tbuckley/cabot-search huggingface dataset:
Leukemia Inhibitory Factor Is Involved in Tubular Regeneration after Experimental Acute Renal Failure
Authors: Jun Yoshino, Toshiaki Monkawa, Mihoko Tsuji, Matsuhiko Hayashi, Takao Saruta
Journal: Journal of the American Society of Nephrology (2003)

Leukemia inhibitory factor (LIF) is known to play a crucial role in the conversion of mesenchyme into epithelium during nephrogenesis. This study was carried out to test the hypothesis that LIF and LIF receptor (LIFR) are involved in the renal epithelial regeneration after acute renal failure. First, the authors investigated the spatiotemporal expression of LIF and LIFR in fetal and adult rat kidney. In developing kidney, LIF was expressed in the ureteric buds and LIFR was located in nephrogenic mesenchyme and the ureteric buds; in adult kidney, LIF and LIFR expression was confined to the collecting ducts. Next, the authors examined the expression of LIF and LIFR during the recovery phase after ischemia-reperfusion injury. Real-time PCR analysis revealed that LIF mRNA expression was significantly increased from day 1 to day 7 after reperfusion and that LIFR mRNA was upregulated from day 4 to day 14. Histologic analysis demonstrated that the increased expression of LIF mRNA and protein was most marked in the outer medulla, especially in the S3 segment of the proximal tubules. To elucidate the mitogenic role of LIF in the regeneration process, cultured rat renal epithelial (NRK 52E) cells were subjected to ATP depletion (an in vitro model of acute renal failure), and LIF expression was found to be enhanced during recovery after ATP depletion. Blockade of endogenous LIF with a neutralizing antibody significantly reduced the cell number and DNA synthesis during the recovery period. These results suggest that LIF participates in the regeneration process after tubular injury.
The chronic bronchitis phenotype in subjects with and without COPD: the PLATINO study
Authors: Maria Montes de Oca, Ronald J. Halbert, Maria Victorina Lopez, Rogelio Perez-Padilla, Carlos Tálamo, Dolores Moreno, Adrianna Muiño, José Roberto B. Jardim, Gonzalo Valdivia, Julio Pertuzé, Ana Maria B. Menezes
Journal: European Respiratory Journal (2012)

Little information exists regarding the epidemiology of the chronic bronchitis phenotype in unselected chronic obstructive pulmonary disease (COPD) populations. We examined the prevalence of the chronic bronchitis phenotype in COPD and non-COPD subjects from the PLATINO study, and investigated how it is associated with important outcomes. Post-bronchodilator forced expiratory volume in 1 s/forced vital capacity &lt;0.70 was used to define COPD. Chronic bronchitis was defined as phlegm on most days, at least 3 months per year for ≥2 yrs. We also analysed another definition: cough and phlegm on most days, at least 3 months per year for ≥2 yrs. Spirometry was performed in 5,314 subjects (759 with and 4,554 without COPD). The proportion of subjects with and without COPD with chronic bronchitis defined as phlegm on most days, at least 3 months per year for ≥2 yrs was 14.4 and 6.2%, respectively. Using the other definition the prevalence was lower: 7.4% with and 2.5% without COPD. Among subjects with COPD, those with chronic bronchitis had worse lung function and general health status, and had more respiratory symptoms, physical activity limitation and exacerbations. Our study helps to understand the prevalence of the chronic bronchitis phenotype in an unselected COPD population at a particular time-point and suggests that chronic bronchitis in COPD is possibly associated with worse outcomes.
Imatinib GIST Keeps Finding New Indications: Successful Treatment of Dermatofibrosarcoma Protuberans by Targeted Inhibition of the Platelet-Derived Growth Factor Receptor
Authors: Charles L. Sawyers
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.17.3568 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12202652 Imatinib GIST Keeps Finding New Indications: Successful Treatment of Dermatofibrosarcoma Protuberans by Targeted Inhibition of the Platelet-Derived Growth Factor Receptor Charles L. SawyersxCharles L. SawyersSearch for articles by this author Show More David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA https://doi.org/10.1200/JCO.2002.20.17.3568 Full Text PDF Figures and Tables "Imatinib GIST Keeps Finding New Indications: Successful Treatment of Dermatofibrosarcoma Protuberans by Targeted Inhibition of the Platelet-Derived Growth Factor Receptor." Journal of Clinical Oncology, 20(17), pp. 3568–3569© 2002 by American Society of Clinical Oncology
Risk of deep vein thrombosis and pulmonary embolism in asthma
Authors: Christof J. Majoor, Pieter W. Kamphuisen, Aeilko H. Zwinderman, Anneke ten Brinke, Marijke Amelink, Lucia Rijssenbeek-Nouwens, Peter J. Sterk, Harry R. Büller, Elisabeth H. Bel
Journal: European Respiratory Journal (2012)

Increasing evidence suggests that patients with asthma have activated coagulation within the airways. Whether this leads to an increase in venous thromboembolic events is unknown. We therefore assessed the incidence of venous thromboembolic events in patients with mild-to-moderate and severe asthma as compared with an age- and sex-matched reference population. 648 patients with asthma (283 with severe and 365 patients with mild-to-moderate asthma) visiting three Dutch outpatient asthma clinics were studied. All patients completed a questionnaire about a diagnosis of deep vein thrombosis and pulmonary embolism in the past, their risk factors, history of asthma and medication use. All venous thromboembolic events were objectively verified. In total, 35 venous thromboembolic events (16 deep vein thrombosis and 19 pulmonary embolism) occurred at a median age of 39 (range 20–63) years. The incidence of pulmonary embolism in patients with severe asthma was 0.93 (95% CI 0.42–1.44) per 1000 person-years, 0.33 (95% CI 0.07–0.60) in mild-to-moderate asthma and 0.18 (95% CI 0.03–0.33) in the general population, respectively. Severe asthma and oral corticosteroid use were independent risk factors of pulmonary embolism (hazard ratios 3.33 (1.16–9.93) and 2.82 (1.09–7.30), respectively). Asthma was not associated with deep vein thrombosis. Severe asthma greatly enhances the risk of pulmonary embolism, particularly if chronic corticosteroids are used.
CD10 expression and risk of relapse in DCIS
Authors: J. Toussaint, V. Durbecq, G. Rouas, S. Altintas, C. Desmedt, D. Larsimont, M. Piccart, C. Sotiriou
Journal: Journal of Clinical Oncology (2009)

e22053 Background: DCIS is a heterogeneous malignant condition of the breast with no standard of care. The Van Nuys Prognostic Index (VNPI) is the most useful tool to predict local recurrence. However, assessment of the VNPI score is not easy and many women with DCIS are offered the same treatment. Experimental evidence has indicated that a local death of the myo-epithelial cells (MECs) in the DCIS is a pre-requisite to tumor invasion. In this study we hypothesized that loss of CD10, (a marker of MECs), would be a surrogate for basement membrane disruption and tumor invasion. The aim of the present study was to retrospectively evaluate the prognostic value of CD10 in DCIS. Methods: CD10 expression was evaluated by qRT-PCR and immuno-histochemistry (IHC) using FFPE tissues on normal samples (N=11) and two independent DCIS populations: a training set (N=66) and a validating set (N=88). Results: MECs were the only cells that showed a CD10 staining using IHC in normal and DCIS samples. All normal tissue samples demonstrated high expression levels of CD10 using both IHC and RT-PCR. In contrast, DCIS samples showed a wide range of CD10 expression levels. Of interest, 66% of DCIS showed lower expression values of CD10 compared to normal tissues. The group of DCIS with low expression of CD10 was statistically associated with higher risk of relapse [HR: 2.49 (CI.95%= 1.13–5.49), P= 0.02]. These results were independently validated in our validation set using both techniques (qRT-PCR: HR: 1.805 (CI.95%= 1.11–2.92), P= 0.02]; IHC [HR: 1.84 (CI.95%= 1.00–3.40), P= 0.05]. In multivariate analysis, CD10 remained significant (HR=2.25; [95CI: 1.24–4.09], p=0.008) together with VNPI [HR: 2.03 (CI.95%= 1.23–3.35), P= 0.006]. Conclusions: Decrease of CD10 expression in MECs is associated with higher risk of relapse in DCIS and it has the potential to improve DCIS management. These promising results are currently being validated in a larger patient's series. No significant financial relationships to disclose.
Small plants in high places: The conservation and biology of epiphytes
Authors: N.Michele Holbrook
Journal: Trends in Ecology & Evolution (1991)

Large numbers of epiphytic bromeliads are regularly harvested from the canopy of cloud forests for traditional uses and illegal trade, with detrimental effects on the viability of populations. Since a significant proportion of natural mortality in epiphytes is caused by detachment from the support trees, harvesting of fallen plants represents a potential supply for commercial use that would have no impact on bromeliad population dynamics. We evaluated the potential of four cloud forest sites in southern Mexico to supply epiphytic bromeliads for commercialization. Bromeliad diversity and abundance was determined by sampling eight trees in each forest site and the number of fallen plants from these trees was recorded over three years. To determine the size of the potential harvest from the forest floor, the rate of bromeliad fall, and the species, condition and size of fallen individuals were recorded monthly in 10 plots (10 × 10 m) at each site over a period of five months. Bromeliad fall rate varied from 26,910 to 92,712 rosettes ha−1 y−1. Of these, ca. 60% (16,770 to 55,992 rosettes ha−1 y−1) of the 18 species identified were in a suitable condition for commercialization. Diversity and abundance in the canopy were positively related to that of the fallen rosettes (P < 0.05), indicating that the harvesting rate can be estimated from population densities in the host trees and that the fallen plants could therefore be used to indirectly evaluate the epiphyte community. Assessment revealed that the forest canopy could act as a nursery to supply a constant “rain” of bromeliads with minimum production costs. Even one ha of cloud forest can supply thousands of marketable bromeliads every year. Harvesting of fallen epiphytic bromeliads could add to the diversification of cloud forest management, contribute to the reduction of excessive canopy harvesting pressure and supply plants for forest enrichment programs. The results of this study are discussed in the context of the local stakeholder participation and national conditions.
L-Selectin Shedding Does Not Regulate Constitutive T Cell Trafficking but Controls the Migration Pathways of Antigen-activated T Lymphocytes
Authors: Elena Galkina, Kyriakos Tanousis, Graham Preece, Mauro Tolaini, Dimitris Kioussis, Oliver Florey, Dorian O. Haskard, Thomas F. Tedder, Ann Ager
Journal: The Journal of Experimental Medicine (2003)

L-Selectin mediates rolling of lymphocytes in high endothelial venules (HEVs) of peripheral lymph nodes (PLNs). Cross-linking of L-selectin causes proteolytic shedding of its ectodomain, the physiological significance of which is unknown. To determine whether L-selectin shedding regulates lymphocyte migration, a mutant form that resists shedding (LΔP-selectin) was engineered. Transgenic mice expressing either LΔP or wild-type (WT) L-selectin on T cells were crossed with L-selectin knockout (KO) mice. The cellularity and subset composition of secondary lymphoid organs did not differ between LΔP and WT mice, however, they were different from C57BL/6. Plasma levels of soluble L-selectin in LΔP mice were reduced to &amp;lt;5% of WT and C57BL/6 mice. The rolling properties of T lymphocytes from LΔP and WT mice on immobilized L-selectin ligands were similar. Furthermore, similar numbers of LΔP and WT T lymphocytes were recruited from the bloodstream into PLNs in mice, although LΔP T cells transmigrated HEVs more slowly. WT, but not LΔP-selectin, underwent rapid, metalloproteinase-dependent shedding after TCR engagement, and LΔP T cells retained the capacity to enter PLNs from the bloodstream. These results suggest that the ability to shed L-selectin is not required for T cell recirculation and homing to PLNs. However, L-selectin shedding from antigen-activated T cells prevents reentry into PLNs.
Autoregulation of Single Nephron Filtration Rate in the Presence and the Absence of Flow to the Macula Densa
Authors: FRANKLYN G. KNOX, COBERN OTT, JEAN-LOUIS CUCHE, JOSIANNE GASSER, JOHN HAAS
Journal: Circulation Research (1974)

Flow of tubule fluid to the macula densa is part of a proposed feedback loop for autoregulation of glomerular filtration rate. In the present study, autoregulation of single nephron filtration rate was tested in the presence and the absence of flow to the macula densa in the rat. Filtration rates were measured at elevated arterial blood pressures caused by carotid occlusion and vagal section and at reduced renal perfusion pressures caused by partial aortic constriction. Measurements of single nephron filtration rate in the presence and the absence of flow to the macula densa were obtained by complete volume collections from the distal nephron beyond the macula densa and from the proximal tubule, respectively. Mean blood pressure was 130 ± 4 (SE) mm Hg for the initial collections, and renal perfusion pressure was 100 ± 1 mm Hg for the repeat collections (nine rats). Distal single nephron filtration rate was 42 ± 1 nliters/min at elevated perfusion pressure and 41 ± 1 nliters/min at reduced perfusion pressure; proximal single nephron filtration rate was 41 ± 1 nliters/min at elevated perfusion pressure and 41 ± 1 nliters/min at reduced perfusion pressure. Similarly, glomerular filtration rate was 4.6 ± 0.4 ml/min kg -1 body weight and 4.7 ± 0.3 ml/min kg -1 body weight at elevated and reduced perfusion pressures, respectively. Additional studies in seven dogs showed good correlation between autoregulation of single nephrons in the absence of flow to the macula densa and autoregulation of the micropunctured kidney. It is concluded that autoregulation of single nephron filtration rate is unaltered by interruption of tubule fluid flow to the macula densa.
Genetic and genomic insights into age at natural menopause
Authors: Francisco Moron, Agustin Ruiz, Jose Galan
Journal: Genome Medicine (2009)

The age at natural menopause shows great variability. It has been proposed that early age at menopause is a risk factor for osteoporosis and cardiovascular disease, whereas later age at menopause is a risk factor for breast cancer. In addition, it is thought that the genetic factors accounting for the genetic variability in age at menopause could also play a role in those diseases, as well as infertility in women. In this minireview we comment on the latest genetics and genomics insights into age at natural menopause.
Ambient Particulate Matter as a Risk Factor for Suicide
Authors: Changsoo Kim, Sang Hyuk Jung, Dae Ryong Kang, Hyeon Chang Kim, Ki Tae Moon, Nam Wook Hur, Dong Chun Shin, Il Suh
Journal: American Journal of Psychiatry (2010)

The authors assessed the relationship between exposure to ambient particulate matter and suicide in urban settings during a 1-year period.The association between particulate matter and suicide was determined using a time-stratified case-crossover approach in which subjects served as their own controls. All suicide cases (4,341) in 2004 that occurred in seven cities in the Republic of Korea were included. Hourly mean concentrations of particulate matter < or =10 microm in aerodynamic diameter (at 106 sites in the seven cities) and particulate matter < or =2.5 microm in aerodynamic diameter (at 13 sites in one city) were measured. The percent increase in suicide risk associated with an interquartile range increase in particulate matter was determined by conditional logistic regression analysis after adjusting for national holidays and meteorological factors. Subgroup analysis was performed after stratification by underlying disease (cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, cancer, and psychiatric illness).The largest associations were a 9.0% increase (95% CI=2.4-16.1) and a 10.1% (95% CI=2.0-19.0) increase in suicide risk related to an interquartile range increase in particulate matter < or =10 microm (average of 0 to 2 days prior to the day of suicide) and particulate matter < or =2.5 microm (1 day prior to the day of suicide), respectively. Among individuals with cardiovascular disease, a significant association between particulate matter < or =10 microm (average of 0 to 2 days prior to the day of suicide) and suicide was observed (18.9%; 95% CI=3.2-37.0).Conclusions: A transient increase in particulate matter was associated with increased suicide risk, especially for individuals with preexisting cardiovascular disease.
CYP3A4 inducible model for in vitro analysis of human drug metabolism using a bioartificial liver
Authors: Tohru Iwahori, Tomokazu Matsuura, Haruka Maehashi, Ken Sugo, Masaya Saito, Masakiyo Hosokawa, Kan Chiba, Takahiro Masaki, Hideki Aizaki, Kiyoshi Ohkawa, Tetsuro Suzuki
Journal: Hepatology (2003)

CYP3A is responsible for approximately 50% of the therapeutic drug–metabolizing activity in the liver. The present study was undertaken to establish the CYP3A4 inducible model for analysis of human drug metabolism using a bioartificial liver composed of the functional hepatocellular carcinoma cell (HCC) line FLC–5. A radial–flow bioreactor (RFB), which is a carrier–filled type bioreactor, was used for 3–dimensional perfusion culture of FLC–5 cells. The CYP3A4 messenger RNA (mRNA) expression level 48 hours after rifampicin treatment in the RBF was approximately 100 times higher than that in a monolayer culture. Western blot analysis also demonstrated an increase in expression of the CYP3A protein. When testosterone, a substrate for CYP3A4, was added to the rifampicin–treated cell culture, 6β–hydroxy testosterone as a metabolite was formed. Electrophoretic mobility shift assay (EMSA) with a CYP3A4 ER6 probe demonstrated that relatively high molecular weight complex containing pregnane X receptor (PXR)/retinoid X receptorα(RXRα), compared with that in the monolayer culture, is possibly generated in the RFB culture of FLC–5 treated with rifampicin. Similarly, the assay with a probe of HNF–4α–binding motif indicated the formation of a large protein complex in the RFB culture. Because it is known that PXR transactivates CYP3A4 gene via its response element and expression of PXR is regulated by HNF–4α, the large complexes binding to response elements of PXR or HNF–4α in the RFB culture may contribute to up–regulation of CYP3A4 mRNA. In conclusion, the bioartificial liver composed of human functional HCC cell line was useful in studying drug interactions during induction of human CYP3A4.
Loss of Complex I due to Mitochondrial DNA Mutations in Renal Oncocytoma
Authors: Johannes A. Mayr, David Meierhofer, Franz Zimmermann, Rene Feichtinger, Christian Kögler, Manfred Ratschek, Nikolaus Schmeller, Wolfgang Sperl, Barbara Kofler
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Many solid tumors exhibit abnormal aerobic metabolism characterized by increased glycolytic capacity and decreased cellular respiration. Recently, mutations in the nuclear encoded mitochondrial enzymes fumarate hydratase and succinate dehydrogenase have been identified in certain tumor types, thus demonstrating a direct link between mitochondrial energy metabolism and tumorigenesis. Although mutations in the mitochondrial genome (mitochondrial DNA, mtDNA) also can affect aerobic metabolism and mtDNA alterations are frequently observed in tumor cells, evidence linking respiratory chain deficiency in a specific tumor type to a specific mtDNA mutation has been lacking. Experimental Design: To identify mitochondrial alterations in oncocytomas, we investigated the activities of respiratory chain enzymes and sequenced mtDNA in 15 renal oncocytoma tissues. Results: Here, we show that loss of respiratory chain complex I (NADH/ubiquinone oxidoreductase) is associated with renal oncocytoma. Enzymatic activity of complex I was undetectable or greatly reduced in the tumor samples (n = 15). Blue Native gel electrophoresis of the multisubunit enzyme complex revealed a lack of assembled complex I. Mutation analysis of the mtDNA showed frame-shift mutations in the genes of either subunit ND1, ND4, or ND5 of complex I in 9 of the 15 tumors. Conclusion: Our data indicate that isolated loss of complex I is a specific feature of renal oncocytoma and that this deficiency is frequently caused by somatic mtDNA mutations.
Community-Centered Psychiatric Intervention: A Pilot Project in the 13th Arrondissement, Paris
Authors: MICHAEL A. WOODBURY, MARGARITA M. WOODBURY
Journal: American Journal of Psychiatry (1969)

The authors describe a system of intensive psychiatric services they developed to deal with the emergencies and difficult cases in a catchment area of 200,000 people in a low socioeconomic section of Paris. Mobile emergency and visiting teams including "indigenous" homemakers focus their intervention on the family of the designated patient in its home setting. The dynamics and techniques of home visiting are outlined as well as the process of "metabolism of anxiety" in the team that enables it to function as a therapeutic small group in its encounter with patients, families, and social networks.
Pirfenidone Is Renoprotective in Diabetic Kidney Disease
Authors: Satish P. RamachandraRao, Yanqing Zhu, Timothy Ravasi, Tracy A. McGowan, Irene Toh, Stephen R. Dunn, Shinichi Okada, Michael A. Shaw, Kumar Sharma
Journal: Journal of the American Society of Nephrology (2009)

Although several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. Here, we evaluated the role of PFD in regulation of the extracellular matrix. In mouse mesangial cells, PFD decreased TGF-beta promoter activity, reduced TGF-beta protein secretion, and inhibited TGF-beta-induced Smad2-phosphorylation, 3TP-lux promoter activity, and generation of reactive oxygen species. To explore the therapeutic potential of PFD, we administered PFD to 17-wk-old db/db mice for 4 wk. PFD treatment significantly reduced mesangial matrix expansion and expression of renal matrix genes but did not affect albuminuria. Using liquid chromatography with subsequent electrospray ionization tandem mass spectrometry, we identified 21 proteins unique to PFD-treated diabetic kidneys. Analysis of gene ontology and protein-protein interactions of these proteins suggested that PFD may regulate RNA processing. Immunoblotting demonstrated that PFD promotes dosage-dependent dephosphorylation of eukaryotic initiation factor, potentially inhibiting translation of mRNA. In conclusion, PFD is renoprotective in diabetic kidney disease and may exert its antifibrotic effects, in part, via inhibiting RNA processing.