tbuckley/cabot-search huggingface dataset:
A Pathogenetic Role for Endothelin-1 in Peritoneal Dialysis-Associated Fibrosis
Authors: Oscar Busnadiego, Jesús Loureiro-Álvarez, Pilar Sandoval, David Lagares, Javier Dotor, María Luisa Pérez-Lozano, María J. López-Armada, Santiago Lamas, Manuel López-Cabrera, Fernando Rodríguez-Pascual
Journal: Journal of the American Society of Nephrology (2014)

In patients undergoing peritoneal dialysis (PD), chronic exposure to nonphysiologic PD fluids elicits low-grade peritoneal inflammation, leading to fibrosis and angiogenesis. Phenotype conversion of mesothelial cells into myofibroblasts, the so-called mesothelial-to-mesenchymal transition (MMT), significantly contributes to the peritoneal dysfunction related to PD. A number of factors have been described to induce MMT in vitro and in vivo, of which TGF-β1 is probably the most important. The vasoconstrictor peptide endothelin-1 (ET-1) is a transcriptional target of TGF-β1 and mediates excessive scarring and fibrosis in several tissues. This work studied the contribution of ET-1 to the development of peritoneal damage and failure in a mouse model of PD. ET-1 and its receptors were expressed in the peritoneal membrane and upregulated on PD fluid exposure. Administration of an ET receptor antagonist, either bosentan or macitentan, markedly attenuated PD-induced MMT, fibrosis, angiogenesis, and peritoneal functional decline. Adenovirus-mediated overexpression of ET-1 induced MMT in human mesothelial cells in vitro and promoted the early cellular events associated with peritoneal dysfunction in vivo. Notably, TGF-β1-blocking peptides prevented these actions of ET-1. Furthermore, a positive reciprocal relationship was observed between ET-1 expression and TGF-β1 expression in human mesothelial cells. These results strongly support a role for an ET-1/TGF-β1 axis as an inducer of MMT and subsequent peritoneal damage and fibrosis, and they highlight ET-1 as a potential therapeutic target in the treatment of PD-associated dysfunction.
First Experience With Direct Factor Xa Inhibition in Patients With Stable Coronary Disease
Authors: Christopher K. Dyke, Richard C. Becker, Neal S. Kleiman, Judith S. Hochman, Edwin G. Bovill, A. Michael Lincoff, Gary Gerstenblith, Vladimir Dzavik, Laura H. Gardner, Vic Hasselblad, Linda A. Zillman, Yoshimasa Shimoto, Thomas L. Robertson, Satoshi Kunitada, Paul W. Armstrong, Robert A. Harrington
Journal: Circulation (2002)

Background — Thrombin generation is critical to the formation of an arterial thrombus after rupture of an atherosclerotic plaque. In patients with stable coronary disease receiving standard medical therapy, we evaluated the pharmacokinetics, pharmacodynamics, and safety profile of DX-9065a, a novel small-molecule anticoagulant that directly, selectively, and reversibly inhibits factor Xa. Methods and Results — In a double-blind trial, 73 patients (median age, 63 years; 29% women) were randomly assigned to receive a fixed-dose intravenous bolus, followed by a 72-hour infusion of placebo or 1 of 4 weight-adjusted regimens of DX-9065a. Plasma samples were collected during infusion and a 24-hour elimination period. Only minor bleeding occurred, predominantly ecchymoses at infusion sites, and its incidence did not differ significantly among the groups, including placebo. Median hemoglobin, platelet count, serum creatinine level, and liver function tests did not change significantly from baseline during infusion or elimination. Significant predictors of pharmacokinetic response included infusion dose and weight. At 60 hours into the DX-9065a infusion, plasma drug levels correlated strongly with anti–factor Xa activity ( r =0.97), prothrombin time ( r =0.77), and international normalized ratio ( r =0.72) but less so with activated partial thromboplastin time ( r =0.56; all P &lt;0.001). Conclusions — This is the first study of a selective, reversible, and direct small-molecule factor Xa inhibitor in patients with stable coronary disease. These data lay the foundation for further investigation of factor Xa inhibitors in the treatment of patients with coronary atherothrombosis.
ELICITATION OF ALLERGIC CONTACT DERMATITIS IN THE GUINEA PIG
Authors: Herman N. Eisen, Milton Tabachnick
Journal: The Journal of Experimental Medicine (1958)

When one or two drops of a dilute, non-irritating solution of 2,4-dinitrochlorobenzene (DNCB) is applied to a small area of skin of the intact guinea pig, about 20 per cent of the applied material, or some derivative of it, is soon excreted in urine. In normal, as well as in specifically sensitized guinea pigs, DNCB at the site of local application becomes rapidly bound to skin protein through primary chemical bonds. Twenty-four hours after application roughly half of the material present at the local skin site is still extractable with organic solvents. Of the non-extractable dinitrophenyl groups, about 99 per cent are in epidermis, and about 85 per cent are substituted in epsilon-NH(2) groups of lysine residues. Only traces of bound dinitrophenyl groups were observed in the corium. It is uncertain whether these are formed in situ, or are experimental contaminants, or are migratory epidermally formed conjugates. Even when DNCB is injected intradermally it combines predominantly with overlying epidermis and with epidermal components of hair follicles, but only slightly with corium. The 2,4-dinitrophenyl conjugates which are localized in the deeper, viable half of the epidermis, close to the epidermal-dermal junction, are inferred to be the agents responsible for specifically evoking the allergic response in sensitized animals. Conjugates which are situated in the outer, cornified half of the epidermis are shown to be incapable of eliciting the allergic response. The results furnish a basis for interpreting a common pattern of lesions in allergic contact dermatitis as it occurs spontaneously in man.
Serum 25-Hydroxyvitamin D Concentration and Subsequent Risk of Type 2 Diabetes
Authors: Catharina Mattila, Paul Knekt, Satu Männistö, Harri Rissanen, Maarit A. Laaksonen, Jukka Montonen, Antti Reunanen
Journal: Diabetes Care (2007)

t has been suggested that vitamin D reduces the risk of type 2 diabetes.The finding that vitamin D deficiency is associated with impaired ␤-cell function and insulin resistance in animals (1,2) and humans (3,4) is in line with that hypothesis.In the only cohort study publ i s h e d , t h e i n t a k e o f v i t a m i n D supplements was inversely associated with the development of type 2 diabetes (5).Since vitamin D intake covers only a part of the total vitamin D available, the purpose of this study was to evaluate the prediction of serum 25-hydroxyvitamin D (25OHD) on subsequent type 2 diabetes incidence. RESEARCH DESIGN AND METHODS -The study population, collected from 1978 to 1980 as part of the Mini-Finland Health Survey (6), consisted of 4,423 men and women aged 40 -69 years.After exclusion of 247 individuals with type 2 diabetes at baseline (i.e., fasting plasma glucose Ͼ7.0 mmol/l on two occasions or Ͼ11.0 mmol/l on a single occasion) and 79 individuals with missing values of serum 25OHD, the final sample size was 4,097.Data on education, smoking, leisure-time exercise, and hypertension medication were collected in a health examination (6).Height, weight, and blood pressure were measured, and blood samples were collected and stored at Ϫ20°C.In 2003-2004, radioimmunoassay ( 125 I RIA kit; DiaSorin, Stillwater, MN) was used to assess serum 25OHD in thawed samples.The coefficient of variation for serum 25OHD varied from 8 to 13%.During 17 years of
Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin.
Authors: D Feng, J A Nagy, J Hipp, H F Dvorak, A M Dvorak
Journal: The Journal of Experimental Medicine (1996)

In contrast to normal microvessels, those that supply tumors are strikingly hyperpermeable to circulating macromolecules such as plasma proteins. This leakiness is largely attributable to a tumor-secreted cytokine, vascular permeability factor (VPF). Tracer studies have shown that macromolecules cross tumor vascular endothelium by way of a recently described cytoplasmic organelle, the vesiculo-vacuolar organelle or VVO (VVOs are grapelike clusters of interconnected, uncoated vesicles and vacuoles). However, equivalent VVOs are also present in the cytoplasm of normal venules that do not leak substantial amounts of plasma protein. To explain these findings, we hypothesized that VPF increased the permeability of tumor blood vessels by increasing VVO function and that the VVOs of normal venules were relatively impermeable in the absence of VPF stimulation. To test this hypothesis, VPF was injected intradermally in normal animals after intravenous injection of a soluble macromolecular tracer, ferritin, whose extravasation could be followed by electron microscopy. VPF caused normal venules to leak ferritin, and, as predicted by our hypothesis, ferritin extravasated by way of VVOs, just as in hyperpermeable tumor microvessels. Ultrathin (14-nm) serial electron microscopic sections and computer-aided three-dimensional reconstructions better defined VVO structure. VVOs occupied 16-18% of endothelial cytoplasm in normal venules. Individual VVOs were clusters of numerous (median, 124) interconnected vesicles and vacuoles that formed complex pathways across venular endothelium with multiple openings to both luminal and abluminal surfaces. Like VPF, histamine and serotonin also stimulated ferritin extravasation across venules by way of VVOs. Together, these data establish VVOs as the major pathway by which soluble plasma proteins exit venules in response to several mediators that increase venular hyperpermeability. These same mediators also increased the extravasation of colloidal carbon, but this large particulate nonphysiological tracer exited venules primarily through endothelial gaps.
Prospective Study of TNFα Blockade with Infliximab in Anti-Neutrophil Cytoplasmic Antibody-Associated Systemic Vasculitis
Authors: Anthony Booth, Lorraine Harper, Tariq Hammad, Paul Bacon, Megan Griffith, Jeremy Levy, Caroline Savage, Charles Pusey, David Jayne
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Tumor necrosis factor α (TNFα) plays an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. TNFα blockade is a potential therapy for these disorders. Methods: An open-label, multi-center, prospective clinical trial in two subgroups was performed. Study I examined acute disease, either first presentation or relapse (Birmingham Vasculitis Activity Score [BVAS] ≥ 10; n = 16); study II examined persistent disease (BVAS ≥ 4; n = 16). Patients received infliximab (5 mg/kg) at 0, 2, 6, and 10 wk. Concomitant therapy in study I included prednisolone and cyclophosphamide. Study II patients continued their existing treatment regimens, with prednisolone tapered according to clinical status. Results: Mean age was 52.4 yr, 53% of the patients were female, and follow-up was 16.8 mo. Twenty-eight patients (88%) achieved remission (14 per study group). BVAS decreased from 12.3 (confidence interval [CI] = 10.5 to 14.0) at entry to 0.3 (CI = 0.2 to 0.9) at wk 14 (P < 0.001). C-reactive protein (mg/L) decreased from 29.4 (CI = 16.8 to 42.0) at entry to 7.0 (CI = 3.3 to 10.9) by wk 14 (P = 0.001). Mean prednisolone dose (mg/d) in study II decreased from 23.8 (CI = 15.0 to 32.5) at entry to 8.8 (CI = 5.9 to 11.7) at wk 14 (P = 0.002). There were two deaths and seven serious infections. Relapse occurred in five patients (three in study II) after a mean of 27 wk. Conclusion: TNFα blockade with infliximab was effective at inducing remission in 88% of patients with antibody-associated systemic vasculitis and permitted reduction in steroid doses. Severe infections were seen in 21% of patients, and despite continued infliximab, 20% of initial responders experienced disease flares. Infliximab is a promising new therapy for vasculitis both as a component of initial therapy and in the management of refractory disease. These results need confirmation in larger randomized trials.
The situation of extrapulmonary tuberculosis in Japan: Affected organ and rate of bacteriologically detection
Authors: Susumu Hirao, Masaki Ota, Akihiro Ohkado, Kunihiko Ito, Nobukatsu Ishikawa
Journal: European Respiratory Journal (2012)

Introduction:  To bacteriologically confirm diagnosis of tuberculosis (TB) is preferable. However, extrapulmonary TB (EPTB) is difficult because collecting samples are not simple like sputum samples, and burden for patients and doctors. In addition, smear examination tend to be negative. In Japan, patients access to examination easily because of health system. That is why, EPTB may be more bacteriologically confirmed in Japan.   Objectives:  It is interesting to look into % of EPTBs bacteriologically confirmed by organs, because it would be a good guide for national TB programmes in high-burden countries which type of EPTBs are more likely to be confirmed.   Methods:  EPTB data were collected from public health centre from 2008 to 2010 in the whole country. Study variables were affected organ of by age group, gender, nationality, month of diagnosis, prefectural, occupational and treatment history.   Results:  The total number of EPTBs in Japan from 2008 to 2010 was 14,711. The most affected organ was pleura (7,043 cases) followed by lymph node excluded hilar lymph node and miliary TB (2,882 and 1,433 cases, respectively). Overall % of bacteriologically confirmed EPTB was 30.6%. The organ which was highest % of all EPTBs was renal/urinary tract (75.9%) followed by auris and joint/bone excluded vertebral bones (75.0% and 65.8%, respectively). Whilst the organ which was lowest % of all EPTBs was oculus (4.1%) followed by pleura and hilar lymph node (16.3% and 21.8%, respectively).   Conclusions:  Our study demonstrated that 14,711 cases of EPTB were found in Japan from 2008 to 2010. The most affected organ was pleura, however, the % of bacteriologically confirmed pleural TB was only 16.3%.
A human model for assaying comedolytic substances
Authors: O.H. Mills, A.M. Kligman
Journal: British Journal of Dermatology (1982)

The comedolytic activity of topical medicaments may be quantitatively assessed by inducing microcomedones on the backs of black males by a 2-week occlusive exposure to 10% crude coal tar. The test agents are then applied for 2 weeks and the reduction in density of microcomedones is determined by the non-invasive ‘follicular biopsy’ technique using cyanoacrylate adhesive. Only two of the many agents that were tested demonstrated appreciable comedolytic activity, namely retinoic acid (tretinoin) and salicylic acid. The former was more potent in dosage response assays.
Membrane-bound Delta-4 Notch ligand reduces the proliferative activity of primitive human hematopoietic CD34+CD38low cells while maintaining their LTC-IC potential
Authors: E Lauret, C Catelain, M Titeux, S Poirault, J S Dando, M Dorsch, J-L Villeval, A Groseil, W Vainchenker, F Sainteny, A Bennaceur-Griscelli
Journal: Leukemia (2004)
Revisiting the Contribution of cis-Elements to Expression Divergence between Duplicated Genes: The Role of Chromatin Structure
Authors: J. Li, Z. Yuan, Z. Zhang
Journal: Molecular Biology and Evolution (2010)

Although divergence in expression is thought to be a hallmark of functional dispersal between paralogs postduplication, there is currently a limited understanding of the mechanisms underlying the necessary transcriptional alterations as recent studies have suggested that only a very small proportion of expression variation could be explained by transcriptional variation between paralogs. To further this understanding, we examined comprehensively curated regulatory interactions and genomewide nucleosome occupancy in budding yeast to specifically determine the contribution of cis-elements to expression divergence between extant duplicates. We found that divergence in activation by transcription factors plays a more important role in expression divergence of paralogs than previously appreciated; further, analysis of promoter chromatin structure demonstrated that differential nucleosome organization is coupled with divergent expression of paralogs. By incorporating information of cis-elements encoding transcriptional regulation and chromatin structure, we improved the fraction of expression variation that was previously shown to be explained based on known cis-transcriptional effects by approximately 3-fold. Taken together, our analysis highlights the importance of chromatin divergence involved in expression evolution between paralogs.
An historical note on pyoderma faciale
Authors: T. JANSEN, G. PLEWIG
Journal: British Journal of Dermatology (1993)

Journal Article An historical note on pyoderma faciale Get access T. JANSEN, T. JANSEN Department of Dermatology, Ludwig‐Maximilians‐University, Frauenlobstrasse 9–11, 80337 Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar G. PLEWIG G. PLEWIG Department of Dermatology, Ludwig‐Maximilians‐University, Frauenlobstrasse 9–11, 80337 Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 5, 1 November 1993, Pages 594–596, https://doi.org/10.1111/j.1365-2133.1993.tb00491.x Published: 01 November 1993 Article history Accepted: 12 February 1993 Published: 01 November 1993
microRNA-7 Inhibits the Epidermal Growth Factor Receptor and the Akt Pathway and Is Down-regulated in Glioblastoma
Authors: Benjamin Kefas, Jakub Godlewski, Laurey Comeau, Yunqing Li, Roger Abounader, Michael Hawkinson, Jeongwu Lee, Howard Fine, E. Antonio Chiocca, Sean Lawler, Benjamin Purow
Journal: Cancer Research (2008)

microRNAs are noncoding RNAs inhibiting expression of numerous target genes, and a few have been shown to act as oncogenes or tumor suppressors. We show that microRNA-7 (miR-7) is a potential tumor suppressor in glioblastoma targeting critical cancer pathways. miR-7 potently suppressed epidermal growth factor receptor expression, and furthermore it independently inhibited the Akt pathway via targeting upstream regulators. miR-7 expression was down-regulated in glioblastoma versus surrounding brain, with a mechanism involving impaired processing. Importantly, transfection with miR-7 decreased viability and invasiveness of primary glioblastoma lines. This study establishes miR-7 as a regulator of major cancer pathways and suggests that it has therapeutic potential for glioblastoma.
From Small Area Variations to Accountable Care Organizations: How Health Services Research Can Inform Policy
Authors: Harold S. Luft
Journal: Annual Review of Public Health (2012)

Much of health services research seeks to inform particular policy choices and is best characterized as policy-driven research. The reverse, research-driven policy, occurs when studies alter how people perceive reality, which eventually leads to new policy. An example of the latter is nearly four decades of work by John Wennberg and colleagues. Observing variations in practice across small geographic areas led to the notion that some care is preference sensitive, whereas other care is supply constrained. For the former, patient, rather than physician, preferences should be honored, after acquiring and effectively communicating the best available information on the benefits and risks of treatment options. Finding that areas with high use of services have no better quality or outcomes than do areas with lower use led to the notion of accountable care organizations (ACOs). Eventually, both patient engagement and ACOs were written into the Affordable Care Act of 2010.
ELECTRON MICROSCOPE STUDIES ON THE DEGRANULATION OF RABBIT PERITONEAL LEUKOCYTES DURING PHAGOCYTOSIS
Authors: Dorothea Zucker-Franklin, James G. Hirsch
Journal: The Journal of Experimental Medicine (1964)

Electron microscopic observations have established the mechanisms underlying degranulation of neutrophils and eosinophils during phagocytosis. The content of the granules is released into the phagocytic vacuole when their membranes fuse with the membrane lining the vacuole. The discharge mechanism appears to be applicable to the various morphological types of granules seen in rabbit polymorphs. It has been proposed that the release of material to the outside of the cell or the discharge of material into intracellular vacuoles, events involving membrane fusion, be termed "exoplasmosis."
Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study
Authors: Belen Ponte, Menno Pruijm, Daniel Ackermann, Philippe Vuistiner, Idris Guessous, Georg Ehret, Heba Alwan, Sonia Youhanna, Fred Paccaud, Markus Mohaupt, Antoinette Péchère-Bertschi, Bruno Vogt, Michel Burnier, Pierre-Yves Martin, Olivier Devuyst, Murielle Bochud
Journal: Journal of the American Society of Nephrology (2014)

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.
Ecological association between asbestos-related diseases and historical asbestos consumption: an international analysis
Authors: Ro-Ting Lin, Ken Takahashi, Antti Karjalainen, Tsutomu Hoshuyama, Donald Wilson, Takashi Kameda, Chang-Chuan Chan, Chi-Pang Wen, Sugio Furuya, Toshiaki Higashi, Lung-Chang Chien, Megu Ohtaki
Journal: The Lancet (2007)