tbuckley/cabot-search huggingface dataset:
Peritumoral Fibroblast SPARC Expression and Patient Outcome With Resectable Pancreatic Adenocarcinoma
Authors: Jeffrey R. Infante, Hiroyuki Matsubayashi, Norihiro Sato, James Tonascia, Alison P. Klein, Taylor A. Riall, Charles Yeo, Christine Iacobuzio-Donahue, Michael Goggins
Journal: Journal of Clinical Oncology (2007)

SPARC (secreted protein acidic and rich in cysteine) is a protein involved in cell matrix interactions, wound repair, and cell migration, and has been reported to inhibit cancer growth. SPARC undergoes epigenetic silencing in many pancreatic cancers, but stromal fibroblasts adjacent to infiltrating pancreatic adenocarcinomas frequently express SPARC. We evaluated the prognostic significance of tumor and peritumoral SPARC expression in patients with pancreatic adenocarcinoma.The expression patterns of SPARC were characterized by immunohistochemistry in 299 primary pancreatic ductal adenocarcinoma resection specimens from patients who underwent pancreaticoduodenectomy at Johns Hopkins Hospital (Baltimore, MD) between 1998 and 2003. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk associated with the presence or absence of tumor SPARC and peritumoral SPARC status.By Kaplan-Meier analysis, patients whose pancreatic cancer stromal fibroblasts expressed SPARC (median survival, 15 months) had a significantly worse prognosis than patients whose tumor stroma did not express SPARC (median survival, 30 months; log-rank P < .001). In contrast, the expression of SPARC in pancreatic cancer cells was not associated with prognosis (log-rank P = .13). Controlling for other prognostic factors (tumor size, positive lymph nodes, margin status, tumor grade, and age), the relative hazard for patients whose stroma expressed SPARC compared with those whose stroma did not was 1.89 (95% CI, 1.31 to 2.74); the expression of SPARC in pancreatic cancer cells remained unrelated to prognosis (relative hazard, 1.02; 95% CI, 0.73 to 1.42).The expression of SPARC by peritumoral fibroblasts portends a poorer prognosis for patients with pancreatic cancer.
Increased expression of interleukin 17 in inflammatory bowel disease
Authors: S Fujino
Journal: Gut (2002)

Background and aim: Interleukin (IL) 17 is a cytokine which exerts strong proinflammatory activities. In this study we evaluated changes in IL-17 expression in the inflamed mucosa and in the serum of patients with inflammatory bowel disease (IBD). Methods: Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n=20), Crohn’s disease (CD) (n=20), infectious colitis (n=5), ischaemic colitis (n=8), and normal colorectal tissues (n=15). IL-17 expression was evaluated by a standard immunohistochemical procedure. Serum IL-17 levels were determined by ELISA. IL-17 mRNA expression was analysed by reverse transcriptase-polymerase chain reaction. Results: IL-17 expression was not detected in samples from normal colonic mucosa, infectious colitis, or ischaemic colitis. In the inflamed mucosa of active UC and CD patients, IL-17 expression was clearly detectable in CD3+ T cells or CD68+ monocytes/macrophages. The average number of IL-17+ cells was significantly increased in active UC and CD patients compared with inactive patients. IL-17 mRNA expression was not detected in normal mucosa but was detectable in the mucosa from active UC and CD patients. IL-17 was not detected in the sera from normal individuals, infectious colitis, or ischaemic colitis patients but IL-17 levels were significantly elevated in IBD patients. Conclusions: IL-17 expression in the mucosa and serum was increased in IBD patients. It is likely that IL-17 expression in IBD may be associated with altered immune and inflammatory responses in the intestinal mucosa.
Risk Stratification for Coronary Bypass Surgery in Patients With Left Ventricular Dysfunction : Analysis of the Coronary Artery Bypass Grafting Patch Trial Database
Authors: M. Argenziano, H. M. Spotnitz, W. Whang, J. T. Bigger, M. Parides, E. A. Rose
Journal: Circulation (1999)

Preoperative characteristics may influence morbidity and mortality in patients undergoing coronary artery bypass grafting (CABG). The CABG Patch Trial was designed to assess the impact of prophylactic insertion of an implantable cardioverter-defibrillator in patients undergoing high-risk CABG. This database was used to investigate the influence of symptomatic congestive heart failure (CHF) and angina on morbidity and mortality in CABG patients with ventricular dysfunction.Data were analyzed for 900 randomized patients with an ejection fraction </=35% and an abnormal signal-averaged ECG. Single-variable and stepwise multiple logistic regression analyses were used for mortality and length-of-stay (LOS) data. Severity of CHF and angina was graded by the New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classifications, respectively. Perioperative mortality was 3.5% in 454 patients without clinical signs of heart failure versus 7.7% in 443 patients with NYHA class I to IV heart failure (P=0.018). By multiple logistic regression analysis, mortality was significantly higher in patients with preoperative symptomatic (NYHA class I to IV) heart failure (odds ratio, 2.4; P=0.01) or reoperation (odds ratio, 3.8; P<0.0001). Mortality was not significantly influenced by age, sex, the presence or severity of angina, hypertension, left main coronary artery disease, pulmonary disease, or severity of CHF (although LOS was increased 0.7 days per NYHA class). Patients with a history of stroke had a higher rate of perioperative stroke (16.4% versus 3.6%, P=0.001) and an increased LOS (by 3.5 days).Symptomatic heart failure and reoperation are predictors of increased operative mortality in patients with ventricular dysfunction and a positive signal-averaged ECG. Conversely, patients without heart failure symptoms may undergo CABG with relatively low mortality despite low ejection fraction. LOS is prolonged significantly by advanced age, history of stroke, and the presence and severity of heart failure.
Combination Antimicrobial Therapy for<i>Staphylococcus aureus</i>Endocarditis in Patients Addicted to Parenteral Drugs and in Nonaddicts
Authors: OKSANA KORZENIOWSKI
Journal: Annals of Internal Medicine (1982)

Single (nafcillin for 6 weeks) and combined (nafcillin for 6 weeks plus gentamicin for 2 weeks) drug regimens were compared in two separate multicenter prospective randomized trials. Forty-eight parenteral drug addicts and 30 nonaddicts with clinically and bacteriologically documented Staphylococcus aureus endocarditis were studied. In the addicts, combined therapy effected a more rapid mean clinical response (defervescence and normalization of leukocyte count) and a reduced duration of bacteremia in patients with right-sided endocarditis. In the nonaddicts, combined therapy effected more rapid clearance of bacteremia, but was associated with a higher incidence of azotemia. The addition of gentamicin did not alter morbidity or mortality in either group.
Comment on: Hanssen et al. Associations Between the Ankle-Brachial Index and Cardiovascular and All-Cause Mortality Are Similar in Individuals Without and With Type 2 Diabetes: Nineteen-Year Follow-Up of a Population-Based Cohort Study. Diabetes Care 2012;35:1731–1735
Authors: Ilker Tasci
Journal: Diabetes Care (2013)

In their article, Hanssen et al. (1) reported no associations between ankle-brachial index (ABI) and cardiovascular and all-cause mortality in individuals with and without diabetes in the Hoorn cohort. The results are considered important with regards to the long follow-up period in the study as well as some yet unidentified issues on the clinical role of ABI testing. However, I need to make several comments on the presented data.

1.  In the Hoorn study, the ankle pressure was measured only from the posterior tibial artery. Whenever the operators found a normal ABI in the respective ankle, they took a further measurement from the dorsalis pedis artery or peroneal artery. …
Extravascular lung water and its association with weight, height, age, and gender: a study in intensive care unit patients
Authors: Wolfgang Huber, Sebastian Mair, Simon Q. Götz, Julia Tschirdewahn, Johanna Siegel, Roland M. Schmid, Bernd Saugel
Journal: Intensive Care Medicine (2012)

With regard to large inter-individual variability of height, body weight (BW), and age, several hemodynamic parameters are adjusted for biometric data. This also applies to extravascular lung water (EVLW), which traditionally was indexed to actual BW (BW-act) resulting in EVLW-index (EVLWI; i.e., EVLWI-act). Since indexation to BW-act might inappropriately diminish EVLWI-act in obese patients, the indexation has been changed to predicted BW (BW-pred) resulting in EVLWI-pred. BW-pred is a weight estimation formula calculated from height and gender that has not been derived from population-based data. The aim of the study was to investigate the independent association of biometric data with EVLW.We analyzed a hemodynamic monitoring database including 3,691 transpulmonary thermodilution-derived EVLW measurements (234 consecutive patients; intensive care unit of a university hospital). We performed univariate and multivariate analyses regarding the association of biometric data with the first EVLW measurement and the mean EVLW value of each patient.In univariate analysis, the first EVLW significantly correlated with height (r = 0.254; p < 0.001), but neither with age nor BW-act. Similar findings were made in the analysis of the patients' EVLW means of all measurements ("one point per patient"). In multivariate analysis (primary endpoint), including BW-act, height, age, and gender, only height was independently associated with EVLW, with each centimeter of height increasing the first measurement of EVLW by 6.882 mL (p < 0.001) and mean EVLW by 6.727 mL (p < 0.001).Height is the only biometric parameter independently associated with the first and mean EVLW. In adult patients, EVLW should be indexed to height.
Nasal septal haematoma
Authors: L. N. Sanyaolu, S. E. J. Farmer, P. J. Cuddihy
Journal: BMJ (2014)

<h3>Abstract</h3> <b>Objective</b> To systematically review the accuracy of physicians9 clinical predictions of survival in terminally ill cancer patients. <b>Data sources</b> Cochrane Library, Medline (1996-2000), Embase, Current Contents, and Cancerlit databases as well as hand searching. <b>Study selection</b> Studies were included if a physician9s temporal clinical prediction of survival (CPS) and the actual survival (AS) for terminally ill cancer patients were available for statistical analysis. Study quality was assessed by using a critical appraisal tool produced by the local health authority. <b>Data synthesis</b> Raw data were pooled and analysed with regression and other multivariate techniques. <b>Results</b> 17 published studies were identified; 12 met the inclusion criteria, and 8 were evaluable, providing 1563 individual prediction-survival dyads. CPS was generally overoptimistic (median CPS 42 days, median AS 29 days); it was correct to within one week in 25% of cases and overestimated survival by at least four weeks in 27%. The longer the CPS the greater the variability in AS. Although agreement between CPS and AS was poor (weighted κ 0.36), the two were highly significantly associated after log transformation (Spearman rank correlation 0.60, P &lt; 0.001). Consideration of performance status, symptoms, and use of steroids improved the accuracy of the CPS, although the additional value was small. Heterogeneity of the studies9 results precluded a comprehensive meta-analysis. <b>Conclusions</b> Although clinicians consistently overestimate survival, their predictions are highly correlated with actual survival; the predictions have discriminatory ability even if they are miscalibrated. Clinicians caring for patients with terminal cancer need to be aware of their tendency to overestimate survival, as it may affect patients9 prospects for achieving a good death. Accurate prognostication models incorporating clinical prediction of survival are needed.
Rapid Cycling in Women and Men With Bipolar Manic-Depressive Disorders
Authors: Leonardo Tondo, Ross J. Baldessarini
Journal: American Journal of Psychiatry (1998)

Objective:This study investigated risks for rapid cycling, as defined by DSM-IV, in women and men with bipolar disorders. Method:The results of 10 studies with a total of 2,057 bipolar patients were meta-analyzed by pooled contingency methods. Results:The proportions of women and men among rapid-cycling cases averaged 72% and 28%, respectively, but the risk of rapid cycling was inconsistently more frequent among women (29.6%) than among men (16.5%). The mean number of episodes per year was much higher in rapid-cycling patients before and during lithium treatment but was similar in rapid-cycling men and women.Conclusions:Rapid cycling was only moderately, and inconsistently, more common in bipolar women than men. Am J Psychiatry 1998; 155: 1434-1436
EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors
Authors: H Kothmaier, F Quehenberger, I Halbwedl, P Morbini, F Demirag, H Zeren, C E Comin, B Murer, P T Cagle, R Attanoos, A R Gibbs, F Galateau-Salle, H H Popper
Journal: Thorax (2007)

<h3>Background:</h3> Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short term survivors (survival &lt;3 years; STS) and long term survivors (survival &gt;3 years; LTS) of MPM. <h3>Methods:</h3> 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology. <h3>Results:</h3> Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was upregulated in STS by signal transducer and activator of transcription 1 (STAT1)–survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS. <h3>Conclusion:</h3> We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.
Differential interactions of thin filament proteins in two cardiac troponin T mouse models of hypertrophic and dilated cardiomyopathies
Authors: Raffaella Lombardi, Achim Bell, Vinitha Senthil, Jasvinder Sidhu, Michela Noseda, Robert Roberts, Ali J. Marian
Journal: Cardiovascular Research (2008)

Mutations in a sarcomeric protein can cause hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM), the opposite ends of a spectrum of phenotypic responses of the heart to mutations. We posit the contracting phenotypes could result from differential effects of the mutant proteins on interactions among the sarcomeric proteins. To test the hypothesis, we generated transgenic mice expressing either cardiac troponin T (cTnT)-Q92 or cTnT-W141, known to cause HCM and DCM, respectively, in the heart. We phenotyped the mice by echocardiography, histology and immunoblotting, and real-time polymerase chain reaction. We detected interactions between the sarcomeric proteins by co-immunoprecipitation and determined Ca2+ sensitivity of myofibrillar protein ATPase activity by Carter assay. The cTnT-W141 mice exhibited dilated hearts and decreased systolic function. In contrast, the cTnT-Q92 mice showed smaller ventricles and enhanced systolic function. Levels of cardiac troponin I, cardiac α-actin, α-tropomyosin, and cardiac troponin C co-immunoprecipitated with anti-cTnT antibodies were higher in the cTnT-W141 than in the cTnT-Q92 mice, as were levels of α-tropomyosin co-immunoprecipitated with an anti-cardiac α-actin antibody. In contrast, levels of cardiac troponin I co-immunoprecipitated with an anti-cardiac α-actin antibody were higher in the cTnT-Q92 mice. Ca2+ sensitivity of myofibrillar ATPase activity was increased in HCM but decreased in DCM mice compared with non-transgenic mice. Differential interactions among the sarcomeric proteins containing cTnT-Q92 or cTnT-W141 are responsible for the contrasting phenotypes of HCM or DCM, respectively.
Adult Weight Gain and Adiposity-Related Cancers: A Dose-Response Meta-Analysis of Prospective Observational Studies
Authors: NaNa Keum, Darren C. Greenwood, Dong Hoon Lee, Rockli Kim, Dagfinn Aune, Woong Ju, Frank B. Hu, Edward L. Giovannucci
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Adiposity, measured by body mass index, is implicated in carcinogenesis. While adult weight gain has diverse advantages over body mass index in measuring adiposity, systematic reviews on adult weight gain in relation to adiposity-related cancers are lacking.
International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors
Authors: Andreas Klos, Elisabeth Wende, Kathryn J. Wareham, Peter N. Monk
Journal: Pharmacological Reviews (2013)

The activation of the complement cascade, a cornerstone of the innate immune response, produces a number of small (74–77 amino acid) fragments, originally termed anaphylatoxins, that are potent chemoattractants and secretagogues that act on a wide variety of cell types. These fragments, C5a, C4a, and C3a, participate at all levels of the immune response and are also involved in other processes such as neural development and organ regeneration. Their primary function, however, is in inflammation, so they are important targets for the development of anti-inflammatory therapies. Only three receptors for complement peptides have been found, but there are no satisfactory antagonists as yet, despite intensive investigation. In humans, there is a single receptor for C3a (C3a receptor), no known receptor for C4a, and two receptors for C5a (C5a<sub>1</sub> receptor and C5a<sub>2</sub> receptor). The most recently characterized receptor, the C5a<sub>2</sub> receptor (previously known as C5L2 or GPR77), has been regarded as a passive binding protein, but signaling activities are now ascribed to it, so we propose that it be formally identified as a receptor and be given a name to reflect this. Here, we describe the complex biology of the complement peptides, introduce a new suggested nomenclature, and review our current knowledge of receptor pharmacology.
Trends in the Prevalence of Preexisting Diabetes and Gestational Diabetes Mellitus Among a Racially/Ethnically Diverse Population of Pregnant Women, 1999–2005
Authors: Jean M. Lawrence, Richard Contreras, Wansu Chen, David A. Sacks
Journal: Diabetes Care (2008)

The purpose of this study was to assess changes in the prevalence of preexisting diabetes (diabetes antedating pregnancy) and gestational diabetes mellitus (GDM) from 1999 through 2005.In this retrospective study of 175,249 women aged 13-58 years with 209,287 singleton deliveries of >or=20 weeks' gestation from 1999 through 2005 in all Kaiser Permanente hospitals in southern California, information from clinical databases and birth certificates was used to estimate the prevalence of preexisting diabetes and GDM.Preexisting diabetes was identified in 2,784 (1.3%) of all pregnancies, rising from an age- and race/ethnicity-adjusted prevalence of 0.81 per 100 in 1999 to 1.82 per 100 in 2005 (P(trend) < 0.001). Significant increases were observed in all age-groups and all racial/ethnic groups. After women with preexisting diabetes were excluded, GDM was identified in 15,121 (7.6%) of 199,298 screened pregnancies. The age- and race/ethnicity-adjusted GDM prevalence remained constant at 7.5 per 100 in 1999 to 7.4 per 100 in 2005 (P(trend) = 0.07). Among all deliveries to women with either form of diabetes, 10% were due to preexisting diabetes in 1999, rising to 21% in 2005, with GDM accounting for the remainder.The stable prevalence of GDM and increase in the prevalence of preexisting diabetes were independent of changes in the age and race/ethnicity of the population. The increase in preexisting diabetes, particularly among younger women early in their reproductive years, is of concern.
Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis
Authors: Luke W. Garratt, Erika N. Sutanto, Kak-Ming Ling, Kevin Looi, Thomas Iosifidis, Kelly M. Martinovich, Nicole C. Shaw, Elizabeth Kicic-Starcevich, Darryl A. Knight, Sarath Ranganathan, Stephen M. Stick, Anthony Kicic
Journal: European Respiratory Journal (2015)

Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, the causal link between neutrophil elastase and airway damage is not well understood. Matrix metalloproteinases (MMPs) play a crucial role in extracellular matrix modelling and are activated by neutrophil elastase. The aim of this study was to assess if MMP activation positively correlates with neutrophil elastase activity, disease severity and bronchiectasis in young children with cystic fibrosis.Total MMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 levels were measured in bronchoalveolar lavage fluid collected from young children with cystic fibrosis during annual clinical assessment. Active/pro-enzyme ratio of MMP-9 was determined by gelatin zymography. Annual chest computed tomography imaging was scored for bronchiectasis.A higher MMP-9/TIMP-1 ratio was associated with free neutrophil elastase activity. In contrast, MMP-2/TIMP-2 ratio decreased and MMP-1 and MMP-7 were not detected in the majority of samples. Ratio of active/pro-enzyme MMP-9 was also higher in the presence of free neutrophil elastase activity, but not infection. Across the study cohort, both MMP-9/TIMP-1 and active MMP-9 were associated with progression of bronchiectasis.Both MMP-9/TIMP-1 and active MMP-9 increased with free neutrophil elastase and were associated with bronchiectasis, further demonstrating that free neutrophil elastase activity should be considered an important precursor to cystic fibrosis structural disease.
Human Autoantibody Silencing by Immunoglobulin Light Chains
Authors: Hedda Wardemann, Johanna Hammersen, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2004)

Several newly arising human antibodies are polyreactive, but in normal individuals the majority of these potentially autodestructive antibodies are removed from the repertoire by receptor editing or B cell deletion in the bone marrow. To determine what proportion of naturally arising autoantibodies can be silenced by immunoglobulin (Ig) light chain receptor editing, we replaced the light chains in 12 such antibodies with a panel of representative Igκ and Igλ chains. We found that most naturally arising autoantibodies are readily silenced by light chain exchange. Thus, receptor editing may account for most autoreactive antibody silencing in humans. Light chain complementarity determining region (CDR) isoelectric points did not correlate with silencing activity, but Igλ genes were more effective than Igκ genes as silencers. The greater efficacy of Igλ chains as silencer of autoreactivity provides a possible explanation for the expansion and altered configuration of the Igλ locus in evolution.