tbuckley/cabot-search huggingface dataset:
Genetic control of leucocyte—endothelial cell interaction in collagen-induced arthritis
Authors: Hoang Tu-Rapp, Liying Pu, Andreia Marques, Christoph Kulisch, Xinhua Yu, Philip Gierer, Saleh M Ibrahim, Brigitte Vollmar
Journal: Annals of the Rheumatic Diseases (2010)

Despite considerable work on defining disease pathways, several aspects of collagen-induced arthritis (CIA) remain poorly defined, in particular those contributing to the initiation phase of the disease. It is thought that in CIA the activation of circulating leucocytes, their interaction with the endothelial lining followed by subsequent transendothelial migration and infiltration into tissue represents the first and determining step in a complex sequence of processes mediating tissue injury. In this study we attempted to define the genetic basis of this stage of disease using genetic linkage studies, in-vivo imaging and expression profiling.A genome scan with 132 informative markers was performed on 155 (DBA/1JxFVB/N) F2 mice. Linkage analysis was performed by combining genotyping data from the genome scan and the phenotypic data of leucocyte adherence, leucocyte rolling fraction, functional capillary density, centre line red blood cell velocity and capillary width as well as the expression level of the selected genes Cd44, Il13ralpha1, Ccr3, Defb3, Sele, Sell, Selp, Xcl1, Il1beta, Tnfalpha and Ifngamma as traits.Multiple classic quantitative trail loci (QTL) controlling leucocyte-endothelial cell interactions were identified on chromosomes 8 and 17 as well as expression QTL controlling the expression of several differentially expressed adhesion molecules and cytokines on chromosomes 1, 2, 5, 6, 7, 8, 12, 15, 16 and 17.The study describes for the first time QTL controlling the CIA initiating leucocyte-endothelial cell interaction.
Comparative genomics of Steinernema reveals deeply conserved gene regulatory networks
Authors: Adler R. Dillman, Marissa Macchietto, Camille F. Porter, Alicia Rogers, Brian Williams, Igor Antoshechkin, Ming-Min Lee, Zane Goodwin, Xiaojun Lu, Edwin E. Lewis, Heidi Goodrich-Blair, S. Patricia Stock, Byron J. Adams, Paul W. Sternberg, Ali Mortazavi
Journal: Genome biology (2015)

Parasitism is a major ecological niche for a variety of nematodes. Multiple nematode lineages have specialized as pathogens, including deadly parasites of insects that are used in biological control. We have sequenced and analyzed the draft genomes and transcriptomes of the entomopathogenic nematode Steinernema carpocapsae and four congeners (S. scapterisci, S. monticolum, S. feltiae, and S. glaseri). We used these genomes to establish phylogenetic relationships, explore gene conservation across species, and identify genes uniquely expanded in insect parasites. Protein domain analysis in Steinernema revealed a striking expansion of numerous putative parasitism genes, including certain protease and protease inhibitor families, as well as fatty acid- and retinol-binding proteins. Stage-specific gene expression of some of these expanded families further supports the notion that they are involved in insect parasitism by Steinernema. We show that sets of novel conserved non-coding regulatory motifs are associated with orthologous genes in Steinernema and Caenorhabditis. We have identified a set of expanded gene families that are likely to be involved in parasitism. We have also identified a set of non-coding motifs associated with groups of orthologous genes in Steinernema and Caenorhabditis involved in neurogenesis and embryonic development that are likely part of conserved protein–DNA relationships shared between these two genera.
Hepatocarcinogenic potential of the glucocorticoid antagonist RU486 in B6C3F1 mice: effect on apoptosis, expression of oncogenes and the tumor suppressor gene p53.
Authors: Jihan A Youssef, Mostafa Z Badr
Journal: Molecular Cancer (2003)

Glucocorticoids inhibit hepatocellular proliferation and modulate the expression of oncogenes and tumor suppressor genes via mechanisms involving the glucocorticoid receptor. Glucocorticoids also produce a receptor-mediated inhibitory effect on both basal and hormone-stimulated expression of a newly discovered family of molecules important for shutting off cytokine action. We therefore hypothesized that inhibiting glucocorticoid receptors may disturb hepatocellular growth and apoptosis. Consequently, we investigated the effect of RU486, a potent antagonist of the glucocorticoid receptor, on basal levels of hepatocellular proliferation and apoptosis in male B6C3F1 mice. Furthermore, we evaluated the effect of this compound on cellular genes involved in the regulation of these important processes. Data show that treatment of male B6F3C1 mice with RU486 (2 mg/kg/d, ip) for 7 days dramatically inhibited liver cell proliferation by about 45% and programmed hepatocellular death by approximately 66%. RU 486 also significantly increased hepatic expression of the oncogenes mdm2 and JunB, while reducing that of the tumor suppressor gene p53. Exposure to RU486 may ultimately enhance the susceptibility of the liver to cancer risk by diminishing its ability to purge itself of pre-cancerous cells via apoptosis. This effect may be mediated through increases in the hepatic expression of the oncogene mdm2, coupled with decreases in that of the tumor suppressor gene p53. The decrease in hepatocellular proliferation caused by RU 486 may be related to effects other than its anti-glucocorticoid activity.
An Outbreak of Herpes Simplex Virus Type I Gingivostomatitis in a Dental Hygiene Practice
Authors: John P. Manzella
Journal: JAMA (1984)

An outbreak of herpes simplex virus (HSV) type I gingivostomatitis occurred in a dental hygiene practice in November 1981. An epidemiologic investigation disclosed that 20 of 46 patients seen by the dental hygienist during a four-day period had this illness, whereas none of 26 patients seen by the dentist alone became ill. One day after the outbreak, the hygienist was found to have a herpetic whitlow. Identical endonuclease restriction enzyme type I HSV was isolated from the left index finger of the hygienist and from nine of 16 patients. The nine patients with positive cultures all had at least a fourfold increase in complement fixing antibody titer. A similar significant increase in titer indicated another seven cases.
Doing What I Like
Authors: K. Frank Austen
Journal: Annual Review of Immunology (2007)

I have spent my entire professional life at Harvard Medical School, beginning as a medical student. I have enjoyed each day of a diverse career in four medical subspecialties while following the same triad of preclinical areas of investigation-cysteinyl leukotrienes, mast cells, and complement-with occasional translational opportunities. I did not envision a career with a predominant preclinical component. Such a path simply evolved because I chose instinctively at multiple junctures to follow what proved to be propitious opportunities. My commentary notes some of the highlights for each area of interest and the mentors, collaborators, and trainees whose counsel has been immensely important at particular intervals or over an extended period.
Recent Advances in the Pathophysiology of Ischemic Acute Renal Failure
Authors: Joseph V. Bonventre, Joel M. Weinberg
Journal: Journal of the American Society of Nephrology (2003)

As covered in the preceding sections, acute renal failure (ARF) is a syndrome associated with high mortality in humans. Current therapy is limited to supportive measures and preventive strategies, none of which have been definitively shown to alter mortality. Ischemic ARF is often associated with
MEASURING THE ECCENTRIC EXTERNAL ROTATOR STRENGTH IN THE OVERHEAD ATHLETE, USING A HAND HELD DYNAMOMETER: NORMATIVE DATA IN HEALTHY OVERHEAD ATHLETES
Authors: A Cools, F Johansson, B Cagnie
Journal: British Journal of Sports Medicine (2014)

Background Recently, a novel reliable and valid protocol has been described for the measurement of eccentric strength of the external rotators of the shoulder, using a Hand Held Dynamometer (HHD). These muscles are prone to weakness in healthy as well as in injured overhead athletes. Objective assessment of muscle strength is imperative in the prevention and rehabilitation of shoulder injuries in the overhead athlete. Objective To provide a normative database of eccentric muscle strength in overhead athletes from several disciplines (tennis, volleyball, swimming, and gymnastics). Design Descriptive laboratory study. Participants 200 healthy overhead athletes, active in different sport disciplines participated in the study. Risk factor assessment Eccentric rotator cuff strength of the external rotators was assessed from a position of 90°–90° abduction/external rotation to 90° abduction in neutral rotation at a speed of 30°/sec, and correlated to isometric rotator cuff muscle strength values in several positions. Results The study will be executed sept-jan 2013, results are to be presented from March 2014. Conclusion This study provides a normative database of eccentric muscle strength data, measured with a HHD. This device is easy to use in a field or training center environment, and therefore valuable in the prevention and rehabilitation of shoulder injuries in the overhead athlete.
Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma
Authors: Richard W. J. Groen, Willy A. Noort, Reinier A. Raymakers, Henk-Jan Prins, Linda Aalders, Frans M. Hofhuis, Petra Moerer, Jeroen F. van Velzen, Andries C. Bloem, Berris van Kessel, Henk Rozemuller, Ellen van Binsbergen, Arjan Buijs, Huipin Yuan, Joost D. de Bruijn, Michel de Weers, Paul W. H. I. Parren, Jan Jacob Schuringa, Henk M. Lokhorst, Tuna Mutis, Anton C. M. Martens
Journal: Blood (2012)
Prospective Comparative Study of Integrated Positron Emission Tomography-Computed Tomography Scan Compared With Remediastinoscopy in the Assessment of Residual Mediastinal Lymph Node Disease After Induction Chemotherapy for Mediastinoscopy-Proven Stage IIIA-N2 Non–Small-Cell Lung Cancer: A Leuven Lung Cancer Group Study
Authors: Paul De Leyn, Sigrid Stroobants, Walter De Wever, Toni Lerut, Willy Coosemans, Georges Decker, Philippe Nafteux, Dirk Van Raemdonck, Luc Mortelmans, Kristiaan Nackaerts, Johan Vansteenkiste
Journal: Journal of Clinical Oncology (2006)

Mediastinal restaging after induction therapy for non-small-cell lung cancer remains a difficult and controversial issue. The goal of this prospective study was to compare the performance of integrated positron emission tomography (PET)--computed tomography (CT) and remediastinoscopy in the evaluation of mediastinal lymph node metastasis after induction chemotherapy.Thirty consecutive stage IIIA-N2 non-small-cell lung cancer patients surgically treated at our institution were entered onto this prospective study. N2 disease was proven by cervical mediastinoscopy, at which a mean number of 3.8 lymph node levels were biopsied. After completion of induction chemotherapy, the mediastinum was reassessed by integrated PET-CT and remediastinoscopy. All patients underwent thoracotomy with attempted complete resection and systematic nodal dissection.PET-CT showed no evidence of nodal disease (N0) in 13 patients, Hilar nodal disease (N1) disease in three patients, and residual mediastinal disease (N2) in 14 patients. Remediastinoscopy was positive in only five patients. The preinduction involved lymph node level could be accurately re-evaluated in 18 patients. This was not the case in the other 12 because of extensive fibrosis and adhesions. In 17 patients, persistent N2 disease was found at thoracotomy. The sensitivity, specificity, and accuracy of PET-CT were 77%, 92%, and 83%, respectively. These parameters for remediastinoscopy were 29%, 100%, and 60%, respectively. Sensitivity (P < .0001) and accuracy (P = .012) were significantly better for PET-CT.After a thorough staging mediastinoscopy, postinduction remediastinoscopy had a disappointing sensitivity because of adhesions and fibrosis. Integrated PET-CT yielded a better result than that obtained in previous studies with side-by-side PET and CT images.
Gene Expression Profiling Shows Medullary Breast Cancer Is a Subgroup of Basal Breast Cancers
Authors: François Bertucci, Pascal Finetti, Nathalie Cervera, Emmanuelle Charafe-Jauffret, Emilie Mamessier, José Adélaïde, Stéphane Debono, Gilles Houvenaeghel, Dominique Maraninchi, Patrice Viens, Colette Charpin, Jocelyne Jacquemier, Daniel Birnbaum
Journal: Cancer Research (2006)

Medullary breast cancer (MBC) is a rare but enigmatic pathologic type of breast cancer. Despite features of aggressiveness, MBC is associated with a favorable prognosis. Morphologic diagnosis remains difficult in many cases. Very little is known about the molecular alterations involved in MBC. Notably, it is not clear whether MBC and ductal breast cancer (DBC) represent molecularly distinct entities and what genes/proteins might account for their differences. Using whole-genome oligonucleotide microarrays, we compared gene expression profiles of 22 MBCs and 44 grade III DBCs. We show that MBCs are less heterogeneous than DBCs. Whereas different molecular subtypes (luminal A, luminal B, basal, ERBB2-overexpressing, and normal-like) exist in DBCs, 95% MBCs display a basal profile, similar to that of basal DBCs. Supervised analysis identified gene expression signatures that discriminated MBCs from DBCs. Discriminator genes are associated with various cellular processes related to MBC features, in particular immune reaction and apoptosis. As compared with MBCs, basal DBCs overexpress genes involved in smooth muscle cell differentiation, suggesting that MBCs are a distinct subgroup of basal breast cancer with limited myoepithelial differentiation. Finally, MBCs overexpress a series of genes located on the 12p13 and 6p21 chromosomal regions known to contain pluripotency genes. Our results contribute to a better understanding of MBC and of mammary oncogenesis in general.
Smoking and back pain.
Authors: E Ernst
Journal: Annals of the Rheumatic Diseases (1991)

Worsening of Felty's syndrome with methotrexate Sir: Drs Hughes and Abdulla recently reported a favourable response to low dose oral metho- trexate treatment in a patient with Felty's syndrome,' confirming earlier reports.2 3 In contrast, we found such treatment failed, with worsening of neutropenia.
Use of cyclosporin in pregnancy
Authors: A Jayaprakash
Journal: Gut (2004)

A hallmark of secondary hemophagocytic lymphohistiocytosis (sHLH), a severe form of cytokine storm syndrome, is the emergence of overactivated macrophages that engulf healthy host blood cells (i.e., hemophagocytosis) and contribute to the dysregulated inflammation-driven pathology. In this study, we show that depleting SIRPα (SIRPα<sup>−/−</sup>) in mice during TLR9-driven inflammation exacerbates and accelerates the onset of fulminant sHLH, in which systemic hemophagocytosis, hypercytokinemia, consumptive cytopenias, hyperferritinemia, and other hemophagocytic lymphohistiocytosis hallmarks were apparent. In contrast, mice expressing SIRPα, including those deficient of the SIRPα ligand CD47 (CD47<sup>−/−</sup>), do not phenocopy SIRPα deficiency and fail to fully develop sHLH, albeit TLR9-inflamed wild-type and CD47<sup>−/−</sup> mice exhibited hemophagocytosis, anemia, and splenomegaly. Although IFN-γ is largely considered a driver of hemophagocytic lymphohistiocytosis pathology, IFN-γ neutralization did not preclude the precipitation of sHLH in TLR9-inflamed SIRPα<sup>−/−</sup> mice, whereas macrophage depletion attenuated sHLH in SIRPα<sup>−/−</sup> mice. Mechanistic studies confirmed that SIRPα not only restrains macrophages from acquiring a hemophagocytic phenotype but also tempers their proinflammatory cytokine and ferritin secretion by negatively regulating Erk1/2 and p38 activation downstream of TLR9 signaling. In addition to TLR9 agonists, TLR2, TLR3, or TLR4 agonists, as well as TNF-α, IL-6, or IL-17A, but not IFN-γ, similarly induced sHLH in SIRPα<sup>−/−</sup> mice but not SIRPα<sup>+</sup> mice. Collectively, our study suggests that SIRPα plays a previously unappreciated role in sHLH/cytokine storm syndrome pathogenesis by preventing macrophages from becoming both hemophagocytic and hyperactivated under proinflammation.
Endothelial progenitor cell biology in disease and tissue regeneration
Authors: Andrea L George, Pradeep Bangalore-Prakash, Shilpi Rajoria, Robert Suriano, Arulkumaran Shanmugam, Abraham Mittelman, Raj K Tiwari
Journal: Journal of Hematology & Oncology (2011)

Abstract Endothelial progenitor cells are increasingly being studied in various diseases ranging from ischemia, diabetic retinopathy, and in cancer. The discovery that these cells can be mobilized from their bone marrow niche to sites of inflammation and tumor to induce neovasculogenesis has afforded a novel opportunity to understand the tissue microenvironment and specific cell-cell interactive pathways. This review provides a comprehensive up-to-date understanding of the physiological function and therapeutic utility of these cells. The emphasis is on the systemic factors that modulate their differentiation/mobilization and survival and presents the challenges of its potential therapeutic clinical utility as a diagnostic and prognostic reagent.
ALTERATIONS OF MACROPHAGE FUNCTIONS BY MEDIATORS FROM LYMPHOCYTES
Authors: Carl F. Nathan, Manfred L. Karnovsky, John R. David
Journal: The Journal of Experimental Medicine (1971)

Sensitized lymphocytes were incubated in vitro with the specific antigen Supernatants from these cultures were chromatographed on Sephadex G-100 columns. Supernatant fractions containing MIF, chemotactic factor, and lymphotoxin, but free of antigen and antibody, were incubated with normal peritoneal exudate macrophages. Macrophage adherence, phagocytosis, spreading, motility, and direct hexose monophosphate oxidation were enhanced, while protein synthesis was unaffected. Thus, antigen-stimulated lymphocytes secrete a factor or factors which enhance certain macrophage functions. Implications for models of cellular immunity and cellular hypersensitivity are discussed.
CHANGES IN THE OXYGEN CONTENT OF HEPATIC VENOUS BLOOD DURING EXERCISE IN PATIENTS WITH RHEUMATIC HEART DISEASE
Authors: J. M. Bishop, K. W. Donald, O. L. Wade
Journal: Journal of Clinical Investigation (1955)

In a study of the effect of exercise on the cardiac output of patients with rheumatic heart disease (1) small and frequent samples of mixed venous blood were drawn from the pulmonary artery during a period of leg exercise and subsequent recovery. Thus a continuous record of the oxygen saturation of this blood and of the arterio-venous oxygen content difference (A-V difference) was obtained. In most patients abnormally large A-V differences were found during exercise and in some the mixed venous blood was less than 10 per cent saturated. This low saturation suggested that even were oxygen completely extracted from the blood perfusing the exercising limbs, there must also be a considerable reduction of blood flow to other regions of the body. This possibility has been investigated by following changes in the oxygen saturation of venous blood returning from various regions and organs of the body at rest and during exercise, by taking frequent blood samples through an intravenous catheter. In this paper, the effect of exercise on the oxygen saturation of hepatic venous blood and on the hepatic arterio-venous oxygen content difference (hepatic A-V difference) in patients with rheumatic heart disease is reported. On the assumption that there is little change in the oxygen uptake of the splanchnic region during brief periods of exercise, alterations in the splanchnic blood flow, inversely related to the changes in the hepatic A-V differences, have been inferred.
Basal Versus Sliding-Scale Regular Insulin in Hospitalized Patients With Hyperglycemia During Enteral Nutrition Therapy
Authors: Guillermo E. Umpierrez
Journal: Diabetes Care (2009)

A large number of hospitalized patients are in a catabolic state, with resultant increased caloric and protein needs. In such patients, inadequate oral intake can lead to undernutrition in 8 to 12 days (1). A collaborative study involving nutrition screening of 3,047 patients at admission to 33 hospitals reported that more than 50% of hospitalized patients were malnourished (2). Malnutrition is seen in several patient groups with diabetes, especially in the elderly (3) and those with complications such as renal failure or neurological dysfunctions (4). Nutrition guidelines state that any patient unable to consume adequate nutrients orally (60% nutrition needs) for at least 5 days in the critically ill or 7 to 14 days in the general population should be a candidate for specialized nutrition support (5,6). Delayed feeding, resulting in malnutrition, may increase the risk of hospital complications (relative risk 1.60), higher mortality (12.4 vs. 4.7% in the well-nourished patients [relative risk 2.63]), and longer hospital stay (16.7 ± 24 vs. 10.1 ± 12 days in the nourished patients) and may increase hospital costs by 308% (7). A recent meta-analysis reported that providing early versus delayed nutrition support results in lower infectious complications and length of hospital stay (8). Nutritional support via enteral or parenteral nutrition in malnourished patients may prevent such complications. Although both forms of nutrition support have been shown to be successful in preventing the effects of starvation and malnutrition, oral or enteral nutrition is preferable to parenteral nutrition in clinical practice (9,10). Advantages of enteral feeding over parenteral nutrition include lower costs, avoidance of central catheter–related complications, its more physiological route, and its trophic effect on gastrointestinal cells (11).

Standard enteral formulas reflect the reference values for macro- and micronutrients for a …