tbuckley/cabot-search huggingface dataset:
A Validation of Event-Related fMRI Comparisons Between Users of Cocaine, Nicotine, or Cannabis and Control Subjects
Authors: Kevin Murphy, B.A. Veronica Dixon, B.A. Kathleen LaGrave, Jacqueline Kaufman, Robert Risinger, Alan Bloom, Hugh Garavan
Journal: American Journal of Psychiatry (2006)

Objective: Noninvasive brain imaging techniques are a powerful tool for researching the effects of drug abuse on brain activation measures. However, because many drugs have direct vascular effects, the validity of techniques that depend on blood flow measures as a reflection of neuronal activity may be called into question. This may be of particular concern in event-related functional magnetic resonance imaging (fMRI), where current analytic techniques search for a specific shape in the hemodynamic response to neuronal activity. Method: To investigate possible alterations in task-related activation as a result of drug abuse, fMRI scans were conducted on subjects in four groups as they performed a simple event-related finger-tapping task: users of cocaine, nicotine, or cannabis and control subjects. Results: Activation measures, as determined by two different analytic methods, did not differ between the groups. A comparison between an intravenous saline and an intravenous cocaine condition in cocaine users found a similar null result. Further in-depth analyses of the shape of the hemodynamic responses in each group also showed no differences. Conclusions: This study demonstrates that drug groups may be compared with control subjects using event-related fMRI without the need for any post hoc procedures to correct for possible drug-induced cardiovascular alterations. Thus, fMRI activation differences reported between these drug groups can be more confidently interpreted as reflecting neuronal differences.
Antioxidant Intervention Blunts Renal Injury in Experimental Renovascular Disease
Authors: Alejandro R. Chade, Martin Rodriguez-Porcel, Joerg Herrmann, Xiangyang Zhu, Joseph P. Grande, Claudio Napoli, Amir Lerman, Lilach O. Lerman
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Atherosclerotic renovascular disease (RVD) amplifies damage in a stenotic kidney by inducing pro-inflammatory mechanisms and disrupting tissue remodeling. Oxidative stress is increased in RVD, but its direct contribution to renal injury has not been fully established. The authors hypothesized that chronic antioxidant intervention in RVD would improve renal function and attenuate tissue injury. Single-kidney hemodynamics and function at baseline and during vasoactive challenge were quantified using electron-beam computed tomography in pigs after 12 wk of experimental RVD (simulated by concurrent hypercholesterolemia and renal artery stenosis, n = 7), RVD daily supplemented with antioxidant vitamins C (1 g), and E (100 IU/kg) (RVD+Vitamins, n = 7), or controls (normal, n = 7). Renal tissue was studied ex vivo using Western blot analysis and immunohistochemistry. Basal renal blood flow (RBF) and glomerular filtration rate (GFR) were similarly decreased in the stenotic kidney of both RVD groups. RBF and GFR response to acetylcholine was blunted in RVD, but significantly improved in RVD+Vitamins (P < 0.05 versus RVD). RVD+Vitamins also showed increased renal expression of endothelial nitric oxide synthase (eNOS) and decreased expression of NAD(P)H-oxidase, nitrotyrosine, inducible-NOS, and NF-κB, suggesting decreased superoxide abundance and inflammation. Furthermore, decreased expression of pro-fibrotic factors in RVD+Vitamins was accompanied by augmented expression of extracellular (matrix metalloproteinase–2) and intracellular (ubiquitin) protein degradation systems, resulting in significantly attenuated glomerulosclerosis and renal fibrosis. In conclusion, chronic antioxidant intervention in early experimental RVD improved renal functional responses, enhanced tissue remodeling, and decreased structural injury. This study supports critical pathogenic contribution of increased oxidative stress to renal injury and scarring in RVD and suggests a role for antioxidant strategies in preserving the atherosclerotic and ischemic kidney.
SIRT1, an Antiinflammatory and Antiaging Protein, Is Decreased in Lungs of Patients with Chronic Obstructive Pulmonary Disease
Authors: Saravanan Rajendrasozhan, Se-Ran Yang, Vuokko L. Kinnula, Irfan Rahman
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Abnormal inflammation and accelerated decline in lung function occur in patients with chronic obstructive pulmonary disease (COPD). Human sirtuin (SIRT1), an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins.To determine the expression of SIRT1 in lungs of smokers and patients with COPD, and to elucidate the regulation of SIRT1 in response to cigarette smoke in macrophages, and its impact on nuclear factor (NF)-kappaB regulation.SIRT1 and NF-kappaB levels were assessed in lung samples of nonsmokers, smokers, and patients with COPD. Human monocyte-macrophage cells (MonoMac6) were treated with cigarette smoke extract (CSE) to determine the mechanism of CSE-mediated regulation of SIRT1 and its involvement in RelA/p65 regulation and IL-8 release.Peripheral lungs of smokers and patients with COPD showed decreased levels of nuclear SIRT1, as compared with nonsmokers, associated with its post-translational modifications (formation of nitrotyrosine and aldehyde carbonyl adducts). Treatment of MonoMac6 cells with CSE showed decreased levels of SIRT1 associated with increased acetylation of RelA/p65 NF-kappaB. Mutation or knockdown of SIRT1 resulted in increased acetylation of nuclear RelA/p65 and IL-8 release, whereas overexpression of SIRT1 decreased IL-8 release in response to CSE treatment in MonoMac6 cells.SIRT1 levels were reduced in macrophages and lungs of smokers and patients with COPD due to its post-translational modifications by cigarette smoke-derived reactive components, leading to increased acetylation of RelA/p65. Thus, SIRT1 plays a pivotal role in regulation of NF-kappaB-dependent proinflammatory mediators in lungs of smokers and patients with COPD.
Chromosome 16 Loss of Heterozygosity in Tuberous Sclerosis and Sporadic Lymphangiomyomatosis
Authors: JANE YU, ARISTOTELIS ASTRINIDIS, ELIZABETH PETRI HENSKE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

In previous work we found loss of heterozygosity (LOH) of the wild-type TSC2 allele in the abnormal pulmonary smooth muscle cells and renal angiomyolipoma cells from patients with sporadic pulmonary lymphangiomyomatosis (LAM). Here we report TSC2 LOH in microdissected pulmonary LAM cells from a patient with tuberous sclerosis complex (TSC), demonstrating for the first time that the two-hit tumor suppressor gene model applies to the TSC-associated, as well as sporadic LAM. We also compared the chromosome 16 LOH region between angiomyolipoma and pulmonary LAM from two patients with sporadic LAM. Previously we found that these patients had TSC2 mutations and TSC2 LOH in their angiomyolipomas and pulmonary LAM cells but not in normal lung or kidney cells. This suggests that pulmonary LAM may result from the migration of smooth muscle cells from renal angiomyolipomas to the lung. In this case, one would predict that the angiomyolipoma and LAM cells would have identical LOH patterns. We found that at each chromosome 16 marker, the results were concordant between angiomyolipoma and LAM. This is consistent with a model in which pulmonary LAM cells and angiomyolipoma cells have a common genetic origin.
THE ABNOEMAL CANTHARIDIN BLISTER IN ATOPY: AN EXPLANATION OF ITS PRODUCTION.
Authors: J. H. ALLISON, D. H. WILLIAMSON
Journal: British Journal of Dermatology (1960)

Journal Article THE ABNOEMAL CANTHARIDIN BLISTER IN ATOPY: AN EXPLANATION OF ITS PRODUCTION. Get access J. H. ALLISON, M.B., M.R.C.P., J. H. ALLISON, M.B., M.R.C.P. St. John's Hospital for Diseases of the Skin, Lisle St., London, W.C.2, and the S.A. Courtauld Institute of Biochemistry, the Middlesex Hospital, London, W.I Search for other works by this author on: Oxford Academic Google Scholar D. H. WILLIAMSON, F.I.M.L.T. D. H. WILLIAMSON, F.I.M.L.T. St. John's Hospital for Diseases of the Skin, Lisle St., London, W.C.2, and the S.A. Courtauld Institute of Biochemistry, the Middlesex Hospital, London, W.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 72, Issue 11, 1 November 1960, Pages 383–402, https://doi.org/10.1111/j.1365-2133.1960.tb13825.x Published: 01 November 1960
MicroRNA-206: a Promising Theranostic Marker
Authors: Jan Novák, Peter Kružliak, Julie Bienertová-Vašků, Ondřej Slabý, Miroslav Novák
Journal: Theranostics (2014)

MicroRNAs (miRs) are small non-coding RNAs that negatively regulate gene expression by binding to the 3` untranslated regions (3`UTR) of their target mRNAs. MiRs were shown to play pivotal roles in tissue development and function and are also involved in the pathogenesis of various diseases including cancer. MicroRNA-206, which belongs to the group of so-called "myomiRs", is one of the most studied miRs thus far. In addition to being involved in skeletal muscle development and pathology, it has also been established that it is involved in the pathogenesis of numerous diseases including heart failure, chronic obstructive pulmonary disease, Alzheimer's disease and various types of cancers. The aim of this review is to provide a complex overview of microRNA-206, including regulating its expression, a brief description of its known functions in skeletal muscle and a complex overview of its roles in the biology and pathology of other tissues, emphasizing its significant diagnostic and therapeutic potential.
The Challenge of Drugging Undruggable Targets in Cancer: Lessons Learned from Targeting BCL-2 Family Members
Authors: Gregory L. Verdine, Loren D. Walensky
Journal: Clinical Cancer Research (2007)

Abstract The genomic and proteomic revolutions have provided us with an ever-increasing number of mechanistic insights into cancer pathogenesis. Mutated genes and pathologic protein products have emerged as the basis for modern anticancer drug development. With the increasing realization of the importance of disrupting oncogenic protein-protein interaction, new challenges have emerged for classical small molecule and protein-based drug modalities, i.e., the critical need to target flat and extended protein surfaces. Here, we highlight two distinct technologies that are being used to bridge the pharmacologic gap between small molecules and protein therapeutics. With the BCL-2 family of survival proteins as their substrate for intracellular targeting, we conclude that peptide stapling and fragment-based drug discovery show promise to traverse the critical surface features of proteins that drive human cancer.
Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease
Authors: Lawrence J. Appel, Jackson T. Wright, Tom Greene, Lawrence Y. Agodoa, Brad C. Astor, George L. Bakris, William H. Cleveland, Jeanne Charleston, Gabriel Contreras, Marquetta L. Faulkner, Francis B. Gabbai, Jennifer J. Gassman, Lee A. Hebert, Kenneth A. Jamerson, Joel D. Kopple, John W. Kusek, James P. Lash, Janice P. Lea, Julia B. Lewis, Michael S. Lipkowitz, Shaul G. Massry, Edgar R. Miller, Keith Norris, Robert A. Phillips, Velvie A. Pogue, Otelio S. Randall, Stephen G. Rostand, Miroslaw J. Smogorzewski, Robert D. Toto, Xuelei Wang
Journal: New England Journal of Medicine (2010)

In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients.
Statistical significance testing was not meant for weak corroborations of weaker theories
Authors: Fred L. Bookstein
Journal: Behavioral and Brain Sciences (1998)

Chow sets his version of statistical significance testing in an impoverished context of “theory corroboration” that explicitly excludes well-posed theories admitting of strong support by precise empirical evidence. He demonstrates no scientific usefulness for the problematic procedure he recommends instead. The important role played by significance testing in today's behavioral and brain sciences is wholly inconsistent with the rhetoric he would enforce.
UNEXPLAINED INCREASES IN CANCER INCIDENCE IN THE UNITED STATES FROM 1975 TO 1994: Possible Sentinel Health Indicators?
Authors: Gregg E. Dinse, David M. Umbach, Annie J. Sasco, David G. Hoel, Devra L. Davis
Journal: Annual Review of Public Health (1999)

▪ Abstract To search for unexplained patterns in cancer incidence, we analyzed data from 1975 to 1994 that represent ∼10% of the population of the United States. Our analysis focused on long-term time trends in incidence and on deviations from those trends attributable to birth cohorts or to calendar periods. On average, cancer incidence rose 0.8% annually in white women and 1.8% in white men. After removing several cancers related to smoking and increased screening, average annual increases fell to 0.1% in white women but persisted at 1.7% in white men. In particular, yearly increases in non-Hodgkin's lymphoma averaged 2.4% in white women and 4.7% in white men. Among men, incidence changes attributable to cohorts grew progressively larger from one cohort to the next. Cancer incidence patterns among black men and women were similar to those among whites despite smaller population sizes. Unexplained patterns of cancer incidence may signal changes in underlying risk factors and highlight the continuing need for research on cancer etiology and prevention.
CXCL10-CXCR3 Enhances the Development of Neutrophil-mediated Fulminant Lung Injury of Viral and Nonviral Origin
Authors: Akihiko Ichikawa, Keiji Kuba, Masayuki Morita, Shinsuke Chida, Hiroyuki Tezuka, Hiromitsu Hara, Takehiko Sasaki, Toshiaki Ohteki, V. Marco Ranieri, Claudia C. dos Santos, Yoshihiro Kawaoka, Shizuo Akira, Andrew D. Luster, Bao Lu, Josef M. Penninger, Stefan Uhlig, Arthur S. Slutsky, Yumiko Imai
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Patients who developed acute respiratory distress syndrome (ARDS) after infection with severe respiratory viruses (e.g., severe acute respiratory syndrome-coronavirus, H5N1 avian influenza virus), exhibited unusually high levels of CXCL10, which belongs to the non-ELR (glutamic-leucine-arginine) CXC chemokine superfamily. CXCL10 may not be a bystander to the severe virus infection but may directly contribute to the pathogenesis of neutrophil-mediated, excessive pulmonary inflammation.We investigated the contribution of CXCL10 and its receptor CXCR3 axis to the pathogenesis of ARDS with nonviral and viral origins.We induced nonviral ARDS by acid aspiration and viral ARDS by intratracheal influenza virus infection in wild-type mice and mice deficient in CXCL10, CXCR3, IFNAR1 (IFN-α/β receptor 1), or TIR domain-containing adaptor inducing IFN-β (TRIF).We found that the mice lacking CXCL10 or CXCR3 demonstrated improved severity and survival of nonviral and viral ARDS, whereas mice that lack IFNAR1 did not control the severity of ARDS in vivo. The increased levels of CXCL10 in lungs with ARDS originate to a large extent from infiltrated pulmonary neutrophils, which express a unique CXCR3 receptor via TRIF. CXCL10-CXCR3 acts in an autocrine fashion on the oxidative burst and chemotaxis in the inflamed neutrophils, leading to fulminant pulmonary inflammation.CXCL10-CXCR3 signaling appears to be a critical factor for the exacerbation of the pathology of ARDS. Thus, the CXCL10-CXCR3 axis could represent a prime therapeutic target in the treatment of the acute phase of ARDS of nonviral and viral origins.
Association of Postdischarge Rehabilitation with Mortality in Intensive Care Unit Survivors of Sepsis
Authors: Pei-wen Chao, Chia-Jen Shih, Yi-Jung Lee, Ching-Min Tseng, Shu-Chen Kuo, Yu-Ning Shih, Kun-Ta Chou, Der-Cherng Tarng, Szu-Yuan Li, Shuo-Ming Ou, Yung-Tai Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Intensive care unit (ICU)-acquired weakness is a common issue for sepsis survivors that is characterized by impaired muscle strength and causes functional disability. Although inpatient rehabilitation has not been found to reduce in-hospital mortality, the impact of postdischarge rehabilitation on sepsis survivors is uncertain.To investigate the benefit of postdischarge rehabilitation to long-term mortality in sepsis survivors.We conducted a nationwide, population-based, high-dimensional propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. The rehabilitation cohort comprised 15,535 ICU patients who survived sepsis and received rehabilitation within 3 months after discharge between 2000 and 2010. The control cohort consisted of 15,535 high-dimensional propensity score-matched subjects who did not receive rehabilitation within 3 months after discharge. The endpoint was mortality during the 10-year follow-up period.Compared with the control cohort, the rehabilitation cohort had a significantly lower risk of 10-year mortality (adjusted hazard ratio, 0.94; 95% confidence interval, 0.92-0.97; P < 0.001), with an absolute risk reduction of 1.4 per 100 person-years. The frequency of rehabilitation was inversely associated with 10-year mortality (≥3 vs. 1 course: adjusted hazard ratio, 0.82; P < 0.001). Compared with the control cohort, improved survival was observed in the rehabilitation cohort among ill patients who had more comorbidities, required more prolonged mechanical ventilation, and had longer ICU or hospital stays, but not among those with the opposite conditions (i.e., less ill patients).Postdischarge rehabilitation may be associated with a reduced risk of 10-year mortality in the subset of patients with particularly long ICU courses.
Cognitive Behavioral Therapy for Posttraumatic Stress Disorder in Women
Authors: Paula P. Schnurr, Matthew J. Friedman, Charles C. Engel, Edna B. Foa, M. Tracie Shea, Bruce K. Chow, Patricia A. Resick, Veronica Thurston, Susan M. Orsillo, Rodney Haug, Carole Turner, Nancy Bernardy
Journal: JAMA (2007)

<h3>Context</h3> The prevalence of posttraumatic stress disorder (PTSD) is elevated among women who have served in the military, but no prior study has evaluated treatment for PTSD in this population. Prior research suggests that cognitive behavioral therapy is a particularly effective treatment for PTSD. <h3>Objective</h3> To compare prolonged exposure, a type of cognitive behavioral therapy, with present-centered therapy, a supportive intervention, for the treatment of PTSD. <h3>Design, Setting, and Participants</h3> A randomized controlled trial of female veterans (n=277) and active-duty personnel (n=7) with PTSD recruited from 9 VA medical centers, 2 VA readjustment counseling centers, and 1 military hospital from August 2002 through October 2005. <h3>Intervention</h3> Participants were randomly assigned to receive prolonged exposure (n = 141) or present-centered therapy (n = 143), delivered according to standard protocols in 10 weekly 90-minute sessions. <h3>Main Outcome Measures</h3> Posttraumatic stress disorder symptom severity was the primary outcome. Comorbid symptoms, functioning, and quality of life were secondary outcomes. Blinded assessors collected data before and after treatment and at 3- and 6-month follow-up. <h3>Results</h3> Women who received prolonged exposure experienced greater reduction of PTSD symptoms relative to women who received present-centered therapy (effect size, 0.27;<i>P</i> = .03). The prolonged exposure group was more likely than the present-centered therapy group to no longer meet PTSD diagnostic criteria (41.0% vs 27.8%; odds ratio, 1.80; 95% confidence interval, 1.10-2.96;<i>P</i> = .01) and achieve total remission (15.2% vs 6.9%; odds ratio, 2.43; 95% confidence interval, 1.10-5.37;<i>P</i> = .01). Effects were consistent over time in longitudinal analyses, although in cross-sectional analyses most differences occurred immediately after treatment. <h3>Conclusions</h3> Prolonged exposure is an effective treatment for PTSD in female veterans and active-duty military personnel. It is feasible to implement prolonged exposure across a range of clinical settings. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00032617
Cancer and the Risk of Suicide in Older Americans
Authors: Matthew Miller, Helen Mogun, Deborah Azrael, Katherine Hempstead, Daniel H. Solomon
Journal: Journal of Clinical Oncology (2008)

To determine whether the risk of suicide is greater among patients with cancer than among patients with other medical illnesses.A case-control study of the suicide risk associated with medical illness among older Americans that used healthcare utilization data linked to prescription and mortality files. The patient population was comprised of 1,408 New Jersey residents age 65 years or older who were enrolled in Medicare and in a pharmaceutical insurance program. Patient cases (n = 128) died as a result of suicide during the study period of 1994 to 2002. Control patients (n = 1,280) were frequency-matched to patient cases on age and sex. Data were analyzed by using the odds ratio (OR) of suicide adjusted for age, sex, ethnicity, medical and psychiatric comorbidity, and use of prescription medications.In adjusted analyses, the only medical condition that remained associated with suicide was cancer (OR, 2.3; 95% CI, 1.1 to 4.8). Suicide also remained associated with a diagnosis of affective disorder (OR, 2.3; 95% CI, 1.3 to 4.2), anxiety/personality disorder (OR, 2.2; 95% CI, 1.3 to 3.6), treatment with antidepressants (OR, 2.0; 95% CI, 1.2 to 3.2), and treatment with opioid analgesics (OR, 1.6; 95% CI, 1.0 to 2.5).The risk of suicide in older adults is higher among patients with cancer than among patients with other medical illnesses, even after psychiatric illness and the risk of dying within a year were accounted for.