tbuckley/cabot-search huggingface dataset:
Predicted relative prevalence estimates for obstructive sleep apnoea and the associated healthcare provision across the UK
Authors: Joerg Steier, Alistair Martin, Judy Harris, Ian Jarrold, Darien Pugh, Adrian Williams
Journal: Thorax (2013)

We surveyed the UK distribution of five factors commonly associated with obstructive sleep apnoea (OSA) to produce an overall risk map that could be used to predict relative prevalence estimates. The weighting and mapping of selected risk factors associated with OSA highlighted significant regional variation in predicted prevalence estimates. These data provide the first attempt to systematically map the UK for OSA and identify areas where the condition is likely to be more prevalent. The data show a significant mismatch between areas identified as having a high predicted prevalence estimate and the distribution of existing sleep centres.
<i>TRIB3</i> Functional Q84R Polymorphism Is a Risk Factor for Metabolic Syndrome and Carotid Atherosclerosis
Authors: Hui-ping Gong, Zhi-hao Wang, Hao Jiang, Ning-ning Fang, Ji-sheng Li, Yuan-yuan Shang, Yun Zhang, Ming Zhong, Wei Zhang
Journal: Diabetes Care (2009)

OBJECTIVE To determine the association of TRIB3 Q84R polymorphism with metabolic syndrome (MetS) and carotid atherosclerosis. RESEARCH DESIGN AND METHODS A case-control study enrolled 513 Chinese subjects in three groups: control, MetS, and obese. The functional TRIB3 Q84R polymorphism was genotyped among subjects undergoing carotid ultrasonography. The clinical and biochemical characteristics were determined. RESULTS For individuals with the TRIB3 R84 allele, the odds ratio for developing MetS was 2.349 (P = 0.018), abdominal obesity 2.351 (P = 0.012), hypertriglyceridemia 2.314 (P = 0.00003), and insulin resistance 1.697 (P = 0.023). Likewise, the odds ratio for individuals with the TRIB3 R84 allele to develop thickened intima-media thickness was 2.208 (P = 0.040). CONCLUSIONS Individuals with the functional TRIB3 Q84R polymorphism are at risk for MetS. The TRIB3 R84 allele especially predisposes to carotid atherosclerosis in part through the effects of abdominal obesity, hypertriglyceridemia, and insulin resistance.
Anti-Laminin Receptor Antibody Targeting of Liposomes With Encapsulated Doxorubicin to Human Breast Cancer Cells In Vitro
Authors: A. Rahman, M. Panneerselvam, R. Guirguis, V. Castronovo, M. E. Sobel, K. Abraham, P. E. Daddona, L. A. Liotta
Journal: JNCI Journal of the National Cancer Institute (1989)

The tumor cell laminin receptor is a cell-surface protein that binds laminin with high affinity (Kd = 1.0 nM). The putative ligand-binding domain of the laminin receptor has been molecularly cloned and sequenced. In the present study, we used the predicted amino acid sequence of the laminin receptor to generate synthetic peptide antigens and produced immunoglobulin M (IgM) anti-laminin receptor monoclonal antibodies. The disulfide bond group of the IgM molecule was used to couple the antibodies to the surface of liposomes encapsulating doxorubicin. The anti-laminin receptor monoclonal antibodies coupled to the liposomes bound avidly to the surface of MDA-MB-435S (MDA-435) human breast carcinoma cells, which have high numbers of laminin receptors. These antibody-coupled liposomes exhibited a low degree of binding to Hs 578Bst (Hs 578) normal human breast epithelial cells, which express a low number of laminin receptors. Excess liposomes competed for the binding of unbound laminin to the tumor cell surface, and excess laminin competed for binding with the liposomes. Antibody-coupled liposomes encapsulating doxorubicin were specifically more efficient in inhibiting colony formation by MDA-435 cells in vitro than unbound doxorubicin or liposomes without anti-laminin receptor monoclonal antibodies. Unbound doxorubicin inhibited thymidine uptake by 10%-20% in both Hs 578 and MDA-435 cells, whereas the antibody-coupled liposomes encapsulating doxorubicin inhibited thymidine uptake by 90% in MDA-435 cells but only 15% in Hs 578 cells. Thus, use of anti-laminin receptor monoclonal antibodies coupled with liposomes encapsulating doxorubicin represents a new strategy for selective targeting of doxorubicin to carcinoma cells with exposed laminin receptors.
Impact of an educational intervention to improve adherence to treatment with continuous pressure airway positive
Authors: Nuria Feu Collado, Inmaculada Jurado Robles, Beatriz Villar Pastor, Liz Cordova Pacheco, Manolo Garcia Amores, Natalia Pascual Martinez, Bernabe Jurado Gamez, Luis Muñoz Cabrera
Journal: European Respiratory Journal (2012)

The treatment of choice for sleep apnea syndrome (SAS) is continuous pressure airway positive (CPAP). One of medical objectives is to improve compliance.  OBJECTIVES: To determine the role of an educational intervention on the adherence to CPAP after four months of treatment.  PATIENTS AND METHODS: This study has been undertaken at the Sleep Unit of a Tertiary Hospital. During 5 months all patients who were consecutively diagnosed of SAS and had indication for CPAP were enrolled.  Patients were classified exclusively according to the weekday when polysomnography was performed. The interventional group was composed by subjects who underwent polysomnography from Monday to Thursday. After testing, patients were shown the results of polysomnography on the computer screen. The control group included those patients who underwent polysomnography from Friday to Sunday. In both groups, the nurses explained the process of adaptation to CPAP. The patients were evaluated at the end of the first and fourth month. The treatment compliance at four months was measured by the ratio hours of use per day stored in the memory of the CPAP device.  RESULTS: We included 175 patients; 43 of them were women (25%), mean age = 54 ± 11 years, BMI = 31 ± 4, and score on the Epworth scale = 13 ± 2.4. The interventional group consisted of 101 patients. The average use of CPAP in the interventional group was significantly higher than that of the control group (4,7 ± 2,1 hours vs 3,6 ± 2,5 hours p = 0.005).  CONCLUSIONS: A vision of the sleep test by patients and an explanation by a physician is an intervention that significantly improves compliance with CPAP.
A Mouse Model for Meckel Syndrome Type 3
Authors: Susan A Cook, Gayle B Collin, Roderick T Bronson, Jürgen K Naggert, Dong P Liu, Ellen C Akeson, Muriel T Davisson
Journal: Journal of the American Society of Nephrology (2009)

Meckel-Gruber syndrome type 3 (MKS3; OMIM 607361) is a severe autosomal recessive disorder characterized by bilateral polycystic kidney disease. Other malformations associated with MKS3 include cystic changes in the liver, polydactyly, and brain abnormalities (occipital encephalocele, hydrocephalus, and Dandy Walker-type cerebellar anomalies). The disorder is hypothesized to be caused by defects in primary cilia. In humans, the underlying mutated gene, TMEM67, encodes transmembrane protein 67, also called meckelin (OMIM 609884), which is an integral protein of the renal epithelial cell and membrane of the primary cilium. Here, we describe a spontaneous deletion of the mouse ortholog, Tmem67, which results in polycystic kidney disease and death by 3 wk after birth. Hydrocephalus also occurs in some mutants. We verified the mutated gene by transgenic rescue and characterized the phenotype with microcomputed tomography, histology, scanning electron microscopy, and immunohistochemistry. This mutant provides a mouse model for MKS3 and adds to the growing set of mammalian models essential for studying the role of the primary cilium in kidney function.
Variates of Survival in Metastatic Uveal Melanoma
Authors: Petra Rietschel, Katherine S. Panageas, Christine Hanlon, Ami Patel, David H. Abramson, Paul B. Chapman
Journal: Journal of Clinical Oncology (2005)

The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival.All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy.The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis.A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.
Diurnal variation in serum levels of cartilage oligomeric matrix protein in patients with knee osteoarthritis or rheumatoid arthritis
Authors: M L E Andersson, I F Petersson, K E Karlsson, E N Jonsson, B Mansson, D Heinegard, T Saxne
Journal: Annals of the Rheumatic Diseases (2006)

To monitor changes in serum concentrations of cartilage oligomeric matrix protein (COMP) during a 24-h period to determine any diurnal variation, and to estimate the half life of COMP in the circulation in patients with symptomatic knee osteoarthritis and in those with rheumatoid arthritis.Serum samples were drawn every 4 h (7 samples/patient over 24 h) in 10 patients with knee osteoarthritis and 14 patients with rheumatoid arthritis. Osteoarthritis was defined radiographically and clinically (American College of Rheumatology (ACR) criteria) and rheumatoid arthritis according to the 1987 ACR criteria. Serum COMP was measured by sandwich ELISA. A statistical model for the diurnal variation in the COMP levels was developed using the computer program NONMEM.No considerable changes in COMP levels were observed during the day between 08:00 and 21:00 in either group. A significant decrease in serum COMP was apparent during bed rest at night, reaching the lowest levels between 04:00 and 05:00 (p<0.03 or better v all other time points) in patients with osteoarthritis and in those with rheumatoid arthritis. From the rate of decreasing serum COMP levels, a putative half life of COMP in the circulation was estimated to be 7.4 h.During normal daytime activities, serum COMP levels are constant. The decrease during the night indicates a rapid elimination of COMP once it has reached the circulation. The stable COMP levels during the day suggest that it is not necessary to further standardise the time of serum sampling in clinical practice.
IMPORTANCE OF GENETIC VARIANTS AND ETHNICITY IN NON-CONTACT MUSCULOSKELETAL SOFT TISSUE INJURIES
Authors: Pruna Ricard, Artells Rosa, Ribas Jordi, Montoro Bruno, Monzo Mariano
Journal: British Journal of Sports Medicine (2013)

Background The prevention, diagnosis, and management of noncontact musculoskeletal soft tissue injuries (NCMSTI) related to participation in sport are key components of sport and exercise medicine physician. Epidemiological data have demonstrated the existence of interindividual differences in NCMSTI severity indicating that those injuries occur as a consequence of a combination of both, extrinsic and intrinsic factors, including genetic variations. Methodology We examined 8 single nucleotide polymorphisms (SNPs) in the following genes (ELN, TTN, SOX15, IGF2, CCL2, COL1A1, COL5A1 and TNC) related to tissue recovery and tissue repair in a total of 73 elite european football players population from white, black-african and hispanic origin and, at the same time, we have collected NCMSTI suffered by these population during three consecutive seasons. Finally we have correlated results with type, degree and recovery time in injuries collected and then with the distribution of injuries in the three studied populations. Results 242 injuries were recorded (203 were muscle, 24 were ligament, and 15 were tendon). The degree of muscle injury was related to IGF2 (P=0.032). Moreover, we observed a close but non-significant relation between degree of muscle injury and CCL2 (P=0.1) and COL5A1 (P=0.07). We also found a close relation between ELN and degree (P=0.09) and a significant relation between ELN and recovery time (P=0.027) of ligament injuries. The frequency of the SNPs varied among the three sub-groups in the present study (p&lt;0.0001). Our results shown a significant relation between ligament injuries and ELN (p=0.001) and a significant relation between tendinous injuries and ELN (p=0.05) and IGF2 (p=0.05) in white population. Moreover, we have observed a significant relation between muscle injuries and ELN (p=0.032) and IGF2 (p=0.016) in Hispanic population. Conclusions SNPs study constitutes a new field of investigation in Sports Medicine which will help us to identify individuals with shorter recovery and those with greater risk of injury. Our results are only the pave to demonstrate that these genotyping interracial differences are important when studying injuries and let us to indicate that the genetic profile based on the SNPs can be use to describe, as objectively as possible each individuals injurability risk and may well be a useful tool for football players to receive a more specific treatment and preventive care options.
A New Inbred Subline of Mice (129/terSv) with a High Incidence of Spontaneous Congenital Testicular Teratomas2
Authors: Leroy C. Stevens
Journal: JNCI Journal of the National Cancer Institute (1973)

About 30% of the males of a new inbred subline of mice, 129/terSv, developed spontaneous congenital testicular teratomas. This subline is closely related to strain 129/Sv, and the high incidence of teratomas was probably due to a single gene mutation. Hybrids of 129/terSv and other 129 sublines, presumably heterozygous at this locus, showed an intermediate incidence. Histologically the teratomas in 129/terSv mice were like those in strain 129/Sv. They contained many types of normal appearing immature and adult tissues derived from undifferentiated embryonic stem cells. They rarely metastasized. There was no maternal influence on the incidence of teratomas. Teratomas were experimentally induced in 129/terSv mice by grafting 11-, 12-, or 13-day fetal genital ridges to the testes of adults. The male genital ridges developed into testes, and most had teratomas. The primordial germ cells in 14-day and older genital ridges were resistant to the teratocarcinogenic process. The earliest spontaneous teratomas were observed in the testes of 16-day fetuses, and were composed of small clusters of embryonic cells within the seminiferous tubules. The number of countable foci ranged from 1–17. Grafts of female genital ridges developed into ovaries without teratomas.
Paradoxical sphincter contraction is rarely indicative of anismus
Authors: W A Voderholzer, D A Neuhaus, A G Klauser, K Tzavella, S A Müller-Lissner, N E Schindlbeck
Journal: Gut (1997)

Background —Anismus is thought to be a cause of chronic constipation by producing outlet obstruction. The underlying mechanism is paradoxical contraction of the anal sphincter or puborectalis muscle. However, paradoxical sphincter contraction (PSC) also occurs in healthy controls, so anismus may be diagnosed too often because it may be based on a non-specific finding related to untoward conditions during the anorectal examination. Aims —To investigate the pathophysiological importance of PSC found at anorectal manometry in constipated patients and in patients with stool incontinence. Methods —Digital rectal examination and anorectal manometry were performed in 102 chronically constipated patients, 102 patients with stool incontinence, and in 18 controls without anorectal disease. In 120 of the 222 subjects defaecography was also performed. Paradoxical sphincter contraction was defined as a sustained increase in sphincter pressure during straining. Anismus was assumed when PSC was present on anorectal manometry and digital rectal examination and the anorectal angle did not widen on defaecography. Results —Manometric PSC occurred about twice as often in constipated patients as in incontinent patients (41.2% versus 25.5%, p&lt;0.017) and its prevalence was similar in incontinent patients and controls (25.5% versus 22.2%). Oroanal or rectosigmoid transit times in constipated patients with and without PSC did not differ significantly (total 64.6 (8.9) hours versus 54.2 (8.1) hours; rectosigmoid 14.9 (2.4) hours versus 13.8 (2.5) hours). Conclusions —Paradoxical sphincter contraction is a common finding in healthy controls as well as in patients with chronic constipation and stool incontinence. Hence, PSC is primarily a laboratory artefact and true anismus is rare.
Pulmonary arterial hypertension: a comparison between children and adults
Authors: R.J. Barst, S.I. Ertel, M. Beghetti, D.D. Ivy
Journal: European Respiratory Journal (2011)

The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults. The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension. Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children. Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines. In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).
Overexpression of Smoothened Activates the Sonic Hedgehog Signaling Pathway in Pancreatic Cancer–Associated Fibroblasts
Authors: Kimberly Walter, Noriyuki Omura, Seung-Mo Hong, Margaret Griffith, Audrey Vincent, Michael Borges, Michael Goggins
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Accumulating evidence suggests that cancer-associated stromal fibroblasts (CAF) contribute to tumor growth by actively communicating with cancer cells. Our aim is to identify signaling pathways involved in tumor-stromal cell interactions in human pancreatic cancer. Experimental Design: We established primary fibroblast cultures from human pancreatic adenocarcinomas and nonneoplastic pancreas tissues. To identify differentially expressed genes in CAFs, we did gene expression profiling of human pancreatic CAFs and nonneoplastic pancreatic fibroblasts. Results: The Hedgehog receptor Smoothened (SMO) was upregulated in CAFs relative to control fibroblasts. CAFs expressing SMO could transduce the Sonic hedgehog signal to activate Gli1 expression, and small interfering RNA knockdown of SMO blocked the induction of Gli1 in these cells. Stromal fibroblasts of human primary pancreatic adenocarcinomas overexpressed Smo compared with normal pancreatic fibroblasts. Conclusions: These findings implicate overexpression of Smo as a mechanism for the activation of Hedgehog signaling in human pancreatic CAFs and suggest that stromal cells may be a therapeutic target for Smo antagonists in pancreatic cancer. Clin Cancer Res; 16(6); 1781–9
A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate
Authors: Yin C Lin, Suchit Jhunjhunwala, Christopher Benner, Sven Heinz, Eva Welinder, Robert Mansson, Mikael Sigvardsson, James Hagman, Celso A Espinoza, Janusz Dutkowski, Trey Ideker, Christopher K Glass, Cornelis Murre
Journal: Nature Immunology (2010)
BRG1 Increases Transcription of Proinflammatory Genes in Renal Ischemia
Authors: Masayo Naito, Richard A. Zager, Karol Bomsztyk
Journal: Journal of the American Society of Nephrology (2009)

Acute kidney injury stimulates renal production of inflammatory mediators, including TNF-alpha and monocyte chemoattractant protein 1 (MCP-1). These responses reflect, in part, injury-induced transcription of proinflammatory genes by proximal tubule cells. Because of the compact structure of chromatin, a series of events at specified loci remodel chromatin to provide access for transcription factors and RNA polymerase II (Pol II). Here, we examined the role of Brahma-related gene-1 (BRG1), a chromatin remodeling enzyme, in the transcription of TNF-alpha and MCP-1 in response to renal ischemia. Two hours after renal ischemic injury in mice, renal TNF-alpha and MCP-1 mRNA increased and remained elevated for at least 1 wk. Matrix chromatin immunoprecipitation assays revealed sustained increases in Pol II at these genes, suggesting that the elevated mRNA levels were, at least in part, transcriptionally mediated. The profile of BGR1 binding to the genes encoding TNF-alpha and MCP-1 resembled Pol II recruitment. Knockdown of BRG1 by small interfering RNA blocked an ATP depletion-induced increase in TNF-alpha and MCP-1 transcription in a human proximal tubule cell line; this effect was associated with decreased recruitment of BRG1 and Pol II to these genes. In conclusion, BRG1 promotes increased transcription of TNF-alpha and MCP-1 by the proximal tubule in response to renal ischemia.
Risk Factors for Intraprocedural and Clinically Significant Delayed Bleeding After Wide-field Endoscopic Mucosal Resection of Large Colonic Lesions
Authors: Nicholas G. Burgess, Andrew J. Metz, Stephen J. Williams, Rajvinder Singh, William Tam, Luke F. Hourigan, Simon A. Zanati, Gregor J. Brown, Rebecca Sonson, Michael J. Bourke
Journal: Clinical Gastroenterology and Hepatology (2013)