tbuckley/cabot-search huggingface dataset:
Refinement of the 22q12-q13 Breast Cancer–Associated Region: Evidence of <i>TMPRSS6</i> as a Candidate Gene in an Eastern Finnish Population
Authors: Jaana M. Hartikainen, Hanna Tuhkanen, Vesa Kataja, Matti Eskelinen, Matti Uusitupa, Veli-Matti Kosma, Arto Mannermaa
Journal: Clinical Cancer Research (2006)

Abstract Although many risk factors for breast cancer are known, most of the genetic background and molecular mechanisms still remain to be elucidated. We have previously published an autosome-wide microsatellite scan for breast cancer association and here we report a follow-up study for one of the detected regions. Ten single nucleotide polymorphisms (SNP) were genotyped in an Eastern Finnish population sample of 497 breast cancer cases and 458 controls to refine the 550-kb region on 22q12-q13 and identify the breast cancer–associated gene(s) in this region. We also studied 22q12-q13 for allelic imbalance for the detection of a possible tumor suppressor gene and to see whether the breast cancer association and allelic imbalance in this region could be connected. A SNP (rs733655) in matriptase-2 gene (TMPRSS6) was detected to associate with breast cancer risk. The genotype frequencies of rs733655 differed significantly between cases and controls in the entire sample and in the geographically and genetically more homogeneous subsample with P = 0.044 and P = 0.0003, respectively. The heterozygous genotype TC was observed to be the risk genotype in both samples (odds ratios, 1.39; 95% confidence intervals, 1.06-1.83 and odds ratios, 2.11; 95% confidence intervals, 1.46-3.05). An associated two-marker haplotype involving SNP rs733655 (empirical P = 0.041) provides further evidence for breast cancer risk factor locating on 22q12-q13, possibly being TMPRSS6. Our results suggest that matriptase-2 gene is associated with breast cancer risk in the Eastern Finnish population.
Tuberculosis pyopneumothorax: Retrospective study of 16 cases in Tunisia
Authors: Besma Ourari, Sameh Dhaoui, Leila El Gharbi, Jihen Ben Amar, Saloua Azzabi, Med Ali Baccar, Hichem Aouina, Hend Bouacha
Journal: European Respiratory Journal (2013)

Despite of the well conducted program, severe cases of tuberculosis have been recently recorded in Tunisia. Tuberculosis pyopneumothorax is a clinical event, which leads to severe complications and a set of treatment challenges.  The objective of this case study is to analyze and present the clinical features, the treatment and the prognostic factors of tuberculosis pyopneumothorax. The case study relies on sixteen (16)patients, fourteen (14) men and two (2)women with a mean age of thirty four (34) and suffering from pyopneumothorax.  They have been consulted after an average of four (4)weeks. Their major manifested symptoms were dyspnea, chest pain and fever.  At thorax x-ray, the pyopneumothorax was prevailing on the right lung(60% of the cases),it was associated with pulmonary tuberculosis lesions in 75% of the cases. Seven (7) patients had bilateral pulmonary lesions.  The treatment consisted of anti tubercular chemotherapy during six (6)months associated with a chest drain and a pleural kinesitherapy.  After the treatment, twelve (12) patients had a successful evolution; four (4) patients had radiologic persisted lesions.  Tuberculous pneumothorax is a severe pathology which requires other anti tuberculor drugs eventually surgical treatment for drainage and lung decortications to improve their prognosis.
Sex and drugs and HCV?
Authors: W ROSENBERG
Journal: Gut (1999)

<h3>ABSTRACT</h3> Lipid metabolism is spatiotemporally regulated within cells, yet intervention into lipid functions at subcellular resolution remains difficult. Here we report a method that enables site-specific release of sphingolipids and cholesterol inside the vacuole in <i>Saccharomyces cerevisiae</i>. Using this approach, we monitored real-time sphingolipid metabolic flux out of the vacuole by mass spectrometry and found that the ER-vacuole tethering protein Mdm1 facilitated the metabolism of sphingoid bases into ceramides. In addition, we showed that cholesterol, once delivered into yeast using our method, could restore cell proliferation induced by ergosterol deprivation, overcoming the previously described sterol-uptake barrier under aerobic conditions. Together, these data define a new way to study intracellular lipid metabolism and transport from the vacuole in yeast.
Negative Selection in the Thymus Includes Semimature T Cells
Authors: Hidehiro Kishimoto, Jonathan Sprent
Journal: The Journal of Experimental Medicine (1997)

The thymic medulla plays a key role in negative selection (self-tolerance induction) and contains differentiated T cells en route to the extrathymic environment. However, being relatively mature, medullary T cells are thought to be beyond the stage of tolerance induction. This paradox is resolved by the finding that medullary T cells (CD4+8− thymocytes) comprise two distinct subsets. Medullary thymocytes expressing a fully mature (HSAlo) phenotype are strongly resistant to tolerance induction, whereas cells with a semimature (HSAhi) phenotype are tolerance susceptible. These findings suggest that the differentiated T cells reaching the medulla from the cortex remain sensitive to tolerance induction for a brief period before acquiring a fully mature tolerance-resistant phenotype. The semimature subset of medullary T cells displays unique requirements for tolerance induction; depending upon the conditions used, tolerizing these cells can involve either a Fas (CD95)-dependent or a Fas-independent pathway.
Long term evaluation of radiographic disease progression in a subset of patients with rheumatoid arthritis treated with leflunomide beyond 2 years
Authors: D van der Heijde, J Kalden, D Scott, J Smolen, V Strand
Journal: Annals of the Rheumatic Diseases (2004)

To assess the effect of long term (>2 years) leflunomide treatment on radiographic progression in patients with RA.Patients treated with leflunomide for >2 years in one of three phase III trials and subsequent extensions, for whom paired, evaluable radiographs at baseline and study end point were available, were included. Radiographs of hands and feet were assessed according to the modified Sharp/van der Heijde scoring method, for erosion, joint space narrowing, and total score. Changes from baseline were assessed, and a predicted yearly progression rate estimated for each patient.128 of the original 824 patients were included, with mean disease duration 5.1 years and mean leflunomide treatment duration 4.3 years until the final x ray examination. The mean change from baseline in total score was 8.6 with yearly adjusted rate 1.9, and the median change was 2 with yearly adjusted rate 0.5, compared with 7.9 and 4.9, respectively, before leflunomide treatment. After treatment, the rate improved in 92/128 (72%) patients and deteriorated in 21/128 (16%). In 42 (33%) patients who had a total score >0 at baseline, no radiographic progression occurred after leflunomide treatment.In a subset of patients who continued treatment long term, leflunomide treatment reduced the rate of radiographic damage.
Neuroendocrine islet cell tumour producing gastrin and ACTH in a patient with calcifying chronic pancreatitis.
Authors: M C Allison, C C Renfrew, W J Webb, M E Chappell, R E Pounder
Journal: Gut (1985)

A patient with a calcifying chronic pancreatitis was found to have a neuroendocrine islet cell tumour (a previously unreported association). The tumour secreted both gastrin and ACTH leading to clinical manifestations of both the Zollinger-Ellison syndrome and Cushing9s syndrome.
Coronary Artery Stenosis in Moyamoya Disease
Authors: Ju-Hee Lee, Tae-Jin Youn, Yeonyee E. Yoon, Jin Joo Park, Su Jin Hong, Eun Ju Chun, Sang Il Choi, Young-Seok Cho, Goo-Yeong Cho, In-Ho Chae, Dong-Ju Choi
Journal: Circulation (2013)
Deposition of kappa and lambda light chains in amyloid filaments of dialysis-related amyloidosis.
Authors: D Brancaccio, G M Ghiggeri, P Braidotti, A Garberi, M Gallieni, V Bellotti, U Zoni, R Gusmano, G Coggi
Journal: Journal of the American Society of Nephrology (1995)

beta 2-Microglobulin (beta 2m) is considered to be the amyloidogenic precursor in dialysis-related amyloidosis, although the implication of other relevant cofactors in the pathogenesis of this disease has also been hypothesized. It is conceivable that substances found in amyloid deposits might represent something more than simple codeposition, possibly playing a pathogenic role in amyloidogenesis. Along these lines, a detailed analysis of the protein composition of amyloid fibrils purified from synovial material surgically obtained from nine patients on long-term dialysis was carried out. By the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, several other protein components, in addition to beta 2m, were found. These were characterized by NH2 amino-terminal sequencing and immunoblotting. In fibrils obtained by water extraction, which fulfill the electron microscopy criteria of highly pure amyloid material, polyclonal kappa and lambda light chains were detected with a concentration of 15 micrograms/mL in the water extraction material; the beta 2m concentration was 200 micrograms/mL. Light microscopy immunohistochemistry was performed on samples from five patients. Amyloid deposits reacted with anti-beta 2m, and anti-light (kappa, lambda), chain antibodies. The immunoreaction of amyloid filaments to anti-beta 2m, anti-lambda, and anti-kappa light chain antibodies was also tested by electron microscopy by use of the immunogold staining procedure. Amyloid filaments were labeled by the three antibodies and showed a different intensity of immunostaining apparently related to their different aggregation pattern. These observations demonstrate that polyclonal immunoglobulin light chains (kappa and lambda) are not contaminants but, together with beta 2m, represent a major constituent of amyloid deposits in dialysis-related osteoarticular amyloidosis, thus indicating their possible role in amyloidogenesis.
PTH-047 A Prospective Study on the Impact of a ‘Bowel Cleansing Care Bundle’ on Inpatient Colonoscopy Visualisation Scores: A London District Hospital Experience: Abstract PTH-047 Table 1
Authors: R K Fofaria, N Hamilton, V J Blackwell, D Sherman, A W Sharif
Journal: Gut (2013)

<h3>Introduction</h3> It is recognised that a well prepared colon increases adenoma detection and removal rates<sup>1</sup> and the discovery of other significant pathology at endoscopy. Several factors can lead to a suboptimal outcome at inpatient colonoscopy but inadequate bowel preparation is a major contributor<sup>2</sup>. Potentially, this leads to repeat and/or alternative procedures and costly and prolonged hospital length of stays. ‘Care Bundles’ improve outcomes by decreasing the unwanted variation in clinical care and ensure the application of accepted clinical practices<sup>3</sup>. Consequently, we created a <i>bowel cleansing bundle</i> to address these issues and see whether it would lead to better visualisation scores. <h3>Methods</h3> All inpatients requiring colonoscopy were recruited over two six-month periods at a London district hospital. A bowel cleansing bundle was devised formalising accepted clinical guidelines and it was implemented for all subsequent inpatient colonoscopies during the latter study phase. The bundle included sections on timings for the administration of bowel preparation agents, cessation of anti-motility agents, nutrition and hydration. Visualisation scores were noted from the endoscopists’ reports (good, moderate and poor) and patients were followed up until discharge. <h3>Results</h3> In total there were 93 eligible procedures. 53 patients in the pre-bundle population [56% Male, average age 69 years] and 40 patients in the post-bundle population [three exclusions, 57% male, average age 64 years] of which: ‘good’ visualisation scores = 45% vs 81%, ‘moderate’ = 21% vs 1% and ‘poor’ = 34% vs 16%. Implementation of the bundle led to significantly superior ‘good’ visualisation scores (p = &lt; 0.001). P-value = 0.0008; two-tailed Fisher’s exact test. <h3>Conclusion</h3> Our study - the first looking at the effect of a bowel cleansing care bundle on inpatients - shows that its implementation conferred significantly better visualisation scores at colonoscopy with a dramatic reduction in poor visualisation. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Adler A, Wegscheider K, Lieberman D<i> et al. Factors determining the quality of screening colonoscopy: a prospective study on adenoma detection rates, from 12 134 examinations.</i> (BECOP-3). Gut. 2013 Feb; 62(2):236–41. Epub 2012 Mar 22. Canard JM, Arpurt JP, Boustiere C, <i>et al.</i><i>La coloscopie en France en 2004: résultat d’une enquête prospective nationale de la Société Française d’Endoscopie Digestive</i>. Endoscopy 2006; 38: A1467. Resar R, Griffin FA, Haraden C, <i>et al. Using Care Bundles to Improve Health Care Quality</i>. IHI Innovation Series white paper. Cambridge, Massachusetts: Institute for Healthcare Improvement; 2012.
A Prospective Analysis of Plasma Adiponectin and Risk of Incident Cancer: The Dallas Heart Study
Authors: Muhammad Shaalan Beg, Sadia Saleem, Aslan Turer, Colby Ayers, James A. de Lemos, Amit Khera, Philipp E. Scherer, Susan G. Lakoski
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: Adiponectin dysregulation is postulated to affect cancer risk via modulation of insulin resistance and inflammation. Epidemiologic studies evaluating this relationship have conflicting results and data from non-white cohorts are lacking. We examined the association between adiponectin and risk of cancer incidence in the multiethnic Dallas Heart Study (DHS). Methods: Participants enrolled in the DHS and known adiponectin values were included. Incident cancer cases were identified through a systematic linkage of the DHS and the Texas Cancer Registry. Univariate/multivariate analysis were performed to test the association between adiponectin and incident cancer after adjusting for age, diabetes status, gender, ethnicity, C-reactive protein level, smoking status, and body mass index. Adiponectin level was evaluated both as a continuous variable and in race/ethnicity specific quartiles. Results: Of 3444 individuals, there were 152 incident cancers. The study population was comprised of 44.4% men, and 51.05% were black. Baseline median adiponectin levels were 6.43 mcg/mL (interquartile range [IQR], 4.37–9.45 mcg/mL) in the incident cancer group versus 6.33 mcg/mL (IQR, 4.57–9.97 mcg/mL) in those without cancer. In multivariable analysis, adiponectin level was not associated with cancer incidence after adjusting for covariates. In analyses stratified by race/ethnic group, no association was observed in white, Hispanic, or African American subgroups. Conclusions: In this study of a predominant ethnic minority population, no association between adiponectin and cancer incidence was demonstrated. Despite preclinical rationale and confirmatory findings in other studies, this association may not replicate across all ethnic populations. Additional studies with trong minority representation are warranted to further examine this association.
Impact of inappropriate antimicrobial therapy on outcome in patients with hospital-acquired pneumonia caused by Acinetobacter baumannii
Authors: Mi Kyong Joung, Ki Tae Kwon, Cheol-In Kang, Hae Suk Cheong, Ji-young Rhee, Dong Sik Jung, Seung Min Chung, Jeong A. Lee, Soo-youn Moon, Kwan Soo Ko, Doo Ryeon Chung, Nam Yong Lee, Jae-Hoon Song, Kyong Ran Peck
Journal: Journal of Infection (2010)
Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin receptor A in cardiovascular morphogenesis
Authors: N KANZAKIKATO, T TAMAKOSHI, Y FU, A CHANDRA, T ITAKURA, T UEZATO, T TANAKA, D CLOUTHIER, T SUGIYAMA, M YANAGISAWA
Journal: Cardiovascular Research (2004)

Foxc2/MFH-1 is a member of the forkhead family of transcription factors and Foxc2-deficient mice exhibit aortic arch anomalies (type B interruption of the aortic arch). Endothelin receptor type-A (ETA) is one of the two known endothelin receptors that belong to the G-protein-coupled receptor family. ETA-deficient mice show defects in the great arteries, primarily type B interruption of the aortic arch. Based on similar phenotypes in the cardiovascular system of Foxc2- and ETA-deficient mice, we investigated whether Foxc2 and ETA have a close relationship in aortic arch patterning.The Foxc2 and ETA homozygotes were obtained by crossing the Foxc2 and ETA heterozygotes, respectively. The double Foxc2/ETA homozygotes were obtained by crossing the double Foxc2/ETA heterozygotes.We investigated the expression of ETA in Foxc2-null mice and the expression of Foxc2 in ETA-null mice and found that the absence of either Foxc2 or ETA had no effect on the expression of the other. Next, we analyzed mice lacking both Foxc2 and ETA to examine the relationship between Foxc2 and ETA on aortic arch patterning in vivo. We found that the majority of Foxc2/ETA double-mutant embryos died around 11.5 dpc and that all surviving mice had persistent truncus arteriosus.The results suggest that Foxc2- and ETA-expressing cells additively form the aorticopulmonary septum.
P38 inhibition in COPD; cautious optimism
Authors: Dave Singh
Journal: Thorax (2013)

The nature of inflammation varies greatly between COPD patients, leading to heterogeneity in clinical manifestations. For example, emphysema is severe in some patients but minimal in others.1 The varied nature of COPD inflammation means that a novel anti-inflammatory drug is unlikely to be effective in all patients. This is certainly true for established anti-inflammatory therapies such as inhaled corticosteroids, which are most effective in the subgroup of patients with a history of exacerbations,2 and also those with evidence of increased sputum eosinophils.3 The PDE4 inhibitor, roflumilast, also shows greater efficacy in a COPD subgroup; those with chronic bronchitis and a history of exacerbations.4 

The p38 mitogen activated protein kinase (MAPK) signalling pathway promotes inflammation by enhancing inflammatory gene transcription, stabilising mRNAs and increasing protein translation.5 p38 MAPK signalling is activated by different extracellular stimuli that are relevant to COPD, such as cytokines, toll-like receptor agonists and oxidative stress including components of cigarette smoke.5–7 Furthermore, lung immunohistochemistry studies have demonstrated increased p38 MAPK activation in COPD patients compared with healthy controls.8 ,9 p38 MAPK inhibitors reduce cytokine production from different COPD lung cells in vitro, including alveolar macrophages,6 lymphocytes and bronchial epithelial cells.8 These observations from laboratory studies indicate that p38 MAPK activation contributes to COPD inflammation, and have encouraged the development of p38 MAPK inhibitors to treat COPD.10 ,11 

Orally administered p38 MAPK inhibitors have been developed for the treatment of inflammatory diseases including rheumatoid arthritis.12 ,13 Unfortunately, these drugs have caused unacceptable side effects including liver toxicity and skin reactions. Additionally, the efficacy appears to be transient; initial improvements in systemic inflammatory biomarkers including C-reactive protein (CRP) disappear within weeks.12 ,13 This may be due to ‘redundancy’, where blocking one pathway within a …
Effect of Baseline or Changes in Adrenergic Activity on Clinical Outcomes in the β-Blocker Evaluation of Survival Trial
Authors: M.R. Bristow, H. Krause-Steinrauf, R. Nuzzo, Cheng-Seng Liang, J. Lindenfeld, B.D. Lowes, B. Hattler, W.T. Abraham, L. Olson, S. Krueger, S. Thaneemit-Chen, J.M. Hare, H.S. Loeb, M.J. Domanski, E.J. Eichhorn, R. Zelis, P. Lavori
Journal: Circulation (2004)

Adrenergic activation is thought to be an important determinant of outcome in subjects with chronic heart failure (CHF), but baseline or serial changes in adrenergic activity have not been previously investigated in a large patient sample treated with a powerful antiadrenergic agent.Systemic venous norepinephrine was measured at baseline, 3 months, and 12 months in the beta-Blocker Evaluation of Survival Trial (BEST), which compared placebo treatment with the beta-blocker/sympatholytic agent bucindolol. Baseline norepinephrine level was associated with a progressive increase in rates of death or death plus CHF hospitalization that was independent of treatment group. On multivariate analysis, baseline norepinephrine was also a highly significant (P<0.001) independent predictor of death. In contrast, the relation of the change in norepinephrine at 3 months to subsequent clinical outcomes was complex and treatment group-dependent. In the placebo-treated group but not in the bucindolol-treated group, marked norepinephrine increase at 3 months was associated with increased subsequent risks of death or death plus CHF hospitalization. In the bucindolol-treated group but not in the placebo-treated group, the 1st quartile of marked norepinephrine reduction was associated with an increased mortality risk. A likelihood-based method indicated that 18% of the bucindolol group but only 1% of the placebo group were at an increased risk for death related to marked reduction in norepinephrine at 3 months.In BEST, a subset of patients treated with bucindolol had an increased risk of death as the result of sympatholysis, which compromised the efficacy of this third-generation beta-blocker.
Effect of complementary and alternative medicine on the survival and health-related quality of life among terminally ill cancer patients: a prospective cohort study
Authors: Y.H. Yun, M.K. Lee, S.M. Park, Y.A. Kim, W.J. Lee, K.S. Lee, J.S. Choi, K.H. Jung, Y.R. Do, S.Y. Kim, D.S. Heo, H.T. Kim, S.R. Park
Journal: Annals of Oncology (2012)
A Pilot Study of Isotretinoin in the Treatment of Juvenile Chronic Myelogenous Leukemia
Authors: Robert P. Castleberry, Peter D. Emanuel, Kenneth S. Zuckerman, Susan Cohn, Lewis Strauss, Rebecca L. Byrd, Alan Homans, Sarah Chaffee, Ruprecht Nitschke, Richard J. Gualtieri
Journal: New England Journal of Medicine (1994)

Juvenile chronic myelogenous leukemia (CML) is a rare myeloproliferative disease of infants and young children for which there is no effective therapy other than allogeneic bone marrow transplantation. In vitro, isotretinoin (13-cis-retinoic acid) attenuates both the spontaneous proliferation of leukemic peripheral-blood progenitor cells (granulocyte-macrophage colony-forming units) and their selective hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). We conducted a pilot study to evaluate the clinical efficacy of isotretinoin in juvenile CML.
Prospective randomized controlled clinical and histopathological study of acne vulgaris treated with dual mode of quasi-long pulse and Q-switched 1064-nm Nd:YAG laser assisted with a topically applied carbon suspension
Authors: Jae Yoon Jung, Jong Soo Hong, Chang Ho Ahn, Ji Young Yoon, Hyuck Hoon Kwon, Dae Hun Suh
Journal: Journal of the American Academy of Dermatology (2011)