tbuckley/cabot-search huggingface dataset:
Differentiated B lymphocytes. Potential to express particular antibody variable and constant regions depends on site of lymphoid tissue and antigen load.
Authors: P J Gearhart, J J Cebra
Journal: The Journal of Experimental Medicine (1979)

B cells have the potential to respond to an antigen by producing antibodies with a variety of variable and constant regions. We have quantitatively analyzed B-cell potential at the single cell level to determine the effect of lymphoid tissue site and antigen load on the expression of variable and constant regions. Concerning variable region expression, although the total frequency of B-cell precursors for phosphorylcholine is similar between nonimmune spleen and gut-associated Peyer's patch tissues, the proportion of cells producing non-TEPC 15 idiotypes is greater from Peyer's patch than from spleen. Oral immunization with phosphorylcholine-containing Ascaris suum increased the frequency of non-TEPC 15 B cells. Thus variation in the proportion of cells bearing different variable regions may be related to the distinct antigenic environment of cells in Peyer's patches compared to that of cells in spleen. Regarding constant region expression, although B cells from both spleen and Peyer's patches generate clones producing IgM, IgGl, and IgA singly and in all combinations, cells from Peyer's patches generate more clones secreting only IgA than cells from spleen. B cells specific for phosphorylcholine and inulin, which are found on intestinal bacteria, produce more IgA-only clones than B cells specific for the dinitrophenyl determinant. This striking correlation between IgA expression and variable region specificity for antigen implies that environmental antigens have expanded certain B cells in Peyer's patches which then have the ability to generate progeny that express only IgA. Evidence supporting the secondary nature of precursors for IgA-only clones is obtained by their ability to produce this isotype after stimulation with histoincompatible T cells. The role of gut antigens may be to clonally expand IgA precursors and perhaps to stimulate the proliferation of less differentiated cells within the unique microenvironment of the Peyer's patches, allowing them to differentiate to IgA precursors.
The ProtecT trial: what can we expect?
Authors: Monique J Roobol, Leonard P Bokhorst
Journal: The Lancet Oncology (2014)

Profound changes in the detection of prostate cancer have occurred since prostate-specifi c antigen (PSA) was introduced as a biomarker test for prostate cancer. Instead of the disease being detected at an advanced stage when symptoms caused by invasive growth emerged—with palliative treatment the main option—prostate cancer is diagnosed early on in the disease course.  

However, not only were potentially lethal tumours detected at an early, treatable stage, but also many non-lethal tumours were diagnosed. This over-diagnosis leads to substantial overtreatment with its associated side-effects. Therefore,
whether treatment of early detected, localised cancers will result in a benefit or mainly cause harm is unclear.
Winning poem takes a doctor's life as its inspiration
Authors: H. Mooney
Journal: BMJ (2010)

The winners of the first annual Hippocrates prize for a poem on a medical subject have been announced.

Wendy French, who facilitates creative writing in healthcare and community settings, won the prize in the competition’s NHS category for her poem It’s About a Man , which details the life of a doctor.⇓



Ms French said: “I’m thrilled to have …
COMPARISON OF THE PROGNOSTIC UTILITY OF VARIOUS CLINICAL AND ANGIOGRAPHIC RISK SCORES IN PATIENTS WITH ACUTE CORONARY SYNDROMES: ANALYSIS FROM THE ACUITY TRIAL
Authors: Tullio Palmerini, Adriano Caixeta, Philippe Genereux, Ecaterina Cristea, Alexandra Lansky, Roxana Mehran, George Dangas, Dana Lazar, Rachel Sanchez, Maria Corral, Ivana Jankovic, Martin Fahy, Ke Xu, Gregg Stone
Journal: Journal of the American College of Cardiology (2011)
Tumor-Specific T-Cell Memory: Clearing the Regulatory T-Cell Hurdle
Authors: Anik L. Côté, Edward J. Usherwood, Mary Jo Turk
Journal: Cancer Research (2008)

Antitumor immune responses can be stimulated by interfering with regulatory T-cell (T(reg)) function. However, this effect is short lived unless T-cell memory to tumor antigens can be generated. Our recent studies show that T(reg) cells not only limit primary responses to tumor/self-antigens in tumor-bearing hosts but also prevent the natural generation of T-cell memory to such antigens. Here, we discuss the role of T(reg) cells in suppressing T-cell memory after surgical excision of tumors and the potential clinical benefits of overcoming this suppression.
Screening techniques to identify people at high risk for diabetic foot ulceration: a prospective multicenter trial.
Authors: H Pham, D G Armstrong, C Harvey, L B Harkless, J M Giurini, A Veves
Journal: Diabetes Care (2000)

OBJECTIVE: Diabetic foot ulceration is a preventable long-term complication of diabetes. A multicenter prospective follow-up study was conducted to determine which risk factors in foot screening have a high association with the development of foot ulceration. RESEARCH DESIGN AND METHODS: A total of 248 patients from 3 large diabetic foot centers were enrolled in a prospective study. Neuropathy symptom score, neuropathy disability score (NDS), vibration perception threshold (VPT), Semmes-Weinstein monofilaments (SWFs), joint mobility, peak plantar foot pressures, and vascular status were evaluated in all patients at the beginning of the study. Patients were followed-up every 6 months for a mean period of 30 months (range 6-40), and all new foot ulcers were recorded. The sensitivity, specificity, and positive predictive value of each risk factor were evaluated. RESULTS: Foot ulcers developed in 95 feet (19%) or 73 patients (29%) during the study. Patients who developed foot ulcers were more frequently men, had diabetes for a longer duration, had nonpalpable pedal pulses, had reduced joint mobility, had a high NDS, had a high VPT, and had an inability to feel a 5.07 SWE NDS alone had the best sensitivity, whereas the combination of the NDS and the inability to feel a 5.07 SWF reached a sensitivity of 99%. On the other hand, the best specificity for a single factor was offered by foot pressures, and the best combination was that of NDS and foot pressures. Univariate logistical regression analysis yielded a statistically significant odds ratio (OR) for sex, race, duration of diabetes, palpable pulses, history of foot ulceration, high NDSs, high VPTs, high SWFs, and high foot pressures. In addition, 94 (99%) of the 95 ulcerated feet had a high NDS and/or SWF which resulted in the highest OR of 26.2 (95% CI 3.6-190). Furthermore, in multivariate logistical regression analysis, the only significant factors were high NDSs, VPTs, SWFs, and foot pressures. CONCLUSIONS: Clinical examination and a 5.07 SWF test are the two most sensitive tests in identifying patients at risk for foot ulceration, especially when the tests are used in conjunction with each other. VPT measurements are also helpful and can be used as an alternative. Finally, foot pressure measurements offer a substantially higher specificity and can be used as a postscreening test in conjunction with providing appropriate footwear.
Smoking and Myocardial Infarction
Authors: MARTIN JEFFREY FRANK
Journal: Annals of Internal Medicine (1977)

Comments and Correction1 April 1977Smoking and Myocardial InfarctionMARTIN JEFFREY FRANK, M.D.MARTIN JEFFREY FRANK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-4-509_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent letter by Nixon and colleagues "Myocardial Infarction in Men in the Third Decade of Life" (Ann Intern Med 85:759-760, 1976), was thought-provoking. Six of the eight patients were cigarette smokers. Among these six patients, there were three with angiographic normal coronary arteries.There may be a causal relation between cigarette smoking and those young men with myocardial infarction and radiographically patent coronary arteries. Smoking may induce coronary artery spasm to produce a myocardial infarction; when a patient is studied after infarction, the spasm subsides and the vessels appear normal.Khan and Haywood (1) mention coronary...References1. KHANHAYWOOD AL: Myocardial infarction in nine patients with radiographically patent coronary arteries. N Engl J Med 291:427-431, 1974 CrossrefMedlineGoogle Scholar2. ARNETTROBERTS EW: Acute myocardial infarction and angiographic normal coronary arteries: an unproven combination. Circulation 53:395-400, 1976 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cardiology Department Yater Clinic 1780 Massachusetts Avenue, N.W. Washington, DC 20036 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1977Volume 86, Issue 4Page: 509-509KeywordsCoronary arteriesInfarctionMyocardial infarction Issue Published: 1 April 1977 PDF DownloadLoading ...
Muscarinic acetylcholine receptor autoantibodies in patients with Sjogren's syndrome
Authors: Y Naito
Journal: Annals of the Rheumatic Diseases (2004)

Sjogren’s syndrome (SS) is an autoimmune disease characterised by lymphocytic infiltration into the lachrymal and salivary glands, leading to dry eyes and mouth. Infiltration is also found in the kidneys, lungs, thyroid, and liver. Immunohistochemical studies have shown that most infiltrating lymphocytes around the labial salivary and lachrymal glands, and kidneys are CD4 positive αβ T cells. Previous studies with polymerase chain reaction provide evidence about the T cell receptor Vβ and Vα genes on these T cells, and sequence analysis of the CDR3 region indicates some conserved amino acid motifs, supporting the notion that infiltrating T cells recognise relatively few epitopes on autoantigens.1

Candidate autoantigens recognised by T cells infiltrating the labial salivary glands of patients with SS have been analysed, and Ro/SSA 52 kDa, α-amylase, heat shock protein, and T cell receptor BV62 have been identified. However, there is no direct evidence that these reactive T cells really attack and destroy the salivary glands. In contrast, the presence of autoantibodies (Abs) against M3 muscarinic acetylcholine receptor (M3R) has been reported, and it is suggested that an immune reaction to M3R plays a crucial …
Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling
Authors: Francoise Denoyelle, Sandrine Marlin, Dominique Weil, Lucien Moatti, Pierre Chauvin, Éréa-Noël Garabédian, Christine Petit
Journal: The Lancet (1999)
PSA in the New Millennium: A Powerful Predictor of Prostate Cancer Prognosis and Radical Prostatectomy Outcomes — Results from the SEARCH Database
Authors: Stephen J. Freedland, James M. Hotaling, Nicholas J. Fitzsimons, Joseph C. Presti, Christopher J. Kane, Martha K. Terris, William J. Aronson, Christopher L. Amling
Journal: European Urology (2007)
FDA committees say keep rosiglitazone available but increase warnings
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

Two Food and Drug Administration advisory committees recommended this week that the FDA should keep rosiglitazone (Avandia), which is used to treat type 2 diabetes, on the market, despite concerns about the raised risk of heart attack in some patients.

Warnings will be increased, however, about use in subgroups of patients. Whether the warnings will be of the most serious “black box” type is yet to be determined. The FDA usually follows the advice of advisory committees but is not required to. The FDA will consider the committees' discussion and make recommendations for changes to labelling.

The FDA's advisory committees on endocrinological and metabolic drugs and the drug safety and risk management advisory committees met jointly at a crowded public meeting in a hotel near the FDA headquarters, outside Washington, DC, on Monday.

The FDA brought forwards its meeting to consider rosiglitazone's risks in light of a paper by researchers at the Cleveland Clinic that showed …
"Absurd" rules are hampering research into controlled drugs, says former drugs adviser
Authors: K. Chinthapalli
Journal: BMJ (2013)

All NHS hospitals should be allowed to hold all controlled drugs and use them for clinical research, according to the former chair of the government’s Advisory Council on the Misuse of Drugs.

David Nutt, who is now professor of neuropsychopharmacology at Imperial College London and president of the British Neuroscience Association, spoke about barriers to research into illicit drugs, following on from his criticisms last year.1 At a press briefing on 5 April, ahead of the British Neuroscience Association Festival of Neuroscience on 7-10 April, he said that currently only four hospitals in the UK may hold and administer Schedule 1 controlled drugs. 

Under the Misuse of Drugs …
North American Indian Rock Art and Hallucinogenic Drugs
Authors: Klaus F. Wellmann
Journal: JAMA (1978)

It is proposed that the aboriginal rock paintings in two areas of North America may have been produced by shamans while they were under the influence of hallucinogenic agents derived from plants. The first of these areas is the Chumash and Yokuts Indian region of California, where polychrome paintings show designs similar to those visualized during the trance induced by decoctions of jimsonweed (Datura species). The second area is the lower Pecos River region of Texas, where shamanistic figures display traits considered to be conceptual analogues of the mescal bean (Sophora secundiflora) cult as practiced during historic times by Great Plains Indians. Although the evidence is only circumstantial, the proposed connections between these rock drawings and mind-expanding pharmacologic compounds fit well into the documented relationship that encompasses hallucinogenic drugs and certain movable objects of pre-Columbian American art.
Review: Lithium is associated with adverse events in patients with mood disorders
Authors: Adrian Preda
Journal: Annals of Internal Medicine (2012)

ACP Journal Club17 July 2012Review: Lithium is associated with adverse events in patients with mood disordersAdrian Preda, MDAdrian Preda, MDUniversity of California Irvine College of Medicine, Irvine, California, USA (A.P.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-2-201207170-02010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationMcKnight RF, Adida M, Budge K, et al. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379:721-8. https://pubmed.ncbi.nlm.nih.gov/22265699Clinical Impact RatingsGIM/FP/GP: Mental Health: Endocrinology: Nephrology: Reference1 Werneke U, Ott M, Renberg ES, Taylor D, Stegmayr B. A decision analysis of long-term lithium treatment and the risk of renal failure. Acta Psychiatr Scand. 2012 Mar 9 [Epub ahead of print]. [PMID: 22404233] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of California Irvine College of Medicine, Irvine, California, USA (A.P.)This article was published at Annals.org on 3 July 2012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByLithium 17 July 2012Volume 157, Issue 2Page: JC1-10KeywordsAdverse eventsBipolar disorderCohort studiesGlomerular filtration rateHypothyroidismRenal failureRetrospective studiesSafetyThyroid-stimulating hormoneWeight gain ePublished: 17 July 2012 Issue Published: 17 July 2012 CopyrightCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Untangling the Genetics of a Complex Disease
Authors: Mark J. Daly
Journal: JAMA (1998)

5confers a roughly 3-fold increased risk of developing the common, later-onset form of the disease. Because of its frequency (approximately 15% in the general population), this allele accounts for nearly all of the currently identified genetic risk associated with AD. It is clear, however, that other genetic risk factors for the common form of AD must exist as these 4 factors account for only 50% of the total genetic risk. 6
Lipoic acid supplementation prevents angiotensin II–induced renal injury
Authors: Eero Mervaala, Piet Finckenberg, Risto Lapatto, Dominik N. Müller, Joon-Keun Park, Ralf Dechend, Detlev Ganten, Heikki Vapaatalo, Friedrich C. Luft
Journal: Kidney International (2003)
3 alpha-hydroxysteroid dehydrogenase activity of the Y' bile acid binders in rat liver cytosol. Identification, kinetics, and physiologic significance.
Authors: A Stolz, H Takikawa, Y Sugiyama, J Kuhlenkamp, N Kaplowitz
Journal: Journal of Clinical Investigation (1987)

Rat Y' bile acid binders (33 kD) have been previously recognized as cytosolic bile acid binding proteins (Sugiyama, Y., T. Yamada, and N. Kaplowitz, 1983, J. Biol. Chem., 258:3602-3607). We have now determined that these Y' binders are 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSD), bile acid-metabolizing enzymes. 3 alpha-HSD activity copurified with lithocholic acid-binding activity after sequential gel filtration, chromatofocusing, and affinity chromatography. Three peaks of 3 alpha-HSD activity (I, II, III) were observed in chromatofocusing and all were identified on Western blot by a specific Y' binder antiserum. 3 alpha-HSD-I, the predominant form, was purified and functioned best as a reductase at pH 7.0 with a marked preference for NADPH. Michaelis constant values for mono- and dihydroxy bile acids were 1-2 microM, and cholic acid competitively inhibited the reduction of 3-oxo-cholic acid. Under normal redox conditions, partially purified 3 alpha-HSD-I and freshly isolated hepatocytes catalyzed the rapid reduction of 3-oxo-cholic to cholic acid without formation of isocholic acid, whereas the reverse reaction was negligible. The Y' bile acid binders are therefore 3 alpha-HSD, which preferentially and stereospecifically catalyze the reduction of 3-oxo-bile acids to 3 alpha-hydroxy bile acids.
Health professions pledge action against socioeconomic factors responsible for health inequalities
Authors: I. Torjesen
Journal: BMJ (2013)

The medical royal colleges and other bodies representing health professionals have pledged to do more to tackle health inequalities through direct action on the social determinants of health.

The Royal College of Physicians, the Royal College of Surgeons, and the Royal College of General Practitioners are among 21 organisations to make firm commitments to act, which include investigating a patient’s social and economic circumstances as well as their medical history when assessing health.

The commitments are included in a report, Working for Health Equity: The Role of Health Professionals ,1 launched on Monday by University College London’s Institute of Health Equity at a conference at the BMA in London.

In 2010 the government commissioned an independent …
Accurate Assessment of Patient Effective Radiation Dose and Associated Detriment Risk From Radiofrequency Catheter Ablation Procedures
Authors: Kostas Perisinakis, John Damilakis, Nicholas Theocharopoulos, Emmanouel Manios, Panayiotis Vardas, Nicholas Gourtsoyiannis
Journal: Circulation (2001)

Background— Radiofrequency (RF) cardiac catheter ablation procedures may require extended fluoroscopic exposure resulting in elevated radiation risk. The aim of the present study was to accurately establish RF ablation radiation risk levels and to provide means for accurate patient risk estimation from studies performed in any electrophysiology laboratory. Methods and Results— Fluoroscopy required during cardiac ablation was classified into 4 types identified by beam orientation and irradiated tissue: (1) posteroanterior exposure during catheter advancing from the groin to the heart, (2) posteroanterior heart exposure, (3) left anterior oblique heart exposure, and (4) right anterior oblique heart exposure. The duration of each exposure was monitored in 24 patients undergoing RF cardiac ablation. Dose per minute of fluoroscopy was measured at 15 organs/tissues for each projection with the use of anthropomorphic phantom and thermoluminescence dosimetry. The effective dose rate was 219, 144, 136, and 112 μGy/min for groin-to-heart posteroanterior, posteroanterior, left anterior oblique, and right anterior oblique exposure, respectively. A typical ablation procedure results in a total effective dose of 8.3 mSv per hour of fluoroscopy. The average excess of fatal cancers was estimated to be 650 and 480 per million patients undergoing RF ablation requiring 1 hour of fluoroscopy for US and UK populations, respectively. The average risk for genetic defects was determined to be 1 per million births. Conclusions— Radiation risk from RF cardiac ablation is moderate compared with other complications, but it may highly exceed radiation risk from common radiological procedures. Efforts should be made toward minimization of patient radiation risk from RF ablation procedures.
Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension.
Authors: P Verdecchia, G Schillaci, M Guerrieri, C Gatteschi, G Benemio, F Boldrini, C Porcellati
Journal: Circulation (1990)

The effects of circadian blood pressure (BP) changes on the echocardiographic parameters of left ventricular (LV) hypertrophy were investigated in 235 consecutive subjects (137 unselected untreated patients with essential hypertension and 98 healthy normotensive subjects) who underwent 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) and cross-sectional and M-mode echocardiography. In the hypertensive group, LV mass index correlated with nighttime (8:00 PM to 6:00 AM) systolic (r = 0.51) and diastolic (r = 0.35) blood pressure more closely than with daytime (6:00 AM to 8:00 PM) systolic (r = 0.38) and diastolic (r = 0.20) BP, or with casual systolic (r = 0.33) and diastolic (r = 0.27) BP. Hypertensive patients were divided into two groups by presence (group 1) and absence (group 2) of a reduction of both systolic and diastolic BP during the night by an average of more than 10% of the daytime pressure. Casual BP, ambulatory daytime systolic and diastolic BP, sex, body surface area, duration of hypertension, prevalence of diabetes, quantity of sleep during monitoring, funduscopic changes, and serum creatinine did not differ between the two groups. LV mass index, after adjustment for the age, the sex, the height, and the daytime BP differences between the two groups (analysis of covariance) was 82.4 g/m2 in the normotensive patient group, 83.5 g/m2 in hypertensive patients of group 1 and 98.3 g/m2 in hypertensive patients of group 2 (normotensive patients vs. group 1, p = NS; group 1 vs. group 2, p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)