tbuckley/cabot-search huggingface dataset:
Usefulness of procalcitonin as a diagnostic marker of pleural effusion
Authors: Maha Yousif, Rana El-Helbawy, Amr Darwish, Heba Fathy, Nesrin El-Helbawy
Journal: European Respiratory Journal (2012)

Pleural effusions are common and are associated with many diseases. We investigated the usefulness of procalcitonin (PCT) as a diagnostic marker for the cause of pleural effusion. The study was carried out on 54 patients with pleural effusion divided into groups; transudate (n=6),empyema (n=9),T.B (n=8),parapneumonic effusions (PPE) (n=9) and malignant effusions (n=22). Levels of procalcitonin were measured both in serum & pleural effusions. Pleural fluid procalcitonin was highest in empyema 1.17±0.86 ng/ml, next highest in PPE (0.57±0.56 ng/ml), & lowest in transudative effusions (0.06±0.03 ng/ml). Pleural fluid & serum procalcitonin levels positively correlate in both empyema & PPE. The optimal discrimination of patients with empyema could be performed at a cut-off point of pleural fluid procalcitonin 0.09 ng/ml with area under the curve (AUC) of 0.93 (sensitivity 80%,specificity 95%) and at a serum procalcitonin 0.08 ng/ml with AUC of 0.74 (sensitivity 80%,specificity 60%). However, the optimal discrimination of PPE could be performed at a cut-off point of pleural fluid procalcitonin 0.065 ng/ml (sensitivity 78%, specificity 53%) and at a serum procalcitonin 0.054 ng/ml (sensitivity 89%,specificity 33%). The optimal discrimination of patients with (empyema & PPE) could be performed at a cut-off point of pleural fluid procalcitonin 0.075 ng/ml (sensitivity 83%,specificity 58%) and at a serum procalcitonin 0.07 ng/ml (sensitivity 83%,specificity 47%). In conclusion: Pleural fluid PCT is a good and early marker of infection in the pleural space and correlates with the serum PCT in patients with PPE or empyema. Pleural PCT had better diagnostic accuracy than the serum PCT in cases of PPE & empyema.
Correlation Between Midthigh Low- Density Muscle and Insulin Resistance in Obese Nondiabetic Patients in Korea
Authors: Dolmi Kim, Suyoun Nam, Chulwoo Ahn, Kyungwook Kim, Soojee Yoon, Junuh Kim, Bongsoo Cha, Sungkil Lim, Kyungrae Kim, Hyunchul Lee, Kapbum Huh
Journal: Diabetes Care (2003)

OBJECTIVE—We investigated the link between lipid-rich skeletal muscle, namely low-density muscle, and insulin resistance in Korea. RESEARCH DESIGN AND METHODS—Abdominal adipose tissue areas and midthigh skeletal muscle areas of 75 obese nondiabetic subjects (23 men, 52 women; mean age ± SD, 41.9 ± 14.1 years) were measured by computed tomography (CT). The midthigh skeletal muscle areas were subdivided into low-density muscle (0 to +30 Hounsfield units) and normal-density muscle (+31 to +100 Hounsfield units). The homeostasis model assessment (HOMA) score was calculated to assess whole-body insulin sensitivity. RESULTS—The abdominal visceral fat area and the midthigh low-density muscle area were found to be well correlated with the HOMA score (r = 0.471, P &amp;lt; 0.01 and r = 0.513, P &amp;lt; 0.01, respectively). The correlation between low-density muscle area and insulin resistance persisted after adjusting for BMI or total body fat mass (r = 0.451, P &amp;lt; 0.01 and r = 0.522, P &amp;lt; 0.01, respectively) and even after adjusting for abdominal visceral fat area (r = 0.399, P &amp;lt; 0.01). CONCLUSIONS—The midthigh low-density muscle area seems to be a reliable determinant of insulin resistance in Korean obese nondiabetic patients.
The dynamics of nuclear receptors and nuclear receptor coregulators in the pathogenesis of endometriosis
Authors: Sang Jun Han, Bert W. O'Malley
Journal: Human Reproduction Update (2014)

Endometriosis is defined as the colonization and growth of endometrial tissue at anatomic sites outside the uterine cavity. Up to 15% of reproductive-aged women in the USA suffer from painful symptoms of endometriosis, such as infertility, pelvic pain, menstrual cycle abnormalities and increased risk of certain cancers. However, many of the current clinical treatments for endometriosis are not sufficiently effective and yield unacceptable side effects. There is clearly an urgent need to identify new molecular mechanisms that critically underpin the initiation and progression of endometriosis in order to develop more specific and effective therapeutics which lack the side effects of current therapies. The aim of this review is to discuss how nuclear receptors (NRs) and their coregulators promote the progression of endometriosis. Understanding the pathogenic molecular mechanisms for the genesis and maintenance of endometriosis as modulated by NRs and coregulators can reveal new therapeutic targets for alternative endometriosis treatments. This review was prepared using published gene expression microarray data sets obtained from patients with endometriosis and published literature on NRs and their coregulators that deal with endometriosis progression. Using the above observations, our current understanding of how NRs and NR coregulators are involved in the progression of endometriosis is summarized. Aberrant levels of NRs and NR coregulators in ectopic endometriosis lesions are associated with the progression of endometriosis. As an example, endometriotic cell-specific alterations in gene expression are correlated with a differential methylation status of the genome compared with the normal endometrium. These differential epigenetic regulations can generate favorable cell-specific NR and coregulator milieus for endometriosis progression. Genetic alterations, such as single nucleotide polymorphisms and insertion/deletion polymorphisms of NR and coregulator genes, are frequently detected in ectopic lesions compared with the normal endometrium. These genetic variations impart new molecular properties to NRs and coregulators to increase their capacity to stimulate progression of endometriosis. Finally, post-translational modifications of NR coregulators, such as proteolytic processing, generate endometriosis-specific isoforms. Compared with the unmodified coregulators, these coregulator isoforms have unique functions that enhance the pathogenesis of endometriosis. Epigenetic/genetic variations and posttranslational modifications of NRs and coregulators alter their original function so that they become potent 'drivers' of endometriosis progression.
<i>CXCL12 G801A</i> Polymorphism Is a Risk Factor for Sporadic Prostate Cancer Susceptibility
Authors: Hiroshi Hirata, Yuji Hinoda, Nobuyuki Kikuno, Ken Kawamoto, Angela V. Dahiya, Yutaka Suehiro, Yuichiro Tanaka, Rajvir Dahiya
Journal: Clinical Cancer Research (2007)

The chemokine CXCL12 and its receptor CXCR4 have been found to be associated with cancer metastasis. A single nucleotide polymorphism of CXCL12 G801A has been described and is regarded as a target for cis-acting factor that has the ability to up-regulate CXCL12 expression. Currently, there are no reports investigating the role of CXCL12 G801A polymorphism in prostate cancer (PC).We genotyped CXCL12 G801A and p53Arg72Pro in 167 PC patients and 167 age-matched healthy subjects. Genotyping was done with PCR-RFLP and confirmed by direct DNA sequencing. To investigate the effect of the CXCL12 G801A polymorphism on CXCL12 and CXCR4 expression, immunohistochemistry was done in genotyped PC tissues.A significant increase in the GA + AA genotype of the CXCL12 G801A polymorphism was observed in PC patients compared with healthy controls. The frequency of CXCL12 AA genotype was significantly higher in a group of patients with lymph node metastasis (23%) compared with those without metastasis (7%). The frequency of CXCL12 expression in AA + GA genotype carriers was significantly higher than that in GG genotype carriers. Among the carriers with CXCL12 GA + AA genotypes, CXCR4 expression was also significantly higher compared with those with the GG genotype. Moreover, among the groups with both CXCL12- and CXCR4-positive staining, the frequency of the CXCL12 GA + AA genotype was high. Although we did not find a significant relationship between the frequency of the Arg/Pro + Pro/Pro genotype of p53 Arg72Pro and susceptibility in PC, there was a combined effect of CXCL12 GA + AA genotype and the p53 72Arg/Pro + Pro/Pro genotype on the frequency of PC. These results indicate that the p53 codon 72 polymorphism may interact with CXCL12 G801A.This is the first report showing that CXCL12 G801A polymorphism may be a risk factor for PC. Moreover, this study suggests that this polymorphism can be an important marker for detecting microinvasion and PC metastasis.
Smoking and Mortality — Beyond Established Causes
Authors: Brian D. Carter, Christian C. Abnet, Diane Feskanich, Neal D. Freedman, Patricia Hartge, Cora E. Lewis, Judith K. Ockene, Ross L. Prentice, Frank E. Speizer, Michael J. Thun, Eric J. Jacobs
Journal: New England Journal of Medicine (2015)

Mortality among current smokers is 2 to 3 times as high as that among persons who never smoked. Most of this excess mortality is believed to be explained by 21 common diseases that have been formally established as caused by cigarette smoking and are included in official estimates of smoking-attributable mortality in the United States. However, if smoking causes additional diseases, these official estimates may significantly underestimate the number of deaths attributable to smoking.
A Functional Variant at 19q13.3, rs967591G&amp;gt;A, Is Associated with Shorter Survival of Early-Stage Lung Cancer
Authors: Hyo-Sung Jeon, Guang Jin, Hyo-Gyoung Kang, Yi Young Choi, Won Kee Lee, Jin Eun Choi, Eun Young Bae, Seung Soo Yoo, Shin Yup Lee, Eung Bae Lee, Young Tae Kim, Jaehee Lee, Seung-Ick Cha, Chang Ho Kim, Sanghoon Jheon, In San Kim, Jae Yong Park
Journal: Clinical Cancer Research (2013)

This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) in 19q13.3 and survival of patients with early-stage non-small cell lung cancer (NSCLC), and to define the causative functional SNP of the association.A two-stage study design was used to evaluate five SNPs in relation to survival outcomes in 328 patients and then to validate the results in an independent patient population (n = 483). Luciferase assay and real-time PCR were conducted to examine functional relevance of a potentially functional SNP.Of the five SNPs, three SNPs (rs105165C>T, rs967591G>A, and rs735482A>C) were significantly associated with survival outcomes in a stage I study. The rs967591A allele had significantly higher activity of the CD3EAP promoter compared with the rs967591G allele (P = 0.002), but the SNP did not have an effect on the activity of PPP1R13L promoter. The rs967591G>A was associated with the level of CD3EAP mRNA expression in lung tissues (P = 0.01). The rs967591G>A exhibited consistent associations in a stage II study. In combined analysis, the rs967591 AA genotype exhibited a worse overall survival (adjusted HR = 1.69; 95% confidence interval = 1.29-2.20; P = 0.0001).The rs967591G>A affects CD3EAP expression and thus influences survival in early-stage NSCLC. The analysis of the rs967591G>A polymorphism can help identify patients at high risk of a poor disease outcome.
Influence of procainamide on sodium and potassium exchange and permeabilities in cultured human cells
Authors: D. MCCALL
Journal: Cardiovascular Research (1976)

Journal Article Influence of procainamide on sodium and potassium exchange and permeabilities in cultured human cells Get access DAVID MCCALL DAVID MCCALL From the Division of Cardiology, Department of Internal Medicine, Room 3462, Medical Science Building, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 10, Issue 5, September 1976, Pages 537–548, https://doi.org/10.1093/cvr/10.5.537 Published: 01 September 1976
Characteristics of human large granular lymphocytes and relationship to natural killer and K cells
Authors: T Timonen, Ortaldo JR, RB Herberman
Journal: The Journal of Experimental Medicine (1981)

Recent evidence, has demonstrated an association between a subpopulation of peripheral blood mononuclear cells, morphologically identified as large granular lymphocytes (LGL), and natural killer (NK) activity. We have now evaluated more directly the role of LGL in both NK activity and antibody- dependent cellular cytotoxicity (ADCC), by using highly enriched populations of LGL, obtained by centrifugation of peripheral blood mononuclear cells on Percoll discontinuous density gradients. Both spontaneous and interferon- augmented NK and ADCC activities were exclusively associated with the LGL- enriched, low density fractions. The majority of LGL formed conjugates with NK-susceptible and antibody-coated target cells. Approximately 20 percent of small conventional lymphocytes also formed conjugates with the target cells for NK, but this was not associated with cytotoxic activity. Virtually all LGL were found to have receptors for the Fc portion of IgG (FcγR). The frequency of LGL among blood leukocytes was 2-6 percent. LGL could be enriched to an average purity of 95 percent by combining discontinuous density gradient centrifugation with subsequent adsorptions of the low density fractions on monolayers of immobilized immune complexes. About 50 percent of LGL were found to be FcγR-bearing T cells (T(G)), forming low affinity rosettes with sheep erythrocytes at 4 degrees C. Only 10-20 percent of LGL formed high affinity rosettes with sheep erythrocytes at 29 degrees C. LGL could be enriched to a purity of more than 90 percent by depleting high affinity rosette-forming cells from low density Percoll fractions. LGL were only a subpopulation of T(G) cells, because some lymphocytes with conventional morphology also adhered to the immobilized immune complex monolayers and formed high affinity rosettes with sheep erythrocytes. Separation of these cells from LGL by discontinuous density gradient centrifugation indicated that they are not cytotoxic, suggesting a morphological and functional subdivision of T(G) cells. The verification in this study that virtually all human NK and K cells have a characteristic morphology adds a useful parameter to the monitoring of human lymphocytes, and the ability to purify these cells by simple physical procedures should be invaluable in their further characterization.
Chronic Progressive Cardiac Dysfunction Years After Doxorubicin Therapy for Childhood Acute Lymphoblastic Leukemia
Authors: Steven E. Lipshultz, Stuart R. Lipsitz, Stephen E. Sallan, Virginia M. Dalton, Suzanne M. Mone, Richard D. Gelber, Steven D. Colan
Journal: Journal of Clinical Oncology (2005)

Cross-sectional studies show that cardiac abnormalities are common in long-term survivors of doxorubicin-treated childhood malignancies. Longitudinal data, however, are rare.Serial echocardiograms (N = 499) were obtained from 115 doxorubicin-treated long-term survivors of childhood acute lymphoblastic leukemia (median age at diagnosis, 4.8 years; median follow-up after completion of doxorubicin, 11.8 years). Results were expressed as z scores to indicate the number of standard deviations (SDs) above (+) or below (-) the normal predicted value. Median individual and cumulative doxorubicin doses were 30 mg/m2 per dose and 352 mg/m2, respectively.Left ventricular fractional shortening was significantly reduced after doxorubicin therapy, and the reduction was related to cumulative dose. z scores for fractional shortening transiently improved before falling to -2.76 more than 12 years after diagnosis. Reduced fractional shortening was related to impaired contractility and increasing afterload, consequences of a progressive reduction of ventricular mass, and wall thickness relative to body-surface area. Left ventricular contractility fell significantly over time and was depressed at last follow-up in patients receiving more than 300 mg/m2 of doxorubicin. Systolic and diastolic blood pressures were below normal more than 9 years after diagnosis. Even patients receiving lower cumulative doxorubicin doses experienced reduced mass and dimension. Fractional shortening and dimension at the end of therapy predicted these parameters 11.8 years later.Cardiac abnormalities were persistent and progressive after doxorubicin therapy. Inadequate ventricular mass with chronic afterload excess was associated with progressive contractile deficit and possibly reduced cardiac output and restrictive cardiomyopathy. The deficits were worst after highest cumulative doses of doxorubicin, but appeared even after low doses.
Suppression of Lung Tumor Formation by the Regulatory Subunit of Ribonucleotide Reductase
Authors: Ashish Gautam, Gerold Bepler
Journal: Cancer Research (2006)

Abstract The nucleotide metabolism enzyme ribonucleotide reductase is composed of a regulatory subunit (RRM1) and a catalytic subunit (RRM2). The RRM1 locus has frequent loss of heterozygosity in lung cancers, ectopic expression of RRM1 suppresses proliferation of ras-transformed mouse fibroblasts, and high levels of RRM1 expression are associated with a significant survival benefit in patients with lung cancer. In RRM1 transgenic human lung and colon cancer cell lines, we observed induction of G2 cell cycle arrest, apoptosis, and efficient DNA damage repair. We generated strains of RRM1 transgenic mice and found that carcinogen-induced lung tumor formation was significantly suppressed. The tumor suppression was more pronounced in strains with high levels of RRM1 expression than in those with low levels of expression. DNA damage repair capacity in transgenic animals was determined, and RRM1 transgenic animals repaired chemically induced DNA damage with greater efficiency than control animals. We conclude that the regulatory subunit of ribonucleotide reductase has tumor suppressor activity that is mediated through efficient DNA damage repair. (Cancer Res 2006; 66(13): 6497-502)
Iron lung: bronchoscopic and pathological consequences of aspiration of ferrous sulphate.
Authors: D J Godden, K M Kerr, S J Watt, J S Legge
Journal: Thorax (1991)

Abstract Acute bronchial damage was caused by aspiration of a ferrous sulphate tablet, early histological changes (unlike in the few previously reported cases) being observed in the biopsy specimens.
Relationship between changes in haemoglobin mass and maximal oxygen uptake after hypoxic exposure
Authors: Philo U Saunders, Laura A Garvican-Lewis, Walter F Schmidt, Christopher J Gore
Journal: British Journal of Sports Medicine (2013)

Background Endurance athletes have been using altitude training for decades to improve near sea-level performance. The predominant mechanism is thought to be accelerated erythropoiesis increasing haemoglobin mass (Hb mass ) resulting in a greater maximal oxygen uptake ( O 2max ). Not all studies have shown a proportionate increase in O 2max as a result of increased Hb mass . The aim of this study was to determine the relationship between the two parameters in a large group of endurance athletes after altitude training. Methods 145 elite endurance athletes (94 male and 51 female) who participated in various altitude studies as altitude or control participants were used for the analysis. Participants performed Hb mass and O 2max testing before and after intervention. Results For the pooled data, the correlation between per cent change in Hb mass and per cent change in O 2max was significant (p&lt;0.0001, r 2 =0.15), with a slope (95% CI) of 0.48 (0.30 to 0.67) intercept free to vary and 0.62 (0.46 to 0.77) when constrained through the origin. When separated, the correlations were significant for the altitude and control groups, with the correlation being stronger for the altitude group (slope of 0.57 to 0.72). Conclusions With high statistical power, we conclude that altitude training of endurance athletes will result in an increase in O 2max of more than half the magnitude of the increase in Hb mass , which supports the use of altitude training by athletes. But race performance is not perfectly related to relative O 2max , and other non-haematological factors altered from altitude training, such as running economy and lactate threshold, may also be beneficial to performance.
Genomic Profiling Reveals Alternative Genetic Pathways of Meningioma Malignant Progression Dependent on the Underlying<i>NF2</i>Status
Authors: Stéphane Goutagny, Hong Wei Yang, Jessica Zucman-Rossi, Jennifer Chan, Jonathan M. Dreyfuss, Peter J. Park, Peter M. Black, Marco Giovannini, Rona S. Carroll, Michel Kalamarides
Journal: Clinical Cancer Research (2010)

Meningiomas are the most common central nervous system tumors in the population of age 35 and older. WHO defines three grades predictive of the risk of recurrence. Clinical data supporting histologic malignant progression of meningiomas are sparse and underlying molecular mechanisms are not clearly depicted.We identified genetic alterations associated with histologic progression of 36 paired meningioma samples in 18 patients using 500K SNP genotyping arrays and NF2 gene sequencing.The most frequent chromosome alterations observed in progressing meningioma samples are early alterations (i.e., present both in lower- and higher-grade samples of a single patient). In our series, NF2 gene inactivation was an early and frequent event in progressing meningioma samples (73%). Chromosome alterations acquired during progression from grade I to grade II meningioma were not recurrent. Progression to grade III was characterized by recurrent genomic alterations, the most frequent being CDKN2A/CDKN2B locus loss on 9p.Meningiomas displayed different patterns of genetic alterations during progression according to their NF2 status: NF2-mutated meningiomas showed higher chromosome instability during progression than NF2-nonmutated meningiomas, which had very few imbalanced chromosome segments. This pattern of alterations could thus be used as markers in clinical practice to identify tumors prone to progress among grade I meningiomas.