tbuckley/cabot-search huggingface dataset:
Cryoballoon Versus Open Irrigated Radiofrequency Ablation in Patients With Paroxysmal Atrial Fibrillation
Authors: Armin Luik, Andrea Radzewitz, Meinhard Kieser, Marlene Walter, Peter Bramlage, Patrick Hörmann, Kerstin Schmidt, Nicolas Horn, Maria Brinkmeier-Theofanopoulou, Kevin Kunzmann, Tobias Riexinger, Gerhard Schymik, Matthias Merkel, Claus Schmitt
Journal: Circulation (2015)

There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency (RF) and cryoballoon catheter (CB) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation.In a prospective, noninferiority study, 315 patients were randomly assigned to RF (n=159) or CB (n=156) ablation. The primary end point was freedom from atrial arrhythmia with absence of persistent complications. Patients were largely comparable between groups with more vascular disease in the RF group (8.2% versus 2.6% for CB; P=0.028). The primary end point at 12 months was achieved by 70.7% with RF and 73.6% with CB (multiple procedure success), including 31 redo procedures in each group (19.5% of RF versus 19.9% of CB; P=0.933). For the intention-to-treat population, noninferiority of CB was revealed for the predefined inferiority margin (risk difference, 0.029; 95% confidence interval, -0.074 to 0.132; P<0.001). Rates at 6 months were 63.1% and 64.1% for the RF and CB groups (single procedure success), and noninferiority was confirmed (risk difference, 0.010; 95% confidence interval, -0.097 to 0.116; P=0.002). Periprocedural complications for the index procedure were more frequent in the CB group (5.0% RF, 12.2% CB; P=0.022) with a significant difference in phrenic nerve palsies (0% RF, 5.8% CB; P=0.002).This large, prospective, randomized, controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00774566.
Final Version of 2009 AJCC Melanoma Staging and Classification
Authors: Charles M. Balch, Jeffrey E. Gershenwald, Seng-jaw Soong, John F. Thompson, Michael B. Atkins, David R. Byrd, Antonio C. Buzaid, Alistair J. Cochran, Daniel G. Coit, Shouluan Ding, Alexander M. Eggermont, Keith T. Flaherty, Phyllis A. Gimotty, John M. Kirkwood, Kelly M. McMasters, Martin C. Mihm, Donald L. Morton, Merrick I. Ross, Arthur J. Sober, Vernon K. Sondak
Journal: Journal of Clinical Oncology (2009)

To revise the staging system for cutaneous melanoma on the basis of data from an expanded American Joint Committee on Cancer (AJCC) Melanoma Staging Database.The melanoma staging recommendations were made on the basis of a multivariate analysis of 30,946 patients with stages I, II, and III melanoma and 7,972 patients with stage IV melanoma to revise and clarify TNM classifications and stage grouping criteria.Findings and new definitions include the following: (1) in patients with localized melanoma, tumor thickness, mitotic rate (histologically defined as mitoses/mm(2)), and ulceration were the most dominant prognostic factors. (2) Mitotic rate replaces level of invasion as a primary criterion for defining T1b melanomas. (3) Among the 3,307 patients with regional metastases, components that defined the N category were the number of metastatic nodes, tumor burden, and ulceration of the primary melanoma. (4) For staging purposes, all patients with microscopic nodal metastases, regardless of extent of tumor burden, are classified as stage III. Micrometastases detected by immunohistochemistry are specifically included. (5) On the basis of a multivariate analysis of patients with distant metastases, the two dominant components in defining the M category continue to be the site of distant metastases (nonvisceral v lung v all other visceral metastatic sites) and an elevated serum lactate dehydrogenase level.Using an evidence-based approach, revisions to the AJCC melanoma staging system have been made that reflect our improved understanding of this disease. These revisions will be formally incorporated into the seventh edition (2009) of the AJCC Cancer Staging Manual and implemented by early 2010.
Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn's disease
Authors: A Di Sabatino
Journal: Gut (2003)

To verify whether targeting defective mucosal T cell death underlies the sustained therapeutic benefit of infliximab in Crohn's disease, we explored its in vivo proapoptotic effect after 10 weeks of treatment, and its in vitro killing activity on lamina propria T cells (LPT) and peripheral blood T cells (PBT), both isolated from Crohn's disease patients.Endoscopic intestinal biopsies were collected from 10 Crohn's disease patients (six steroid refractory and four fistulising) before and after three consecutive infusions of infliximab, administered at week 0, 2, and 6 in a single intravenous dose (5 mg/kg), and from 10 subjects who proved to have functional diarrhoea. Apoptosis was determined in vivo by TUNEL assay, and in vitro by fluorescein isothiocyanate-annexin V/propidium iodide staining on LPT and PBT from Crohn's disease patients cultured with infliximab. The effect of the broad caspase inhibitor Z-VAD-FMK and the neutralising anti-Fas antibody ZB4 was tested in vitro on LPT and PBT treated with infliximab. Caspase-3 activity was determined by immunoblotting.In Crohn's disease patients, infliximab treatment induced a sustained LPT apoptosis, still evident four weeks after the last infusion. In vitro infliximab induced death of LPT from Crohn's disease patients occurred via apoptosis rather than necrosis. LPT showed a higher susceptibility to infliximab induced apoptosis than PBT in Crohn's disease patients. The signalling pathway underlying the restoration of infliximab induced LPT apoptosis occurred via the caspase pathway but not Fas-Fas ligand interaction in Crohn's disease.These findings demonstrate that apoptosis is the major mechanism by which infliximab exerts its killing activity on LPT in Crohn's disease. The sustained LPT proapoptotic action of infliximab, which extends far beyond its circulating half life, may be responsible for the sustained remission induced in Crohn's disease patients by infliximab retreatment.
Prognosis in Therapy-Related Acute Myeloid Leukemia and Impact of Karyotype
Authors: Wolfgang Kern, Torsten Haferlach, Susanne Schnittger, Wolfgang Hiddemann, Claudia Schoch
Journal: Journal of Clinical Oncology (2004)

TO THE EDITOR: The treatment of patients with therapyrelated acute myeloid leukemia (t-AML) has been a matter of debate because of the unfavorable prognosis in these cases. This has led to the suggestion to treat patients by intensive standard therapies only in case of an available allogeneic stem cell donor. In fact, several large series indicated an overall dismal outcome in patients with t-AML, 1-4 backing up the general reluctance to intensively treat these patients. The results reported in a recent contribution by
Role of Crosstalk Between Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathways in Artery–Vein Specification
Authors: Charles C. Hong, Tsutomu Kume, Randall T. Peterson
Journal: Circulation Research (2008)

Functional and structural differences between arteries and veins lie at the core of the circulatory system, both in health and disease. Therefore, understanding how artery and vein cell identities are established is a fundamental biological challenge with significant clinical implications. Molecular genetic studies in zebrafish and other vertebrates in the past decade have begun to reveal in detail the complex network of molecular pathways that specify artery and vein cell fates during embryonic development. Recently, a chemical genetic approach has revealed evidence that artery–vein specification is governed by cross talk between phosphoinositide 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in artery–vein specification. We discuss recent findings on the signaling pathways involved in artery–vein specification during zebrafish development and compare and contrast these results to those from mammalian systems. It is anticipated that the complementary approaches of genetics and chemical biology, involving a variety of model organisms and systems, will lead to a better understanding of artery–vein specification and possibly to novel therapeutic approaches to treat vascular diseases.
Malignant melanoma; a correlation between histological features and tumour-directed cell-mediated immunity
Authors: Rona M. MacKie, A.J. Cochran, R.M. Grant, C.E. Ross, D.E. Hoyle
Journal: British Journal of Dermatology (1974)

Journal Article Malignant melanoma; a correlation between histological features and tumour‐directed cell‐mediated immunity Get access Rona M. MacKie, Rona M. MacKie University Departments of Dermatology and Pathology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar A.J. Cochran, A.J. Cochran University Departments of Dermatology and Pathology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar R.M. Grant, R.M. Grant University Departments of Dermatology and Pathology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar C.E. Ross, C.E. Ross University Departments of Dermatology and Pathology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar D.E. Hoyle D.E. Hoyle University Departments of Dermatology and Pathology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Page 24, https://doi.org/10.1111/j.1365-2133.1974.tb12490.x Published: 01 July 1974
ABT-737 Induces Apoptosis in Mantle Cell Lymphoma Cells with a Bcl-2<i>high</i>/Mcl-1<i>low</i> Profile and Synergizes with Other Antineoplastic Agents
Authors: Cyrille Touzeau, Christelle Dousset, Linda Bodet, Patricia Gomez-Bougie, Stéphanie Bonnaud, Anne Moreau, Philippe Moreau, Catherine Pellat-Deceunynck, Martine Amiot, Steven Le Gouill
Journal: Clinical Cancer Research (2011)

Mantle cell lymphoma (MCL) is considered to be incurable. ABT-737 is a BH3 mimetic that targets Bcl-2, which is overexpressed in MCL and implicated in drug resistance. The present work investigated the antitumor effect of ABT-737.Six MCL cell lines and primary MCL cells (n = 13) were used. Sensitivity to ABT-737 was assessed, and expression levels of Bcl-2 and Mcl-1 were analyzed. Finally, ABT-737 was combined with other cytotoxic agents to promote tailored therapy.MINO and GRANTA-519 cell lines were highly sensitive to ABT-737 [the median lethal dose (LD₅₀) = 20 and 80 nmol/L, respectively], whereas other cell lines were resistant. In primary MCL cells, 46% of patients' samples were sensitive to ABT-737. The analysis of protein expression levels revealed that both sensitive cell lines and primary MCL cells could be characterized by a Bcl-2(high)/Mcl-1(low) profile, whereas resistant MCL cells contained high levels of Mcl-1. ABT-737 induced a rapid disruption of both Bcl-2/Bax and Bcl-2/Bik complexes. In addition, silencing of Mcl-1 by siRNA sensitized MCL cell lines to ABT-737. Similarly, flavopiridol, which induces Mcl-1 downregulation, in combination with ABT-737 led to a synergistic anti-MCL effect in ABT-737-resistant cell lines. This synergy was also observed when ABT-737 was combined with either bortezomib or cytarabine.The present work shows that ABT-737 induces strong apoptosis in MCL cells expressing a Bcl-2(high)/Mcl-1(low) profile. In ABT-737-resistant MCL cells, downregulation of Mcl-1 overcomes Mcl-1-induced resistance and synergizes ABT-737 effects. Our results strongly support the use of ABT-737 according to the Bcl-2/Mcl-1 tumor cell profiles in the treatment of MCL.
Natural history of seminiferous tubule degeneration in Klinefelter syndrome
Authors: Lise Aksglæde, Anne M. Wikström, Ewa Rajpert-De Meyts, Leo Dunkel, Niels E. Skakkebæk, Anders Juul
Journal: Human Reproduction Update (2005)

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatically at the time of puberty with complete hyalinization of the seminiferous tubules, although a few tubules with spermatogenesis may be present in adult life. Activation of the pituitary-gonadal axis at 3 months of age is seen in Klinefelter boys similar to healthy boys. However, the level of testosterone in Klinefelter boys is significantly lower than in controls. After this ‘minipuberty’, the hormone levels decline to normal prepubertal levels until puberty. In puberty, an initial rise in testosterone, inhibin B, LH and FSH occurs in Klinefelter boys. However, the rise in testosterone levels off and ends at a low-normal level in young adults. Likewise, serum concentration of inhibin B exhibits a dramatic decline to a low, often undetectable level, concomitantly with a rise in FSH, reflecting the degeneration of the seminiferous tubules. Many hypotheses about the underlying mechanism of the depletion of the germ cells in Klinefelter males have been reported and include insufficient supranumerary X-chromosome inactivation, Leydig cell insufficiency and disturbed regulation of apoptosis of Sertoli and Leydig cells. However, at present, the exact mechanism remains unclear. In this article, we summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome.
Can oestrogen influence skeletal muscle damage, inflammation, and repair?
Authors: P M Tiidus
Journal: British Journal of Sports Medicine (2005)

More research is needed before the use of oestrogen can be recommended for muscle damage

Oestrogen may affect muscle damage and inflammation, but the physiological significance of this, particularly potential effects on muscle repair and recovery in humans, and the mechanisms of its actions are as of yet unknown.

Over the last decade, evidence has accumulated that oestrogen may act to diminish skeletal muscle damage and inflammatory responses after unaccustomed exercise or other damaging insult. These prophylactic effects are similar to the effect of oestrogen in diminishing damage and inflammation in other tissues such as cardiac muscle, liver, and nervous tissue.1–3 What is not clear is the physiological significance of this effect of oestrogen and whether it is physiologically meaningful or results in significantly differential responses in skeletal muscle after over-exertion in humans.4 The mechanisms by which oestrogen exerts its effect on skeletal muscle responses to damaging exercise, and whether its influence extends to differential rates of muscle repair and recovery also require further investigation.

The primary practical implication of a role for oestrogen in post-exercise muscle damage, recovery, and repair mechanisms is likely to be for postmenopausal women who have reduced oestrogen concentrations, and thus may be more susceptible to muscle damage and slower recovery than premenopausal women. Sex differences in susceptibility to muscle damage are also of interest. This overview will briefly examine these questions and summarise the current evidence for oestrogenic influence on skeletal muscle damage, inflammation, and repair. Considerable research is still needed before any conclusions can be reached about the physiological significance of these effects of oestrogen in humans.

Oestrogen is a strong antioxidant and a membrane stabiliser.5,6 We have proposed that these properties, which are unique to oestrogen as a steroid hormone, may account for some of its mitigating …
THE SUPRARENAL CORTEX AND BLOOD CHOLESTEROL IN DEMENTIA PRÆCOX
Authors: Charles E. Gibbs
Journal: American Journal of Psychiatry (1925)

That some disturbance of lipoid metabolism may occur in dementia præcox and may involve the suprarenal cortex, has been suggested by the following: (a) Previous observations on the sexual development and behavior of these patients. (b) The evidence that the suprarenal cortex is involved in these disturbances of sexual development. (c) The evidence that the suprarenal has both an embryologic and functional relation to the gonads on the one hand and to the brain on the other. (d) Substances of a lipoid nature play an essential part in the functional metabolism of each of these organs. (e) The female sex hormone and the vitamine for reproduction are both of a lipoid nature. (f) The low basal metabolic rate frequently observed in dementia præcox suggests an involvement of the suprarenal. The evidence for these considerations is reviewed. The significance of cholesterol is discussed. Blood cholesterol determinations, by the Bloor method, are reported on 40 patients with dementia præcox and on 27 with other psychoses. In 16 males with dementia præcox classed as deteriorated the average for the blood cholesterol was 118.3 mg. per 100 c. c., while for 11 similar females it was 144.6 mg. In 5 males recently admitted and selected as representing the acute excited phase of dementia præcox, the average was 104.6 mg. In 6 males without deterioration it was 176.6 mg. In 6 males with other functional psychoses not in acute phase 149.2 mg. In 13 males with general paralysis 167.3 mg. In 6 females classed as manicdepressive 162.7 mg. Other possible causes of a low blood cholesterol were eliminated. Four patients were given extra diet including 4 eggs daily with no persistent increase in the blood cholesterol. Two of them were also fed 1 gm. cholesterol daily with the same result. The results seem to show that in many patients with dementia præcox the blood cholesterol is unusually low, and that it may be more directly correlated with the psychosis and with sex than with any other recognized factors. That some correlation with sex seems to exist is considered significant and in accord with the considerations which suggested the work.
The interactive-alignment model: Developments and refinements
Authors: Martin J. Pickering, Simon Garrod
Journal: Behavioral and Brain Sciences (2004)

The interactive-alignment model of dialogue provides an account of dialogue at the level of explanation normally associated with cognitive psychology. We develop our claim that interlocutors align their mental models via priming at many levels of linguistic representation, explicate our notion of automaticity, defend the minimal role of "other modeling," and discuss the relationship between monologue and dialogue. The account can be applied to social and developmental psychology, and would benefit from computational modeling.
Once-daily fluticasone furoate alone or combined with vilanterol in persistent asthma
Authors: Paul M. O’Byrne, Eugene R. Bleecker, Eric D. Bateman, William W. Busse, Ashley Woodcock, Richard Forth, William T. Toler, Loretta Jacques, Jan Lötvall
Journal: European Respiratory Journal (2013)

The inhaled corticosteroid fluticasone furoate (FF) and the long-acting β 2 agonist vilanterol (VI) are in development as a combined once-daily therapy for asthma and chronic obstructive pulmonary disease. Our study objectives were to compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily fluticasone propionate (FP) in patients aged ≥12 years with moderate-to-severe persistent asthma. Patients (n=586) received FF/VI 200/25 μg or FF 200 μg once-daily (evening dosing), or FP 500 μg twice-daily for 24 weeks. Co-primary end-points were change from baseline in trough forced expiratory volume in 1 s (FEV 1 ) weighted mean (wm) 0–24 h serial FEV 1 . Secondary end-points included change from baseline in percentage of rescue-free 24-h periods, percentage of symptom-free 24-h periods and total Asthma Quality of Life Questionnaire (AQLQ). Safety assessments included adverse events, 24-h urinary cortisol excretion, vital signs and ECG. FF/VI significantly improved trough FEV 1 and wmFEV 1 versus FF and FP. Significantly more rescue-free and symptom-free 24-h periods were reported with FF/VI versus FF. Treatment differences for AQLQ were not significant. Incidence of adverse events was similar across groups. No clinically significant differences were seen for 24-h urinary cortisol excretion, vital signs or ECG. FF/VI resulted in statistically greater improvements in lung function and symptomatic end-points versus FF, and was well tolerated in this asthma population.
Distribution of integrin subunits in human diabetic kidneys.
Authors: D K Jin, A J Fish, E A Wayner, M Mauer, S Setty, E Tsilibary, Y Kim
Journal: Journal of the American Society of Nephrology (1996)

Integrins are cell-surface protein receptors that participate in cell adhesion to multiple extracellular matrix ligands, and consist of alpha and beta chain heterodimers. This study examined altered integrin distribution in diabetic nephropathy by investigating 12 human diabetic kidney biopsies, which were compared with normal human kidney. Diabetic nephropathy is characterized by mesangial expansion and progressive thickening of the glomerular basement membrane. Based on morphometric studies of mesangial expansion, diabetic nephropathy was determined to be moderate or severe. Three different patterns (P) of altered intensity of integrin staining were observed. In the mesangial integrin P, the intensity of integrin subunit staining of mesangial cells (alpha 1, alpha 2, alpha 3, beta 1, alpha V, alpha V beta 5) was increased in moderate diabetic nephropathy and further increased in severe diabetic nephropathy. In the epithelial integrin P, integrin subunits localized to epithelial cells (alpha V, beta 3, alpha V beta 3, alpha V beta 5) were increased to the same extent in moderate and severe diabetic nephropathy. In the endothelial integrin P, integrin subunits localized to endothelial cells (alpha 3, alpha 5, alpha 6, beta 1) were increased in moderate diabetic nephropathy but returned to normal kidney staining intensity in severe diabetic nephropathy. From these observations, it was concluded that there is significant alteration in the expression of integrin subunits in diabetic nephropathy that is related to the severity of diabetic mesangial expansion. Additionally, the spectrum of integrin subunit alteration appears to be unique to individual glomerular cell types. Given the role of integrins in cell-surface interactions with extracellular matrix components, abnormalities in the expression of these molecules may be important in the pathogenesis of diabetic nephropathy.