tbuckley/cabot-search huggingface dataset:
Estimated Risk of Radiation-Induced Breast Cancer From Mammographic Screening for Young BRCA Mutation Carriers
Authors: A. Berrington de Gonzalez, C. D. Berg, K. Visvanathan, M. Robson
Journal: JNCI Journal of the National Cancer Institute (2009)

BRCA mutation carriers are recommended to start mammographic screening for breast cancer as early as age 25–30 years. We used an excess relative risk model (based on a pooled analysis of three cohorts with 7600 subjects who received radiation exposure) to estimate the lifetime risk of radiation-induced breast cancer from five annual mammographic screenings in young (<40 years) BRCA mutation carriers. We then estimated the reduction in breast cancer mortality required to outweigh the radiation risk. Breast cancer rates for mutation carriers were based on a pooled analysis of 22 pedigree studies with 8139 subjects. For BRCA1 mutation carriers, the estimated lifetime risk of radiation-induced breast cancer mortality per 10 000 women resulting from annual mammography was 26 (95% confidence interval [CI] = 14 to 49) for screening at age 25–29 years, 20 (95% CI = 11 to 39) for screening at age 30–34 years, and 13 (95% CI = 7 to 23) for screening at age 35–39 years. To outweigh these risks, screening would have to reduce breast cancer mortality by 51% (95% CI = 27% to 96%) at age 25–29 years, by 12% (95% CI = 6% to 23%) at age 30–34 years, and by 4% (95% CI = 2% to 7%) at age 35–39 years; estimates were similar for BRCA2 mutation carriers. If we assume that the mortality reduction from mammography is 15%–25% or less for young women, these results suggest that there would be no net benefit from annual mammographic screening of BRCA mutation carriers at age 25–29 years; the net benefit would be zero or small at age 30–34 years, but there should be some net benefit at age 35 or older. These results depend on a number of assumptions due to the absence of empiric data. The impact of varying these assumptions was therefore examined.
Hyperglycemia Predicts Persistently Lower Muscle Strength With Aging
Authors: Rita Rastogi Kalyani, E. Jeffrey Metter, Josephine Egan, Sherita H. Golden, Luigi Ferrucci
Journal: Diabetes Care (2014)

OBJECTIVE Persons with diabetes have accelerated muscle loss compared with their counterparts. The relationship of hyperglycemia per se to declines in muscle function has not been explored yet has implications for developing appropriate intervention strategies to prevent muscle loss. RESEARCH DESIGN AND METHODS We examined 984 participants aged 25–96 years in the Baltimore Longitudinal Study of Aging (2003–2011) with HbA1c, knee extensor strength (isokinetic dynamometer), and lean body mass (DEXA) measured at baseline. Participants had repeated measurements up to 7.5 years later. Muscle quality was defined as knee extensor strength/leg lean mass. Participants were categorized by HbA1c quartile (&amp;lt;5.5, 5.5–5.79, 5.8–6.09, and ≥6.1% or &amp;lt;37, 37–40, 40–43, and ≥43 mmol/mol). Mixed-effects regression models were used to examine the regression of muscle outcomes on HbA1c. RESULTS Muscle strength and quality were significantly lower across HbA1c quartiles (both P &amp;lt; 0.001), without differences in muscle mass at baseline. Comparing highest versus lowest HbA1c quartiles and adjusting for age, race, sex, weight, and height, strength was significantly lower (−4.70 ± 2.30 N · m; P value trend = 0.02) and results were unchanged after adjustment for physical activity (P value trend = 0.045) but of borderline significance after additional adjustment for peripheral neuropathy (P value trend = 0.05). Adjusting for demographics, muscle quality was significantly lower (−0.32 ± 0.15 N · m/kg; P value trend = 0.02) in the highest versus lowest HbA1c quartiles, but differences were attenuated after adjusting for weight and height (−0.25 ± 0.15 N · m/kg; P value trend = 0.07). Muscle mass measures were similar across HbA1c quartiles. CONCLUSIONS Hyperglycemia is associated with persistently lower muscle strength with aging, but this effect may be mediated, at least in part, by peripheral neuropathy. Future studies should explore if better glycemic control can preserve muscle function in diabetes.
Differential expression patterns of recombination-activating genes in individual mature B cells in juvenile idiopathic arthritis
Authors: C Faber
Journal: Annals of the Rheumatic Diseases (2006)

Re-expression of the recombination-activating genes (RAG) in peripheral B cells may be relevant in the development of autoreactive antibodies in autoimmune diseases. The presence of antinuclear antibodies (ANA) as a hallmark of oligoarticular juvenile idiopathic arthritis (o-JIA, early-onset type) indicates a breakdown in immunological tolerance.To examine the expression of RAG genes in peripheral blood mature B lymphocytes in patients with o-JIA.777 memory B cells from peripheral blood, CD19+ CD27+ CD5+ or CD19+ CD27+ CD5-, isolated from three ANA+ children with o-JIA and three healthy age-matched children, were examined for the expression of RAG1 and RAG2 mRNA. mRNA transcripts of activation-induced cytidine deaminase and immunoglobulin G were searched to further determine their developmental stage.mRNA was present for any of the two RAG genes in the B cells of children with JIA and controls. However, the predominance of RAG1 or RAG2 was different. A significantly decreased frequency of RAG2-expressing memory B cells in both CD5+ and CD5- populations was noted in children with JIA (p<0.001), whereas the number of RAG1-expressing B cells was slightly increased. The coordinate expression of both the RAG genes was a rare event, similar in the CD5+ populations (1% in controls, 2% in children with JIA), but different among the CD5- compartments (5% v 0%; p<0.01).These results argue for a reduced coordinate RAG expression in the peripheral CD5- memory B cells of patients with o-JIA. Thus, it was hypothesised that impaired receptor revision contributes to autoimmune pathogenesis in JIA.
Protease-Activated Receptor-1 Contributes to Cardiac Remodeling and Hypertrophy
Authors: Rafal Pawlinski, Michael Tencati, Craig R. Hampton, Tetsuro Shishido, Tara A. Bullard, Liam M. Casey, Patricia Andrade-Gordon, Matthias Kotzsch, Denise Spring, Thomas Luther, Jun-ichi Abe, Timothy H. Pohlman, Edward D. Verrier, Burns C. Blaxall, Nigel Mackman
Journal: Circulation (2007)

Background— Protease-activated receptor-1 (PAR-1) is the high-affinity receptor for the coagulation protease thrombin. It is expressed by a variety of cell types in the heart, including cardiomyocytes and cardiac fibroblasts. We have shown that tissue factor (TF) and thrombin contribute to infarct size after cardiac ischemia-reperfusion (I/R) injury. Moreover, in vitro studies have shown that PAR-1 signaling induces hypertrophy of cardiomyocytes and proliferation of cardiac fibroblasts. The purpose of the present study was to investigate the role of PAR-1 in infarction, cardiac remodeling, and hypertrophy after I/R injury. In addition, we analyzed the effect of overexpression of PAR-1 on cardiomyocytes. Methods and Results— We found that PAR-1 deficiency reduced dilation of the left ventricle and reduced impairment of left ventricular function 2 weeks after I/R injury. Activation of ERK1/2 was increased in injured PAR-1 −/− mice compared with wild-type mice; however, PAR-1 deficiency did not affect infarct size. Cardiomyocyte-specific overexpression of PAR-1 in mice induced eccentric hypertrophy (increased left ventricular dimension and normal left ventricular wall thickness) and dilated cardiomyopathy. Deletion of the TF gene in cardiomyocytes reduced the eccentric hypertrophy in mice overexpressing PAR-1. Conclusions— Our results demonstrate that PAR-1 contributes to cardiac remodeling and hypertrophy. Moreover, overexpression of PAR-1 on cardiomyocytes induced eccentric hypertrophy. Inhibition of PAR-1 after myocardial infarction may represent a novel therapy to reduce hypertrophy and heart failure in humans.
Intestinal expression of SHIP in inflammatory bowel diseases
Authors: Ingrid Arijs, Gert De Hertogh, Bart Lemmens, Jan Van der Goten, Séverine Vermeire, Frans Schuit, Paul Rutgeerts
Journal: Gut (2011)

We read with interest the recent paper in Gut by Kerr and colleagues1 describing a new mouse model of Crohn's disease (CD)-like ileitis caused by Src homology 2 domain-containing inositol-5′-phosphatase (SHIP) deficiency. The human SHIP protein, encoded by the INPP5D gene on chromosome 2q37.1, is an enzyme that hydrolyses the 5′-phosphate of phosphatidylinositol-(3,4,5)-trisphosphate so that it counteracts stimulatory pathways such as phosphoinositide 3-kinase. The enzyme is regulated by tyrosine phosphorylation in haematopoietic cells following activation of surface receptors for various cytokines or in response to B cell antigen receptor cross-linking or T cell activation. In previous studies, the authors showed that SHIP signalling plays …
Large-scale exploration of growth inhibition caused by overexpression of genomic fragments in Saccharomyces cerevisiae.
Authors: Jeanne Boyer, Gwenaël Badis, Cécile Fairhead, Emmanuel Talla, Florence Hantraye, Emmanuelle Fabre, Gilles Fischer, Christophe Hennequin, Romain Koszul, Ingrid Lafontaine, Odile Ozier-Kalogeropoulos, Miria Ricchetti, Guy-Franck Richard, Agnès Thierry, Bernard Dujon
Journal: Genome biology (2004)

Abstract We have screened the genome of Saccharomyces cerevisiae for fragments that confer a growth-retardation phenotype when overexpressed in a multicopy plasmid with a tetracycline-regulatable (Tet-off) promoter. We selected 714 such fragments with a mean size of 700 base-pairs out of around 84,000 clones tested. These include 493 in-frame open reading frame fragments corresponding to 454 distinct genes (of which 91 are of unknown function), and 162 out-of-frame, antisense and intergenic genomic fragments, representing the largest collection of toxic inserts published so far in yeast.
The Superiority of Steroid-occlusive Therapy for Bromoderma.
Authors: R. M. Caplan, R. R. Sullivan
Journal: British Journal of Dermatology (1964)

Journal Article The Superiority of Steroid‐occlusive Therapy for Bromoderma. Get access R. M. Caplan, R. M. Caplan Iowa City Search for other works by this author on: Oxford Academic Google Scholar R. R. Sullivan R. R. Sullivan Iowa City Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 3, 1 March 1964, Pages 146–147, https://doi.org/10.1111/j.1365-2133.1964.tb14494.x Published: 01 March 1964
H <sub>2</sub> O <sub>2</sub> -Induced Dilation in Human Coronary Arterioles: Role of Protein Kinase G Dimerization and Large-Conductance Ca <sup>2+</sup> -Activated K <sup>+</sup> Channel Activation
Authors: David X. Zhang, Lena Borbouse, Debebe Gebremedhin, Suelhem A. Mendoza, Natalya S. Zinkevich, Rongshan Li, David D. Gutterman
Journal: Circulation Research (2011)

Hydrogen peroxide (H(2)O(2)) serves as a key endothelium-derived hyperpolarizing factor mediating flow-induced dilation in human coronary arterioles (HCAs). The precise mechanisms by which H(2)O(2) elicits smooth muscle hyperpolarization are not well understood. An important mode of action of H(2)O(2) involves the oxidation of cysteine residues in its target proteins, including protein kinase G (PKG)-Iα, thereby modulating their activities.Here we hypothesize that H(2)O(2) dilates HCAs through direct oxidation and activation of PKG-Iα leading to the opening of the large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel and subsequent smooth muscle hyperpolarization.Flow and H(2)O(2) induced pressure gradient/concentration-dependent vasodilation in isolated endothelium-intact and -denuded HCAs, respectively. The dilation was largely abolished by iberiotoxin, a BK(Ca) channel blocker. The PKG inhibitor Rp-8-Br-PET-cGMP also markedly inhibited flow- and H(2)O(2)-induced dilation, whereas the soluble guanylate cyclase inhibitor ODQ had no effect. Treatment of coronary smooth muscle cells (SMCs) with H(2)O(2) elicited dose-dependent, reversible dimerization of PKG-Iα, and induced its translocation to the plasma membrane. Patch-clamp analysis identified a paxilline-sensitive single-channel K(+) current with a unitary conductance of 246-pS in freshly isolated coronary SMCs. Addition of H(2)O(2) into the bath solution significantly increased the probability of BK(Ca) single-channel openings recorded from cell-attached patches, an effect that was blocked by the PKG-Iα inhibitor DT-2. H(2)O(2) exhibited an attenuated stimulatory effect on BK(Ca) channel open probability in inside-out membrane patches.H(2)O(2) dilates HCAs through a novel mechanism involving protein dimerization and activation of PKG-Iα and subsequent opening of smooth muscle BK(Ca) channels.
Inflammatory synovial tissue mononuclear cells release leucocyte migration inhibition factor in antigen- and mitogen-free cultures.
Authors: T Egeland, O.J Mellbye, J.A Pahle
Journal: Annals of the Rheumatic Diseases (1981)

The presence of leucocyte migration inhibition factor (LIF) in supernatants from apparently antigen- and mitogen-free cultures of mononuclear cells (MNC) was studied. MNC were eluted from inflamed synovial tissue or isolated from blood. Untreated supernatants, supernatants in which any LIF had been inactivated, and culture medium were compared in their ability to affect the migration of homologous polymorphonuclear leucocytes. LIF was released by synovial tissue MNC from all of the 9 patients studied, consisting of 5 patients with rheumatoid arthritis, 2 with psoriatic arthropathy, and 2 with juvenile rheumatoid arthritis. Blood MNC of the patients and of 8 healthy blood donors did not release LIF. When synovial tissue MNC supernatants from 2 patients were examined, LIF activity increased as time of incubation was extended. In at least 2 synovial tissue MNC supernatants in which LIF had been inactivated a migration enhancement activity was revealed.
A Cohort Study of Summary Reports of Controlled Trials
Authors: lain Chalmers
Journal: JAMA (1990)

Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly.
Factors affecting epicardial dispersion of repolarization: a mapping study in the isolated porcine heart
Authors: D Lacroix
Journal: Cardiovascular Research (1999)

Objective: Non-uniform drug-induced prolongation of repolarization predominating in the midmyocardial (M) cell layers has been shown to be responsible for perpetuation of reentry, giving rise to torsade de pointes. However, the absence of M cells in immature animals, especially the pig, suggests other possible underlying mechanisms. We sought to examine, in this species, the effects of predisposing factors to torsade de pointes on the dispersion of epicardial repolarization and their contribution to arrhythmogenesis. Methods: Computerized mapping of repolarization and activation was conducted on the epicardial surface in 29 Langendorff-perfused hearts of eight-week-old pigs. Activation–recovery intervals were measured simultaneously from 128 unipolar electrograms. Results: Baseline iso-interval maps were dipolar (41%) or multipolar (59%). Dispersion of repolarization was reverse frequency-dependent but was unaffected by lowering [K+]o. dl-Sotalol (0.1 mmol/l) reinforced local gradients and thus increased epicardial dispersion, whereas intramural recordings did not demonstrate any predominant effect in midmyocardial layers. Phenylephrine (1 μmol/l) notably augmented dl-sotalol effects. After [Mg++]o lowering, although dispersion was not significantly increased, dl-sotalol was associated with the spontaneous occurrence of polymorphic ventricular tachycardia in seven out of nine experiments. When maps of repolarization of escape beats were compared with activation maps of first arrhythmic beats, an arc of functional dissociation was observed in the vicinity of a steep gradient of repolarization in two out of nine tachycardias. Conclusion: Epicardial dispersion of repolarization is increased by slow rates, dl-sotalol and phenylephrine but is not the only requirement for initiation of polymorphic ventricular tachycardia. In combination with other factors, it helps continuation of the arrhythmia in this model.
International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides
Authors: Michelle L. Halls, Ross A. D. Bathgate, Steve W. Sutton, Thomas B. Dschietzig, Roger J. Summers
Journal: Pharmacological Reviews (2015)

Relaxin, insulin-like peptide 3 (INSL3), relaxin-3, and INSL5 are the cognate ligands for the relaxin family peptide (RXFP) receptors 1–4, respectively. RXFP1 activates pleiotropic signaling pathways including the signalosome protein complex that facilitates high-sensitivity signaling; coupling to G<i>α</i><sub>s</sub>, G<i>α</i><sub>i</sub>, and G<i>α</i><sub>o</sub> proteins; interaction with glucocorticoid receptors; and the formation of hetero-oligomers with distinctive pharmacological properties. In addition to relaxin-related ligands, RXFP1 is activated by Clq-tumor necrosis factor-related protein 8 and by small-molecular-weight agonists, such as ML290 [2-isopropoxy-<i>N</i>-(2-(3-(trifluoromethylsulfonyl)phenylcarbamoyl)phenyl)benzamide], that act allosterically. RXFP2 activates only the G<i>α</i><sub>s</sub>- and G<i>α</i><sub>o</sub>-coupled pathways. Relaxin-3 is primarily a neuropeptide, and its cognate receptor RXFP3 is a target for the treatment of depression, anxiety, and autism. A variety of peptide agonists, antagonists, biased agonists, and an allosteric modulator target RXFP3. Both RXFP3 and the related RXFP4 couple to G<i>α</i><sub>i</sub>/G<i>α</i><sub>o</sub> proteins. INSL5 has the properties of an incretin; it is secreted from the gut and is orexigenic. The expression of RXFP4 in gut, adipose tissue, and <i>β</i>-islets together with compromised glucose tolerance in INSL5 or RXFP4 knockout mice suggests a metabolic role. This review focuses on the many advances in our understanding of RXFP receptors in the last 5 years, their signal transduction mechanisms, the development of novel compounds that target RXFP1–4, the challenges facing the field, and current prospects for new therapeutics.
The High DSS1 Expression Involved in BRCA2 Stability is a Marker for Breast Cancer of Poor Prognosis
Authors: A. Rezano, K. Kuwahara, M. Yamamoto-Ibusuki, M. Kitabatake, P. Moolthiya, T. Suda, S. Tone, Y. Yamamoto, H. Iwase, N. Sakaguchi
Journal: Annals of Oncology (2014)
Mechanisms of ENaC Regulation and Clinical Implications
Authors: Vivek Bhalla, Kenneth R. Hallows
Journal: Journal of the American Society of Nephrology (2008)

Frontal variant frontotemporal dementia (fvFTD) can present with a range of social and cognitive impairments. Complicating this clinical picture is a group of non-progressive or ‘phenocopy’ patients. We present a patient and his father with very slowly progressive fvFTD over decades. Stable MRI and positron emission tomography (PET) imaging abnormalities were present in the presenting patient, with serial neuropsychological assessments that showed no significant change over 15 years. His father also had a 20-year history of functional decline, associated with neuropsychological evidence of change. Neuropathological confirmation of the condition of his father became available. This revealed gross bilateral frontal atrophy and spongiosis in the frontal cortical regions with mild neuronal loss and rounded ubiquitinated perinuclear inclusions, consistent with early stage frontotemporal lobar degeneration with ubiquitin by current neuropathological criteria. The phenotype of frontal variant FTD is broad. Many patients present with frontal networks dysfunction. We present evidence that some patients with a very slow clinical progression do have FTD.
Concerning thromboembolism associated with left ventricular assist devices
Authors: D Gross
Journal: Cardiovascular Research (1999)

Time for primary review 17 days. 

Cardiac surgeons are obligated to find solutions for patients with end-stage cardiac failure. Cardiac transplantation has provided the most successful option thus far but demand far exceeds the supply of donor hearts and demand is projected to increase while supply will level off, or perhaps decline [1]. Because of this shortfall in donor hearts there has been continued effort and emphasis on development of alternatives to cardiac transplantation [2]. Recently it was estimated that by the year 2010 between 35 000 and 70 000 patients in the USA alone would be candidates for permanent cardiac replacement or support [3].

Early versions of blood pumping devices, most containing silicone rubber blood sacs, experienced major problems with thrombosis. [4] Dacron-flocked surfaces were promulgated as a solution, the theory being that the formation of a ‘pseudo-intimal’ lining on these devices would be non-thrombogenic [5]. Early efforts with textured surfaces resulted in impaired diaphragm flexibility, hemolysis, and embolization [6], but these problems seem to have been resolved in the more modern devices. A major breakthrough in materials was made with the introduction of segmental polyurethanes in 1967. That led to adoption of this ‘smooth’ material for almost all devices [7]. Problems related to blood sac calcification, soft tissue pannus at the atrial cuff, and major thrombosis problems were gradually resolved with the introduction of low profile valves, and a host of iterative improvements in geometry, design, control systems, power sources, and driving systems. We are now to the point where … 

* Tel.: +1-217-333-2506; fax +1-217-244-1560. Dr. Gross was formerly Professor and Director of the Cardiovascular Surgery Research Laboratories, Division of Cardiovascular and Thoracic Surgery, College of Medicine, University of Kentucky. He is currently Professor and Head, Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign.
Adiponectin inhibits vascular endothelial growth factor-induced migration of human coronary artery endothelial cells
Authors: Kalyankar Mahadev, Xiangdong Wu, Sylvia Donnelly, Raogo Ouedraogo, Andrea D. Eckhart, Barry J. Goldstein
Journal: Cardiovascular Research (2008)

AimsVascular endothelial growth factor (VEGF)-induced endothelial cell migration and angiogenesis are associated with the vascular complications of diabetes mellitus, and adiponectin is an abundant plasma adipokine that exhibits salutary effects on endothelial function. We investigated whether adiponectin suppresses VEGF-induced migration and related signal transduction responses in human coronary artery endothelial cells (HCAECs).