tbuckley/cabot-search huggingface dataset:
Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes
Authors: Kangmin He, Xiaoli Shi, Xuejie Zhang, Song Dang, Xiaowei Ma, Fei Liu, Ming Xu, Zhizhen Lv, Dong Han, Xiaohong Fang, Youyi Zhang
Journal: Cardiovascular Research (2011)

Intercellular interactions between cardiomyocytes (CMs) and cardiofibroblasts (FBs) are important in the physiological and pathophysiological heart. Understanding such interactions is important for developing effective heart disease therapies. However, until recently, little has been known about these interactions. We aimed to investigate structural and functional connections between CMs and FBs that are distinct from gap junctions. By membrane dye staining, we observed long, thin membrane nanotubular structures containing actin and microtubules that connected neonatal rat ventricular CMs and FBs. By single-particle tracking, we observed vehicles moving between CMs and FBs within the membrane nanotubes. By dual colour staining, confocal imaging and flow cytometry, we observed mitochondria exchange between CMs and FBs in a coculture system. By combined atomic force microscopy (AFM) and confocal microscopy, we observed calcium signal propagation from AFM-stimulated CM (or FB) to unstimulated FB (or CM) via membrane nanotubes. By membrane and cytoskeleton staining, we observed similar nanotubular structures in adult mouse heart tissue, which suggests their physiological relevance. As a novel type of CM to FB communication, membrane nanotubes observed in vitro and in vivo provide structural and functional connectivity between CMs and FBs over long distances.
GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis
Authors: J. J. Lepore
Journal: Journal of Clinical Investigation (2006)

GATA transcription factors play critical roles in restricting cell lineage differentiation during development. Here, we show that conditional inactivation of GATA-6 in VSMCs results in perinatal mortality from a spectrum of cardiovascular defects, including interrupted aortic arch and persistent truncus arteriosus. Inactivation of GATA-6 in neural crest recapitulates these abnormalities, demonstrating a cell-autonomous requirement for GATA-6 in neural crest–derived SMCs. Surprisingly, the observed defects do not result from impaired SMC differentiation but rather are associated with severely attenuated expression of semaphorin 3C, a signaling molecule critical for both neuronal and vascular patterning. Thus, the primary function of GATA-6 during cardiovascular development is to regulate morphogenetic patterning of the cardiac outflow tract and aortic arch. These findings provide new insights into the conserved functions of the GATA-4, -5, and -6 subfamily members and identify GATA-6 and GATA-6–regulated genes as candidates involved in the pathogenesis of congenital heart disease.
Thalassemia 2016: Modern medicine battles an ancient disease
Authors: Deborah Rund
Journal: American Journal of Hematology (2015)

Thalassemia was first clinically described nearly a century ago and treatment of this widespread genetic disease has greatly advanced during this period. DNA‐based diagnosis elucidated the molecular basis of the disease and clarified the variable clinical picture. It also paved the way for modern methods of carrier identification and prevention via DNA‐based prenatal diagnosis. Every aspect of supportive care, including safer blood supply, more regular transfusions, specific monitoring of iron overload, parenteral and oral chelation, and other therapies, has prolonged life and improved the quality of life of these patients. Significant advances have also been made in allogenic bone marrow transplantation, the only curative therapy. Recently, there has been a rejuvenated interest in studying thalassemia at the basic science level, leading to the discovery of previously unknown mechanisms leading to anemia and enabling the development of novel therapies. These will potentially improve the treatment of, and possibly cure the disease. Pathways involving activin receptors, heat shock proteins, JAK2 inhibitors and macrophage targeted therapy, among others, are being studied or are currently in clinical trials for treating thalassemia. Novel types of genetic therapies are in use or under investigation. In addition to the challenges of treating each individual patient, the longer survival of thalassemia patients has raised considerations regarding worldwide control of thalassemia, since prevention is not universally implemented. This review will trace a number of the original medical milestones of thalassemia diagnosis and treatment, as well as some of the most recent developments which may lead to innovative therapeutic modalities. Am. J. Hematol. 91:15–21, 2016. © 2015 Wiley Periodicals, Inc.
The Murine Male Antigen. III. Variable Expression of H-Y by Murine Tumors2
Authors: Carol J. Wikstrand, Geoffrey Haughton
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article The Murine Male Antigen. III. Variable Expression of H-Y by Murine Tumors Get access Carol J. Wikstrand, Carol J. Wikstrand Search for other works by this author on: Oxford Academic PubMed Google Scholar Geoffrey Haughton Geoffrey Haughton Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 2, August 1974, Pages 527–532, https://doi.org/10.1093/jnci/53.2.527 Published: 01 August 1974 Article history Received: 22 February 1974 Accepted: 30 April 1974 Published: 01 August 1974
Cannabis use and risk of lung cancer: a case-control study
Authors: S. Aldington, M. Harwood, B. Cox, M. Weatherall, L. Beckert, A. Hansell, A. Pritchard, G. Robinson, R. Beasley
Journal: European Respiratory Journal (2008)

The aim of the present study was to determine the risk of lung cancer associated with cannabis smoking. A case-control study of lung cancer in adults <or=55 yrs of age was conducted in eight district health boards in New Zealand. Cases were identified from the New Zealand Cancer Registry and hospital databases. Controls were randomly selected from the electoral roll, with frequency matching to cases in 5-yr age groups and district health boards. Interviewer-administered questionnaires were used to assess possible risk factors, including cannabis use. The relative risk of lung cancer associated with cannabis smoking was estimated by logistic regression. In total, 79 cases of lung cancer and 324 controls were included in the study. The risk of lung cancer increased 8% (95% confidence interval (CI) 2-15) for each joint-yr of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 5-9) for each pack-yr of cigarette smoking, after adjustment for confounding variables including cannabis smoking. The highest tertile of cannabis use was associated with an increased risk of lung cancer (relative risk 5.7 (95% CI 1.5-21.6)), after adjustment for confounding variables including cigarette smoking. In conclusion, the results of the present study indicate that long-term cannabis use increases the risk of lung cancer in young adults.
Major Congenital Malformations after First-Trimester Exposure to ACE Inhibitors
Authors: William O. Cooper, Sonia Hernandez-Diaz, Patrick G. Arbogast, Judith A. Dudley, Shannon Dyer, Patricia S. Gideon, Kathi Hall, Wayne A. Ray
Journal: New England Journal of Medicine (2006)

Use of angiotensin-converting-enzyme (ACE) inhibitors during the second and third trimesters of pregnancy is contraindicated because of their association with an increased risk of fetopathy. In contrast, first-trimester use of ACE inhibitors has not been linked to adverse fetal outcomes. We conducted a study to assess the association between exposure to ACE inhibitors during the first trimester of pregnancy only and the risk of congenital malformations.We studied a cohort of 29,507 infants enrolled in Tennessee Medicaid and born between 1985 and 2000 for whom there was no evidence of maternal diabetes. We identified 209 infants with exposure to ACE inhibitors in the first trimester alone, 202 infants with exposure to other antihypertensive medications in the first trimester alone, and 29,096 infants with no exposure to antihypertensive drugs at any time during gestation. Major congenital malformations were identified from linked vital records and hospitalization claims during the first year of life and confirmed by review of medical records.Infants with only first-trimester exposure to ACE inhibitors had an increased risk of major congenital malformations (risk ratio, 2.71; 95 percent confidence interval, 1.72 to 4.27) as compared with infants who had no exposure to antihypertensive medications. In contrast, fetal exposure to other antihypertensive medications during only the first trimester did not confer an increased risk (risk ratio, 0.66; 95 percent confidence interval, 0.25 to 1.75). Infants exposed to ACE inhibitors were at increased risk for malformations of the cardiovascular system (risk ratio, 3.72; 95 percent confidence interval, 1.89 to 7.30) and the central nervous system (risk ratio, 4.39; 95 percent confidence interval, 1.37 to 14.02).Exposure to ACE inhibitors during the first trimester cannot be considered safe and should be avoided.
S85 British Thoracic Oncology Group Trial, BTOG2: Randomised phase III clinical trial of gemcitabine combined with cisplatin 50 mg/m2 (GC50) vs cisplatin 80 mg/m2 (GC80) vs carboplatin AUC 6 (GCb6) in advanced NSCLC
Authors: D. Ferry, L. J. Billingham, H. W. Jarrett, D. Dunlop, J. Thompson, M. Kumar, G. Skailes, M. Nicolson, R. Shah, P. Leonard, A. Chetiyawardana, P. Wells, C. Lewanski, P. Woll, B. Crosse, M. Hill, S. Pirrie, K. J. O'Byrne
Journal: Thorax (2011)

<h3>Background</h3> Platins are considered key drugs in treating advanced NSCLC. Carboplatin has been reported as inferior to cisplatin in meta-analyses while the optimal dose of cisplatin is unclear. <h3>Methods</h3> Eligibility was by histologically proven NSCLC, PS 0–2, stage IIIB/IV disease and a GFR of &gt;60 ml/min, using the Wright equation. Treatment was gemcitabine (1250 mg/m<sup>2</sup>) combined with cisplatin 50 mg/m<sup>2</sup>, cisplatin 80 mg/m<sup>2</sup> or carboplatin AUC 6, for up to four cycles. Carboplatin dosing was calculated using the Calvert equation. At the time of analysis 1223 deaths had been reported, allowing analysis according to the statistical plan. <h3>Results</h3> 1363 patients were randomised between April 2005 and November 2009. Trial arms were well balanced for PS, stage and age. Median age was 63, 32% were PS0, 60% PS1 and 8% PS2. The median delivered dose intensities (planned=100%) for platinum were GC50 99%, GC80 96% and GCb6 87%, for gemcitabine were 95%, 88% and 80% respectively. During treatment the proportion of patients experiencing at least one grade 3/4 AE were; GC50 27%, GC80 41% and GCb6 57%. At analysis 140 patients were alive and median follow-up was 21 months. Response rates were significantly different between arms; GC50 23%, GC80 33% and GCb6 28% (p=0.01). Median survival was: GC50 8.3 months, GC80 9.5 months and GCb6 10.0 months, with the GC50 arm statistically identified as differing from the other two. For subsequent primary comparisons of non-inferiority of GC50 v GC80 (HR=1.11) and GCb6 v GC80 (HR=0.96), the 95% CI for the cisplatin dose comparison (0.96, 1.27) did not exclude the pre-defined inferiority region of HR&gt;1.2 whereas the 95% CI for the GCb6 v GC80 comparison (0.84, 1.10) fell well below this inferiority region. <h3>Conclusion</h3> In advanced NSCLC the dose of cisplatin is important with GC50 giving the poorest outcome in terms of overall survival and response rate. GCb6 is not inferior to GC80 thus, in combination with gemcitabine, and in relation to survival time, carboplatin is clinically equivalent to that of cisplatin but other factors, such as quality of life, may influence treatment choice.
Treatment of chronic hepatitis C with interferon alfa-n3: A multicenter, randomized, open-label trial
Authors: D M Simon, S C Gordon, M M Kaplan, R S Koff, F Regenstein, G Everson, Y M Lee, F Weiner, A Silverman, T Plasse, D Fedorczyk, M Liao
Journal: Hepatology (1997)

ABSTRACT We studied the antiviral effectiveness and safety of interferon alfa–n3, a natural alpha interferon which contains multiple interferon species, in the treatment of previously untreated patients with chronic hepatitis C. Seventy–seven patients were randomized to receive either 1.0, 2.5, 5.0, or 10.0 million units (MU) of interferon alfa–n3 three times a week for 24 weeks and were then followed for an additional 24 weeks. At the end of therapy, 67% of patients in the 10 MU group normalized serum alanine transaminase (ALT) levels and 59% had no hepatitis C virus (HCV) RNA detected by polymerase chain reaction. At the end of the follow–up period, 44% of patients in the 10 MU group maintained normal ALT, and 24% had nondetectable HCV RNA. Lower doses were much less effective. Interferon alfa–n3 was well tolerated and no patient developed neutralizing anti–interferon antibodies during or after the treatment period. Interferon alfa–n3 appears to be effective against hepatitis C virus and deserves further study in larger randomized controlled trials.
Prevalence of Mental Health and Substance Use Disorders Among Homeless and Low-Income Housed Mothers
Authors: Ellen L. Bassuk, John C. Buckner, Jennifer N. Perloff, Shari S. Bassuk
Journal: American Journal of Psychiatry (1998)

Objective:This study compared the prevalence of DSM-III-R disorders among homeless and low-income housed mothers with the prevalence of these disorders among all women in the National Comorbidity Survey.Method:The authors used an unmatched case-control design for assessing 220 homeless and 216 housed mothers receiving public assistance.Results:Homeless and housed mothers had similar rates of psychiatric and substance use disorders. Both groups had higher lifetime and current rates of major depression and substance abuse than did all women in the National Comorbidity Survey. Both groups also had high rates of posttraumatic stress disorder and two or more lifetime conditions. Conclusions:The prevalence of trauma-related disorders among poor women was higher than that among women in the general population. Programs and policies designed for low-income mothers must respond to the high prevalence of DSM-III-R disorders. Am J Psychiatry 1998; 155: 1561-1564
New Strategies in Melanoma: Molecular Testing in Advanced Disease
Authors: Scott E. Woodman, Alexander J. Lazar, Kenneth D. Aldape, Michael A. Davies
Journal: Clinical Cancer Research (2012)

Melanoma is one of the most aggressive forms of skin cancer. The management of melanoma is evolving rapidly due to an improved understanding of the molecular heterogeneity of this disease and the development of effective, personalized, targeted therapy strategies. Although previous classification systems were based predominantly on clinical and histologic criteria, there is now a strong rationale for adding molecular markers to the diagnostic evaluation of these tumors. Research has shown that the types and prevalence of genetic alterations vary among melanoma subtypes. Thus, rational molecular testing should be based on an understanding of the events that are likely to occur in a given tumor and the clinical implications of test results. This review summarizes the existing data that support the rationale for molecular testing in clinically defined melanoma subtypes. Emerging challenges and controversies regarding the use of various molecular testing platforms, and their implications for clinical testing, are also discussed.
Investigating the role of IREB2 genetic variants in susceptibility to COPD
Authors: Noor Kalsheker, Sally Chappell, Tamar Guetta-Baranes, Aiman Alsaegh
Journal: European Respiratory Journal (2012)

The IREB2 gene encodes the iron-binding protein 2, which is a major regulator of iron homeostasis. Several studies have shown that the IREB2 locus is a contributor to COPD susceptibility. Previously, we observed significant associations of seven IREB2 genetic variants with increased risk of COPD in a large case-control study. Subsequent in-silico analysis showed that six of these SNPs were in tight linkage disequilibrium with two variants that lie within the promoter (rs2656070) and the 39UTR (rs12899351) of IREB2 gene. The promoter SNP is predicted to disrupt the binding of two transcription factors while the 39UTR SNP is located in a region that is predicted to be a target site of mir-1285 and mir-5096. The aims of this study were to evaluate the functional effect of these variants on IREB2 expression. To test the effect of the promoter SNP, two fragments (one for each allele) of the 59region of IREB2 were inserted upstream of the luciferase gene in the pGL3-Basic vector and then transfected into the A549 cells. Our results show that there was no difference in luciferase expression from cells transfected with rs2656070 wild type construct compared with the risk allele under basal conditions. Further analysis will be undertaken to examine the effect of the rs2656070 under different stimulatory conditions. For the 39UTR SNP, two fragments (for both alleles) spanning the potential miRNA target site was cloned downstream of the luciferase gene in pmirGLO vector and then transfected into HepG2 cells that are known to express mir-1285. Luciferase assay showed that mir-1285 did not recognize the cloned sequence. Additional investigation will consider the regulatory role of mir-5096 on IREB2 expression.
Behcet's syndrome in 32 patients in Yorkshire.
Authors: M.A Chamberlain
Journal: Annals of the Rheumatic Diseases (1977)

Thirty-two patients with Behcet's syndrome were surveyed clinically, radiologically, and immunologically. HLA antigens were determined in a proportion. The patients were culled from a defined geographical area (Yorkshire) with a population of 5 million. 21 patients satisfied Mason and Barnes's (1969) criteria for major disease. 100% had mouth ulceration, 91% genital ulceration, 66% skin complaints, and 63% arthritis (of the nonerosive type previously documented). 3 patients had gastrointestinal involvement, one of whom had proven Crohn's disease. One patient had psoriasis. One patient had a popliteal artery aneurysm resected and one has since had surgery after the development of a tracheo-osophageal fistula. No sacroilititis was found.
CICATRIZATION OF WOUNDS
Authors: P. Lecomte du Noüy
Journal: The Journal of Experimental Medicine (1919)

1. The law of cicatrization, of surface wounds may be expressed by an exponential formula in which the two coefficients may be determined. 2. A simple relation exists between these coefficients and the index, i, of cicatrization, previously established in function of the age of the patient and of the area of the wound. 3. The proposed equation with a simplified exponent, reduced to a single coefficient, expresses satisfactorily the phenomenon of contraction.
Differential Effects of Inhaled Corticosteroids in Smokers/Ex-Smokers and Nonsmokers with Asthma
Authors: Nicolas Roche, Dirkje S. Postma, Gene Colice, Anne Burden, Theresa W. Guilbert, Elliot Israel, Richard J. Martin, Willem M. C. van Aalderen, Jonathan Grigg, Elizabeth V. Hillyer, Julie von Ziegenweidt, David B. Price
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial
Authors: William T Cefalu, Lawrence A Leiter, Kun-Ho Yoon, Pablo Arias, Leo Niskanen, John Xie, Dainius A Balis, William Canovatchel, Gary Meininger
Journal: The Lancet (2013)
Detection of hypermethylation of the p16INK4A gene promoter in chronic hepatitis and cirrhosis associated with hepatitis B or C virus
Authors: H Kaneto
Journal: Gut (2001)

<h3>BACKGROUND/AIM</h3> Inactivation of the <i>p16</i><sup><i>INK4A</i></sup>(<i>p16</i>) tumour suppressor gene by promoter region hypermethylation has been demonstrated not only in many types of tumours, including hepatocellular carcinoma (HCC), but also in early preneoplastic lesions in the lung, colon, oesophagus, and pancreas. The aim of this study was to examine the methylation status of the<i>p16</i> promoter in pre- and/or non-neoplastic liver diseases. <h3>PATIENTS/SUBJECTS/METHODS</h3> The methylation status of <i>p16</i> was evaluated in 22 HCC, 17 cirrhosis, 17 chronic hepatitis, nine primary biliary cirrhosis (PBC), eight autoimmune hepatitis, seven drug induced liver disease, six fatty liver, and three normal liver tissues using methylation specific polymerase chain reaction (MSP). p16 protein expression was also examined by immunohistochemical staining. <h3>RESULTS</h3> Methylation of the <i>p16</i> promoter was detected in HCC (72.7%, 16/22) and also in cirrhosis (29.4%, 5/17) and chronic hepatitis (23.5%, 4/17), all of which were positive for hepatitis B or C virus infections. Methylation was not detected in any of the other samples. All methylation positive HCC, cirrhosis, and chronic hepatitis samples showed loss of p16 expression, and a significant correlation was found between methylation and loss of expression. Analysis of serial samples from individual patients with methylation positive HCC revealed that loss of p16 expression with promoter methylation occurred in 18 of 20 patients at the stage of chronic hepatitis without clinically detectable carcinoma. <h3>CONCLUSIONS</h3> Our results suggest that methylation of the <i>p16</i>promoter and the resulting loss of p16 protein expression are early events in a subset of hepatocarcinogenesis and that their detection is useful in the follow up of patients with a high risk of developing HCC, such as those with hepatitis B or C viral infections.
The Growing Problem of Multidrug-Resistant Tuberculosis in North Korea
Authors: Kwonjune J. Seung, Stephen W. Linton
Journal: PLoS Medicine (2013)

Kwonjune Seung and Stephen Linton from the non-governmental organization EugeneBell discuss the worryingly high levels of multidrug-resistant tuberculosis they have observed in North Korea's tuberculosis sanatoria. Please see later in the article for the Editors' Summary