tbuckley/cabot-search huggingface dataset:
Lack of Association of Alcohol and Tobacco with HPV16-Associated Head and Neck Cancer
Authors: Katie M. Applebaum, C. Sloane Furniss, Ariana Zeka, Marshall R. Posner, Judith F. Smith, Janine Bryan, Ellen A. Eisen, Edward S. Peters, Michael D. McClean, Karl T. Kelsey
Journal: JNCI Journal of the National Cancer Institute (2007)

Human papillomavirus type 16 (HPV16) seropositivity and alcohol and tobacco use have been associated with risk of head and neck squamous cell carcinoma (HNSCC). However, it is less clear whether HPV16 influences HNSCC risk associated with alcohol and tobacco use.Incident cases of HNSCC diagnosed between December 1999 and December 2003 were identified from nine medical facilities in Greater Boston, MA. Control subjects were frequency matched to case subjects on age, sex, and town of residence. A total of 485 case subjects and 549 control subjects reported information on lifetime smoking and alcohol consumption and provided sera, which was used to determine presence of HPV16 antibodies. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of HNSCC risk by alcohol consumption (drinks per week: < 3, 3 to < 8, 8 to < 25, > or = 25) and smoking (pack-years: none, > 0 to < 20, 20 to < 45, > or = 45), adjusting for age, sex, race, education, and HPV16 serology. Polytomous logistic regression was used to estimate odds ratios and 95% confidence intervals for the association of HPV16 serology, alcohol consumption, and tobacco use in site-specific analyses. All statistical tests were two-sided.The strongest risk factors by tumor site were smoking for laryngeal cancer, alcohol for cancer of the oral cavity, and HPV16 for pharyngeal cancer. For pharyngeal cancer, risk increased with increasing alcohol consumption (OR(> or = 25 versus < 3 drinks per week) = 5.1, 95% CI = 2.4 to 11.0) and smoking (OR(> or = 45 pack-years versus never smoker) = 6.9, 95% CI = 3.1 to 15.1) among HPV16-seronegative subjects but not among HPV16-seropositive subjects (P(interaction, HPV16 serology and alcohol) = .002; P(interaction, HPV16 serology and smoking) = .007). Among light drinkers or never smokers, HPV16 seropositivity was associated with a 30-fold increased risk of pharyngeal cancer.Alcohol or tobacco use does not further increase risk of HPV16-associated pharyngeal cancer. HNSCC risk associated with smoking, alcohol, and HPV16 differs by tumor site.
Quantitative volumetric analysis of conventional MRI response in recurrent glioblastoma treated with bevacizumab
Authors: B. M. Ellingson, T. F. Cloughesy, A. Lai, P. L. Nghiemphu, P. S. Mischel, W. B. Pope
Journal: Neuro-Oncology (2011)

Although the effects of bevacizumab on magnetic resonance images (MRIs) of recurrent glioblastoma multiforme (GBM) are well documented, to our knowledge, no studies have explicitly quantified the volumetric changes resulting from initial treatment, nor have there been studies examining the ability for volumetric changes in conventional MRI to predict progression-free survival (PFS) and overall survival (OS). In the current study, we retrospectively examined volumetric changes on conventional MRI scans in 84 patients with recurrent GBM. MRIs were obtained before (mean, 11 days) and after (mean, 42 days) treatment with bevacizumab. The volume of abnormal fluid-attenuated inversion recovery (FLAIR) signal intensity, the volume of contrast enhancement, and the ratio of the 2 were quantified for each patient before and after initial treatment. Results demonstrated that initial treatment with bevacizumab resulted in a significant decrease in both the volume of abnormal FLAIR signal and the volume of contrast enhancement. Initial, residual, and change in FLAIR volume were not predictive of PFS or OS. Initial contrast-enhancing volume was predictive of PFS but not OS. The pretreatment relative nonenhancing tumor ratio, defined as the ratio of FLAIR to contrast-enhancing volume, was found to be predictive of both PFS and OS.
The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation
Authors: Nicholas A. Veldhuis, Daniel P. Poole, Megan Grace, Peter McIntyre, Nigel W. Bunnett
Journal: Pharmacological Reviews (2014)

Sensory nerves are equipped with receptors and ion channels that allow them to detect and respond to diverse chemical, mechanical, and thermal stimuli. These sensory proteins include G protein–coupled receptors (GPCRs) and transient receptor potential (TRP) ion channels. A subclass of peptidergic sensory nerves express GPCRs and TRP channels that detect noxious, irritant, and inflammatory stimuli. Activation of these nerves triggers protective mechanisms that lead to withdrawal from danger (pain), removal of irritants (itch, cough), and resolution of infection (neurogenic inflammation). The GPCR-TRP axis is central to these mechanisms. Signals that emanate from the GPCR superfamily converge on the small TRP family, leading to channel sensitization and activation, which amplify pain, itch, cough, and neurogenic inflammation. Herein we discuss how GPCRs and TRP channels function independently and synergistically to excite sensory nerves that mediate noxious and irritant responses and inflammation in the skin and the gastrointestinal and respiratory systems. We discuss the signaling mechanisms that underlie the GPCR-TRP axis and evaluate how new information about the structure of GPCRs and TRP channels provides insights into their functional interactions. We propose that a deeper understanding of the GPCR-TRP axis may facilitate the development of more selective and effective therapies to treat dysregulated processes that underlie chronic pain, itch, cough, and inflammation.
NO-independent stimulation or activation of soluble guanylyl cyclase during early reperfusion limits infarct size
Authors: Justin S. Bice, Yvonne Keim, Johannes-Peter Stasch, Gary F. Baxter
Journal: Cardiovascular Research (2013)

AimsGuanylyl cyclase-cyclic guanosine monophosphate signalling plays an important role in endogenous cardioprotective signalling. The aim was to assess the potential of direct pharmacological activation and stimulation of soluble guanylyl cyclase, targeting different redox states of the enzyme, to limit myocardial necrosis during early reperfusion.
Effect of Patient Socioeconomic Status on Access to Early-Phase Cancer Trials
Authors: Aisyah Mohd Noor, Debashis Sarker, Suzanne Vizor, Blair McLennan, Sarah Hunter, Aneta Suder, Henrik Moller, James F. Spicer, Sophie Papa
Journal: Journal of Clinical Oncology (2012)

Purpose Little is known about the influence of socioeconomic factors on patient access to cancer trials. Differences should be considered to ensure generalizability of trial results and equality of access. Methods Phase I trials unit referrals at our center over 5 years, from 2007 to 2012, were reviewed. Socioeconomic status was defined by the Index of Multiple Deprivation (IMD; 1, least deprived; 5, most deprived). Multivariate analysis was performed comparing incident cancer cases with referred patients and those ultimately enrolled onto a trial. Results Four hundred thirty patients were referred (median age, 62 years). Compared with 10,784 incident cases, referral was less likely for patients in the more-deprived quintiles compared with the least deprived (IMD 5: odds ratio [OR], 0.53; 95% CI, 0.38 to 0.74). Once reviewed in the unit, enrollment onto a trial was not affected (IMD 5: OR, 0.81; 95% CI, 0.40 to 1.63). Ethnicity analysis showed the nonwhite population was less likely to be recruited (OR, 0.48; 95% CI, 0.26 to 0.88). This relationship was lost with adjustment for age, sex, cancer type, and deprivation index. Conclusion We show for the first time to our knowledge that socioeconomic status affects early-phase cancer trial referrals. The least-deprived patients are almost twice as likely to be referred compared with the most deprived. This may be because more-deprived patients are less suitable for a trial—as a result of comorbidities, for example—or because of inequalities that could be addressed by patient or referrer education. Once reviewed at the unit, enrollment onto a trial is not affected by deprivation.
A Randomized, Double-blind Trial Comparing Combinations of Nevirapine, Didanosine, and Zidovudine for HIV-Infected Patients
Authors: Julio S. G. Montaner, Peter Reiss, David Cooper, Stefano Vella, Marianne Harris, Brian Conway, Mark A. Wainberg, D. Smith, Patrick Robinson, David Hall, Maureen Myers, Joep M. A. Lange, None for the INCAS Study Group
Journal: JAMA (1998)

Context.—Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA.Objective.—To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine.Design.—Double-blind, controlled, randomized trial.Setting.—University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada, and Australia (INCAS).Patients.—Antiretroviral therapy–naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60×109/L (200-600/µL).Intervention.—Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine.Main Outcome Measure.—Plasma HIV-1 RNA.Results.—Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P&lt;.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P&lt;.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08).Conclusions.—Triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.
A complication of peroral bronchoscopy
Authors: A. A. R. Thompson, C. S. Raistrick, O. M. Pirzada, P. B. Anderson
Journal: European Respiratory Journal (2009)

A complication of peroral bronchoscopyTo the Editors:Flexible fibreoptic bronchoscopy is a safe procedure with a major complication rate of ,1% in most published studies [1].In one retrospective study of .4,000bronchoscopies, major complications (respiratory failure, pneumothorax and pulmonary haemorrhage of .50mLs) occurred in 0.5% of procedures and minor complications (laryngospasm, vomiting, bronchospasm, vasovagal syncope and epistaxis) in 0.8% of procedures [2].Herein we report an important, rare complication of bronchoscopy that, once recognised, is treatable by prompt action.
Narrowing of the superior vena cava–right atrium junction during radiofrequency catheter ablation for inappropriate sinus tachycardia: analysis with intracardiac echocardiography
Authors: David J Callans, Jian-Fang Ren, David Schwartzman, Charles D Gottlieb, Farooq A Chaudhry, Francis E Marchlinski
Journal: Journal of the American College of Cardiology (1999)
Abnormal intestinal bile acid distribution in azotaemic man: a possible role in the pathogenesis of uraemic diarrhoea.
Authors: S J Gordon, L J Miller, L J Haeffner, M D Kinsey, O D Kowlessar
Journal: Gut (1976)

Proximal intestinal bile acids have been studied in 14 ambulatory patients with varying degrees of azotaemia. When compared with normal subjects, the azotaemic patients showed a significant decrease in deoxycholic acid. Analysis of faecal bile acids of a patient with low intestinal deoxycholic acid also showed low deoxycholic acid with a preponderance of primary bile acids, and contrast with faecal bile acids of a normal subject and a patient with normal intestinal deoxycholic acid. It is suggested that impairment of deconjugation or 7alpha-dehydroxylation might be contributing to the low deoxycholic acid observed in azotaemic patients. Unusual bile acids: ursodeoxycholic acid, 3-hydroxy-7-keto-cholanic acid, and 3,12-dihydroxy-7-keto-cholanic acid were also noted in intestinal aspirates of azotaemic patients. The presence of these bile acids in conjunction with low deoxycholic acid correlates with the symptom of diarrhoea in azotaemic patients, and may contribute to the pathogenesis of diarrhoea in these patients.
Activation of the Signal Transducer and Activator of Transcription Signaling Pathway in Renal Proximal Tubular Cells by Albumin
Authors: Hideaki Nakajima, Masaru Takenaka, Jun-Ya Kaimori, Takayuki Hamano, Hirotsugu Iwatani, Takeshi Sugaya, Takahito Ito, Masatsugu Hori, Enyu Imai
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Renal proximal tubular cells activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. It was hypothesized that the signal transducer and activator of transcription (STAT) proteins may be activated by proteinuria in proximal tubular cells. To test this hypothesis, murine proximal tubular cells were treated with albumin (30 mg/ml medium) for various lengths of time. The results showed that albumin could activate Stat1 and Stat5 within 15 min in proximal tubular cells. The activation of STATs was mediated mostly by Jak2 and required no protein synthesis. In addition, activation of Stat1 occurred even after neutralization of IFN-γ. The activation of STATs was inhibited by N-acetyl-L-cysteine, a precursor of glutathione and a reactive oxygen species (ROS) scavenger, and fluorescence-activated cell sorter analysis showed upregulation of intracellular ROS after albumin overloading, suggesting that albumin per se could generate ROS in proximal tubular cells. The activation of STATs occurred by way of the ROS generating system, and especially through the membrane-bound NADPH oxidase system. Reduced activities of glutathione peroxidase and catalase could also be responsible for the accumulation of intracellular ROS. Hence, not only the ROS generating system, but also the ROS scavenging system may contribute to the induction of ROS by albumin. These findings support the hypothesis that proximal tubular cells are activated and generate ROS by reabsorption of abundant urinary proteins filtered through the glomerular capillaries, and as a consequence, various IFN-γ–inducible proteins are synthesized through IFN-γ–independent activation of STAT signaling.
Vitamin D metabolism in acute and chronic cholestasis
Authors: R. T. Jung, M. Davie, P. Siklos, T. M. Chalmers, J. O. Hunter, D. E. M. Lawson
Journal: Gut (1979)

To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected <sup>3</sup>H vitamin D<sub>3</sub> (<sup>3</sup>HD<sub>3</sub>) and the subsequent production of <sup>3</sup>H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less <sup>3</sup>H 25OHD than expected were receiving vitamin D supplements. The urinary tritium (<sup>3</sup>H) excretion after the injection of <sup>3</sup>HD<sub>3</sub> correlated with the serum bilirubin. After the injection of <sup>3</sup>H 25OHD<sub>3</sub> the urinary excretion of <sup>3</sup>H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the <sup>3</sup>H vitamin D<sub>3</sub> injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.
T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection
Authors: Robert J. Lee, Guoxiang Xiong, Jennifer M. Kofonow, Bei Chen, Anna Lysenko, Peihua Jiang, Valsamma Abraham, Laurel Doghramji, Nithin D. Adappa, James N. Palmer, David W. Kennedy, Gary K. Beauchamp, Paschalis-Thomas Doulias, Harry Ischiropoulos, James L. Kreindler, Danielle R. Reed, Noam A. Cohen
Journal: Journal of Clinical Investigation (2012)

Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection.
Separation of Notch1 Promoted Lineage Commitment and Expansion/Transformation in Developing T Cells
Authors: David Allman, Fredrick G. Karnell, Jennifer A. Punt, Sonia Bakkour, Lanwei Xu, Peggy Myung, Gary A. Koretzky, John C. Pui, Jon C. Aster, Warren S. Pear
Journal: The Journal of Experimental Medicine (2001)

Notch1 signaling is required for T cell development. We have previously demonstrated that expression of a dominant active Notch1 (ICN1) transgene in hematopoietic stem cells (HSCs) leads to thymic-independent development of CD4+CD8+ double-positive (DP) T cells in the bone marrow (BM). To understand the function of Notch1 in early stages of T cell development, we assessed the ability of ICN1 to induce extrathymic T lineage commitment in BM progenitors from mice that varied in their capacity to form a functional pre-T cell receptor (TCR). Whereas mice repopulated with ICN1 transduced HSCs from either recombinase deficient (Rag-2−/−) or Src homology 2 domain–containing leukocyte protein of 76 kD (SLP-76)−/− mice failed to develop DP BM cells, recipients of ICN1-transduced Rag-2−/− progenitors contained two novel BM cell populations indicative of pre-DP T cell development. These novel BM populations are characterized by their expression of CD3ε and pre-Tα mRNA and the surface proteins CD44 and CD25. In contrast, complementation of Rag-2−/− mice with a TCRβ transgene restored ICN1-induced DP development in the BM within 3 wk after BM transfer (BMT). At later time points, this population selectively and consistently gave rise to T cell leukemia. These findings demonstrate that Notch signaling directs T lineage commitment from multipotent progenitor cells; however, both expansion and leukemic transformation of this population are dependent on T cell–specific signals associated with development of DP thymocytes.
Prognostic Significance of Serum S100B Protein in High-Risk Surgically Resected Melanoma Patients Participating in Intergroup Trial ECOG 1694
Authors: Ahmad A. Tarhini, Joseph Stuckert, Sandra Lee, Cindy Sander, John M. Kirkwood
Journal: Journal of Clinical Oncology (2008)

We evaluated adjuvant trial E1694 to more precisely define the prognostic significance of serum S100B in patients with high-risk resected melanoma.Sera from 670 E1694 patients banked at baseline and three additional time points were tested for S100B protein using chemiluminescence.S100B testing results showed that the higher the S100B level is, the higher the risk of relapse and death, regardless of the cutoff value. Univariate analysis showed that baseline S100B > or = 0.15 microg/L is significantly correlated with overall survival (OS; P = .01). Multivariate analysis was performed adjusting for significant prognostic factors (ulceration and lymph node status) and treatment. Baseline S100B was a significant prognostic factor for survival (hazard ratio = 1.39; 95% CI, 1.01 to 1.92; P = .043). S100B values measured at later time points over 1 year were also demonstrated to be significant prognostic factors for relapse-free survival (RFS) and OS. Lower S100B values at baseline and during follow-up were associated with longer survival. A changing S100B from low at baseline to high on follow-up seemed to be associated with the worst RFS and OS.For patients with high-risk surgically resected melanoma, a high baseline or increasing serum S100B is an independent prognostic marker of risk for mortality that may allow us to refine the application of adjuvant therapy in the future.
Nutrition For Endurance Competition
Authors: William E. Connor
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The elegant studies of Bergström and Hultman (221:999, 1972), which included the measurement of glycogen content of quadriceps muscles under various conditions, pointed out the importance of carbohydrate stores in relationship to high levels of energy expenditures. They suggested a method of building up the glycogen content of muscles prior to endurance performance. We are currently studying the diet and blood lipid characteristics of the Tarahumara Indians of northern Mexico, who are probably the world's greatest endurance runners. These primitive Indians living in the caves of the Sierra Madre Mountains at altitudes up to 7,000 feet have a kickball game called raripuri in which competing teams run continuously for 100 to 200 miles. The length of the competition lasts 24 to 48 hours or more, depending on the length of the course. These stone-age Indians are essentially vegetarians deriving most of their calories from corn and beans.