tbuckley/cabot-search huggingface dataset:
Hypoxia-Inducible Factor-1 α Expression Predicts Superior Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP
Authors: Andrew M. Evens, Laurie H. Sehn, Pedro Farinha, Beverly P. Nelson, Adekunle Raji, Yi Lu, Adam Brakman, Vamsi Parimi, Jane N. Winter, Paul T. Schumacker, Randy D. Gascoyne, Leo I. Gordon
Journal: Journal of Clinical Oncology (2010)

PURPOSE Hypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1alpha in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated. PATIENTS AND METHODS We studied the immunohistochemical protein expression of HIF-1alpha on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome. Results Median follow-up for all patients was 80 months. Among all patients, HIF-1alpha was expressed in 62% of germinal center and 59% of non-germinal center patients. With HIF-1alpha analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1alpha protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1alpha-positive patients was 71% v 43% for HIF-1alpha-negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1alpha remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1alpha correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1alpha and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2). CONCLUSION The expression of HIF-1alpha protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP.
Treatment of Severe Hyponatremia
Authors: PETER GROSS, DOREEN REIMANN, JANA HENSCHKOWSKI, MAXWELL DAMIAN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Hyponatremia is a frequent electrolyte disorder. A hyponatremia is called acute severe (<115 mM) when the duration has been <36 to 48 h. Such patients often have advanced symptoms as a result of brain edema. Acute severe hyponatremia is a medical emergency. It should be corrected rapidly to approximately 130 mM to prevent permanent brain damage. In contrast, in chronic severe hyponatremia (>4 to 6 d), there is no brain edema and symptoms are usually mild. In such patients, a number of authors have recommended a correction rate <0.5 mM/h to approximately 130 mM to minimize the risk of cerebral myelinolysis. Sometimes it is not possible to diagnose whether a severe hyponatremia is acute or chronic. In such cases, an initial imaging procedure is helpful in deciding whether rapid or slow correction should be prescribed. The modalities of treatment of severe hyponatremia have so far consisted of infusions of hypertonic saline plus fluid restriction. In the near future, vasopressin antagonists will become available. Preliminary experience has already demonstrated their efficiency of inducing a sustained water diuresis and a correction of hyponatremia.
Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury
Authors: Sarah L. Brown, Terrence E. Riehl, Monica R. Walker, Michael J. Geske, Jason M. Doherty, William F. Stenson, Thaddeus S. Stappenbeck
Journal: Journal of Clinical Investigation (2007)

We identified cellular and molecular mechanisms within the stem cell niche that control the activity of colonic epithelial progenitors (ColEPs) during injury. Here, we show that while WT mice maintained ColEP proliferation in the rectum following injury with dextran sodium sulfate, similarly treated Myd88–/– (TLR signaling–deficient) and prostaglandin-endoperoxide synthase 2–/– (Ptgs2–/–) mice exhibited a profound inhibition of epithelial proliferation and cellular organization within rectal crypts. Exogenous addition of 16,16-dimethyl PGE2 (dmPGE2) rescued the effects of this injury in both knockout mouse strains, indicating that Myd88 signaling is upstream of Ptgs2 and PGE2. In WT and Myd88–/– mice, Ptgs2 was expressed in scattered mesenchymal cells. Surprisingly, Ptgs2 expression was not regulated by injury. Rather, in WT mice, the combination of injury and Myd88 signaling led to the repositioning of a subset of the Ptgs2-expressing stromal cells from the mesenchyme surrounding the middle and upper crypts to an area surrounding the crypt base adjacent to ColEPs. These findings demonstrate that Myd88 and prostaglandin signaling pathways interact to preserve epithelial proliferation during injury using what we believe to be a previously undescribed mechanism requiring proper cellular mobilization within the crypt niche.
eIF4E/4E-BP Ratio Predicts the Efficacy of mTOR Targeted Therapies
Authors: Tommy Alain, Masahiro Morita, Bruno D. Fonseca, Akiko Yanagiya, Nadeem Siddiqui, Mamatha Bhat, Domenick Zammit, Victoria Marcus, Peter Metrakos, Lucie-Anne Voyer, Valentina Gandin, Yi Liu, Ivan Topisirovic, Nahum Sonenberg
Journal: Cancer Research (2012)

Abstract Active-site mTOR inhibitors (asTORi) hold great promise for targeting dysregulated mTOR signaling in cancer. Because of the multifaceted nature of mTORC1 signaling, identification of reliable biomarkers for the sensitivity of tumors to asTORi is imperative for their clinical implementation. Here, we show that cancer cells acquire resistance to asTORi by downregulating eukaryotic translation initiation factor (eIF4E)-binding proteins (4E-BPs—EIF4EBP1, EIF4EBP2). Loss of 4E-BPs or overexpression of eIF4E renders neoplastic growth and translation of tumor-promoting mRNAs refractory to mTOR inhibition. Conversely, moderate depletion of eIF4E augments the anti-neoplastic effects of asTORi. The anti-proliferative effect of asTORi in vitro and in vivo is therefore significantly influenced by perturbations in eIF4E/4E-BP stoichiometry, whereby an increase in the eIF4E/4E-BP ratio dramatically limits the sensitivity of cancer cells to asTORi. We propose that the eIF4E/4E-BP ratio, rather than their individual protein levels or solely their phosphorylation status, should be considered as a paramount predictive marker for forecasting the clinical therapeutic response to mTOR inhibitors. Cancer Res; 72(24); 6468–76. ©2012 AACR.
Spontaneous pneumothorax: the sharp rib syndrome.
Authors: S F Stephenson
Journal: Thorax (1976)

Of 49 patients undergoing operation for benign spontaneous pneumothorax, 28 (57%) were found to have a sharp first or second rib. In a series of 100 patients undergoing thoracotomy for other conditions, only eight (8%) were found to have a sharp rib. The association between sharp ribs, apical scars and bullae, and spontaneous pneumothorax is discussed.
MiR-199a-3p Regulates mTOR and c-Met to Influence the Doxorubicin Sensitivity of Human Hepatocarcinoma Cells
Authors: Francesca Fornari, Maddalena Milazzo, Pasquale Chieco, Massimo Negrini, George Adrian Calin, Gian Luca Grazi, Daniela Pollutri, Carlo Maria Croce, Luigi Bolondi, Laura Gramantieri
Journal: Cancer Research (2010)

MicroRNAs (miRNA) have rapidly emerged as modulators of gene expression in cancer in which they may have great diagnostic and therapeutic import. MicroRNA-199a-3p (miR-199a-3p) is downregulated in several human malignancies including hepatocellular carcinoma (HCC). Here, we show that miR-199a-3p targets mammalian target of rapamycin (mTOR) and c-Met in HCC cells. Restoring attenuated levels of miR-199a-3p in HCC cells led to G(1)-phase cell cycle arrest, reduced invasive capability, enhanced susceptibility to hypoxia, and increased sensitivity to doxorubicin-induced apoptosis. These in vitro findings were confirmed by an analysis of human HCC tissues, which revealed an inverse correlation linking miR-199a-3p and mTOR as well as a shorter time to recurrence after HCC resection in patients with lower miR-199a-3p expression. These results suggest that tactics to regulate mTOR and c-Met by elevating levels of miR-199a-3p may have therapeutic benefits in highly lethal cancers such as HCC.
Usefulness of Measurement of Antibodies in Serum in Diagnosis of Sensitivity to Cow Milk and Soy Proteins in Early Childhood
Authors: C. D. May, L. Remigio, S. A. Bock
Journal: Allergy (1980)

A noteworthy feature of this study is that comparisons were made between specific, sensitive, quantitative measurements of serum antibodies to food proteins and objective appraisal of clinical manifestations buy double‐blind food challenges. Over 50 children, 4–30 months of age, with suspicious histories of adverse reactions to cow milk or soy products were investigated. Levels of serum antibodies to cow‐milk proteins were clearly higher in children with adverse reactions to milk, confirmed by blind challenge; there was no overlap with the lower levels of serum antibodies in children without confirmed reactions. Findings with serial determinations of serum antibodies to cow milk in selected cases are also presented. The levels of serum antibodies evoked by cow milk and soy formulae fed from birth until 4 months of age were similar. The levels of serum antibodies to soy protein in children with and without adverse reactions to soy products were not definitive. The bearing of these data on the comparative “antigenicity” of cow milk and soy products and the distinction between asymptomatic and clinically significant, symptomatic, sensitivity are discussed.
EMT Twists the Road to PI3K
Authors: Matthew J. Niederst, Cyril H. Benes
Journal: Cancer Discovery (2014)

Abstract Summary: Epithelial-to-mesenchymal transition (EMT) is important for many developmental events and has been linked to tumor dissemination and therapeutic resistance. Salt and colleagues identify how EMT affects how proliferation signals flow to phosphoinositide 3-kinase in non–small cell lung cancer. Cancer Discov; 4(2); 149–51. ©2014 AACR. See related article by Salt et al., p. 186
A Five-Gene Molecular Grade Index and <i>HOXB13:IL17BR</i> Are Complementary Prognostic Factors in Early Stage Breast Cancer
Authors: Xiao-Jun Ma, Ranelle Salunga, Sonika Dahiya, Wilson Wang, Erin Carney, Virginie Durbecq, Adrian Harris, Paul Goss, Christos Sotiriou, Mark Erlander, Dennis Sgroi
Journal: Clinical Cancer Research (2008)

Histologic tumor grade is a well-established prognostic factor for breast cancer, and tumor grade-associated genes are the common denominator of many prognostic gene signatures. The objectives of this study are as follows: (a) to develop a simple gene expression index for tumor grade (molecular grade index or MGI), and (b) to determine whether MGI and our previously described HOXB13:IL17BR index together provide improved prognostic information.From our previously published list of genes whose expression correlates with both tumor grade and tumor stage progression, we selected five cell cycle-related genes to build MGI and evaluated MGI in two publicly available microarray data sets totaling 410 patients. Using two additional cohorts (n = 323), we developed a real-time reverse transcription PCR assay for MGI, validated its prognostic utility, and examined its interaction with HOXB13:IL17BR.MGI performed consistently as a strong prognostic factor and was comparable with a more complex 97-gene genomic grade index in multiple data sets. In patients treated with endocrine therapy, MGI and HOXB13:IL17BR modified each other's prognostic performance. High MGI was associated with significantly worse outcome only in combination with high HOXB13:IL17BR, and likewise, high HOXB13:IL17BR was significantly associated with poor outcome only in combination with high MGI.We developed and validated a five-gene reverse transcription PCR assay for MGI suitable for analyzing routine formalin-fixed paraffin-embedded clinical samples. The combination of MGI and HOXB13:IL17BR outperforms either alone and identifies a subgroup ( approximately 30%) of early stage estrogen receptor-positive breast cancer patients with very poor outcome despite endocrine therapy.
Nutrition and hydration concerns of the female football player: Table 1
Authors: Ronald J Maughan, Susan M Shirreffs
Journal: British Journal of Sports Medicine (2007)

There is little information on the nutritional habits of female football players at any level of the game. There is also a shortage of information on the nutrition and hydration strategies that players should adopt. In general, differences in nutritional needs between males and females are smaller than differences between individuals, so that principles developed for male players also apply to women. There is a need to address energy balance and body composition: prolonged energy deficits cannot be sustained without harm to health and performance. Published reports show mean carbohydrate intakes for female players of about 5 g/kg/day, and this seems to be too low to sustain consistent intensive training. The timing of protein intake may be as important as the amounts consumed, provided that the total intake is adequate. Dehydration adversely affects skill and stamina in women as it does in men, so an individualised hydration strategy should be developed. The prevalence of iron deficiency in women generally is high, but it seems to be alarmingly high in female players. All players should adopt dietary habits that ensure adequate iron intake. Football training seems to increase bone mass in the weight-bearing limbs, with positive implications for bone health in later life, but some players may be at risk from inadequate calcium dietary intake.
Dermcidin identification from exhaled air for lung cancer diagnosis
Authors: W. C. Chang, M. S. Huang, C. J. Yang, W. Y. Wang, T. C. Lai, M. Hsiao, C. H. Chen
Journal: European Respiratory Journal (2010)

To the Editors: 

Exhaled breath condensate (EBC) analysis is a simple and truly non-intrusive approach to acquire information on understanding airway inflammation and other diseases of the respiratory system, such as tumourigenesis 1–3. There are several striking advantages to utilising breath testing for screening purposes: 1) it does not influence airway function or cause inflammation 4; 2) it can be performed repeatedly within short intervals 5; 3) it is not significantly affected by age, sex or disease status 5; and 4) it can be considered as a lung-specific analytic approach. Cancer cells have distinct properties from normal cells in that they may synthesise new proteins or change the protein expression levels during tumourigenesis 6. A lot of soluble components of the lung exist in the epithelial lining fluid of alveoli 7; therefore, the secreted new synthetic proteins can be digested into peptides under enzymatic processes. Subsequently, the small peptides have the possibility of adding to exhaled breath like other EBC compounds. The exploration of endogenous peptides, created by enzymatic cleavage of proteins in particular cellular environments, can result in relevant biomarker candidates 8, 9. However, trace amounts of materials in EBC make detection a challenging task. This study was designed to determine the peptidome of EBC and to search for potential biomarkers for lung cancer diagnosis.

The study protocol was approved by the Institutional Review Board of the Kaohsiung Medical University Hospital (Kaohsiung, Taiwan). Patients with histological evidence of primary lung cancer who were admitted to the Division of Pulmonary and Critical Care Medicine (Dept of Internal Medicine, Kaohsiung Medical University Hospital), between January 2008 and August 2008 were enrolled in the study. We enrolled patients with squamous cell carcinoma, adenocarcinoma, small cell carcinoma, pneumonia and chronic obstructive pulmonary disease …
Sex Differences in Hospital Mortality After Coronary Artery Bypass Surgery
Authors: Viola Vaccarino, Jerome L. Abramson, Emir Veledar, William S. Weintraub
Journal: Circulation (2002)

Data are conflicting over whether women have higher mortality than men after coronary artery bypass graft (CABG) surgery. Younger but not older women hospitalized for acute myocardial infarction have higher in-hospital mortality rates than men. We hypothesized that younger women also have higher in-hospital mortality rates after CABG.We studied 51 187 patients (30% women) included in the National Cardiovascular Network database who received CABG at 23 clinical centers between October 1993 and December 1999. Compared with men, fewer women were white and more women had risk factors and comorbidities. These differences were more apparent in younger patients. In all age groups, however, women had higher left ventricular ejection fraction and fewer diseased vessels. Women had higher in-hospital mortality rates than men, but sex differences in mortality were more marked among younger patients. Women <50 years of age were 3 times more likely to die than men (3.4% versus 1.1%), and women 50 to 59 years of age were 2.4 times more likely to die than men (2.6% versus 1.1%). In the older age categories, the sex difference in in-hospital mortality was less marked (P<0.001 for the interaction between sex and age). Adjustment for preoperative risk factors only slightly decreased the strength of this interaction.Younger women undergoing CABG surgery are at a higher risk of in-hospital death than men, but this difference in risk decreases with advancing age. Additional investigation is needed to determine why in-hospital mortality is higher in women after CABG, with particular focus on younger women.
Prostaglandin I2 is not a major metabolite of arachidonic acid in cultured endothelial cells from human foreskin microvessels.
Authors: I F Charo, S Shak, M A Karasek, P M Davison, I M Goldstein
Journal: Journal of Clinical Investigation (1984)

Prostaglandin I2 (PGI2), a potent vasodilator and inhibitor of platelet aggregation, is a major product of arachidonic acid metabolism in endothelial cells that are derived from large blood vessels (e.g., umbilical veins). We have examined whether PGI2 is also a major product of arachidonic acid metabolism in cultured endothelial cells that are derived from dermal microvessels in human newborn foreskin. Supernatants from confluent monolayers of endothelial cells that had been incubated for 20 min with [3H]arachidonic acid and the calcium ionophore A23187 (10 microM) were assayed for prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha (PGF1 alpha) (the stable metabolite of PGI2) by using authentic standards and high performance liquid chromatography. Whereas supernates from stimulated umbilical vein endothelial cells contained 6-keto-PGF 1 alpha much greater than PGF 2 alpha much greater than PGE2, supernates from stimulated foreskin microvessel endothelial cells contained PGF 2 alpha congruent to PGE2 much greater than 6-keto-PGF 1 alpha. Similar results were obtained when supernates from stimulated, unlabeled endothelial cells were analyzed by radioimmunoassay. These data indicate that PGI2 is not a major metabolite of arachidonic acid in cultured endothelial cells from human foreskin microvessels.
Associations of a non-synonymous variant in SLC2A9 with gouty arthritis and uric acid levels in Han Chinese subjects and Solomon Islanders
Authors: H.-P. Tu, C.-J. Chen, S. Tovosia, A. M.-S. Ko, C.-H. Lee, T.-T. Ou, G.-T. Lin, S.-J. Chang, S.-L. Chiang, H.-C. Chiang, P.-H. Chen, S.-J. Wang, H.-M. Lai, Y.-C. Ko
Journal: Annals of the Rheumatic Diseases (2009)

To study the associations of gout, tophi and uric acid levels with the gout-related SLC2A9 (solute carrier family 2, member 9) single nucleotide polymorphisms (SNPs) between two different racial groups.Eight SLC2A9 SNPs were genotyped in 109 subjects with gout and 191 control subjects from Han Chinese men in Taiwan and 69 subjects with gout and 168 control subjects from the Solomon Islands.Non-synonymous SLC2A9 rs3733591 Arg265His was associated with risk for gout and tophaceous gout in Han Chinese subjects (p=0.0012 and p=0.0044). The genetic effect of this SNP on tophaceous gout was replicated in Solomon Islanders (p=0.0184). Patients with SLC2A9 Arg265His risk C-allele consistently had a higher risk for tophi (OR 2.05-2.15) than non-tophi (OR 0.91-1.62). SNP rs3733591 described 3.68% and 5.98% of the total variability in uric acid levels for Chinese and Solomon Island subjects, respectively.Non-synonymous SNP rs3733591 variant within the SLC2A9 gene from two geographically diverse populations served as an important genetic checkpoint for tophaceous gout and increased uric acid levels.
Obesity and Estrogen as Risk Factors for Gastroesophageal Reflux Symptoms
Authors: Magnus Nilsson, Roar Johnsen, Weimin Ye, Kristian Hveem, Jesper Lagergren
Journal: JAMA (2003)

Gastroesophageal reflux and obesity are both increasing in prevalence. The scientific evidence for an association between these conditions is sparse and contradictory. A difference between sexes concerning this relation has been proposed.To evaluate the relation between body mass and gastroesophageal reflux symptoms and determine how this relation is influenced by female sex hormones.Population-based, cross-sectional, case-control study.Two consecutive public health surveys within the county of Nord-Trondelag, Norway, conducted in 1984-1986 and 1995-1997.Among 65 363 adult participants in the second survey, 3113 individuals who reported severe heartburn or regurgitation during the last 12 months were defined as cases, whereas 39 872 persons without reflux symptoms were defined as controls.Risk of reflux, estimated using multivariate logistic regression, with odds ratios (ORs) and 95% confidence intervals (CIs) as measures of association.There was a dose-response association between increasing body mass index (BMI) and reflux symptoms in both sexes (P for trend <.001), with a significantly stronger association in women (P<.001). Compared with those with a BMI less than 25, the risk of reflux was increased significantly among severely obese (BMI >35) men(OR, 3.3; 95% CI, 2.4-4.7) and women (OR, 6.3; 95% CI, 4.9-8.0). The association between BMI and reflux symptoms was stronger among premenopausal women compared with postmenopausal women (P<.001), although use of postmenopausal hormone therapy increased the strength of the association (P<.001). Reduction in BMI was associated with decreased risk of reflux symptoms.There is a significant association between body mass and symptoms of gastroesophageal reflux. The association is stronger among women, especially premenopausally, and use of hormone therapy strengthens the association, suggesting that estrogens may play an important role in the etiology of reflux disease.