tbuckley/cabot-search huggingface dataset:
Energy Metabolism in Obesity: Studies in the Pima Indians
Authors: Eric Ravussin
Journal: Diabetes Care (1993)

To review the major data collected over the past 8 yr regarding energy expenditure in relationship to obesity and the development of obesity in the Pima Indian population.The different components of 24-h energy expenditure (i.e., the RMR, the thermic effect of food, and the energy cost of spontaneous physical activity) were measured in a respiratory chamber after a few days on a weight-maintenance diet.Fat-free body mass, the major determinant of RMR, explains 82% of its variance. However, an extra 7% of the variance in RMR observed between people is related to family membership. The variability of RMR for a given body size and composition is of importance, because a low metabolic rate is a major risk factor for weight gain in man. Also, genetic factors seem to be the cause of the familial aggregation of metabolic rate in man.The high prevalence of obesity and NIDDM in the Pima Indian community might be the consequence of a "thrifty genotype." The increasing evidence that obesity cannot always be attributed to gluttony and sloth forces us to consider obesity as a "real metabolic disease" that needs to be treated as such, using new behavioral and pharmacological therapies.
Chemokines and Chemokine Receptors: Biology and Clinical Relevance in Inflammation and AIDS
Authors: Massimo Locati, MD, Philip M. Murphy, MD
Journal: Annual Review of Medicine (1999)

Chemokines constitute a large family of chemotactic cytokines that act at G protein-coupled receptors to regulate diverse biological processes, including leukocyte trafficking, angiogenesis, hematopoiesis, and organogenesis. They are believed to be both beneficial in host defense against infectious agents and harmful in diseases marked by pathologic inflammation; however, actual clinical roles in these areas have not yet been established. Recently, unexpected ways have been discovered in which medically important pathogens, including HIV-1, exploit or subvert the chemokine system. These and other recent results suggest that targeting specific chemokines and chemokine receptors may have therapeutic utility in both inflammation and infectious disease.
Expression of Tumor-Derived Vascular Endothelial Growth Factor and Its Receptors Is Associated With Outcome in Early Squamous Cell Carcinoma of the Lung
Authors: María J. Pajares, Jackeline Agorreta, Marta Larrayoz, Aurélien Vesin, Teresa Ezponda, Isabel Zudaire, Wenceslao Torre, María D. Lozano, Elisabeth Brambilla, Christian Brambilla, Ignacio I. Wistuba, Carmen Behrens, Jean-Francois Timsit, Ruben Pio, John K. Field, Luis M. Montuenga
Journal: Journal of Clinical Oncology (2012)

Antiangiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have yielded more modest clinical benefit to patients with non-small-cell lung cancer (NSCLC) than initially expected. Clinical data suggest a distinct biologic role of the VEGF pathway in the different histologic subtypes of lung cancer. To clarify the influence of histologic differentiation in the prognostic relevance of VEGF-mediated signaling in NSCLC, we performed a concomitant analysis of the expression of three key elements of the VEGF pathway in the earliest stages of the following two principal histologic subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC).We evaluated tumor cell expression of VEGF, VEGF receptor (VEGFR) 1, and VEGFR2 using automatic immunostaining in a series of 298 patients with early-stage NSCLC recruited as part of the multicenter European Early Lung Cancer Detection Group project. A score measuring the VEGF signaling pathway was calculated by adding the tumor cell expression value of VEGF and its two receptors. The results were validated in two additional independent cohorts of patients with NSCLC.The combination of high VEGF, VEGFR1, and VEGFR2 protein expression was associated with lower risk of disease progression in early SCC (univariate analysis, P = .008; multivariate analysis, hazard ratio, 0.62; 95% CI, 0.42 to 0.92; P = .02). The results were validated in two independent patient cohorts, confirming the favorable prognostic value of high VEGF signaling score in early lung SCC.Our results clearly indicate that the combination of high expression of the three key elements in the VEGF pathway is associated with a good prognosis in patients with early SCC but not in patients with ADC.
Injection of Amniotic Fluid Stem Cells Delays Progression of Renal Fibrosis
Authors: Sargis Sedrakyan, Stefano Da Sacco, Anna Milanesi, Liron Shiri, Astgik Petrosyan, Radka Varimezova, David Warburton, Kevin V. Lemley, Roger E. De Filippo, Laura Perin
Journal: Journal of the American Society of Nephrology (2012)

Injection of amniotic fluid stem cells ameliorates the acute phase of acute tubular necrosis in animals by promoting proliferation of injured tubular cells and decreasing apoptosis, but whether these stem cells could be of benefit in CKD is unknown. Here, we used a mouse model of Alport syndrome, Col4a5−/− mice, to determine whether amniotic fluid stem cells could modify the course of progressive renal fibrosis. Intracardiac administration of amniotic fluid stem cells before the onset of proteinuria delayed interstitial fibrosis and progression of glomerular sclerosis, prolonged animal survival, and ameliorated the decline in kidney function. Treated animals exhibited decreased recruitment and activation of M1-type macrophages and a higher proportion of M2-type macrophages, which promote tissue remodeling. Amniotic fluid stem cells did not differentiate into podocyte-like cells and did not stimulate production of the collagen IVa5 needed for normal formation and function of the glomerular basement membrane. Instead, the mechanism of renal protection was probably the paracrine/endocrine modulation of both profibrotic cytokine expression and recruitment of macrophages to the interstitial space. Furthermore, injected mice retained a normal number of podocytes and had better integrity of the glomerular basement membrane compared with untreated Col4a5−/− mice. Inhibition of the renin-angiotensin system by amniotic fluid stem cells may contribute to these beneficial effects. In conclusion, treatment with amniotic fluid stem cells may be beneficial in kidney diseases characterized by progressive renal fibrosis.
Gastric bacterial overgrowth is a cause of false positive diagnosis of Helicobacter pylori infection using 13C urea breath test
Authors: L MICHAUD, F GOTTRAND, P S GANGA-ZANDZOU, N WIZLA-DERAMBURE, D TURCK, P VINCENT
Journal: Gut (1998)

Editor,—We read with interest the paper by Dominguez-Munos et al ( Gut 1997; 40 :459–62) describing an optimal test drink in the13C-urea breath test (13C UBT) for the diagnosis of Helicobacter pylori infection. In this study all H pylori negative subjects (adults with dyspeptic symptoms) had a negative result with the 13C UBT (specificity 100%) after different meals. In other studies, using13C UBT to document H pylori infection both in adults and children, the sensitivity of the test ranged from 92 to 100% whereas specificity was usually above 92%.1 2However, no explanation has been given for the occurrence of false positive tests. Methodological bias and problems in defining the cut off value are possible reasons. However, there are …
Ehlers-Danlos syndrome type IV with few extrathoracic findings: a newly recognized point mutation in the COL3A1 gene
Authors: A. Watanabe, Y. Kawabata, O. Okada, N. Tanabe, H. Kimura, A. Hatamochi, H. Shinkai, N. Sakai, T. Shimada, K. Hiroshima, T. Kuriyama
Journal: European Respiratory Journal (2001)

Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutation within the COL3A1 gene, resulting in the disorder of type III procollagen. The diagnosis is confirmed by demonstrating the synthesis of abnormal type III procollagen molecules from cultured dermal fibroblasts or by identifying the mutation in the COL3A1 gene. The authors report a case of EDS IV caused by a novel point mutation in the COL3A1 gene in a 16-yr-old female. Recurrent haemoptysis and cavitary formation of the lung were evidence of pulmonary involvement. However, extrathoracic manifestations of EDS IV were mostly absent. To the best of the authors' knowledge, all previously reported Ehlers-Danlos syndrome IV patients with respiratory disease had the characteristic findings or histories of Ehlers-Danlos syndrome IV. In the present case, connective tissue friability was suspected due to tissue laceration observed in the biopsied lung specimen, and the diagnosis was made beginning from this pivotal finding.
Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study
Authors: Mark Roschewski, Kieron Dunleavy, Stefania Pittaluga, Martin Moorhead, Francois Pepin, Katherine Kong, Margaret Shovlin, Elaine S Jaffe, Louis M Staudt, Catherine Lai, Seth M Steinberg, Clara C Chen, Jianbiao Zheng, Thomas D Willis, Malek Faham, Wyndham H Wilson
Journal: The Lancet Oncology (2015)
The Oslo Sports Trauma Research Center questionnaire on health problems: a new approach to prospective monitoring of illness and injury in elite athletes
Authors: Benjamin Clarsen, Ola Rønsen, Grethe Myklebust, Tonje Wåle Flørenes, Roald Bahr
Journal: British Journal of Sports Medicine (2013)

Background Little information exists on the illness and injury patterns of athletes preparing for the Olympic and Paralympic Games. Among the possible explanations for the current lack of knowledge are the methodological challenges faced in conducting prospective studies of large, heterogeneous groups of athletes, particularly when overuse injuries and illnesses are of concern. Objective To describe a new surveillance method that is capable of recording all types of health problems and to use it to study the illness and injury patterns of Norwegian athletes preparing for the 2012 Olympic and Paralympic Games. Methods A total of 142 athletes were monitored over a 40-week period using a weekly online questionnaire on health problems. Team medical personnel were used to classify and diagnose all reported complaints. Results A total of 617 health problems were registered during the project, including 329 illnesses and 288 injuries. At any given time, 36% of athletes had health problems (95% CI 34% to 38%) and 15% of athletes (95% CI 14% to 16%) had substantial problems, defined as those leading to moderate or severe reductions in sports performance or participation, or time loss. Overuse injuries represented 49% of the total burden of health problems, measured as the cumulative severity score, compared to illness (36%) and acute injuries (13%). Conclusions The new method was sensitive and valid in documenting the pattern of acute injuries, overuse injuries and illnesses in a large, heterogeneous group of athletes preparing for the Olympic and Paralympic Games.
Role of the Heat Shock Response and Molecular Chaperones in Oncogenesis and Cell Death
Authors: Caroline Jolly, Richard I. Morimoto
Journal: JNCI Journal of the National Cancer Institute (2000)

Exposure of cells to conditions of environmental stress—including heat shock, oxidative stress, heavy metals, or pathologic conditions, such as ischemia and reperfusion, inflammation, tissue damage, infection, and mutant proteins associated with genetic diseases—results in the inducible expression of heat shock proteins that function as molecular chaperones or proteases. Molecular chaperones are a class of proteins that interact with diverse protein substrates to assist in their folding, with a critical role during cell stress to prevent the appearance of folding intermediates that lead to misfolded or otherwise damaged molecules. Consequently, heat shock proteins assist in the recovery from stress either by repairing damaged proteins (protein refolding) or by degrading them, thus restoring protein homeostasis and promoting cell survival. The events of cell stress and cell death are linked, such that molecular chaperones induced in response to stress appear to function at key regulatory points in the control of apoptosis. On the basis of these observations—and on the role of molecular chaperones in the regulation of steroid aporeceptors, kinases, caspases, and other protein remodeling events involved in chromosome replication and changes in cell structure—it is not surprising that the heat shock response and molecular chaperones have been implicated in the control of cell growth. In this review, we address some of the molecular and cellular events initiated by cell stress—the interrelationships between stress signaling, cell death, and oncogenesis—and chaperones as potential targets for cancer diagnosis and treatment.
ATP-binding Cassette Transporter G1 Deficiency Dysregulates Host Defense in the Lung
Authors: David W. Draper, Jennifer H. Madenspacher, Darlene Dixon, Debra H. King, Alan T. Remaley, Michael B. Fessler
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Mice with genetic deletion of the cholesterol efflux transporter, ATP-binding cassette (ABC) G1, have pulmonary lipidosis and chronic pulmonary inflammation. Whether ABCG1 regulates host defense is unknown.To determine whether ABCG1 regulates pulmonary innate immunity and host defense, and to investigate the underlying molecular/cellular mechanisms.Abcg1(+/+) and Abcg1(-/-) mice were challenged with intrapulmonary lipopolysaccharide (LPS) or Klebsiella pneumoniae, intravenous K. pneumoniae, or intraperitoneal LPS. Phenotypic responses were profiled. Bone marrow chimeras and in vitro assays were used to differentiate and characterize the role of hematopoietic versus nonhematopoietic ABCG1 in host defense.Unexposed Abcg1(-/-) mice had normal numbers of circulating neutrophils, but increased neutrophil recruitment to the airspace and lung parenchyma, and increased airspace cytokines and chemokines in the steady state. After intrapulmonary LPS or K. pneumoniae, Abcg1(-/-) mice displayed exaggerated further neutrophil recruitment to and degranulation in the airspace, and elevated airspace cytokine/chemokine induction. Alveolar macrophage ABCG1 was critical, as ABCG1 deficiency in hematopoietic cells was sufficient to enhance responses in vivo, and Abcg1(-/-) alveolar macrophages adopted a "foam cell" phenotype, and were hyperresponsive ex vivo. Pulmonary compartmentalization and clearance of K. pneumoniae were increased in Abcg1(-/-) mice, indicating enhanced host defense. By contrast, Abcg1(+/+) and Abcg1(-/-) mice had equivalent responses to intravenous K. pneumoniae and intraperitoneal LPS, suggesting that ABCG1 regulates innate immunity in a tissue-selective manner.Abcg1(-/-) mice have an enhanced pulmonary host defense response driven predominantly by hematopoietic cells.
1081-61 Arterial retroperfusion by a percutaneous stent-based ventricle to coronary vein bypass (VVPASS™)
Authors: Peter Boekstegers, Philip Raake, Martin Andrees, Sabrina Beller, Rabea Hinkel, Marie-Luise Von Brühl, Christian Kupatt
Journal: Journal of the American College of Cardiology (2004)
Subxiphoid cross-sectional echocardiography in infants and children with congenital heart disease.
Authors: L W Lange, D J Sahn, H D Allen, S J Goldberg
Journal: Circulation (1979)

We developed anatomically related cross-sectional echocardiographic views to image the heart from the subxiphoid area in 100 children and infants with various forms of congenital heart disease studied prospectively before cardiac catheterization. Wide-angle cross-sectional views were achieved using a mechanical sector scanner in a scan plane oriented parallel to a line between the patient's shoulders (a coronal plane) showing the equivalent anatomy of an anteroposterior angiogram. The subxiphoid technique appeared to be better than chest wall-based imaging in demonstrating obstructive lesions in the proximal portion of the right ventricular outflow tract (19 patients), i.e., the subpulmonic area, which is often at the narrow edge of the sector and behind the transducer artifact in chest wall studies. The subxiphoid technique was also useful for imaging the interatrial and interventricular septae; in subxiphoid views, as opposed to four-chamber apical views, there was significantly less false septal dropout and atrial septal defects (19 patients) as well as ventricular septal aneurysms (seven patients) were easily imaged. Finally, the subxiphoid orientation provided more adequate imaging in patients with discrete diaphragmatic subaortic stenosis (four patients), even when the diaphragm was just beneath the aortic valve. Subxiphoid cross-sectional echocardiography is an easily understood anatomical format for imaging cross-sectional anatomy in congenital heart disease and is a valuable adjunct to cross-sectional echocardiography from the chest wall.
Accounting for Background Nucleotide Composition When Measuring Codon Usage Bias: Brilliant Idea, Difficult in Practice
Authors: Anders Fuglsang
Journal: Molecular Biology and Evolution (2006)

The effective number of codons used in a gene is a commonly used measure of codon usage. It varies between 20 and 61 (standard genetic code) and indicates to which degree the entire genetic code is used. It is a drawback of this method that it does not take background composition into account. This led Novembre to introduce a variant called Nc' (Novembre JA. 2002. Accounting for background nucleotide composition when measuring codon usage bias. Mol Biol Evol 19:1390-4). In this letter, its properties are under the loupe, with special emphasis on phenomena relating to codon homozygosity. A theoretical misunderstanding regarding this estimator is explained in detail, notably Nc varies between 0 and 61 instead of 20 and 61 (with the standard genetic code). Practical examples from the genome of Pseudomonas aeruginosa are given which demonstrate that the problem is not just theoretical.
Prognostic factors of survival and rapid progression in782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Français d’Immunothérapie
Authors: S. Négrier, B. Escudier, F. Gomez, J.-Y. Douillard, A. Ravaud, C. Chevreau, M. Buclon, D. Pérol, C. Lasset
Journal: Annals of Oncology (2002)
CTCFL/BORIS Is a Methylation-Independent DNA-Binding Protein That Preferentially Binds to the Paternal <i>H19</i> Differentially Methylated Region
Authors: Phuongmai Nguyen, Hengmi Cui, Kheem S. Bisht, Lunching Sun, Krish Patel, Richard S. Lee, Hiroyuki Kugoh, Mitsuo Oshimura, Andrew P. Feinberg, David Gius
Journal: Cancer Research (2008)

Abstract The CTCF paralog BORIS (brother of the regulator of imprinted sites) is an insulator DNA-binding protein thought to play a role in chromatin organization and gene expression. Under normal physiologic conditions, BORIS is predominantly expressed during embryonic male germ cell development; however, it is also expressed in tumors and tumor cell lines and, as such, has been classified as a cancer-germline or cancer-testis gene. It has been suggested that BORIS may be a pro-proliferative factor, whereas CTCF favors antiproliferation. BORIS and CTCF share similar zinc finger DNA-binding domains and seem to bind to identical target sequences. Thus, one critical question is the mechanism governing the DNA-binding specificity of these two proteins when both are present in tumor cells. Chromatin immunoprecipitation (ChIP) in HCT116 cells and their hypermethylated variant showed that BORIS binds to methylated DNA sequences, whereas CTCF binds to unmethylated DNA. Electromobility shift assays, using both whole-cell extracts and in vitro translated CTCF and BORIS protein, and methylation-specific ChIP PCR showed that BORIS is a methylation-independent DNA-binding protein. Finally, experiments in murine hybrid cells containing either the maternal or paternal human chromosome 11 showed that BORIS preferentially binds to the methylated paternal H19 differentially methylated region, suggesting a mechanism in which the affinity of CTCF for the unmethylated maternal allele directs the DNA binding of BORIS toward the paternal allele. [Cancer Res 2008;68(14):5546–51]
Ischemic Preconditioning in Pigs: A Graded Phenomenon
Authors: Rainer Schulz, Heiner Post, Christian Vahlhaus, Gerd Heusch
Journal: Circulation (1998)

Background —A threshold concept for ischemic preconditioning (IPc) has been proposed. It is unclear, however, whether IPc, above a certain threshold, is an all-or-nothing or a graded phenomenon. Methods and Results —In 71 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 minutes followed by 2 hours of reperfusion resulted in an infarct size (IS, by triphenyltetrazolium chloride) of 16.7±3.4% (SEM) of the area at risk. IPc by 2 minutes of low-flow ischemia and 15 minutes of reperfusion before the 90-minute target ischemia did not reduce IS (21.9±7.0%). IS was decreased to 9.0±2.6% ( P &lt;0.05) by 3 minutes of IPc and reduced further to 1.9±0.9% ( P &lt;0.05) by 10 minutes of IPc. The interstitial adenosine concentration (microdialysis, high-performance liquid chromatography) was unchanged with 2 and 3 minutes of IPc but increased with 10 minutes of IPc (by 573±144%). The interstitial bradykinin concentration (microdialysis, radioimmunoassay) remained unchanged with 2 minutes of IPc but increased to a similar extent with 3 minutes (by 198±32%) and 10 minutes (by 224±30%) of IPc. The IS reduction by 3 minutes of IPc was abolished by blockade of the bradykinin B 2 receptor with intracoronary HOE 140 (16.6±4.3%) but not with intracoronary infusion of adenosine deaminase (8.4±2.5%, P &lt;0.05). HOE 140, however, did not affect the IS reduction (3.5±1.1%, P &lt;0.05) by 10 minutes of IPc. Combined infusion of HOE 140 and adenosine deaminase abolished the IS reduction by 10 minutes of IPc (15.4±6.7%). Conclusions —IS reduction by IPc is a graded phenomenon. Whereas bradykinin is essential during preconditioning ischemia of shorter duration, adenosine is more important during preconditioning ischemia of longer duration.
Serial testing using interferon- release assays in nursing students in India
Authors: Alice Zwerling, Madhukar Pai, Joy Sarojini Michael, Devasahayam J. Christopher
Journal: European Respiratory Journal (2014)

To the Editor: 

We have previously shown that Indian healthcare workers have higher prevalence of latent tuberculosis infection (LTBI) and are at increased risk for new infection [1]–[4]. Interferon-γ release assays (IGRAs) have been introduced as an alternative to the tuberculin skin test (TST) for diagnosing LTBI in healthcare workers and other high-risk groups. They have logistical advantages over the TST and will not cross-react with the bacille Calmette Guerin vaccine. IGRAs are now being widely used for screening healthcare workers [5], yet recent reports indicate that switching from TST to IGRAs for the serial testing of healthcare workers may result in increased rates of test conversions and reversions [3], [6]–[8]. Most of these studies are from low tuberculosis (TB) incidence settings, with limited opportunity for nosocomial TB exposure; as a result, the increased conversion rates are considered false-positive test conversions, making it difficult for clinicians to interpret IGRA test conversions in these settings [9]. It remains unclear whether IGRA conversions are associated with TB exposure in high TB incidence settings where unprotected exposure to infectious TB patients is more common among healthcare workers.

To evaluate whether IGRA conversions may represent new cases of LTBI, in a high TB incidence setting, in the absence of a gold standard for LTBI, we employed TB exposure as a proxy measure. We established a cohort of nursing students who underwent IGRA testing annually for 3 years at a tertiary level hospital in southern India [1]. Annual rates of conversions and reversions were estimated in this cohort. A relationship between occupational TB exposure and change in continuous interferon-γ (IFN-γ) levels were …