tbuckley/cabot-search huggingface dataset:
Dronedarone for Maintenance of Sinus Rhythm in Atrial Fibrillation or Flutter
Authors: Bramah N. Singh, Stuart J. Connolly, Harry J.G.M. Crijns, Denis Roy, Peter R. Kowey, Alessandro Capucci, David Radzik, Etienne M. Aliot, Stefan H. Hohnloser
Journal: New England Journal of Medicine (2007)

Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects. Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects.In two identical multicenter, double-blind, randomized trials, one conducted in Europe (ClinicalTrials.gov number, NCT00259428 [ClinicalTrials.gov] ) and one conducted in the United States, Canada, Australia, South Africa, and Argentina (termed the non-European trial, NCT00259376 [ClinicalTrials.gov] ), we evaluated the efficacy of dronedarone, with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo. Rhythm was monitored transtelephonically on days 2, 3, and 5; at 3, 5, 7, and 10 months; during recurrence of arrhythmia; and at nine scheduled visits during a 12-month period. The primary end point was the time to the first recurrence of atrial fibrillation or flutter.In the European trial, the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group (P=0.01). The corresponding durations in the non-European trial were 59 and 158 days (P=0.002). At the recurrence of arrhythmia in the European trial, the mean (+/-SD) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group (P<0.001); the corresponding rates in the non-European trial were 116.6+/-31.9 and 104.6+/-27.1 beats per minute (P<0.001). Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group.Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia.
The Transcriptomics of Ecological Convergence between 2 Limnetic Coregonine Fishes (Salmonidae)
Authors: N Derome, L Bernatchez
Journal: Molecular Biology and Evolution (2006)

Species living in comparable habitats often display strikingly similar patterns of specialization, suggesting that natural selection can lead to predictable evolutionary changes. Elucidating the genomic basis underlying such adaptive phenotypic changes is a major goal in evolutionary biology. Increasing evidence indicates that natural selection would first modulate gene regulation during the process of population divergence. Previously, we showed that parallel phenotypic adaptations of the dwarf whitefish (Coregonus clupeaformis) ecotype to the limnetic trophic niche involved parallel transcriptional changes at the same genes involved in muscle contraction and energetic metabolism relative to the sympatric normal ecotype. Here, we tested whether the same genes are also implicated in a limnetic specialist species, the cisco (Coregonus artedi), which is the most likely competitor of dwarf whitefish. Significant upregulation was detected in cisco at the same 6 candidate genes functionally involved in modulating swimming activity, namely 5 variants of a major protein of fast muscle and 1 putative catalytic crystallin enzyme. Moreover, 3 of 5 variants and the same putative catalytic crystallin enzyme were upregulated in cisco relative to the dwarf ecotype, indicating a greater physiological potential of the former for exploiting the limnetic trophic niche. This study provides the first empirical evidence that recent, parallel phenotypic evolution toward the use of the same ecological niche occupied by a specialist competitor involved similar adaptive changes in expression at the same genes. As such, this study provides strong support to the general hypothesis that directional selection acting on gene regulation may promote rapid phenotypic divergence and ultimately speciation.
An outbreak of methicillin resistant Staphylococcus aureus infection in a rugby football team.
Authors: A R Stacey, K E Endersby, P C Chan, R R Marples
Journal: British Journal of Sports Medicine (1998)

Outbreaks of infection caused by methicillin resistant Staphylococcus aureus are common in hospitals and nursing homes, but until now none have been reported in the community. This is a report of an outbreak involving five members of a rugby football team.
Vascular endothelial growth factor in articular cartilage of healthy and osteoarthritic human knee joints
Authors: D Pfander
Journal: Annals of the Rheumatic Diseases (2001)

To determine the levels of vascular endothelial growth factor (VEGF) mRNA and protein expression in normal and osteoarthritic (OA) human articular cartilage, and whether VEGF expression alters during the progression of OA.Sections from normal and OA human knee cartilage were immunotained with a polyclonal antibody recognising VEGF. In addition, total RNA was isolated from normal and osteoarthritic human knee cartilage and analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) for VEGF mRNA expression.VEGF was found to be present in normal and OA human knee cartilage in all cartilage layers. A significant increase of VEGF immunopositive chondrocytes to up to approximately 82% was detected in severe OA cartilage compared with normal articular cartilage (approximately 56% of immunopositive chondrocytes). RT-PCR analysis showed the expression of VEGF also on the mRNA level.VEGF is expressed by articular chondrocytes in normal and OA human knee cartilage. The percentage of VEGF immunopositive chondrocytes significantly increases in late stages of the disease. The VEGF transcript levels encoding all four isoforms shows a big variability in samples from different donors, suggesting a distinct regulation of the expression of the four VEGF isoforms in normal and OA cartilage.
A serological mediator in chronic idiopathic urticaria—a clinical, immunological and histological evaluation
Authors: C.E.H. GRATTAN, T.B. WALLINGTON, R.P. WARIN, C.T.C. KENNEDY, J.W. LBRADFIELD
Journal: British Journal of Dermatology (1986)

Seven of twelve autologous sera from patients with chronic idiopathic urticaria re-injected intradermally produced a weal at the site of injection. There was no response in 19 control subjects. Patients showing a positive response had a shorter duration of disease and shorter duration of spontaneous weals, and their urticaria was less likely to be exacerbated by pressure. There was some serological evidence of circulating immune complexes in both positive and negative responders to autologous serum, but only two showed complement abnormalities. When six of the serum-positive patients were re-tested after one year, five still showed a positive response with their original stored serum, but only two, whose disease remained active, were positive when challenged with freshly drawn serum, suggesting that a serum mediator is only present when the urticaria is active. A marked neutrophil infiltrate was seen within and around small dermal blood vessels at the injection site in the majority of urticaria patients but this appearance did not correlate with weal formation. In control subjects the cellular response was mild and mainly mononuclear.
A memorable patient: A crucial statement
Authors: M. Mizrachi
Journal: BMJ (2002)

One day in early spring Mrs S, a longstanding and familiar patient in the clinic, consulted for cat bites, which had occurred that same morning. She told me (MM) that, without any warning, the cat had jumped on her, scratched her, and bitten her in the right arm. She had already visited the local health authority, which had told her that she didn't need any vaccination. She also told me that our nurse had disinfected and bandaged the wound.

She looked quite bewildered, and when I checked her I noticed that on her right arm she had several deep scratches and numerous bite wounds. It was as if the cat …
Activation of Wnt5A signaling is required for CXC chemokine ligand 12–mediated T-cell migration
Authors: Manik C. Ghosh, Gary D. Collins, Bolormaa Vandanmagsar, Kalpesh Patel, Margaret Brill, Arnell Carter, Ana Lustig, Kevin G. Becker, William W. Wood, Chineye D. Emeche, Amanda D. French, Michael P. O'Connell, Mai Xu, Ashani T. Weeraratna, Dennis D. Taub
Journal: Blood (2009)
Dissecting aneurysm and autoimmune thyroiditis.
Authors: A M Hilton, R S Whittaker
Journal: BMJ (1972)

herbal and other aperients and enemata, and I suspect they often spend long periods straining in an effort to overcome supposed constipation.Could the suggestion that the squatting posture protects leg veins be tested by observing the prevalence of venous dis- orders in communities which have adopted low-residue diets but retained the traditional squatting position (such as some affluent Asian communities)?-Iam, etc.,
Different Prognostic Impact of 24-Hour Mean Blood Pressure and Pulse Pressure on Stroke and Coronary Artery Disease in Essential Hypertension
Authors: Paolo Verdecchia, Giuseppe Schillaci, Gianpaolo Reboldi, Stanley S. Franklin, Carlo Porcellati
Journal: Circulation (2001)

Background —We tested the hypothesis that the steady and pulsatile components of blood pressure (BP) exert a different influence on coronary artery disease and stroke in subjects with hypertension. Methods and Results —We analyzed data on 2311 subjects with essential hypertension. All subjects (mean age 51 years, 47% women) underwent off-therapy 24-hour ambulatory BP monitoring. Over a follow-up period of up to 14 years (mean 4.7 years), there were 132 major cardiac events (1.20 per 100 person-years) and 105 cerebrovascular events (0.90 per 100 person-years). After adjustment for age, sex, diabetes, serum cholesterol, and cigarette smoking (all P &lt;0.01), for each 10 mm Hg increase in 24-hour pulse pressure (PP), there was an independent 35% increase in the risk of cardiac events (95% CI 17% to 55%). Twenty-four–hour mean BP was not a significant predictor of cardiac events after controlling for PP. After adjustment for age, sex, and diabetes (all P &lt;0.05), for every 10 mm Hg increase in 24-hour mean BP, the risk of cerebrovascular events increased by 42% (95% CI 19% to 69%), and 24-hour PP did not yield significance after controlling for 24-hour mean BP. Twenty-four–hour PP was also an independent predictor of fatal cardiac events, and 24-hour mean BP was an independent predictor of fatal cerebrovascular events. Conclusions —In subjects with predominantly systolic and diastolic hypertension, ambulatory mean BP and PP exert a different predictive effect on the cardiac and cerebrovascular complications. Although PP is the dominant predictor of cardiac events, mean BP is the major independent predictor of cerebrovascular events.
THE SPECIFIC SELECTION OF RECIRCULATING LYMPHOCYTES BY ANTIGEN IN NORMAL AND PREIMMUNIZED RATS
Authors: D. A. Rowley, J. L. Gowans, R. C. Atkins, W. L. Ford, Marilyn E. Smith
Journal: The Journal of Experimental Medicine (1972)

Thoracic duct lymphocytes (TDL) from normal rats will restore a primary antibody response to sheep erythrocytes (SRBC) in irradiated recipients and cause a graft-versus-host reaction in F1 hybrid rats; lymphocytes from rats immunized with either tetanus toxoid or dinitrophenylated bovine gamma globulin (DNP BGG) will generate specific antibody after cell transfer and challenge. The ability of TDL to mediate each of these responses is severely depressed by giving a single intravenous dose of the specific antigen shortly before cannulation of the thoracic duct, although the lymphocyte donors themselves respond normally. The injection of antigen does not decrease the output of lymphocytes in the thoracic duct and the effect is specific for the antigen injected. The findings are most readily accounted for by assuming that small subpopulations of specific lymphocytes are selected from the recirculating pool by antigen which has localized in lymphoid tissue. The observation that passive antibody abolishes selection by SRBC supports this interpretation. The strong selection exerted by a subcutaneous injection of SRBC in Freund's complete adjuvant, which induces delayed hypersensitivity but little early antibody, suggests that a common cell type may be involved in the induction of both delayed hypersensitivity and antibody formation. The anti-DNP antibody response generated by TDL from rats immunized with DNP BGG was abolished by a selecting injection of the homologous conjugate. The response was depressed to a smaller degree by injections of either BGG or dinitrophenylated human serum albumin, suggesting that carrier-specific (T) and hapten-specific (B) lymphocytes could be separately selected from the recirculating pool. The regional selection of recirculating lymphocytes by antigen may explain a number of phenomena in which the prior injection of antigen has been found to inhibit a subsequent immune response.
Myocardial Tension and Oxygen Uptake
Authors: SIMON RODBARD, CHRISTINE B. WILLIAMS, DAVID RODBARD, ERIK BERGLUND
Journal: Circulation Research (1964)

Data obtained in 94 tests in nine anesthetized, thoracotomized dogs were re-examined to determine relationships among oxygen uptake per minute ( qO 2 ), cardiac frequency ( F ), mean aortic pressure ( P ), stroke volume ( V ), and heart weight ( G ). Statistical analysis supports the concept that during each systole qO 2 /G is empirically related most closely to the peak mechanical tension ( T ) developed by a spherical heart, in accord with the relationship qO 2 /G-b / F = aT , in which a and b are derived constants for each heart. Peak tension is half the product of the mean pressure and the radius (estimated from the stroke volume). Myocardial oxygen uptake is viewed as developing through a mechanical positive feedback mechanism which triggers the shortening of contractile elements. The number of such elements triggered in each beat determines the peak tension, the oxygen requirement of that beat, the resulting energy release, and the work. The oxygen costs of tension increase with the size of the heart since tension must be applied throughout the entire surface of each shell of contractile elements. Mechanical efficiency varies with the square of the stroke radius; it is not directly affected by mean aortic pressure or cardiac frequency. Factors affecting the all-or-none phenomenon, mobilization of tension, myocardial efficiency, the law of the heart, myocardial oxygen uptake, and the coronary flow are discussed in light of these findings.
Nebulette knockout mice have normal cardiac function, but show Z-line widening and up-regulation of cardiac stress markers
Authors: Giuseppina Mastrototaro, Xingqun Liang, Xiaodong Li, Pierluigi Carullo, Nicoletta Piroddi, Chiara Tesi, Yusu Gu, Nancy D. Dalton, Kirk L. Peterson, Corrado Poggesi, Farah Sheikh, Ju Chen, Marie-Louise Bang
Journal: Cardiovascular Research (2015)

Nebulette is a 109 kDa modular protein localized in the sarcomeric Z-line of the heart. In vitro studies have suggested a role of nebulette in stabilizing the thin filament, and missense mutations in the nebulette gene were recently shown to be causative for dilated cardiomyopathy and endocardial fibroelastosis in human and mice. However, the role of nebulette in vivo has remained elusive. To provide insights into the function of nebulette in vivo, we generated and studied nebulette-deficient (nebl(-) (/-)) mice.Nebl(-) (/-) mice were generated by replacement of exon 1 by Cre under the control of the endogenous nebulette promoter, allowing for lineage analysis using the ROSA26 Cre reporter strain. This revealed specific expression of nebulette in the heart, consistent with in situ hybridization results. Nebl(-) (/-) mice exhibited normal cardiac function both under basal conditions and in response to transaortic constriction as assessed by echocardiography and haemodynamic analyses. Furthermore, histological, IF, and western blot analysis showed no cardiac abnormalities in nebl(-) (/-) mice up to 8 months of age. In contrast, transmission electron microscopy showed Z-line widening starting from 5 months of age, suggesting that nebulette is important for the integrity of the Z-line. Furthermore, up-regulation of cardiac stress responsive genes suggests the presence of chronic cardiac stress in nebl(-) (/-) mice.Nebulette is dispensable for normal cardiac function, although Z-line widening and up-regulation of cardiac stress markers were found in nebl(-) (/-) heart. These results suggest that the nebulette disease causing mutations have dominant gain-of-function effects.
Human T-Cell Lymphotropic Virus Type III Infection in a Cohort of Homosexual Men in New York City
Authors: Cladd E. Stevens
Journal: JAMA (1986)

Using blood samples collected since 1978, we investigated the epidemiology of human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome, in a group of 378 homosexually active men who have resided in New York City since the acquired immunodeficiency syndrome epidemic began. The anti-HTLV-III prevalence was 6.6% in sera from 1978 or 1979, and the subsequent annual incidence of seroconversion among susceptible men ranged between 5.5% and 10.6%. The highest incidences were in recent years, even though these men reported a decrease in their sexual activity during this time. These data demonstrate the continuing risk of HTLV-III infections in the homosexual population studied and emphasize the need for more effective prevention of transmission. The year during which antibody was first present was the only factor identified that was associated with altered cell-mediated immunity in antibody-positive men. Men who became antibody positive in 1981 or earlier currently had significantly lower OKT4/OKT8 ratios than did those who seroconverted more recently. Further follow-up will be necessary to establish the reasons for this association. (<i>JAMA</i>1986;255:2167-2172)
CD74 Is Expressed by Multiple Myeloma and Is a Promising Target for Therapy
Authors: Jack D. Burton, Scott Ely, Praveen K. Reddy, Rhona Stein, David V. Gold, Thomas M. Cardillo, David M. Goldenberg
Journal: Clinical Cancer Research (2004)

CD74 (HLA-DR-associated invariant chain) plays a role in antigen presentation. In addition to its expression on antigen-presenting cells, it is expressed by carcinomas of renal, lung, gastric, and thymic origin and by certain sarcomas. The restricted expression of CD74 by normal tissues and its very rapid internalization make CD74 an attractive therapeutic target for both cancer and immunologic diseases. Preclinical efficacy of anti-CD74 monoclonal antibody (mAb) therapy has been demonstrated in B-lymphoma models. Because there are few validated antigenic targets in multiple myeloma, CD74 expression was examined.CD74 expression was assessed by immunohistochemistry in bone marrow biopsies of known multiple myeloma cases. Its expression was measured by flow cytometry in multiple myeloma lines, and CD74 mRNA expression was determined by reverse transcription-PCR. In addition, the in vitro antiproliferative effect of LL1 mAb was evaluated on a CD74+ multiple myeloma cell line using a [3H]thymidine incorporation assay.CD74 expression was observed in 19 of 22 cases of multiple myeloma, with most expressing moderate to high levels in the majority of malignant plasma cells. CD74 was expressed by most multiple myeloma cell lines, as was CD74 mRNA, at levels mirroring CD74 protein. Also, unlabeled LL1 mAb mediated in vitro growth inhibition of a CD74+ multiple myeloma cell line.CD74 expression is frequent in multiple myeloma, with predominant expression by the malignant plasma cells. Because anti-CD74 mAbs internalize very rapidly and LL1 mAb has shown efficacy in B-lymphoma models, CD74 represents a novel and promising target for treatment of multiple myeloma. Therefore, LL1 mAb is well suited as a carrier of radionuclides, drugs, or toxins, and also has activity as an unlabeled mAb, thereby supporting its development for this unmet need in cancer therapy.
Eccentric calf muscle exercise produces a greater acute reduction in Achilles tendon thickness than concentric exercise
Authors: N L Grigg, S C Wearing, J E Smeathers
Journal: British Journal of Sports Medicine (2008)

To investigate the acute effects of isolated eccentric and concentric calf muscle exercise on Achilles tendon sagittal thickness.Within-subject, counterbalanced, mixed design.Institutional.11 healthy, recreationally active male adults.Participants performed an exercise protocol, which involved isolated eccentric loading of the Achilles tendon of a single limb and isolated concentric loading of the contralateral, both with the addition of 20% bodyweight.Sagittal sonograms were acquired prior to, immediately following and 3, 6, 12 and 24 h after exercise. Tendon thickness was measured 2 cm proximal to the superior aspect of the calcaneus.Both loading conditions resulted in an immediate decrease in normalised Achilles tendon thickness. Eccentric loading induced a significantly greater decrease than concentric loading despite a similar impulse (-0.21 vs -0.05, p<0.05). Post-exercise, eccentrically loaded tendons recovered exponentially, with a recovery time constant of 2.5 h. The same exponential function did not adequately model changes in tendon thickness resulting from concentric loading. Even so, recovery pathways subsequent to the 3 h time point were comparable. Regardless of the exercise protocol, full tendon thickness recovery was not observed until 24 h.Eccentric loading invokes a greater reduction in Achilles tendon thickness immediately after exercise but appears to recover fully in a similar time frame to concentric loading.
Most influenza A virus-specific memory cytotoxic T lymphocytes react with antigenic epitopes associated with internal virus determinants.
Authors: U Kees, P H Krammer
Journal: The Journal of Experimental Medicine (1984)

This paper shows that most murine (C57BL/6) influenza A virus-specific memory cytotoxic T lymphocyte (CTL) clones tested in limiting dilution did not react with the influenza A virus surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). This lysis of syngeneic target cells infected with the influenza A virus strains, Aichi (H3N2), PR8 (H1N1), or recombinant strain X31 (H3N2) indicates that most antigenic epitopes recognized are associated with internal virus determinants. X31 and PR8 share the internal, and X31 and Aichi the external, viral determinants. Extensive CTL cross-reactivity was observed in experiments with target cells infected with virus carrying internal determinants homologous with the priming virus. In contrast, when the internal viral determinants differed between the priming virus and the virus used to infect the target cells, and although HA and NA were homologous, we found almost complete CTL-specificity for the priming virus. Thus, the predominant reactivity of influenza A virus-specific CTL differs from that of anti-influenza A antibodies, which are primarily directed towards epitopes on the virus surface glycoproteins. This finding may be relevant for the role of influenza A virus-specific CTL in recurrent infections with different influenza A viruses.