tbuckley/cabot-search huggingface dataset:
Lymphocyte-Mediated Cytotoxicity
Authors: John H. Russell, Timothy J. Ley
Journal: Annual Review of Immunology (2002)

Virtually all of the measurable cell-mediated cytotoxicity delivered by cytotoxic T lymphocytes and natural killer cells comes from either the granule exocytosis pathway or the Fas pathway. The granule exocytosis pathway utilizes perforin to traffic the granzymes to appropriate locations in target cells, where they cleave critical substrates that initiate DNA fragmentation and apoptosis; granzymes A and B induce death via alternate, nonoverlapping pathways. The Fas/FasL system is responsible for activation-induced cell death but also plays an important role in lymphocyte-mediated killing under certain circumstances. The interplay between these two cytotoxic systems provides opportunities for therapeutic interventions to control autoimmune diseases and graft vs. host disease, but oversuppression of these pathways may also lead to increased viral susceptibility and/or decreased tumor cell killing.
Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer
Authors: Rayjean J. Hung, Cornelia M. Ulrich, Ellen L. Goode, Yonathan Brhane, Kenneth Muir, Andrew T. Chan, Loic Le Marchand, Joellen Schildkraut, John S. Witte, Rosalind Eeles, Paolo Boffetta, Margaret R. Spitz, Julia G. Poirier, David N. Rider, Brooke L. Fridley, Zhihua Chen, Christopher Haiman, Fredrick Schumacher, Douglas F. Easton, Maria Teresa Landi, Paul Brennan, Richard Houlston, David C. Christiani, John K. Field, Heike Bickeböller, Angela Risch, Zsofia Kote-Jarai, Fredrik Wiklund, Henrik Grönberg, Stephen Chanock, Sonja I. Berndt, Peter Kraft, Sara Lindström, Ali Amin Al Olama, Honglin Song, Catherine Phelan, Nicholas Wentzensen, Ulrike Peters, Martha L. Slattery, Thomas A. Sellers, Graham Casey, Stephen B. Gruber, David J. Hunter, Christopher I. Amos, Brian Henderson
Journal: JNCI Journal of the National Cancer Institute (2015)

Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted. We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided. We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10–8, and it showed an association with lung cancer (P = 2.01 x 10–6), colorectal cancer (GECCO P = 6.72x10-6; CORECT P = 3.32x10-5), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10-6), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003). Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer.
Biological basis for human capacitation
Authors: Christopher De Jonge
Journal: Human Reproduction Update (2005)

More than 50 years ago Austin and Chang defined mammalian sperm capacitation as a period of time that sperm must reside in the female reproductive tract before they acquire the ability to fertilize oocytes. Since then numerous investigations have attempted to more clearly define the molecules and processes that are a part of capacitation. The data that have provided a more clear definition of capacitation were primarily derived from in vitro experiments. This is particularly true for studies on human sperm capacitation. While ethical constraints have limited an equal balance of in vivo studies there are those data that when coupled with some of the in vitro data allow for the formulation of a biological framework for human sperm capacitation in vivo. This review will put forth the biological basis for human capacitation.
The ACGME's Final Duty-Hour Standards — Special PGY-1 Limits and Strategic Napping
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2010)

On September 28, the Accreditation Council for Graduate Medical Education (ACGME) released new standards to which residency programs must adhere or risk losing their accreditation. Recognizing societal demands for improved patient safety, the task force that developed the standards has embraced stricter duty-hour limits and greater supervision for trainees in the first postgraduate year (PGY-1). The new standards reflect many of the recommendations made by the Institute of Medicine (IOM) in a 2008 report1 but differ from them on one critical issue — how graduate medical education (GME) programs can best prevent harmful medical errors committed by sleep-deprived residents. The . . .
Organization of the pronephric kidney revealed by large-scale gene expression mapping
Authors: Daniela Raciti, Luca Reggiani, Lars Geffers, Qiuhong Jiang, Francesca Bacchion, Astrid E Subrizi, Dave Clements, Christopher Tindal, Duncan R Davidson, Brigitte Kaissling, André W Brändli
Journal: Genome biology (2008)

Abstract Background The pronephros, the simplest form of a vertebrate excretory organ, has recently become an important model of vertebrate kidney organogenesis. Here, we elucidated the nephron organization of the Xenopus pronephros and determined the similarities in segmentation with the metanephros, the adult kidney of mammals. Results We performed large-scale gene expression mapping of terminal differentiation markers to identify gene expression patterns that define distinct domains of the pronephric kidney. We analyzed the expression of over 240 genes, which included members of the solute carrier, claudin, and aquaporin gene families, as well as selected ion channels. The obtained expression patterns were deposited in the searchable European Renal Genome Project Xenopus Gene Expression Database. We found that 112 genes exhibited highly regionalized expression patterns that were adequate to define the segmental organization of the pronephric nephron. Eight functionally distinct domains were discovered that shared significant analogies in gene expression with the mammalian metanephric nephron. We therefore propose a new nomenclature, which is in line with the mammalian one. The Xenopus pronephric nephron is composed of four basic domains: proximal tubule, intermediate tubule, distal tubule, and connecting tubule. Each tubule may be further subdivided into distinct segments. Finally, we also provide compelling evidence that the expression of key genes underlying inherited renal diseases in humans has been evolutionarily conserved down to the level of the pronephric kidney. Conclusion The present study validates the Xenopus pronephros as a genuine model that may be used to elucidate the molecular basis of nephron segmentation and human renal disease.
Prevalence of Monoclonal Gammopathies in Patients with Hepatitis C Virus Infection
Authors: Pictro Andreone
Journal: Annals of Internal Medicine (1998)

Background: An association between monoclonal gammopathies and chronic liver diseases has been reported. Objective: To determine the prevalence of monoclonal gammopathies in patients with chronic hepatitis C virus (HCV) infection and the possible association of monoclonal gammopathies with HCV genotypes. Design: Prospective study. Setting: Departments of internal medicine and hematology at two university hospitals in Italy. Patients: 239 HCV-positive and 98 HCV-negative patients with chronic liver diseases were recruited consecutively. Measurements: Clinical data were gathered, liver histologic examination was done, serum immunoglobulin and cryoglobulin levels were measured, and immunoelectrophoresis was done for monoclonal component detection. Patients with monoclonal gammopathy had serum HCV RNA measured and HCV genotype determined by polymerase chain reaction and had histologic examination of bone marrow. Results: Monoclonal band was detected in 11% of HCV-positive patients and in 1% of HCV-negative patients (P = 0.004). The prevalence of HCV genotype 2a/c was higher in patients with monoclonal gammopathies than in those without (50% compared with 18%; P = 0.009). Conclusion: The prevalence of monoclonal gammopathies in patients with HCV-related chronic liver disease is striking and is often associated with genotype 2a/c infection.
Left Ventricular Performance at High End-Diastolic Pressures in Isolated, Perfused Dog Hearts
Authors: R. G. MONROE, W. J. GAMBLE, C. G. LAFARGE, A. EDALJI KUMAR, F. J. MANASEK
Journal: Circulation Research (1970)

In the isolated, blood-perfused heart of the dog, left ventricular developed pressure and developed mean wall stress were observed while the ventricle contracted at a constant, nearly isovolumic afterload and while end-diastolic pressure was raised to levels exceeding 100 mm Hg. Coronary perfusion pressure was maintained at the level of the peak systolic pressure. Dilatation of the mitral ring and consequent mitral regurgitation were avoided by left atrial plication. Normalized graphs of percent of peak developed pressure against end-diastolic pressure showed that developed pressure rose abruptly with diastolic pressure, peaked at a diastolic pressure of approximately 30 mm Hg, and declined 14.7% (±0.9 SE) at an end-diastolic pressure of 100 mm Hg. Likewise, developed mean wall stress rose abruptly with diastolic pressure, peaked at a higher diastolic pressure of approximately 50 mm Hg, and declined only 7.5% (±0.8 SE) from this peak at an end-diastolic pressure of 100 mm Hg. Similar findings were observed in hearts acutely depressed with propranolol. Electron micrographs showed sarcomere length to average 2.275µ and 2.300µ in ventricles fixed in diastole while subjected to pressures of 61 and 100 mm Hg, respectively, after potassium arrest, confirming the findings illustrated by the normalized graphs. These observations imply that in the isolated heart of the dog there is no loss of ventricular performance attributable to a descending limb of the Frank-Starling mechanism until the end-diastolic pressure exceeds 60 mm Hg and that this loss is minimal at diastolic pressures as high as 100 mm Hg.
Microbiota-Derived Hydrogen Fuels Salmonella Typhimurium Invasion of the Gut Ecosystem
Authors: Lisa Maier, Rounak Vyas, Carmen Dolores Cordova, Helen Lindsay, Thomas Sebastian Benedikt Schmidt, Sandrine Brugiroux, Balamurugan Periaswamy, Rebekka Bauer, Alexander Sturm, Frank Schreiber, Christian von Mering, Mark D. Robinson, Bärbel Stecher, Wolf-Dietrich Hardt
Journal: Cell Host & Microbe (2013)

The intestinal microbiota features intricate metabolic interactions involving the breakdown and reuse of host- and diet-derived nutrients. The competition for these resources can limit pathogen growth. Nevertheless, some enteropathogenic bacteria can invade this niche through mechanisms that remain largely unclear. Using a mouse model for Salmonella diarrhea and a transposon mutant screen, we discovered that initial growth of Salmonella Typhimurium (S. Tm) in the unperturbed gut is powered by S. Tm hyb hydrogenase, which facilitates consumption of hydrogen (H2), a central intermediate of microbiota metabolism. In competitive infection experiments, a hyb mutant exhibited reduced growth early in infection compared to wild-type S. Tm, but these differences were lost upon antibiotic-mediated disruption of the host microbiota. Additionally, introducing H2-consuming bacteria into the microbiota interfered with hyb-dependent S. Tm growth. Thus, H2 is an Achilles' heel of microbiota metabolism that can be subverted by pathogens and might offer opportunities to prevent infection.
Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23–Th17 pathway
Authors: Alexander Espinosa, Valerie Dardalhon, Susanna Brauner, Aurelie Ambrosi, Rowan Higgs, Fransisco J. Quintana, Maria Sjöstrand, Maija-Leena Eloranta, Joan Ní Gabhann, Ola Winqvist, Birgitta Sundelin, Caroline A. Jefferies, Björn Rozell, Vijay K. Kuchroo, Marie Wahren-Herlenius
Journal: The Journal of Experimental Medicine (2009)

Ro52/Trim21 is targeted as an autoantigen in systemic lupus erythematosus and Sjögren's syndrome. Polymorphisms in the Ro52 gene have been linked to these autoimmune conditions, but the molecular mechanism by which Ro52 may promote development of systemic autoimmune diseases has not been explored. To address this issue, we generated Ro52-null mice (Ro52−/−), which appear phenotypically normal if left unmanipulated. However, Ro52−/− mice develop severe dermatitis extending from the site of tissue injury induced by ear tags. The affected mice further develop several signs of systemic lupus with hypergammaglobulinemia, autoantibodies to DNA, proteinuria, and kidney pathology. Ro52, which was recently identified as an E3 ligase, mediates ubiquitination of several members of the interferon regulatory factor (IRF) family, and the Ro52-deficient mice have an enhanced production of proinflammatory cytokines that are regulated by the IRF transcription factors, including cytokines involved in the Th17 pathway (interleukin [IL] 6, IL-12/IL-23p40, and IL-17). Loss of IL-23/IL-17 by genetic deletion of IL-23/p19 in the Ro52−/− mice conferred protection from skin disease and systemic autoimmunity. These data reveal that the lupus-associated Ro52 protein is an important negative regulator of proinflammatory cytokine production, and they provide a mechanism by which a defective Ro52 function can lead to tissue inflammation and systemic autoimmunity through the IL-23–Th17 pathway.
Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles
Authors: Brandon Renner, Jelena Klawitter, Ryan Goldberg, James W. McCullough, Viviana P. Ferreira, James E. Cooper, Uwe Christians, Joshua M. Thurman
Journal: Journal of the American Society of Nephrology (2013)

Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases.
Etretinate and nodular prurigo
Authors: C.M.E.Rowland Payne
Journal: British Journal of Dermatology (1988)

Journal Article Etretinate and nodular prurigo Get access C.M.E.Rowland Payne C.M.E.Rowland Payne Skin and Therapeutics Research Laboratories, Westminster Hospital, London SW1, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 1, 1 January 1988, Page 135, https://doi.org/10.1111/j.1365-2133.1988.tb01764.x Published: 01 January 1988
Successful conservative treatment of rheumatoid subaxial subluxation resulting in improvement of myelopathy, reduction of subluxation, and stabilisation of the cervical spine. A report of two cases
Authors: J. C M Oostveen, M. A F J van de Laar, J. A G Geelen, R. de Graaff
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To report the efficacy of conservative treatment with cervical traction and immobilisation with a Halo vest, in two consecutive rheumatoid arthritis patients with progressive cervical myelopathy caused by subaxial subluxation. <h3>METHODS</h3> Description of neurological symptoms and signs and findings in plain radiography (PR) and magnetic resonance imaging (MRI) of the cervical spine before and after treatment of the subaxial subluxation by traction and immobilisation with a Halo vest during four months. <h3>RESULTS</h3> During four months of traction and immobilisation neurological examination showed a considerable improvement of the signs and symptoms of cervical myelopathy. Afterwards PR and MRI of the cervical spine showed reduction of the subaxial subluxation. Eventually firm stabilisation was obtained in both patients without surgery of the cervical spine. <h3>CONCLUSION</h3> Cervical traction and immobilisation with a Halo vest can be considered as an independent conservative treatment in rheumatoid arthritis patients with cervical myelopathy caused by subaxial subluxation.
Sketch of a componential subtheory of human intelligence
Authors: Robert J. Sternberg
Journal: Behavioral and Brain Sciences (1980)

This article sketches a subtheory of human intelligence based on the component construct. Components differ in their levels of generality and in their functions. Metacomponents are higher-order control process used for planning how a problem should be solved, for making decisions regarding alternative courses of action during problem solving, and for monitoring solution processes. Performance components are processes used in the execution of a problem-solving strategy. Acquisition components are processes used in learning new information. Retention components are processes used in retrieving previously stored knowledge. Transfer components are used in generalization, that is, in carrying over knowledge from one task or task context to another. A mechanism for the interaction among components of different kinds and multiple components of the same kind can account for certain interesting aspects of laboratory and everyday problem solving. A brief historical overview of alternative basic units for understanding intelligence is followed by a detailed description of one of these units, the component and by a differentiation among various kinds of components. Examples of each kind of component are given, and the use of each of these components in a problem-solving situation is illustrated. Then, a system of interrelations among the various kinds of components is described. Finally, the functions of components in human intelligence are assessed by considering how the proposed subtheory can account for various empirical phenomena in the literature on human intelligence.
<sup>18</sup>F-Fluorodeoxyglucose Positron Emission Tomography Contributes to the Diagnosis and Management of Infections in Patients With Multiple Myeloma: A Study of 165 Infectious Episodes
Authors: T. Mahfouz, M.H. Miceli, F. Saghafifar, S. Stroud, L. Jones-Jackson, R. Walker, M.L. Grazziutti, G. Purnell, A. Fassas, G. Tricot, B. Barlogie, E. Anaissie
Journal: Journal of Clinical Oncology (2005)

Correctly identifying infection in cancer patients can be challenging. Limited data suggest that positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may be useful for diagnosing infection. To determine the role of FDG-PET in the diagnosis of infection in patients with multiple myeloma (MM).The medical records of 248 patients who had FDG-PET performed for MM staging or infection work-up revealing increased uptake at extramedullary sites and/or bones and joints that would be atypical for MM between October 2001 and May 2004 were reviewed to identify infections and evaluate FDG-PET contribution to patient outcome.One hundred sixty-five infections were identified in 143 adults with MM. Infections involved the respiratory tract [99; pneumonia (93), sinusitis (six)], bone, joint and soft tissues [26; discitis (10), osteomyelitis (nine), septic arthritis (one), cellulitis (six)], vascular system [18; septic thrombophlebitis (nine), infection of implantable catheter (eight), septic emboli (one)], gastrointestinal tract [12; colitis (seven), abdominal abscess (three), and diverticulitis and esophagitis (one each)], and dentition [periodontal abscess (10)]. Infections were caused by bacteria, mycobacteria, fungi, and viruses. FDG-PET detected infection even in patients with severe neutropenia and lymphopenia (30 episodes). The FDG-PET findings identified infections not detectable by other methods (46 episodes), determined extent of infection (32 episodes), and led to modification of work-up and therapy (55 episodes). Twenty silent, but clinically relevant, infections were detected among patients undergoing staging FDG-PET.In patients with MM, FDG-PET is a useful tool for diagnosing and managing infections even in the setting of severe immunosuppression.
SCREENING FOR EMOTIONALLY DISTURBED STUDENTS IN AN INDIAN BOARDING SCHOOL. EXPERIENCE WITH THE CORNELL MEDICAL INDEX HEALTH QUESTIONNAIRE
Authors: L. G. NELSON, L. D. TADLOCK, J. W. DAWES, J. L. HIPPLE, N. B. JETMALANI
Journal: American Journal of Psychiatry (1964)

1. The Cornell Medical Index Health Questionnaire was administered to a randomly chosen sample of 47 adolescent Indian boarding school students in an attempt to study the validity of this instrument in detecting psychiatric disturbances in this selected adolescent population. 2. Statistically significant differences in responses to CMI were found in the "normal" and "abnormal" groups of subjects; thus confirming previous statements of the value of CMI in detecting psychiatric disturbances, and extending its applicability to Indian beneficiaries. 3. A question of the validity of the CMI in detecting psychiatric disturbances in Alaskan adolescents (Eskimos) is raised and deserves further study. Statistical data are presented for results of administration to 365 boarding school subjects of the Cornell Medical Index Health Questionnaire. The subjects were Navajo Indians and Alaska Natives (mostly Eskimos) attending a Federal boarding school. It was found that age, sex, academic level, recent boarding school experience or chronic illness did not affect the response to the CMI. The mean number of responses for the entire group of "Indian" adolescents making up this study was 29.6. On the basis of frequency distribution it might be stated that less than 62 "yes" responses in the Alaskan, and less than 85 "yes" responses in the Navajo would fall statistically within the "normal" range (mean plus 2 S.D.).