tbuckley/cabot-search huggingface dataset:
The endogenous cannabinoid system protects against colonic inflammation
Authors: Federico Massa, Giovanni Marsicano, Heike Hermann, Astrid Cannich, Krisztina Monory, Benjamin F. Cravatt, Gian-Luca Ferri, Andrei Sibaev, Martin Storr, Beat Lutz
Journal: Journal of Clinical Investigation (2004)

Excessive inflammatory responses can emerge as a potential danger for organisms' health. Physiological balance between pro- and anti-inflammatory processes constitutes an important feature of responses against harmful events. Here, we show that cannabinoid receptors type 1 (CB1) mediate intrinsic protective signals that counteract proinflammatory responses. Both intrarectal infusion of 2,4-dinitrobenzene sulfonic acid (DNBS) and oral administration of dextrane sulfate sodium induced stronger inflammation in CB1-deficient mice (CB1(-/-)) than in wild-type littermates (CB1(+/+)). Treatment of wild-type mice with the specific CB1 antagonist N-(piperidino-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-pyrazole-3-carboxamide (SR141716A) mimicked the phenotype of CB1(-/-) mice, showing an acute requirement of CB1 receptors for protection from inflammation. Consistently, treatment with the cannabinoid receptor agonist R(-)-7-hydroxy-Delta(6)-tetra-hydrocannabinol-dimethylheptyl (HU210) or genetic ablation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) resulted in protection against DNBS-induced colitis. Electrophysiological recordings from circular smooth muscle cells, performed 8 hours after DNBS treatment, revealed spontaneous oscillatory action potentials in CB1(-/-) but not in CB1(+/+) colons, indicating an early CB1-mediated control of inflammation-induced irritation of smooth muscle cells. DNBS treatment increased the percentage of myenteric neurons expressing CB1 receptors, suggesting an enhancement of cannabinoid signaling during colitis. Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses.
THE CONCEPT OF PSYCHOGENESIS
Authors: JOHN R. REID
Journal: American Journal of Psychiatry (1948)

On the basis of the examination of a number of more or less typical instances of usage, it is inferred that to say of a given syndrome, case of disordered function, or set of pathological changes that it is "psychogenic" is to say that among its causal antecedents are at least some psychic events of the sort characterized as being emotionally reinforced acts of interpretation. Some of the difficulties of applying this definition are examined, and a few concluding remarks are added on the "cash value" (in James' sense) of the concept of psychogenesis in medical practice. As for its cash value, in the literal sense, I leave it to those who practice psychotherapy to estimate—but it must be considerable.
Development of an Orthotopic Model of Invasive Pancreatic Cancer in an Immunocompetent Murine Host
Authors: William W. Tseng, Daniel Winer, Justin A. Kenkel, Okmi Choi, Alan H. Shain, Jonathan R. Pollack, Randy French, Andrew M. Lowy, Edgar G. Engleman
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The most common preclinical models of pancreatic adenocarcinoma utilize human cells or tissues that are xenografted into immunodeficient hosts. Several immunocompetent, genetically engineered mouse models of pancreatic cancer exist; however, tumor latency and disease progression in these models are highly variable. We sought to develop an immunocompetent, orthotopic mouse model of pancreatic cancer with rapid and predictable growth kinetics. Experimental Design: Cell lines with epithelial morphology were derived from liver metastases obtained from KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre mice. Tumor cells were implanted in the pancreas of immunocompetent, histocompatible B6/129 mice, and the mice were monitored for disease progression. Relevant tissues were harvested for histologic, genomic, and immunophenotypic analysis. Results: All mice developed pancreatic tumors by two weeks. Invasive disease and liver metastases were noted by six to eight weeks. Histologic examination of tumors showed cytokeratin-19–positive adenocarcinoma with regions of desmoplasia. Genomic analysis revealed broad chromosomal changes along with focal gains and losses. Pancreatic tumors were infiltrated with dendritic cells, myeloid-derived suppressor cells, macrophages, and T lymphocytes. Survival was decreased in RAG−/− mice, which are deficient in T cells, suggesting that an adaptive immune response alters the course of disease in wild-type mice. Conclusions: We have developed a rapid, predictable orthotopic model of pancreatic adenocarcinoma in immunocompetent mice that mimics human pancreatic cancer with regard to genetic mutations, histologic appearance, and pattern of disease progression. This model highlights both the complexity and relevance of the immune response to invasive pancreatic cancer and may be useful for the preclinical evaluation of new therapeutic agents. Clin Cancer Res; 16(14); 3684–95. ©2010 AACR.
Autoimmune conditions and hairy cell leukemia: an exploratory case-control study
Authors: Lesley A Anderson, Eric A Engels
Journal: Journal of Hematology & Oncology (2010)

Case reports suggest that hairy cell leukemia (HCL) may be associated with autoimmune conditions, however no systematic investigations in this area have been undertaken. Using the United States Surveillance, Epidemiology, and End Results Medicare linked database, we conducted an exploratory study comparing autoimmune conditions in 418 HCL cases (aged ≥65 years) and 160,086 controls. Overall, the proportion with autoimmune conditions was similar between HCL cases and controls (n = 79 (18.9%) and n = 29,284 (18.3%), respectively). Before diagnosis/selection, there was no overall difference in the prevalence of autoimmune conditions in HCL cases (n = 37, 8.9%) compared with controls (n = 14,085, 8.8%), p = 0.969. However, compared with controls, HCL cases more frequently had sarcoidosis (OR 9.6, 95%CI 2.4-39.5), Sjögren syndrome (OR 6.1, 95%CI 2.0-19.3) and erythema nodosum (OR 37, 95%CI 4.9-284) before diagnosis. Autoimmune conditions were also more common in HCL cases than controls around the time of diagnosis/selection (p < 0.001) but not subsequently. The findings do not support an overall relationship between autoimmune conditions and HCL, although the association with some autoimmune conditions prior to HCL diagnosis may warrant further investigation. Our findings also suggest that autoimmune conditions in HCL patients may be detected around the time of diagnosis.
Germ cell transplantation: a review and progress report on ICSI from spermatozoa generated in xenogeneic testes
Authors: N. Sofikitis
Journal: Human Reproduction Update (2003)

Results from the transplantation of donor male germ cells into xenogeneic recipient seminiferous tubules indicate that donor spermatogonia are capable of differentiating to form spermatozoa morphologically characteristic of the donor species. Germ cell transplantation procedures combined with developments in freezing, culturing or enriching germ cell populations have applications of paramount importance in medicine, basic sciences and animal reproduction. Additionally, these techniques can serve as an alternative approach for gonadal protection and fertility preservation in patients with cancer. This article is a chronological critical review of the technological advances that followed the initial successful transplantation of mouse germ cells into recipient mice. Furthermore, the factors responsible for the immunological privilege properties of the testis and the parameters influencing the potential of mammalian germ cells to undergo mitosis and meiosis within a xenogeneic testis are described. Finally, the role of human germ cell transplantation procedures in the therapeutic management of non‐obstructive azoospermia is discussed.
Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells)
Authors: Manoj Puthia, Petter Storm, Aftab Nadeem, Sabrina Hsiung, Catharina Svanborg
Journal: Gut (2013)

<h3>Background</h3> Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. <h3>Objective</h3> To investigate if HAMLET can be used for colon cancer treatment and prevention. <i>Apc<sup>Min</sup></i><sup>/+</sup> mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. <h3>Method</h3> HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. <h3>Results</h3> Peroral HAMLET administration reduced tumour progression and mortality in <i>Apc<sup>Min</sup></i><sup>/+</sup> mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with <i>APC</i> mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. <h3>Conclusions</h3> These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying <i>APC</i> mutations, where colon cancer remains a leading cause of death.
Maintaining a High Physical Activity Level Over 20 Years and Weight Gain
Authors: Arlene L. Hankinson, Martha L. Daviglus, Claude Bouchard, Mercedes Carnethon, Cora E. Lewis, Pamela J. Schreiner, Kiang Liu, Stephen Sidney
Journal: JAMA (2010)

Data supporting physical activity guidelines to prevent long-term weight gain are sparse, particularly during the period when the highest risk of weight gain occurs.To evaluate the relationship between habitual activity levels and changes in body mass index (BMI) and waist circumference over 20 years.The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective longitudinal study with 20 years of follow-up, 1985-1986 to 2005-2006. Habitual activity was defined as maintaining high, moderate, and low activity levels based on sex-specific tertiles of activity scores at baseline. Participants comprised a population-based multicenter cohort (Chicago, Illinois; Birmingham, Alabama; Minneapolis, Minnesota; and Oakland, California) of 3554 men and women aged 18 to 30 years at baseline.Average annual changes in BMI and waist circumference.Over 20 years, maintaining high levels of activity was associated with smaller gains in BMI and waist circumference compared with low activity levels after adjustment for race, baseline BMI, age, education, cigarette smoking status, alcohol use, and energy intake. Men maintaining high activity gained 2.6 fewer kilograms (0.15 BMI units per year; 95% confidence interval [CI], 0.11-0.18 vs 0.20 in the lower activity group; 95% CI, 0.17-0.23), and women maintaining higher activity gained 6.1 fewer kilograms (0.17 BMI units per year; 95% CI, 0.12-0.21 vs 0.30 in the lower activity group; 95% CI, 0.25-0.34). Men maintaining high activity gained 3.1 fewer centimeters in waist circumference (0.52 cm per year; 95% CI, 0.43-0.61 cm vs 0.67 cm in the lower activity group; 95% CI,0.60-0.75 cm) and women maintaining higher activity gained 3.8 fewer centimeters(0.49 cm per year; 95% CI, 0.39-0.58 cm vs 0.67 cm in the lower activity group; 95% CI, 0.60-0.75 cm) [corrected].Maintaining high activity levels through young adulthood may lessen weight gain as young adults transition to middle age, particularly in women.
Human Kallikrein 6: A New Potential Serum Biomarker for Uterine Serous Papillary Cancer
Authors: Alessandro D. Santin, Eleftherios P. Diamandis, Stefania Bellone, Antoninus Soosaipillai, Stefania Cane, Michela Palmieri, Alexander Burnett, Juan J. Roman, Sergio Pecorelli
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The discovery of novel biomarkers might greatly contribute to improve clinical management and outcomes in uterine serous papillary carcinoma (USPC), a highly aggressive variant of endometrial cancer. Experimental Design: Human kallikrein 6 (hK6) gene expression levels were evaluated in 29 snap-frozen endometrial biopsies, including 13 USPC, 13 endometrioid carcinomas, and 3 normal endometrial cells by real-time PCR. Secretion of hK6 protein by 14 tumor cultures, including 3 USPC, 3 endometrioid carcinoma, 5 ovarian serous papillary carcinoma, and 3 cervical cancers, was measured using a sensitive ELISA. Finally, hK6 concentration in 79 serum and plasma samples from 22 healthy women, 20 women with benign diseases, 20 women with endometrioid carcinoma, and 17 USPC patients was studied. Results: hK6 gene expression levels were significantly higher in USPC when compared with endometrioid carcinoma (mean copy number by real-time PCR, 1,927 versus 239, USPC versus endometrioid carcinoma; P &amp;lt; 0.01). In vitro hK6 secretion was detected in all primary USPC cell lines tested (mean, 11.5 μg/L) and the secretion levels were similar to those found in primary ovarian serous papillary carcinoma cultures (mean, 9.6 μg/L). In contrast, no hK6 secretion was detectable in primary endometrioid carcinoma and cervical cancer cultures. hK6 serum and plasma concentrations (mean ± SE) among normal healthy females (2.7 ± 0.2 μg/L), patients with benign diseases (2.4 ± 0.2 μg/L), and patients with endometrioid carcinoma (2.6 ± 0.2 μg/L) were not significantly different. In contrast, serum and plasma hK6 values in USPC patients (6.1 ± 1.1) were significantly higher than those in the noncancer group (P = 0.006), benign group (P = 0.003), and endometrioid carcinoma patients (P = 0.005). Conclusions: hK6 is highly expressed in USPC and is released in the plasma and serum of USPC patients. hK6 may represent a novel biomarker for USPC for monitoring early disease recurrence and response to therapy.
TCT-264 The Systolic Function Was Improved But Diastolic Function Was Not Improved After STEMI Treated With Primary PCI
Authors: Jin Bae Lee, Kyung-Ryun Bae, Sung Gug Chang, Ji Yong Choi, Seung Pyo Hong, Seung-woon Jun, Kee Sik Kim, Young Soo Lee, Jae Kean Ryu
Journal: Journal of the American College of Cardiology (2013)
National, regional, and global sex ratios of infant, child, and under-5 mortality and identification of countries with outlying ratios: a systematic assessment
Authors: Leontine Alkema, Fengqing Chao, Danzhen You, Jon Pedersen, Cheryl C Sawyer
Journal: The Lancet Global Health (2014)

Under natural circumstances, the sex ratio of male to female mortality up to the age of 5 years is greater than one but sex discrimination can change sex ratios. The estimation of mortality by sex and identification of countries with outlying levels is challenging because of issues with data availability and quality, and because sex ratios might vary naturally based on differences in mortality levels and associated cause of death distributions.For this systematic analysis, we estimated country-specific mortality sex ratios for infants, children aged 1-4 years, and children under the age of 5 years (under 5s) for all countries from 1990 (or the earliest year of data collection) to 2012 using a Bayesian hierarchical time series model, accounting for various data quality issues and assessing the uncertainty in sex ratios. We simultaneously estimated the global relation between sex ratios and mortality levels and constructed estimates of expected and excess female mortality rates to identify countries with outlying sex ratios.Global sex ratios in 2012 were 1·13 (90% uncertainty interval 1·12-1·15) for infants, 0·95 (0·93-0·97) for children aged 1-5 years, and 1·08 (1·07-1·09) for under 5s, an increase since 1990 of 0·01 (-0·01 to 0·02) for infants, 0·04 (0·02 to 0·06) for children aged 1-4 years, and 0·02 (0·01 to 0·04) for under 5s. Levels and trends varied across regions and countries. Sex ratios were lowest in southern Asia for 1990 and 2012 for all age groups. Highest sex ratios were seen in developed regions and the Caucasus and central Asia region. Decreasing mortality was associated with increasing sex ratios, except at very low infant mortality, where sex ratios decreased with total mortality. For 2012, we identified 15 countries with outlying under-5 sex ratios, of which ten countries had female mortality higher than expected (Afghanistan, Bahrain, Bangladesh, China, Egypt, India, Iran, Jordan, Nepal, and Pakistan). Although excess female mortality has decreased since 1990 for the vast majority of countries with outlying sex ratios, the ratios of estimated to expected female mortality did not change substantially for most countries, and worsened for India.Important differences exist between boys and girls with respect to survival up to the age of 5 years. Survival chances tend to improve more rapidly for girls compared with boys as total mortality decreases, with a reversal of this trend at very low infant mortality. For many countries, sex ratios follow this pattern but important exceptions exist. An explanation needs to be sought for selected countries with outlying sex ratios and action should be undertaken if sex discrimination is present.The National University of Singapore and the United Nations Children's Fund (UNICEF).
A pilot study of IL-1 inhibition in acute calcific periarthritis of the shoulder
Authors: Pascal Zufferey, Alexander So
Journal: Annals of the Rheumatic Diseases (2012)

Acute calcific periarthritis is a known cause of a painful shoulder. The calcium deposits are composed of different crystalline forms, including hydroxyapatite.1 Usually, these acute episodes are self-limiting. Current treatment approaches include non-steroid anti-inflammatory drug (NSAID) and steroids.2 

Microcrystals are capable of triggering interleukin (IL)-1 mediated inflammation.3 ,4 Therapeutic inhibition of IL-1 signalling has been shown to be effective in gout, and may have a place in the treatment of other crystal-induced inflammatory conditions.5 We have therefore investigated the effects of IL-1RA (anakinra) in acute calcific periarthritis in a pilot study.

Five consecutive patients (mean age of 60 years) were treated. They all had acute shoulder pain for <7 days and had not responded to 48 h …
US issues new guidelines for health workers caring for Ebola patients
Authors: M. McCarthy
Journal: BMJ (2014)

rigorously trained in its use, the US Centers for Disease Control and Prevention (CDC) said in new guidance issued on 20 October. 1 1 US Centers for Disease Control and Prevention.Guidance on personal protective equipment to be used by healthcare workers during management of patients with Ebola virus disease in US hospitals, including procedures for putting on (donning) and removing (doffing).20 October 2014.www.cdc.gov/vhf/ebola/hcp/procedures-for-ppe.html. 2
Peanut-induced intestinal allergy is mediated through a mast cell–IgE–FcεRI–IL-13 pathway
Authors: Meiqin Wang, Katsuyuki Takeda, Yoshiki Shiraishi, Masakazu Okamoto, Azzeddine Dakhama, Anthony Joetham, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2010)
Molecular Mechanisms of Primary Hypercalciuria
Authors: Kevin K. Frick, David A. Bushinsky
Journal: Journal of the American Society of Nephrology (2003)

Nephrolithiasis, with a lifetime incidence of up to 13% ([1–9][1] [⇓][2] [⇓][3] [⇓][4] [⇓][5] [⇓][6] [⇓][7] [⇓][8] [⇓][9]), results in significant morbidity as well as substantial economic costs, not only directly from medical treatment but also indirectly through time lost from
β-Adrenergic Receptor–Stimulated Apoptosis in Cardiac Myocytes Is Mediated by Reactive Oxygen Species/c-Jun NH <sub>2</sub> -Terminal Kinase–Dependent Activation of the Mitochondrial Pathway
Authors: Andrea Remondino, Susan H. Kwon, Catherine Communal, David R. Pimentel, Douglas B. Sawyer, Krishna Singh, Wilson S. Colucci
Journal: Circulation Research (2003)

Stimulation of beta-adrenergic receptors (betaARs) causes apoptosis in adult rat ventricular myocytes (ARVMs). The role of reactive oxygen species (ROS) in mediating betaAR-stimulated apoptosis is not known. Stimulation of betaARs with norepinephrine (10 micromol/L) in the presence of prazosin (100 nmol/L) for 24 hours increased the number of apoptotic myocytes as determined by TUNEL staining by 3.6- fold. The superoxide dismutase/catalase mimetics Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP; 10 micromol/L) and Euk-134 decreased betaAR-stimulated apoptosis by 89+/-6% and 76+/-10%, respectively. Infection with an adenovirus expressing catalase decreased betaAR-stimulated apoptosis by 82+/-15%. The mitochondrial permeability transition pore inhibitor bongkrekic acid (50 micromol/L) decreased betaAR-stimulated apoptosis by 76+/-8%, and the caspase inhibitor zVAD-fmk (25 micromol/L) decreased betaAR-stimulated apoptosis by 62+/-11%. betaAR-stimulated cytochrome c release was inhibited by MnTMPyP. betaAR stimulation caused c-Jun NH2-terminal kinase (JNK) activation, which was abolished by MnTMPyP. Transfection with an adenovirus expressing dominant-negative JNK inhibited betaAR-stimulated apoptosis by 81+/-12%, and the JNK inhibitor SP600125 inhibited both betaAR-stimulated apoptosis and cytochrome c release. Thus, betaAR-stimulated apoptosis in ARVMs involves ROS/JNK-dependent activation of the mitochondrial death pathway.
Persistence of sputum eosinophilia in children with controlled asthma when compared with healthy children
Authors: Y Cai, K Carty, RL Henry, PG Gibson
Journal: European Respiratory Journal (1998)

We aimed to describe induced sputum cell counts in healthy nonasthmatic children, and to compare these to children with controlled and uncontrolled asthma. Following clinical assessment and spirometry, ultrasonically nebulized hypertonic saline was used to induce sputum from children with asthma (n=50) and without asthma (n=72). Sputum was dispersed and cell counts performed to yield total and differential cell counts. Specific stains were used for eosinophil and mast cell counts. All of the children with asthma were receiving inhaled and/or oral corticosteroids. Current asthma control was assessed in terms of symptoms and lung function. Children were classified as controlled on inhaled corticosteroids (no current symptoms, normal lung function n=15), current symptomatic asthma (n=16) and asthma exacerbation (n=11). It was found that eosinophils comprised a median 0.3% (interquartile range (IQR): 0, 1.05) of cells in sputum from healthy children. Sputum eosinophils (4.3% (IQR: 15, 14.1) p=0.0005) and epithelial cells (14% (IQR: 6, 19.4) p=0.0005) were significantly higher in children with asthma than in nonasthmatic children. Children whose asthma was controlled, as well as those with symptoms, had more sputum eosinophils and epithelial cells than the nonasthmatics. Mast cells were found in the sputum of only four of the 42 children with asthma. This study demonstrates that eosinophilic airway inflammation and epithelial damage can occur in children with asthma. Airway inflammation persists even in those children who are receiving inhaled corticosteroids, have normal lung function and good symptomatic control of their disease.