA-IPD as a stand-alone extension to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, tailored to the specific requirements of reporting systematic reviews and meta-analyses of IPD. Although developed primarily for reviews of randomized trials, many items will apply in other contexts, including reviews of diagnosis and prognosis. <h3>Design</h3> Development of PRISMA-IPD followed the EQUATOR Network framework guidance and used the existing standard PRISMA Statement as a starting point to draft additional relevant material. A web-based survey informed discussion at an international workshop that included researchers, clinicians, methodologists experienced in conducting systematic reviews and meta-analyses of IPD, and journal editors. The statement was drafted and iterative refinements were made by the project, advisory, and development groups. The PRISMA-IPD Development Group reached agreement on the PRISMA-IPD checklist and flow diagram by consensus. <h3>Findings</h3> Compared with standard PRISMA, the PRISMA-IPD checklist includes 3 new items that address (1) methods of checking the integrity of the IPD (such as pattern of randomization, data consistency, baseline imbalance, and missing data), (2) reporting any important issues that emerge, and (3) exploring variation (such as whether certain types of individual benefit more from the intervention than others). A further additional item was created by reorganization of standard PRISMA items relating to interpreting results. Wording was modified in 23 items to reflect the IPD approach. <h3>Conclusions and Relevance</h3> PRISMA-IPD provides guidelines for reporting systematic reviews and meta-analyses of IPD.
Increased A&amp;E pressure and agency staff costs put foundation trusts further into red
Authors: Z. Kmietowicz
Journal: BMJ (2015)

NHS foundation trusts in England became “less operationally resilient” in the last three months of 2014, with increased demand for services and their finances overstretched, especially in the acute care sector, the health sector regulator Monitor has reported.

Foundation trusts failed for the third quarter in a row to meet targets set for waiting times in accident and emergency departments, for treatment for cancer, and for elective care, said the quarterly update on performance.1

It showed that the trusts saw 2.7 million people through emergency departments between October and December 2014, the same as in the previous quarter but 8% higher than in the same period last year. Subsequently, hospitals admitted 570 000 for further treatment, 40 000 more patients than in the same three months in 2013, said the report.

The sector failed to meet the emergency department target for 95% …
PHYSIO-THERAPY IN THE TREATMENT OF CHRONIC RHEUMATISM
Authors: F. D. Howitt
Journal: BMJ (1929)

Analysis of "Classified)" Cases of Pulmonary Tuberculosis.With the idea, above mentioned, of comparing the tuber- culin sensitivity in the more severe and the less severe types, an attempt was made to have the pulmonary cases classified on a system described by me5 in 1924; but unfor- tunately only a very small number of cases were so classified amongst the tested patients.Tho results are given for what they are worth, but it is recognized that the numbers are too small to be satisfactory.All the classified cases were in the third stadium of phthisis, that is to say, suffering from advanced disease.Twenty were of the recrudescent " or " 0 " type, twelvo of the " initial " or "A " type.The results of the tuberculin tests are given in the followiing table.TABLE IV.-Tube)cidlin, Reactions in " A " Initial and "C" Recrudescent Cases, Percentages Positive in each Dilution.Type of Total No.Ca,e. of Cases.1 in 10,000.1 in 5,00. 1 in 1,000. 1 in 500..A"I 12 16 33 50 50 "C" 20 15 45 65 90Admitting that the numbers are too small for a con- clusive comparison, the tendency seems to be in the direc- tion of more marked reactions in the moro favourable " recrudescent " group.The classified cases were separated into fresh groups for conisideration from another point of view, according to tho classification of Inmani, who divided tuberculous cases, in terms of their degree of auto- inoculation as indicated by their temperatures, into "'resting febrile," " ambulant febrile," and " ambulant afebrile."Of the 32 patients, 20 were " resting febrile " and 12 " ambulant afebrile."It should be noted that, thouglh tlhe numbers are the same, the cases divided :up quite differently fromii the divisions in Table IV, nearly all the " A " cases beinig in the " restinig febrile " group.TABLE V.-Tubercntlin Reactionsin "BResting Febrile"' and "Ambulant Afrbrile" Cases.Total Percentages Positive in each Dilution.Type of Case.No. of Cases. 1 in 10,000. 1 in 5,000. 1 in 1.000. 1 in 5C0.Resting febrile ... 20 14 38 62 81 Ambulant afebrile 12 16 58 83 100Again it must be recalled that the numbers are very small; but the figures suggest that the patients sufficiently resistant to hold their temperature in control are also the patients with a sharp power of reaction to tuberculin.Summary and Conclusions.
Doctors will need to take bigger role in patient safety in "federal" NHS
Authors: M. Limb
Journal: BMJ (2011)

Frontline clinicians must do more to improve patient safety and stop looking to take their lead from politicians, the NHS’s medical director has said.

Bruce Keogh said clinicians would have to show better leadership than they had done in the past, particularly as the NHS was about to move to a more devolved or “federal” system.

He said clinicians had “failed” to lead on safety issues on a number of occasions.

For example, he argued that MRSA infections had only fallen substantially since the issue of hospital infections was targeted by government despite the fact that clinicians had been well aware there was a problem. …