tbuckley/cabot-search huggingface dataset:
Peritubular Capillary Regression during the Progression of Experimental Obstructive Nephropathy
Authors: Ryuji Ohashi, Akira Shimizu, Yukinari Masuda, Hiroshi Kitamura, Masamichi Ishizaki, Yuichi Sugisaki, Nobuaki Yamanaka
Journal: Journal of the American Society of Nephrology (2002)

Injury to the renal microvasculature may be a major factor contributing to the progression of renal disease. Although severe disruption of peritubular capillaries (PTC) could lead to marked tubulointerstitial scarring, elucidation of that process remains incomplete. This study investigated the morphologic changes in PTC and their likely regulation by vascular endothelial growth factor (VEGF) during the progression of tubulointerstitial injuries. Unilateral ureteral obstruction was induced in Wistar rats by ligation of the left ureter, and the kidneys were then collected at selected times. PTC lumina and the expression of VEGF and its receptor Flk-1 were immunohistochemically detected. Morphologic changes in PTC endothelial cells were examined by using Ki67 staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, and electron-microscopic studies. In the first week of the disease period, immunohistochemical labeling of tubular VEGF intensified, with accompanying deformation and dilation of adjacent thrombomodulin (TM)-positive PTC lumina; an angiogenic response of endothelial cells was demonstrated with Ki67 and TM double-staining. During the subsequent 2 wk, tubular VEGF labeling decreased until it was virtually absent, an effect confirmed by Western blotting. Concomitantly, labeling of the VEGF receptor Flk-1 in PTC endothelial cells decreased and PTC lumina began to regress, demonstrating endothelial cell apoptosis (as detected in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling and electron-microscopic studies). By the end of week 4, the numbers of TM-positive PTC lumina were significantly decreased in areas of marked tubulointerstitial scarring. These results suggest that PTC regression, involving an early, unsustained, angiogenic response followed by progressive endothelial cell apoptosis, could be a potential factor contributing to tubulointerstitial scarring in this unilateral ureteral obstruction model.
Hybrid antibody mediated veto of cytotoxic T lymphocyte responses.
Authors: Y Qi, R Berg, M A Singleton, J E Debrick, U D Staerz
Journal: The Journal of Experimental Medicine (1996)

Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so-called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immune-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antibody (HAb) combining a mAb specific for a class I MHC molecule with a soluble CD8 molecule. We found that this HAb specifically and effectively transferred veto inhibition to different stimulator cell populations. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immune responses.
Multicultural religious and spiritual rituals: Meaning and praxis
Authors: Joan H. Hageman
Journal: Behavioral and Brain Sciences (2006)

This commentary argues against the theory that cultural ritual behavior is meaningless or that ritual action is solely a by-product of fear-based precautionary and action-parsing systems. Humans demonstrate the ability to spontaneously change their use of proximate intentions and attribute ultimate intentions to ritual actions that are not dependent upon fear or physical and emotional/mental dysfunction.
Microelectrode Studies on Retrograde Concealment of Multiple Premature Ventricular Responses
Authors: E. NEIL MOORE
Journal: Circulation Research (1967)

Retrograde concealment of serially evoked premature ventricular responses was studied in an isolated preparation of rabbit atria and ventricles. Transmembrane potentials were recorded simultaneously from single cells within the atrioventricular (A-V) node and ventricular specialized conduction system, together with atrial and ventricular bipolar electrograms. In these experiments, retrograde conduction delays and block occurred within the ventricles, between ventricular muscle and the Purkinje-bundle branch system, between the bundle branch and His bundle, and within the A-V node. The ventricular specialized conduction system was found to be a major location of retrograde conduction delays and block. Many examples of retrograde concealment and block, previously interpreted as due to A-V nodal mechanisms, almost certainly result instead from mechanisms operating within the ventricular specialized conduction system. Antegrade and retrograde block of sequentially evoked premature responses occurred within the A-V node. Reentry "echo" responses occurred in many experiments following premature stimulation of the atria, the ventricles, or both.
Self-management of asthma in general practice
Authors: J C van der Wouden
Journal: Thorax (2003)

We welcome the paper by Thoonen and colleagues on self-management of asthma in general practice1 as we firmly believe that self-management of chronic diseases is a promising area for innovation in general practice.

We wondered whether differential withdrawals—specifically, the difference between groups in the number of patients for whom successfully treated weeks could be calculated—may have affected the outcomes. As reported, 92% of the patients in the usual care (UC) group provided data for this primary outcome compared with 85% of the self-management (SM) group. The mean percentage of successfully treated weeks was 72% and 78% for …
Multiparametric Prognostic Evaluation of Biological Factors in Primary Breast Cancer
Authors: F. Spyratos, P.-M. Martin, K. Hacene, S. Romain, C. Andrieu, M. Ferrero-Pous, S. Deytieux, V. L. Doussal, M. Tubiana-Hulin, M. Brunet
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Multiparametric Prognostic Evaluation of Biological Factors in Primary Breast Cancer Get access Frédérique Spyratos, Frédérique Spyratos * Laboratoire des Récepteurs Hormonaux, Centre RenéHuguenin, St-Cloud, France *Correspondence to : Frédérique Spyratos, Ph.D., Département de Biologie, Centre René Huguenin, 35 rue Dailly, 92211 St-Cloud, France. Search for other works by this author on: Oxford Academic PubMed Google Scholar Pierre-Marie Martin, Pierre-Marie Martin Laboratoire d'Oncologie Biopathologie, Assistance Publique de Marseille, Faculté de Médecine-NordMarseille, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Kamel Hacène, Kamel Hacène Département de Statistiques Médicales, Centre RenéHuguenin, St-Cloud, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Sylvie Romain, Sylvie Romain Laboratoire d'Oncologie Biopathologie, Assistance Publique de Marseille, Faculté de Médecine-NordMarseille, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Catherine Andrieu, Catherine Andrieu Laboratoire des Récepteurs Hormonaux, Centre RenéHuguenin, St-Cloud, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Magali Ferrero-Poüs, Magali Ferrero-Poüs Laboratoire des Récepteurs Hormonaux, Centre RenéHuguenin, St-Cloud, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Stéphanie Deytieux, Stéphanie Deytieux Laboratoire des Récepteurs Hormonaux, Centre RenéHuguenin, St-Cloud, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Viviane Le Doussal, Viviane Le Doussal Département de Pathologie, Centre RenéHuguenin, St-Cloud, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Michéle Tubiana-Hulin, Michéle Tubiana-Hulin Département de Médecine, Centre René HugueninHuguenin, St-Cloud, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Maurice Brunet Maurice Brunet Départements de Statistiques Médicales et Chirurgie, Centre RenéHuguenin, St-Cloud Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 16, 19 August 1992, Pages 1266–1272, https://doi.org/10.1093/jnci/84.16.1266 Published: 19 August 1992 Article history Received: 15 November 1991 Revision received: 22 May 1992 Accepted: 22 May 1992 Published: 19 August 1992
Dendritic Cells Pulsed with Intact <i>Streptococcus pneumoniae</i> Elicit both Protein- and Polysaccharide-specific Immunoglobulin Isotype Responses In Vivo through Distinct Mechanisms
Authors: Jesus Colino, Yi Shen, Clifford M. Snapper
Journal: The Journal of Experimental Medicine (2001)

Immature bone marrow–derived myeloid dendritic cells (BMDCs) are induced to undergo phenotypic maturation and secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12, and IL-10 when pulsed in vitro with intact Streptococcus pneumoniae. After transfer to naive mice, pulsed BMDCs induce immunoglobulin (Ig) isotype responses specific for both protein and polysaccharide pneumococcal antigens, having in common the requirement for viable BMDCs, T cells, and B7-dependent costimulation in the recipient mice. Whereas primary Ig isotype responses to bacterial proteins uniformly require BMDC expression of major histocompatibility complex class II, CD40, and B7, and the secretion of IL-6, but not IL-12, similar requirements for antipolysaccharide Ig responses were only observed for the IgG1 isotype.
Lipopolysaccharide-binding protein and CD14 are increased in the bronchoalveolar lavage fluid of smokers
Authors: V. Regueiro, M. A. Campos, P. Morey, J. Sauleda, A.G.N. Agustí, J. Garmendia, J. A. Bengoechea
Journal: European Respiratory Journal (2008)

Lipopolysaccharide-binding protein (LBP) and CD14 contribute to the recognition of pathogens by cells, which triggers the activation of defence responses. Smoking is a risk factor for the development of chronic obstructive pulmonary disease (COPD) and respiratory infections. The current authors theorised that levels of LBP and CD14 in the lungs of smokers would be higher than those in the lungs of never-smokers. These elevated levels could affect host responses upon infection. LBP, soluble CD14 (sCD14) and interleukin (IL)-8 were detected by ELISA. Nuclear factor (NF)-κB, p38 and the inhibitor IκBα were studied by immunoassays. Gene expression was assessed by RT-PCR. Bronchoalveolar lavage levels of LBP and CD14 were significantly higher in smokers and COPD patients than in never-smokers, whereas levels of both proteins were not significantly different between smokers and COPD patients. IL-6, IL-1β and cigarette smoke condensate induced the expression of LBP and CD14 by airway epithelial cells. LBP and sCD14 inhibited the nontypeable Haemophilus influenzae (NTHi)-dependent secretion of IL-8 and the activation of NF-κB and p38 mitogen-activated protein kinase signalling pathways but they increased the internalisation of NTHi by airway epithelial cells. Thus, in the inflamed airways of smokers both proteins could contribute to inhibit bacteria-dependent cellular activation without compromising the internalisation of pathogens by airway cells.
THE USE OF FAECAL CALPROTECTIN IN PAEDIATRIC INFLAMMATORY BOWEL DISEASE
Authors: J O'Gorman, S Hussey
Journal: Gut (2013)

<h3>Introduction</h3> Faecal calprotectin (FC) is an inflammatory marker that is raised in inflammatory bowel disease (IBD) and so can be used to determine which children require further investigation. <h3>Aims/Background</h3> To evaluate the use of FC in children with possible IBD by establishing if the number of negative endoscopies had been minimised without missing any cases of IBD. <h3>Method</h3> A retrospective analysis of FC measurements carried out from October 2011-September 2012. FC values were obtained from the biochemistry department. Following a computerised search of the departmental records the presenting complaint, endoscopy result if applicable, diagnosis of IBD or alternative diagnosis, and follow-up or discharge were recorded for each patient. <h3>Results</h3> 36 patients (55%) were not scoped. All had at least one symptom indicative of IBD. 25 of these had a FC value of &lt;50 µg/g. 4 of these patients had a FC result &gt;200 µg/g. None of these patients have been diagnosed with IBD. 17 patients were scoped (26%). 3 were diagnosed with IBD. Median FC for the group that were not scoped was 30 µg/g (IQR 30–760 µg/g), compared with 126 µg/g (IQR 52–1590 µg/g) in the scoped group. 8 symptomatic patients with known IBD had a FC test and all values were consistent with GI inflammation. There was a 38% cost saving due to 44 unnecessary endoscopies being avoided. <h3>Conclusion</h3> FC is a valuable test for excluding IBD in children who present with abdominal pain and diarrhoea; and confirming relapse in established disease. However, guidelines are required to ensure the appropriate use of this relatively new test.
REMARKS ON TUBERCULIN IN DERMATOLOGY*
Authors: J. JADASSOHN
Journal: British Journal of Dermatology (1929)

Journal Article REMARKS ON TUBERCULIN IN DERMATOLOGY Get access J. JADASSOHN J. JADASSOHN Breslau Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 41, Issue 12, 1 December 1929, Pages 451–472, https://doi.org/10.1111/j.1365-2133.1929.tb09301.x Published: 01 December 1929
Hepatic insulin resistance is associated with increased apoptosis and fibrogenesis in nonalcoholic steatohepatitis and chronic hepatitis C
Authors: Carmelo García-Monzón, Oreste Lo Iacono, Rafael Mayoral, Águeda González-Rodríguez, María E. Miquilena-Colina, Tamara Lozano-Rodríguez, Leonor García-Pozo, Javier Vargas-Castrillón, Marta Casado, Lisardo Boscá, Ángela M. Valverde, Paloma Martín-Sanz
Journal: Journal of Hepatology (2010)
The challenges and promises of new therapies for cystic fibrosis
Authors: Gerald B. Pier
Journal: The Journal of Experimental Medicine (2012)

Therapeutic intervention in cystic fibrosis (CF) remains a challenge, partly because of the number of organs and tissues affected by the lack of a functional cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF was originally regarded primarily as a gastrointestinal (GI) disease because of the failure to thrive and early death from malnutrition in infants with CF. However, successful interventions for the GI manifestations of CF have left chronic lung infections as the primary cause of morbidity and mortality. Despite a complex microbiology within the CF lung, one pathogen, Pseudomonas aeruginosa, remains the critical determinant of pulmonary pathology. Treatment and management of this infection and its associated symptoms are the major targets of extant and developing CF therapies. Understanding the multitude of effects of CFTR on mucosal physiology and susceptibility and progression of chronic lung disease, and how host immune responses fail to adequately control lung infection, will be essential for the development of improved therapies for CF.
Low-Density Lipoprotein, Non-High-Density Lipoprotein, and Apolipoprotein B as Targets of Lipid-Lowering Therapy
Authors: Scott M. Grundy
Journal: Circulation (2002)

lthough low-density lipoprotein (LDL) is widely recognized as the major atherogenic lipoprotein and the primary target of lipid-lowering therapy, 1 other lipoprotein species nonetheless appear to be involved in atherogenesis.These include very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and highdensity lipoproteins (HDL).Both VLDL and IDL are triglyceride-rich lipoproteins (TGRLP).Thus, in the aftermath of unequivocal evidence that LDL lowering reduces risk for major coronary events and stroke, 2 the field of lipid study is turning more of its attention to the other lipoproteins that appear to be involved in atherosclerosis.The recent Adult Treatment Panel III (ATP III) report 1 of the National Cholesterol Education Program has summarized our current understanding of the relationship between other lipoprotein species and risk for coronary heart disease (CHD).
1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex
Authors: Zakaria Hmama, Devki Nandan, Laura Sly, Keith L. Knutson, Patricia Herrera-Velit, Neil E. Reiner
Journal: The Journal of Experimental Medicine (1999)

1α,25-dihydroxyvitamin D3 (D3) promotes the maturation of myeloid cells and surface expressions of CD14 and CD11b, markers of cell differentiation in response to D3. To examine how these responses are regulated, THP-1 cells were grown in serum-free medium and incubated with D3. This was associated with rapid and transient increases in phosphatidylinositol 3-kinase (PI 3-kinase) activity. Furthermore, induction of CD14 expression in response to D3 was abrogated by (a) the PI 3-kinase inhibitors LY294002 and wortmannin; (b) antisense oligonucleotides to mRNA for the p110 catalytic subunit of PI 3-kinase; and (c) a dominant negative mutant of PI 3-kinase. In THP-1 cells, induction of CD11b expression by D3 was also abrogated by LY294002 and wortmannin. Similarly, LY294002 and wortmannin inhibited D3-induced expression of both CD14 and CD11b in peripheral blood monocytes. In contrast to CD14 and CD11b, hormone-induced expression of the Cdk inhibitor p21 in THP-1 cells was unaffected by either wortmannin or LY294002. These findings suggest that PI 3-kinase selectively regulates D3-induced monocyte differentiation, independent of any effects on p21.
Lifelong patterns of BMI and cardiovascular phenotype in individuals aged 60–64 years in the 1946 British birth cohort study: an epidemiological study
Authors: Marietta Charakida, Tauseef Khan, William Johnson, Nick Finer, John Woodside, Peter H Whincup, Naveed Sattar, Diana Kuh, Rebecca Hardy, John Deanfield
Journal: The Lancet Diabetes & Endocrinology (2014)

Excess body fat is associated with an increase in risk of type 2 diabetes and hypertension in adulthood and these risks can adversely affect progression of arterial disease. We aimed to assess the impact of lifelong patterns of adiposity on cardiovascular risk factors and carotid intima media thickness (cIMT) in later life in participants in the 1946 British birth cohort study.The National Survey of Health and Development Study was a nationally representative sample of 5362 singleton births to married parents in England, Scotland, and Wales, stratified by social class, during 1 week in March 1946. Our present study is based on the 60% of participants still alive and with a known present address in England, Scotland, or Wales who attended a clinic assessment after invitation aged 60-64 years. We included participants with lifetime adiposity measures, cardiovascular risk factors, and cIMT measured at 60-64 years. Participants were classified as normal weight or overweight or obese at each age (36, 43, 53, and 60-64 years) in adulthood, and childhood overweight was defined. Patterns of BMI change were identified and we used BMI to define adiposity status. We used multivariable linear regression to establish the cross-sectional association of BMI category at age 60-64 years with cIMT, adjusted for various confounders.We included 1273 (45%) of 2856 participants eligible in 2006-10 (at age 60-64 years) in this study. Compared with normal weight, overweight and obesity were associated with higher cIMT (0·029 mm, 95% CI 0·014-0·043) and systolic blood pressure (7·95 mm Hg, 5·86-10·0). Increased cIMT, systolic blood pressure, leptin, prevalence of diabetes, and reduced adiponectin were all associated with duration of exposure to adult adiposity (p<0·0001 for all). We noted little additional effect of childhood overweight. Individuals who dropped a BMI category in adulthood had lower cIMT (-0·034 mm, -0·056 to -0·013) and leptin concentrations (-0·4 ng/mL, -0·47 to -0·32), even when this change was not maintained, than did those who never lost weight.Longer exposure to high adiposity in adulthood had a cumulative adverse effect on cardiovascular phenotype in later life. Reductions in BMI category, even if not sustained, were associated with decreases in cIMT and improvements in cardiovascular risk-factor profile, suggesting that weight loss, at any age in adulthood, is worthwhile because it might result in long-term cardiovascular benefit.Medical Research Council and the British Heart Foundation.
Warm Hepatic Ischemia-Reperfusion Promotes Growth of Colorectal Carcinoma Micrometastases in Mouse Liver via Matrix Metalloproteinase-9 Induction
Authors: Ian B. Nicoud, Christopher M. Jones, Janene M. Pierce, T. Mark Earl, Lynn M. Matrisian, Ravi S. Chari, D. Lee Gorden
Journal: Cancer Research (2007)

Surgical resection remains the best treatment for colorectal metastases isolated to the liver; however, 5-year survival rates following liver resection are only 40% to 50%, with liver recurrence being a significant reason for treatment failure. The ischemia-reperfusion (I/R) injury incurred during liver surgery can lead to cellular dysfunction and elevations in proinflammatory cytokines and matrix metalloproteinases (MMP). In rodents, I/R injury to the liver has been shown to accelerate the outgrowth of implanted tumors. The mechanism for increased tumor growth in the setting of liver I/R injury is unknown. To investigate the effect of I/R on tumor growth, an experimental model was used whereby small hepatic metastases form after 28 days. Mice subjected to 30 min of 70% liver ischemia at the time of tumor inoculation had significantly larger tumor number and volume, and had elevated MMP9 serum and liver tissue MMP9 as evidenced by zymography and quantitative real-time PCR. Mice treated with doxycycline, a broad-spectrum MMP inhibitor, had reduced MMP9 levels and significantly smaller tumor number and volume in the liver. MMP9-null mice were used to determine if the effects of doxycycline were due to the absence of stromal-derived MMP9. The MMP9-null mice, with or without doxycycline treatment, had reduced tumor number and volume that was equivalent to wild-type mice treated with doxycycline. These findings indicate that hepatic I/R-induced elevations in MMP9 contribute to the growth of metastatic colorectal carcinoma in the liver and that postresection MMP9 inhibition may be clinically beneficial in preventing recurrence following hepatic surgery.
Tackling Non-Communicable Diseases In Low- and Middle-Income Countries: Is the Evidence from High-Income Countries All We Need?
Authors: Shah Ebrahim, Neil Pearce, Liam Smeeth, Juan P. Casas, Shabbar Jaffar, Peter Piot
Journal: PLoS Medicine (2013)

Shah Ebrahim and colleagues argue that more research on non-communicable diseases (NCDs) in both high-income countries and low- and middle-income countries can result in mutual benefits and will help better address the growing burden of NCDs.