tbuckley/cabot-search huggingface dataset:
Neighborhood Poverty and Racial Disparities in Kidney Transplant Waitlisting
Authors: Rachel E. Patzer, Sandra Amaral, Haimanot Wasse, Nataliya Volkova, David Kleinbaum, William M. McClellan
Journal: Journal of the American Society of Nephrology (2009)

Racial disparities persist in the United States renal transplantation process. Previous studies suggest that the distance between a patient's residence and the transplant facility may associate with disparities in transplant waitlisting. We examined this possibility in a cohort study using data for incident, adult ESRD patients (1998 to 2002) from the ESRD Network 6, which includes Georgia, North Carolina, and South Carolina. We linked data with the United Network for Organ Sharing (UNOS) transplant registry through 2005 and with the 2000 U.S. Census geographic data. Of the 35,346 subjects included in the analysis, 12% were waitlisted, 57% were black, 50% were men, 20% were impoverished, 45% had diabetes as the primary etiology of ESRD, and 73% had two or more comorbidities. The median distance from patient residence to the nearest transplant center was 48 mi. After controlling for multiple covariates, distance from patient residence to transplant center did not predict placement on the transplant waitlist. In contrast, race, neighborhood poverty, gender, age, diabetes, hypertension, body mass index, albumin, and the use of erythropoietin at dialysis initiation was associated with waitlisting. As neighborhood poverty increased, the likelihood of waitlisting decreased for blacks compared with whites in each poverty category; in the poorest neighborhoods, blacks were 57% less likely to be waitlisted than whites. This study suggests that improving the allocation of kidneys may require a focus on poor communities.
Diagnostic Use of Serum Deoxyribonuclease I Activity as a Novel Early-Phase Marker in Acute Myocardial Infarction
Authors: Yasuyuki Kawai, Masahiro Yoshida, Kenichiro Arakawa, Teruhiko Kumamoto, Norihiro Morikawa, Katsuhiko Masamura, Hiroshi Tada, Sachiko Ito, Hiroshi Hoshizaki, Shigeru Oshima, Koichi Taniguchi, Hidekazu Terasawa, Isamu Miyamori, Koichiro Kishi, Toshihiro Yasuda
Journal: Circulation (2004)

Background— The delayed release of serum cardiac markers such as creatine kinase isoenzyme MB and equivocal early electrocardiographic changes have hampered a diagnosis of acute myocardial infarction (AMI) in the early phase after its onset. Therefore, a reliable serum biochemical marker for the diagnosis of AMI in the very early phase is desirable. Methods and Results— Serum samples were collected from the patients with AMI, unstable angina pectoris, stable angina pectoris, and other diseases. Levels of serum deoxyribonuclease I (DNase I) activity in the patients were determined. An abrupt elevation of serum DNase I activity was observed within approximately 3 hours of the onset of symptoms in patients with AMI, with significantly higher activity levels (21.7±5.10 U/L) in this group compared with the other groups with unstable angina pectoris (10.4±4.41 U/L), angina pectoris (10.8±3.70 U/L), and other diseases (9.22±4.16 U/L). Levels of the DNase I activity in serum then exhibited a marked time-dependent decline within 12 hours and had returned to basal levels within 24 hours. Conclusions— We suggest that serum DNase I activity could be used as a new diagnostic marker for the early detection of AMI.
Protein Phosphatase-2A Is a Target of Epigallocatechin-3-Gallate and Modulates p53-Bak Apoptotic Pathway
Authors: Jichao Qin, He-Ge Chen, Qin Yan, Mi Deng, Jinping Liu, Stephan Doerge, Weiya Ma, Zigang Dong, David Wan-Cheng Li
Journal: Cancer Research (2008)

(-)-Epigallocatechin-3-gallate (EGCG) is a well-known chemoprevention factor. Recent studies have revealed that EGCG triggers cancer cells undergoing apoptosis through p53-dependent pathway. How EGCG activates p53-dependent apoptosis is not fully understood. In the present study using JB6 cell as a model system, we have shown that EGCG can negatively regulate protein serine/threonine phosphatase-2A (PP-2A) to positively regulate p53-dependent apoptosis. First, EGCG at physiologic levels down-regulates PP-2A at the protein and enzyme activity levels. Second, EGCG induces apoptosis of JB6 cells, which is associated with hyperphosphorylation of p53 and up-regulation of the proapoptotic gene, Bak. DNA sequence analysis, gel mobility shifting, chromatin immunoprecipitation, and reporter gene activity assays revealed that p53 directly controls Bak in JB6 cells. Knockdown of p53 and Bak expression with RNAi substantially inhibits EGCG-induced apoptosis. Third, PP-2A directly interacts with p53 and dephosphorylates p53 at Ser-15 in vitro and in vivo. Fourth, overexpression of the catalytic subunit for PP-2A down-regulates p53 phosphorylation at Ser15, attenuates expression of the downstream proapoptotic gene, Bak, and antagonizes EGCG-induced apoptosis. Inhibition of PP-2A activity enhances p53 phosphorylation at Ser-15 and up-regulates Bak expression to promote EGCG-induced apoptosis. Finally, in the p53(-/-) H1299 and p53(+/+) H1080 cells, EGCG down-regulates PP-2A similarly but induces differential apoptosis. In summary, our results show that (a) PP-2A directly dephosphorylates p53 at Ser-15; (b) P53 directly controls Bak expression; and (c) EGCG negatively regulates PP-2A. Together, our results show that EGCG-mediated negative regulation of PP-2A is an important molecular event for the activation of p53-dependent apoptosis during its chemoprevention.
Ultrasonography of fractures in sports medicine
Authors: Douglas F Hoffman, Erik Adams, Stefano Bianchi
Journal: British Journal of Sports Medicine (2014)

High-resolution ultrasound is emerging as an important imaging modality in fracture assessment due to its availability, ease of use and multiplanar capabilities. Its usefulness includes injury assessment for the presence of a fracture when obtaining radiographs is not immediately available, detecting occult fractures not revealed on radiographs, and diagnosing bone stress injury before radiographic changes. Sonographic evaluation of bone, however, has limitations and should always be coupled with radiographs and possibly advanced imaging modalities such as CT and MR when clinically indicated.
Quality of Reporting of Noninferiority and Equivalence Randomized Trials
Authors: Anne Le Henanff, Bruno Giraudeau, Gabriel Baron, Philippe Ravaud
Journal: JAMA (2006)

Noninferiority and equivalence trials aim to show that the experimental treatment is not clinically worse than (noninferior) or clinically similar to (equivalent) a control active treatment. These study objectives imply particular planning and analysis.To assess the methodologic quality of reports of randomized controlled trials of noninferiority and equivalence.We searched MEDLINE and the Cochrane Central Register of Controlled Trials for reports of randomized controlled trials of noninferiority and equivalence hypotheses published between January 1, 2003, and December 31, 2004.Data extracted by use of a standardized form involved assessment of choice of noninferiority or equivalence margins, sample size calculation, sets of patients analyzed, method of statistical testing and reporting results, and conclusions.A total of 162 reports were included in the analysis (116 reports of noninferiority and 46 of equivalence). The margin defining noninferiority or equivalence was described in most reports (156 [96.3%]), with justification of the margin in only 33 (20.4%). Almost one quarter of the reports (35 [21.6%]) did not describe a sample size calculation, and an additional 11 (6.8%) did not take into account a prespecified noninferiority or equivalence margin. Less than half of the reports (69 [42.6%]) described both an intent-to-treat (ITT; all randomized patients are included in the analysis) or modified ITT (patients who never received treatment are excluded) and per-protocol (patients who did not complete the treatment are excluded) analysis, and only about half of those (39 [56.5%]) described both types of results. Results were displayed with confidence intervals in 136 reports (84.0%). Only 33 articles (20.3%) fulfilled reporting requirements specific to noninferiority and equivalence trials, 4 of them (12.1%) with misleading conclusions.Reporting of noninferiority and equivalence trials has important deficiencies: absence of noninferiority or equivalence margin, only an ITT (or a per-protocol) analysis performed, and results not adequately reported. Moreover, even for articles fulfilling these requirements, conclusions are sometimes misleading.
Indolent Wegener's granulomatosis.
Authors: D G Macfarlane, J T Bourne, P A Dieppe, D L Easty
Journal: Annals of the Rheumatic Diseases (1983)

Classical Wegener9s granulomatosis is a relentlessly progressive and rapidly fatal disease. A pulmonary 9limited form9 is associated with a much better prognosis. We report 3 cases of Wegener9s granulomatosis which ran a prolonged indolent course despite major manifestations outside the lower respiratory tract and review the literature on survival.
Ryanodine Receptor–Mediated Calcium Leak Drives Progressive Development of an Atrial Fibrillation Substrate in a Transgenic Mouse Model
Authors: Na Li, David Y. Chiang, Sufen Wang, Qiongling Wang, Liang Sun, Niels Voigt, Jonathan L. Respress, Sameer Ather, Darlene G. Skapura, Valerie K. Jordan, Frank T. Horrigan, Wilhelm Schmitz, Frank U. Müller, Miguel Valderrabano, Stanley Nattel, Dobromir Dobrev, Xander H.T. Wehrens
Journal: Circulation (2014)

Background— The progression of atrial fibrillation (AF) from paroxysmal to persistent forms remains a major clinical challenge. Abnormal sarcoplasmic reticulum (SR) Ca 2+ leak via the ryanodine receptor type 2 (RyR2) has been observed as a source of ectopic activity in various AF models. However, its potential role in progression to long-lasting spontaneous AF (sAF) has never been tested. This study was designed to test the hypothesis that enhanced RyR2-mediated Ca 2+ release underlies the development of a substrate for sAF and to elucidate the underlying mechanisms. Methods and Results— CREM-IbΔC-X transgenic (CREM) mice developed age-dependent progression from spontaneous atrial ectopy to paroxysmal and eventually long-lasting AF. The development of sAF in CREM mice was preceded by enhanced diastolic Ca 2+ release, atrial enlargement, and marked conduction abnormalities. Genetic inhibition of Ca 2+ /calmodulin-dependent protein kinase II–mediated RyR2-S2814 phosphorylation in CREM mice normalized open probability of RyR2 channels and SR Ca 2+ release, delayed the development of spontaneous atrial ectopy, fully prevented sAF, suppressed atrial dilation, and forestalled atrial conduction abnormalities. Hyperactive RyR2 channels directly stimulated the Ca 2+ -dependent hypertrophic pathway nuclear factor of activated T cell/Rcan1-4, suggesting a role for the nuclear factor of activated T cell/Rcan1-4 system in the development of a substrate for long-lasting AF in CREM mice. Conclusions— RyR2-mediated SR Ca 2+ leak directly underlies the development of a substrate for sAF in CREM mice, the first demonstration of a molecular mechanism underlying AF progression and sAF substrate development in an experimental model. Our work demonstrates that the role of abnormal diastolic Ca 2+ release in AF may not be restricted to the generation of atrial ectopy but extends to the development of atrial remodeling underlying the AF substrate.
Cardiac mesenchymal stem cells contribute to scar formation after myocardial infarction
Authors: Signe Carlson, JoAnn Trial, Christian Soeller, Mark L. Entman
Journal: Cardiovascular Research (2011)

Therapeutic advances in prevention and treatment of myocardial infarction (MI) have decreased patient mortality and increased concern about efficient repair and scar formation, processes that are necessary to attenuate complications such as adverse remodelling and heart failure. Since the rapid accumulation and activity of cardiac fibroblasts is critical for proper scar formation, we hypothesized that infarct fibroblasts are generated by a cardiac-resident progenitor cell population. We found that infarct fibroblasts in C57BL/6 mice are generated by a mesenchymal stem cell (MSC) population that responds robustly to injury by proliferating and accumulating in the infarct. We report that stem cell-derived fibroblasts contribute to the formation of a scar after an infarction by differentiating into matrix-producing fibroblasts closely associated with fibrillar collagen in the infarct. Further characterization of these cells revealed a heterogenous population with expression of both stem cell and canonical cardiac fibroblast markers, suggesting that some have a commitment to the fibroblast phenotype. Our in vitro study of these cells shows that they have extended self-renewal capability and express the primitive marker Nanog. In keeping with these observations, we also report that these cells are multipotent and differentiate readily into fibroblasts as well as other mesenchymal lineages. Cells with the properties of MSCs participate in wound healing after MI in the adult heart.
Antinucleosome antibodies in the diagnosis of systemic lupus erythematosus
Authors: A P Cairns
Journal: Annals of the Rheumatic Diseases (2003)

reuil et al reported on a patient with Erdheim-Chester disease. 1 We would like to add our experience in a patient who had a good response to steroids.A 46 year old housewife, born in Maceio (Brazil), complained of pain in her legs for a period of eight months, which interfered with her sleep; there were no constitutional symptoms, such as weight loss, asthenia, or fever.On physical examination, there was no systemic involvement or bone inflammation, except for tenderness on palpation of both tibiae.An x ray examination showed bilateral and symmetrical cortical osteosclerosis of the diaphysial regions of the tibiae, which was better illustrated with magnetic resonance imaging (MRI) which showed a low signal on T 1 and a high signal on T 2 of the medullar canal (fig 1).Bone scintigraphy showed intense hypercapitation at the upper and medial regions of the right tibia and the medial region of the left tibia (fig 2).Other MR images (brain, thorax, and abdomen) were normal.A bone biopsy showed only osteosclerosis, which has been described in this disease. 2 She was treated with steroids for six months (prednisone 20 mg/day) and responded well, being asymptomatic and receiv-ing no treatment since December 2000.As bone pain is the first symptom of this xanthogranulomatosis, rheumatologists should be able to recognise the disease in an early phase when treatment gives a better outcome.. . . .
A turbulent cause of bilateral pneumonia
Authors: E. Bathoorn, M. A. Heitbrink, C. L. A. Reichert, W. G. Boersma
Journal: European Respiratory Journal (2009)

A 62-yr-old female presented with complaints of progressive chest pain, increasing in severity with inspiration, a productive cough and fever for 2 days.Moreover, she had lost 12 kg in weight in the last 3 months and was experiencing night sweats.During this period, she had a folliculitis in her axilla.Her medical history yielded diabetes mellitus type II, hypertension and anaemia.Transthoracic echocardiography, performed 4 years ago, had shown flow abnormalities in the pulmonary artery and left ventricular volume overload.The patients' medication included metformin, insulin, hydrochlorothiazide, simvastatin, metoprolol, ferrofumerate and vitamin B.On physical examination, a pale and cachectic patient was seen.Her body temperature was 39uC, with a heart rate of 104 beats?min -1 , respiratory rate of 20 breaths?min -1 and blood pressure of 160/65 mmHg.Chest auscultation revealed normal breath sounds, a 2/6 systolic murmur in the right parasternal area and a 1/6 continuous murmur in the left parasternal area.Otherwise, physical examination was normal.An overview of investigations is presented in table 1.A chest radiograph was performed upon admission (fig. 1) and a contrast-enhanced computed tomography (CT) scan was performed before and after treatment (figs 2 and 3, respectively).A CT scan was also obtained in the parenchymal setting (fig.4).
Prevalence of bronchial reactivity to inhaled methacholine in New Zealand children.
Authors: M R Sears, D T Jones, M D Holdaway, C J Hewitt, E M Flannery, G P Herbison, P A Silva
Journal: Thorax (1986)

The prevalence of bronchial hyperreactivity to inhaled methacholine and of a clinical history of symptoms of asthma was determined in a birth cohort of 9 year old New Zealand children. A history of current or previous recurrent wheezing was obtained in 220 of 815 children. Of 800 who had spirometric tests, 27 (3.4%) had resting airflow obstruction (FEV1/FVC less than 75%). Methacholine challenge was undertaken without problem in 766 children, the abbreviated protocol being based on five breaths and four concentrations. A fall in FEV1 of more than 20% was observed in 176 children (23% of challenges, 22% of the full cohort) after inhalation of methacholine in concentrations of up to 25 mg/ml. The prevalence of bronchial reactivity in children with symptoms was related to the frequency of wheezing episodes in the last year, and the degree of reactivity to the interval since the last episode. Sixty four children (8.0%) with no history of wheeze or recurrent dry cough were, however, also responsive to methacholine 25 mg/ml or less, while 35% of children with current or previous wheezing did not respond to any dose of methacholine. Bronchial challenge by methacholine inhalation was not sufficiently sensitive or specific to be useful as a major criterion for the diagnosis of asthma in epidemiological studies. The occurrence of airway reactivity in children without symptoms of asthma, however, raises the possibility that adult onset asthma and the development of airways obstruction in some subjects with chronic bronchitis could have origins in childhood.
Adjunctive Thrombectomy and Distal Protection in Primary Percutaneous Coronary Intervention
Authors: Manivannan Srinivasan, Charanjit Rihal, David R. Holmes, Abhiram Prasad
Journal: Circulation (2009)

A significant proportion of patients with ST-elevation myocardial infarction have persistent impairment of microvascular blood flow despite successful reperfusion of epicardial vessels. Microvascular dysfunction has been associated with larger infarct size, increased predisposition to ventricular arrhythmias, heart failure, cardiogenic shock, recurrent myocardial infarction, and death. It remains unclear whether this association is of direct mechanistic significance or whether the microcirculatory injury is an epiphenomenon and a manifestation of greater ischemic insult to the myocardium. Although several potential mechanisms have been proposed for the microvascular dysfunction, distal microembolization during mechanical reperfusion is likely to be an important contributor. Consequently, there has been increasing interest in the concept of adjunctive mechanical thrombectomy to improve outcomes in primary percutaneous coronary intervention. Until recently, randomized trials of thrombectomy and distal protection devices during primary percutaneous coronary intervention have provided conflicting results with no definitive evidence for efficacy. The recently published Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study has rekindled the interest in this area. This trial is the largest randomized study of a thrombectomy device published to date and demonstrates that adjunctive treatment with aspiration thrombectomy during primary percutaneous coronary intervention improves surrogate and clinical end points. The aim of the present report is to review the evidence to date on the role of mechanical thrombectomy and embolic protection in native coronary arteries during primary percutaneous coronary intervention.
14-3-3σ in Endometrial Cancer–A Possible Prognostic Marker in Early-Stage Cancer
Authors: Kiyoshi Ito, Takashi Suzuki, Jun-ichi Akahira, Michiko Sakuma, Sumika Saitou, Satoshi Okamoto, Hitoshi Niikura, Kunihiro Okamura, Nobuo Yaegashi, Hironobu Sasano, Satoshi Inoue
Journal: Clinical Cancer Research (2005)

We examined expression of 14-3-3sigma, a regulator of cell proliferation, and evaluated its clinical significance in endometrioid endometrial carcinoma.One hundred three endometrioid endometrial adenocarcinoma cases were examined using immunohistochemistry with archival specimens. We correlated this finding with various clinicopathologic variables, including the status of estrogen receptor, progesterone receptor, and MIB-1 (Ki-57).14-3-3sigma Immunoreactivity was detected in 78 of 103 (75.3%) of carcinoma cases. No statistically significant correlation was detected between status of 14-3-3sigma and any of clinicopathologic variables examined. There was, however, a statistically significant correlation between loss of 14-3-3sigma expression and adverse clinical outcome of the patients (P = 0.0007). In the early stages of cancer (stages I and II), 14-3-3sigma immunoreactivity was absent in 5 of 10 (50.0%) patients who showed recurrence during follow-up, whereas its absence was detected in only 13 of 68 (19.1%) disease-free patients in the same period. In addition, 14-3-3sigma immunoreactivity was absent in 4 of 5 (80.0%) patients who died, whereas its absence was detected in only 14 of 73 (19.2%) patients who had lived during the same period. Patients whose tumors were negative for 14-3-3sigma were at much greater risk to develop recurrent and/or mortal disease (P = 0.0372 and 0.0067). In multivariate analysis using the Cox proportional hazards model, absence of 14-3-3sigma turned out to be statistically independent risk factor in disease-free survival and overall survival even in patients with early-stage disease (P = 0.0321 and 0.0191).Results of our study showed that loss or absence of 14-3-3sigma determined by immunohistochemistry may be an important tool to identify endometrial carcinoma cases at high risk of recurrence and/or death, who are otherwise not detected by current clinical and pathologic evaluation, especially in the early stages of the disease. In addition, results of 14-3-3sigma immunohistochemistry in the early stage of endometrial carcinoma could contribute to planning postoperative follow-up and adjuvant therapy.
Spectrin beta-chain variant associated with hereditary elliptocytosis.
Authors: D Dhermy, M C Lecomte, M Garbarz, O Bournier, C Galand, H Gautero, C Feo, N Alloisio, J Delaunay, P Boivin
Journal: Journal of Clinical Investigation (1982)

An electrophoretically fast-moving variant of the spectrin beta-chain was discovered in the erythrocyte membranes of a woman and her father who both exhibited elliptocytosis and mild hemolytic anemia. This abnormal beta'-subunit (Mr = 214,000) co-existed with a decreased normal beta-chain and represented about half of the total beta-chains in the membrane. In contrast to the spectrin beta-chain, the beta'-chain was phosphorylated neither in the membrane by endogenous protein kinases nor in solution by pure membrane casein kinase whether or not the spectrin was dephosphorylated by erythrocyte cytosolic spectrin phosphatase. The presence of the beta'-chain was associated with a defective self-association of spectrin dimer to form tetramer as manifested by: (a) an excess of spectrin dimer in the 4 degrees C spectrin crude extract, (b) a defective self-association of the spectrin dimer in the 37 degrees C crude spectrin extracts. Gel electrophoretic analysis of the tetramer and dimer species isolated from the proband's 4 degrees C extract showed that the tetramer contained trace amounts of the beta'-chain, whereas in contrast, a large proportion of beta'-chain was present in the dimer. These results demonstrated the responsibility of the beta'-chain for the defective reassociation of spectrin dimer into tetramer. The study of this abnormal spectrin confirms the participation of spectrin beta-chain in dimer-dimer association and strongly suggests that the phosphorylation sites of the normal beta-chain are located at the end of the molecule involved in the dimer-dimer interactions.