tbuckley/cabot-search huggingface dataset:
A new configuration for right ventricular assist with skeletal muscle ventricle. Short-term studies.
Authors: H Niinami, T L Hooper, R L Hammond, R Ruggiero, A Pochettino, M Colson, L W Stephenson
Journal: Circulation (1991)

Previous attempts to provide right heart assistance with skeletal muscle ventricles (SMVs) have been frustrated by the low preload supplied by the systemic venous blood pressure. In the present study, right ventricular pressure was exploited to provide more optimal preload, the SMV being connected by valved conduits between right ventricular free wall and the main pulmonary artery.SMVs were constructed from the right latissimus dorsi muscle in seven mongrel dogs. Following a delay period of 4 weeks, SMVs were preconditioned with 2-Hz continuous stimulation for 5-6 weeks. The SMV was then connected to the right ventricle using a porcine valved Dacron conduit. A similar valved conduit connected the SMV to the main pulmonary artery that had been ligated proximally. SMVs were stimulated with 33-Hz burst frequency to contract synchronously with ventricular diastole in a 1:2 mode. The stimulator was intermittently turned off to permit comparison of assisted and nonassisted circulation. Cardiac output increased by 27% at 1 hour (1,437 +/- 54 versus 1,140 +/- 64 ml/min, p less than 0.005) and by 30% at 4 hours (1,403 +/- 161 versus 1,074 +/- 99 ml/min, p less than 0.005), systemic arterial systolic pressure increased at 1 hour by 12% (87.1 +/- 4.9 versus 78.0 +/- 4.9 mm Hg, p less than 0.05) and by 13% at 4 hours (81.4 +/- 2.8 versus 72.3 +/- 3.4 mm Hg, p less than 0.005), and peak pulmonary arterial pressure increased at 1 hour by 35% (28.0 +/- 2.1 versus 20.9 +/- 1.8 mm Hg, p less than 0.01) and by 37% at 4 hours (31.5 +/- 2.6 versus 23.0 +/- 0.4 mm Hg, p less than 0.05). Peak SMV pressure was 52.8 +/- 2.0 mm Hg at 1 hour and 49.9 +/- 3.3 mm Hg at 4 hours (p = NS).The improved preload supplied by this configuration of right ventricular assist enabled an SMV to provide stable and effective circulatory support throughout the 4-hour duration of the experiment.
Myc Goes Global: New Tricks for an Old Oncogene
Authors: Paul S. Knoepfler
Journal: Cancer Research (2007)

Abstract Myc, a transcription factor commonly deregulated in tumorigenesis, is thought to mediate its diverse cellular effects by altering the expression of specific target genes. However, it has been difficult to gain a precise understanding of how Myc drives cancer because Myc acts rather weakly at many of its target loci, and it has been reported to regulate as many as 10% to 15% of all cellular genes. A new perspective on this issue has been provided by a recent study that revealed Myc can regulate chromatin structure in a global fashion. These findings suggest actions for Myc that extend beyond the traditional concept of a targeted gene regulator. [Cancer Res 2007;67(11):5061–3]
Effect of Esomeprazole 40 mg Once or Twice Daily on Asthma
Authors: Toni O. Kiljander, Ola Junghard, Ola Beckman, Tore Lind
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Gastroesophageal reflux disease (GERD) is common among patients with asthma; however, studies investigating the effect of proton pump inhibitors on asthma outcomes report conflicting results.To investigate the effect of esomeprazole 40 mg once or twice daily on asthma outcomes in patients with concomitant symptoms of GERD.This 26-week, randomized, double-blind, placebo-controlled study (NCT00317044) included adult patients (18-70 yr) with moderate-to-severe asthma and symptomatic GERD. The change in morning peak expiratory flow (primary variable), evening peak expiratory flow, FEV(1), asthma symptoms, Asthma Quality of Life Questionnaire, Reflux Disease Questionnaire, and tolerability were assessed.A total of 961 patients were randomized and 828 completed the study. Relative to baseline, improvement in morning peak expiratory flow was observed for both esomeprazole 40 mg once daily (+3.5 L/min; 95% CI, -3.2 to 10.2) and 40 mg twice daily (+5.5 L/min; 95% CI, -1.2 to 12.2), although no statistically significant between-treatment differences were apparent. At treatment end, both doses of esomeprazole significantly improved FEV(1) versus placebo (+0.09 L and +0.12 L; P = 0.0039 and P < 0.0001, respectively). However, only esomeprazole 40 mg twice daily demonstrated a significant improvement when FEV(1) was calculated over the entire 26-week period (+0.07 L; P = 0.0042). Significant improvements in Asthma Quality of Life Questionnaire total score were demonstrated for both esomeprazole doses compared with placebo (+0.28 and +0.41; P = 0.0006 and P < 0.0001, respectively).Esomeprazole may improve pulmonary function and asthma-related quality of life. However, the improvements were minor and of small clinical significance.
Variation in gene expression patterns in effusions and primary tumors from serous ovarian cancer patients
Authors: Marci E Schaner, Ben Davidson, Martina Skrede, Reuven Reich, Vivi Ann Flørenes, Björn Risberg, Aasmund Berner, Iris Goldberg, Vered Givant-Horwitz, Claes G Tropè, Gunnar B Kristensen, Jahn M Nesland, Anne-Lise Børresen-Dale
Journal: Molecular Cancer (2005)

Abstract Background While numerous studies have characterized primary ovarian tumors, little information is available regarding expression patterns of metastatic sites of this cancer. To define sets of genes that distinguish primary and metastatic ovarian tumors, we used cDNA microarrays to characterize global gene expression patterns in 38 effusions (28 peritoneal, 10 pleural) and 8 corresponding primary ovarian tumors, and searched for associations between expression patterns and clinical parameters. Results We observed multidimensional variation in expression patterns among the cancers. Coordinate variation in expression of genes from two chromosomal regions, 8q and 19q, was seen in subsets of the cancers indicating possible amplifications in these regions. A set of 112 unique genes of known function was differentially expressed between primary tumors and effusions using supervised analysis. Relatively few differences were seen between effusions isolated from the pleural and peritoneal cavities or between effusions from patients diagnosed with stage III and stage IV cancers. A set of 84 unique genes was identified that distinguished high from lower grade ovarian cancers. The results were corroborated using immunocytochemistry, mRNA in situ hybridization, and immunoblotting. Conclusion The extensive variation in expression patterns observed underscores the molecular heterogeneity of ovarian cancer, but suggests a similar molecular profile for ovarian carcinoma cells in serosal cavities.
A murine model of type 2 autoimmune hepatitis: Xenoimmunization with human antigens
Authors: Pascal Lapierre, Idriss Djilali-Saiah, Susana Vitozzi, Fernando Alvarez
Journal: Hepatology (2004)

Autoimmune hepatitis (AIH) is characterized by an immune-mediated injury of the hepatic parenchyma of unknown pathogenesis. Type 2 AIH is identified by the presence of anti-liver-kidney microsomes type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) autoantibodies. The current study shows that a murine model of AIH can be generated by DNA immunization against type 2 AIH self-antigens (P450 2D6 and formiminotransferase-cyclodeaminase). A pCMV plasmid containing the N-terminal region of mouse CTLA-4 and the antigenic region of human CYP2D6 (672-1,377 bp) and human formiminotransferase cyclodeaminase (FTCD; 1,232-1,668 bp) was used for DNA immunization of C57BL/6 female mice. Immunized mice showed elevated levels of alanine aminotransferase (ALT), with peaks at 4 and 7 months postinjection. Periportal, portal, and intralobular liver inflammatory infiltrates were observed at histology. Mainly CD4+ lymphocytes, but also CD8+ and B lymphocytes, were found in the liver. Cytotoxic-specific T cells were found in both the liver and spleen of these animals. Mice developed anti-LKM1 and anti-LC1 antibodies of immunoglobulin G2 (IgG2) subclass, against specific mouse autoantigens. The ALT levels correlated with both the presence of anti-LKM1/anti-LC1 antibodies and the presence of liver necroinflammation. In conclusion, in mice, DNA immunization against human autoantigens breaks tolerance and induces an autoimmune liver disease. Molecular mimicry between foreign and self-antigens explains the liver injury. This model of AIH resembles human type 2 AIH and will be helpful for the study of its pathogenesis. (Hepatology 2004;39:1066-1074.)
Performance of the 2011 ACR/EULAR preliminary remission criteria compared with DAS28 remission in unselected patients with rheumatoid arthritis
Authors: Katja Thiele, Dörte Huscher, Sascha Bischoff, Susanna Späthling-Mestekemper, Marina Backhaus, Martin Aringer, Thomas Kohlmann, Angela Zink
Journal: Annals of the Rheumatic Diseases (2012)

Objective To compare the performance of the preliminary American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria with the 28-joint count Disease Activity Score (DAS28) remission in unselected ‘real-life’ patients. Methods Remission was calculated according to the DAS28 and to both versions of the ACR/EULAR criteria (Boolean or Simplified Disease Activity Index (SDAI)-based) for 6864 patients with rheumatoid arthritis (RA) who were enrolled in the national database of the German Collaborative Arthritis Centres between 2007 and 2009. Logistic regression analyses identified factors that were responsible for patients in DAS28 remission to miss the new criteria. In addition, the functional status of patients who fulfilled the different remission criteria was compared with that of an age- and sex-matched population sample. Results Of all patients, 28% were in DAS28, 7% in Boolean and 11% in SDAI remission. Of those in DAS28 remission, 21.0% were also in Boolean and 34% also in SDAI remission. Higher scores for pain and fatigue, the presence of degenerative spine disease, longer disease duration and male gender were significantly associated with missing the new criteria despite being in DAS28 remission. Compared with age- and sex-matched samples from the general population, patients in DAS28 remission had a similar functional ability while patients in remission according to the new criteria had better functional scores. Conclusions Patients fulfilling the new remission criteria tend to be not only free from active RA, but also from other disabling diseases. If these criteria are applied in clinical practice to guide treatment decisions, the impact of comorbidity should be taken into account.
Gonorrh a; Endometritis; Oophoritis; Ovarian Neuralgia; Lateral Flexion
Authors: T. E. Williams
Journal: BMJ (1874)

<b><i>Article abstract</i></b> Spontaneous arm levitation (SAL) is well-recognized in cortical–basal ganglionic degeneration, but not in other neurodegenerative diseases. We report six cases of progressive supranuclear palsy (PSP) with SAL. Pathologic examination in four revealed the classic features of PSP with additional areas of focal cortical degeneration. We conclude that SAL can occur in PSP and its occurrence may be a marker of cortical degeneration.
1031 HCV INFECTION PROMOTES CYTOSKELETAL REORGANIZATION IN HEPATOCYTES AND A PRO-FIBROGENIC PHENOTYPE IN HEPATIC STELLATE CELLS BY THE ACTIVATION OF FOCAL ADHESION KINASE
Authors: A. Alisi, M. Arciello, S. Petrini, B. Conti, C. Balsano
Journal: Journal of Hepatology (2011)
Correlation of medial/lateral rotation of the humerus with glenohumeral translation
Authors: T P Branch, O Avilla, L London, W C Hutton
Journal: British Journal of Sports Medicine (1999)

OBJECTIVES: To correlate glenohumeral translation in the anterior/posterior direction with medial and lateral rotation of the humerus. In addition, the length of the anterior and posterior component of the glenohumeral capsuloligamentous complex was varied in order to gain insight into the contribution of each component to limiting translation. All measurements were made with the humerus positioned at 90 degrees of abduction and 0 degrees of flexion/ extension. METHODS: Six fresh cadaveric shoulders were used. Each scapula was mounted in a cement pot to rest it in its correct anatomical position. Seven tests were carried out on each shoulder. A series of measurements of translation of the humerus in the anterior direction and posterior direction were taken at 20 degrees intervals of lateral rotation and then at 20 degrees intervals of medial rotation until the limit of lateral or medial rotation had clearly been reached (test 1). The capsuloligamentous complex was then incised and a beaded chain and catches were sutured across the joint to mimic the capsuloligamentous complex at different lengths (tests 2 to 7). RESULTS/CONCLUSIONS: (a) When the glenohumeral capsuloligamentous complex is intact, the humerus translates maximally in the glenoid (between 20 and 30 mm) when the humerus is between 40 degrees and 100 degrees of lateral rotation. (b) As the glenohumeral capsuloligamentous complex increases in length, so does the extent of translation. (c) In medial rotation, the length of the posterior capsule, rather than the length of the anterior capsule, has the greater effect on anterior/posterior translation. (d) In lateral rotation the length of the anterior capsule, rather than the length of the posterior capsule, has the greater effect on anterior/posterior translation. (e) The glenohumeral ligamentous complex acts more as a cuff, enclosing the joint, rather than as a sling, as is commonly thought.
Studies on breath methane: the effect of ethnic origins and lactulose.
Authors: P Pitt, K M de Bruijn, M F Beeching, E Goldberg, L M Blendis
Journal: Gut (1980)

<h3>Objectives</h3> Treatment patterns for patients with myelodysplastic syndromes (MDS) outside clinical trials are not well described. Our objective was to evaluate treatment patterns and patient characteristics that influence time to disease-modifying therapy in patients with MDS in the USA. <h3>Design, participants and outcome measures</h3> Patients with MDS treated with erythropoiesis-stimulating agents (ESAs), iron chelation therapy, lenalidomide (LEN) and the hypomethylating agents (HMAs) azacitidine and decitabine, were retrospectively identified in the GE Centricity Electronic Medical Record database between January 2006 and February 2014; LEN and HMAs were defined as 'disease-modifying' therapies. Multivariable Cox regression models were used to ascertain patient characteristics associated with time to disease-modifying therapy. <h3>Results</h3> Of the 5162 patients with MDS, 35.7%, 40.3% and 4.6% received 1, ≥1 and ≥2 therapies, respectively. ESAs were the first-line (72.5%) and only (64.0%) treatment in the majority of patients who received ≥1 therapy. ESA-only patients were older and had more comorbidities, including isolated anaemia. LEN and HMAs were first-line treatment in 12.4% of patients each; 32.7% received LEN or HMAs at any time. The majority of del(5q) patients (77.6%) received ≥1 therapy, most commonly LEN, compared with 40% of patients without del(5q). A shorter time to disease-modifying therapy was significantly associated with absence of comorbidities, diagnosis after February 2008, lower baseline haemoglobin level, age &lt;80 years and male gender (p&lt;0.002 for all). <h3>Conclusions</h3> A high proportion of patients diagnosed with MDS in the USA do not receive approved disease-modifying therapies. It is important to improve access to these therapies.
Early transfusion reactions due to acquired anti‐IgA antibodies in a patient with acute lymphoblastic leukemia
Authors: P. M. Parikh, Y. S. Iyer, B. C. Mehta
Journal: American Journal of Hematology (1988)

Abstract We report transfusion reactions due to acquired anti‐IgA antibodies in a 32‐year‐old woman with acute lymphoblastic leukemia. Previously, such reactions have been reported only after several hundred transfusions. In our patient they commenced within the first few transfusions.
Chemokine (C-X-C Motif) Ligand 12 Is Associated with Gallbladder Carcinoma Progression and Is a Novel Independent Poor Prognostic Factor
Authors: Hyun Jung Lee, Kyungmin Lee, Dong Gwang Lee, Kwang-Hee Bae, Jang-Seong Kim, Zhe Long Liang, Song Mei Huang, Yoon Suk Oh, Ha Yon Kim, Deog Yeon Jo, Jeong-Ki Min, Jin-Man Kim, Hyo Jin Lee
Journal: Clinical Cancer Research (2012)

Although recent studies have suggested that chemokine (C-X-C motif) ligand 12 (CXCL12) is important in the progression of various malignancies, its role in gallbladder carcinoma (GBC) remains unknown. We investigated CXCL12 expression in GBC and its biologic and prognostic role in GBC tumorigenesis.We examined CXCL12 expression in tumor specimens from 72 patients with GBC by immunohistochemistry and analyzed the correlation between CXCL12 expression and clinicopathologic factors or survival. The functional significance of CXCL12 expression was investigated by CXCL12 treatment and suppression of CXCR4, a major receptor of CXCL12, as well as by CXCL12 overexpression in in vitro and in vivo studies.CXCL12 was differentially expressed in GBC tissues. CXCL12 expression was significantly associated with a high histologic grade (P = 0.042) and nodal metastasis (P = 0.015). Multivariate analyses showed that CXCL12 expression (HR, 8.675; P = 0.014) was an independent risk factor for patient survival. CXCL12 significantly increased anchorage-dependent and -independent growth, migration, invasion, adhesiveness, and survival of GBC cells in vitro, and these effects were dependent on CXCR4. Consistent with these results, overexpression of CXCL12 significantly promoted GBC tumorigenicity in a xenograft model.Our results indicate that GBC cells express both CXCL12 and its receptor CXCR4, and CXCL12 may have a role in GBC progression through an autocrine mechanism. In addition, CXCL12 is a novel independent poor prognostic factor in patients with GBCs. Thus, targeting CXCL12 and CXCR4 may provide a novel therapeutic strategy for GBC treatment.
Developmental Changes in β-Adrenergic Modulation of L-Type Ca <sup>2+</sup> Channels in Embryonic Mouse Heart
Authors: R.H. An, M.P. Davies, P.A. Doevendans, S.W. Kubalak, R. Bangalore, K.R. Chien, R.S. Kass
Journal: Circulation Research (1996)

Abstract In the adult mammalian myocardium, cellular Ca 2+ entry is regulated by the sympathetic nervous system. L-type Ca 2+ channel currents are markedly increased by β-adrenergic (β-A) agonists, which contribute to changes in pacing and contractile activity of the heart. In the developing mammalian heart, the regulation of Ca 2+ entry by this enzyme cascade has not been clearly established, because changes in receptor density and coupling to downstream elements of the signaling cascade are known to occur during embryogenesis. In this study, we systematically investigated the regulation of L-type Ca 2+ channel currents during development of the murine embryonic heart. We used conventional whole-cell and perforated-patch–clamp procedures to study modulation of L-type Ca 2+ channel currents and to assay functional activity of distinct steps in the β-A signaling cascade in murine embryonic myocytes at different stages of gestation. Our data indicate that L-type Ca 2+ channels in early-stage (day-11 to -13) myocytes are unresponsive to either isoproterenol or cAMP. L-type Ca 2+ channels in late-stage (day-17 to -19) murine myocytes, however, exhibit responses to isoproterenol and cAMP similar to responses in adult cells, providing evidence that the β-A cascade becomes functionally active during this period of embryonic development. We found that L-type Ca 2+ channel activity in early-stage cells is increased by cell dialysis with the catalytic subunit of cAMP-dependent protein kinase (cA-PK) and that dialysis of early-stage cells with the holoenzyme of cA-PK restores functional responses to forskolin and cAMP, but not to isoproterenol. Our results provide strong evidence that a key factor in the early-stage insensitivity of L-type Ca 2+ channels to cAMP is the absence, or low expression level, of the holoenzyme of cA-PK but that in addition, another element in the signaling cascade upstream from adenylate cyclase is expressed at a nonfunctional level or is uncoupled from the cascade and thus contributes to L-type Ca 2+ channel insensitivity to β-A agonists in early stages of the developing murine heart.
Short-Term Tropisetron Treatment and Cognitive and P50 Auditory Gating Deficits in Schizophrenia
Authors: Xiang Yang Zhang, Lei Liu, Shaowen Liu, Xiaohong Hong, Da Chun Chen, Mei Hong Xiu, Fu De Yang, Zhijun Zhang, Xiangrong Zhang, Therese A. Kosten, Thomas R. Kosten
Journal: American Journal of Psychiatry (2012)

Objective The α7 nicotinic acetylcholine receptor (nAChR) is associated with cognitive and P50 auditory gating deficits in schizophrenia, and α7 nAChR agonists can potentially reverse these deficits. The authors examined multiple dosages of tropisetron, a partial agonist at the nAChR, for short-term effects on cognition and P50 deficits in schizophrenia. Method In a randomized double-blind design, 40 nonsmoking patients with schizophrenia who had P50 ratios greater than 0.5 and were stabilized on 3–6 mg/day of risperidone were randomly assigned to receive placebo (N=10) or oral tropisetron at 5 mg/day (N=10), 10 mg/day (N=10), or 20 mg/day (N=10). The authors measured P50 inhibitory gating and administered the Chinese-language version of the Repeatable Battery for the Assessment of Neuropsychological Status at baseline and after 10 days of treatment. Results After 10 days of treatment, all three daily doses of tropisetron significantly improved overall cognitive deficits, with 10 mg showing the greatest improvement for the immediate memory index score and 20 mg for the delayed memory index score on the cognitive battery. The P50 deficits were also improved, and that improvement was significantly correlated with cognitive improvement. Two patients in the 20 mg/day group dropped out because of adverse effects, but the other dosages were well tolerated. Conclusions The improvement of cognition with tropisetron appeared to be associated with normalization in P50 deficits. Thus, α7 nAChR agonists appear to be a promising therapeutic approach for the treatment of cognitive deficits that are related to abnormal P50 suppression in schizophrenia.
Hyperextension trauma to the elbow: radiological and ultrasonographic evaluation in handball goalkeepers
Authors: N Popovic, R Lemaire
Journal: British Journal of Sports Medicine (2002)

Objective: To detect elbow lesions produced by hyperextension in 30 elite handball goalkeepers. Methods: Conventional radiographs, stress radiographs, and ultrasound examination of both elbows were used. As a control group, 30 male volunteers from the general population within the same age group with no history of elbow injury were used. Results: Radiographic findings in the goalkeepers were osteophyte formation in 67%, loose bodies in 5.5%, and periarticular calcification in 5.5%. Significantly greater differences in medial joint space opening between stressed and unstressed elbows were measured in both elbows than in the control group. Ultrasonographic findings showed thickening of the medial collateral ligament in 50%, thickening of the tricipital tendon in 11%, and signs of ulnar neuritis in 22%. An intra-articular effusion was found in 66% and small loose bodies in 33%. No significant differences were found between the dominant and non-dominant elbows at radiological and ultrasound examination. The findings in the control group were normal. Conclusions: The findings support the theory that repetitive hyperextension trauma to the elbow in handball goalkeepers results in pathological changes.