tbuckley/cabot-search huggingface dataset:
Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous systemic sclerosis skin and mediates myeloid cell adhesion
Authors: Y Hou, B J Rabquer, M L Gerber, F Del Galdo, S A Jimenez, G K Haines, W G Barr, M C Massa, J R Seibold, A E Koch
Journal: Annals of the Rheumatic Diseases (2009)

Objective: To investigate the role of junctional adhesion molecule-A (JAM-A) in the pathogenesis of systemic sclerosis (SSc). Methods: Biopsy specimens from proximal and distal arm skin and serum were obtained from patients with SSc and normal volunteers. To determine the expression of JAM-A on SSc dermal fibroblasts and in SSc skin, cell surface ELISAs and immunohistology were performed. An ELISA was designed to determine the amount of soluble JAM-A (sJAM-A) in serum. Myeloid U937 cell–SSc dermal fibroblast and skin adhesion assays were performed to determine the role of JAM-A in myeloid cell adhesion. Results: The stratum granulosum and dermal endothelial cells (ECs) from distal arm SSc skin exhibited significantly decreased expression of JAM-A in comparison with normal volunteers. However, sJAM-A was increased in the serum of patients with SSc compared with normal volunteers. Conversely, JAM-A was increased on the surface of SSc compared with normal dermal fibroblasts. JAM-A accounted for a significant portion of U937 binding to SSc dermal fibroblasts. In addition, JAM-A contributed to U937 adhesion to both distal and proximal SSc skin. Conclusions: JAM-A expression is dysregulated in SSc skin. Decreased expression of JAM-A on SSc ECs may result in a reduced response to proangiogenic basic fibroblast growth factor. Increased JAM-A expression on SSc fibroblasts may serve to retain myeloid cells, which in turn secrete angiogenic factors.
Randomized, Controlled Trial of Prednisone, Cyclophosphamide, and Cyclosporine in Lupus Membranous Nephropathy
Authors: Howard A. Austin, Gabor G. Illei, Michelle J. Braun, James E. Balow
Journal: Journal of the American Society of Nephrology (2009)

Patients with lupus membranous nephropathy (LMN) are at substantial long-term risk for morbidity and mortality associated with protracted nephrotic syndrome, including ESRD. The optimal treatment for this condition is controversial. Forty-two patients with LMN participated in a randomized, controlled trial to compare adjunctive immunosuppressive drugs with prednisone alone. Adjunctive regimens included either cyclosporine (CsA) for 11 mo or alternate-month intravenous pulse cyclophosphamide (IVCY) for six doses; the control group received alternate-day prednisone alone. Median proteinuria was 5.4 g/d (range 2.7 to 15.4 g/d). We assessed the primary outcome, time to remission of proteinuria during the 12-mo protocol, by univariate survival analysis. At 1 yr, the cumulative probability of remission was 27% with prednisone, 60% with IVCY, and 83% with CsA. Although both IVCY and CsA were more effective than prednisone in inducing remissions of proteinuria, relapse of nephrotic syndrome occurred significantly more often after completion of CsA than after IVCY. By multivariate survival analysis, treatment with prednisone and high-grade proteinuria (>5 g/d) but not race or ethnicity were independently associated with a decreased probability of remission. Adverse effects during the 12-mo protocol included insulin-requiring diabetes (one with prednisone and two with CsA), pneumonia (one with prednisone and two with CsA), and localized herpes zoster (two with IVCY). In conclusion, regimens containing CsA or IVCY are each more effective than prednisone alone in inducing remission of proteinuria among patients with LMN.
Identifying adult asthma phenotypes using a clustering approach
Authors: V. Siroux, X. Basagaña, A. Boudier, I. Pin, J. Garcia-Aymerich, A. Vesin, R. Slama, D. Jarvis, J.M. Anto, F. Kauffmann, J. Sunyer
Journal: European Respiratory Journal (2011)

There is a need to improve asthma characterisation by integrating multiple aspects of the disease. The aim of the present study was to identify distinct asthma phenotypes by applying latent class analysis (LCA), a model-based clustering method, to two large epidemiological studies. Adults with asthma who participated in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2) (n = 641) and the European Community Respiratory Health Survey (ECRHSII) (n = 1,895) were included. 19 variables covering personal characteristics, asthma symptoms, exacerbations and treatment, age of asthma onset, allergic characteristics, lung function and airway hyperresponsiveness were considered in the LCA. Four asthma phenotypes were distinguished by the LCA in each sample. Two phenotypes were similar in EGEA2 and ECRHSII: active treated allergic childhood-onset asthma and active treated adult-onset asthma. The other two phenotypes were composed of subjects with inactive or mild untreated asthma, who differed by atopy status and age of asthma onset (childhood or adulthood). The phenotypes clearly discriminated populations in terms of quality of life, and blood eosinophil and neutrophil counts. The LCAs revealed four distinct asthma phenotypes in each sample. Considering these more homogeneous phenotypes in future studies may lead to a better identification of risk factors for asthma.
Prognostic Nomogram for Intrahepatic Cholangiocarcinoma After Partial Hepatectomy
Authors: Yizhou Wang, Jun Li, Yong Xia, Renyan Gong, Kui Wang, Zhenlin Yan, Xuying Wan, Guanghua Liu, Dong Wu, Lehua Shi, Wanyee Lau, Mengchao Wu, Feng Shen
Journal: Journal of Clinical Oncology (2013)

This study aimed to establish an effective prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) after partial hepatectomy.The nomogram was based on a retrospectively study on 367 patients who underwent partial hepatectomy for ICC at the Eastern Hepatobiliary Surgery Hospital from 2002 to 2007. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve and compared with five currently used staging systems on ICC. The results were validated using bootstrap resampling and a prospective study on 82 patients operated on from 2007 to 2008 at the same institution.On multivariate analysis of the primary cohort, independent factors for survival were serum carcinoembryonic antigen, CA 19-9, tumor diameter and number, vascular invasion, lymph node metastasis, direct invasion, and local extrahepatic metastasis, which were all selected into the nomogram. The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram for predicting survival was 0.74 (95% CI, 0.71 to 0.77), which was statistically higher than the C-index values of the following systems: American Joint Committee on Cancer (AJCC) seventh edition (0.65), AJCC sixth edition (0.65), Nathan (0.64), Liver Cancer Study Group of Japan (0.64), and Okabayashi (0.67; P < .001 for all). It was also higher (0.74) in predicting survival for the mass-forming type of ICC (P < .001). In the validation cohort, the nomogram discrimination was superior to the five other staging systems (C-index: 0.75 v 0.60 to 0.63; P < .001 for all).The proposed nomogram resulted in more-accurate prognostic prediction for patients with ICC after partial hepatectomy.
THE INFLUENCE OF ADRENALIN IN PHLORHIZIN DIABETES
Authors: A. I. Ringer
Journal: The Journal of Experimental Medicine (1910)

I. Intraperitoneal injections of adrenalin into animals which are completely under the influence of phlorhizin and which are free from glycogen do not result in any extra elimination of sugar. This proves that adrenalin does not cause a conversion of fat into carbohydrates, as is maintained by Blum and by Eppinger, Falta and Rudinger. II. The high D:N ratio 5.2 and 6.1 reported by Eppinger, Falta and Rudinger after adrenalin injections in depancreatized dogs, which were obtained after short periods of six hours and four hours respectively, can be explained by the elimination of carbohydrates present in the organism. III. These results confirm the work of Straub and Ritzmann which indicates that adrenalin, by its constricting effect on the blood vessels, produces anemia of the tissues, resulting in imperfect oxidation, and this anemia is followed by the conversion of glycogen into dextrose by hyperglycemia and consequently by glycosuria.
Acute Renal Failure in Critically Ill Patients&lt;SUBTITLE&gt;A Multinational, Multicenter Study&lt;/SUBTITLE&gt;
Authors: Shigehiko Uchino, John A Kellum, Rinaldo Bellomo, Gordon S Doig, Hiroshi Morimatsu, Stanislao Morgera, Miet Schetz, Ian Tan, Catherine Bouman, Ettiene Macedo, Noel Gibney, Ashita Tolwani, Claudio Ronco
Journal: JAMA (2005)

Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world.To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes.Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries.Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality.Of 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03).In this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.
Genome Wide Analyses Reveal Little Evidence for Adaptive Evolution in Many Plant Species
Authors: T. I. Gossmann, B.-H. Song, A. J. Windsor, T. Mitchell-Olds, C. J. Dixon, M. V. Kapralov, D. A. Filatov, A. Eyre-Walker
Journal: Molecular Biology and Evolution (2010)

The relative contribution of advantageous and neutral mutations to the evolutionary process is a central problem in evolutionary biology. Current estimates suggest that whereas Drosophila, mice, and bacteria have undergone extensive adaptive evolution, hominids show little or no evidence of adaptive evolution in protein-coding sequences. This may be a consequence of differences in effective population size. To study the matter further, we have investigated whether plants show evidence of adaptive evolution using an extension of the McDonald–Kreitman test that explicitly models slightly deleterious mutations by estimating the distribution of fitness effects of new mutations. We apply this method to data from nine pairs of species. Altogether more than 2,400 loci with an average length of ≈280 nucleotides were analyzed. We observe very similar results in all species; we find little evidence of adaptive amino acid substitution in any comparison except sunflowers. This may be because many plant species have modest effective population sizes.
Neuropathy Is Not Associated With Clinical Outcomes in Patients Receiving Adjuvant Taxane-Containing Therapy for Operable Breast Cancer
Authors: Bryan P. Schneider, Fengmin Zhao, Molin Wang, Vered Stearns, Silvana Martino, Vicky Jones, Edith A. Perez, Tom Saphner, Antonio C. Wolff, George W. Sledge, William C. Wood, Nancy E. Davidson, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2012)

Neuropathy is a common and potentially disabling complication of adjuvant taxane therapy. Recent studies have identified candidate single nucleotide polymorphisms associated with taxane-induced neuropathy. Therefore, we sought to determine whether neuropathy was associated with breast cancer recurrence in a clinical trial population who received adjuvant taxane therapy.Trial E1199 included 4,554 eligible women with operable breast cancer who received up to four cycles of doxorubicin and cyclophosphamide every 3 weeks followed by paclitaxel 175 mg/m(2) every 3 weeks for four cycles (P3), paclitaxel 80 mg/m(2) weekly for 12 cycles (P1), docetaxel 100 mg/m(2) every 3 weeks for four cycles (D3), or docetaxel 35 mg/m(2) weekly for 12 cycles (D1). A Cox proportional hazards model was used to determine the relationship between neuropathy and disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) by treating neuropathy status as a time dependent covariate and using a landmark analysis.Of 4,554 patients who received at least one taxane dose, grade 2 to 4 neuropathy developed in 18%, 22%, 15%, and 13% of patients in the P3, P1, D3, and D1 arms, respectively. In a model that included age, race, obesity, menopausal status, tumor size, nodal status, treatment arm, neuropathy, and hyperglycemia, no significant relationship was found between neuropathy and DFS, OS, or RFS.There was no association between taxane-induced neuropathy and outcome.
Quantitative assessment of the epithelial and inflammatory cell populations in large airways of normals and individuals with cystic fibrosis.
Authors: C Danel, S C Erzurum, N G McElvaney, R G Crystal
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Nasal and bronchial brushings and bronchial biopsies were evaluated from patients with cystic fibrosis (CF) and from normal subjects to quantify epithelial and inflammatory cell types. Epithelial in both groups were dominated by ciliated cells. The relative proportions of epithelial cells recovered by brushing and biopsy were similar, but with more basal cells from biopsies than from brushings. In nasal brushings, the numbers and percentages of epithelial subtypes were similar in both groups. In bronchial brushings, the number of recovered cells was 2.5-fold increased in the CF group compared with that in the normal group because of large numbers of neutrophils. The proportion of ciliated cells was lower in the CF group than in the normal group. Thus, even though the CF transmembrane conductance regulator mutations are expressed similarly in the nasal and bronchial epithelium in CF, the consequences are different, with little inflammation and no changes in the proportions of epithelial cells in the nasal epithelium, compared with marked neutrophil inflammation on the epithelial surface and significant changes in epithelial populations in the large airways. Airway brushing permits repetitive evaluation of the airway epithelium in CF, a useful methodology in the assessment of new therapies for this disorder.
Combination Therapy with Oral Sildenafil and Inhaled Iloprost for Severe Pulmonary Hypertension
Authors: Hossein Ardeschir Ghofrani, Ralph Wiedemann, Frank Rose, Horst Olschewski, Ralph Theo Schermuly, Norbert Weissmann, Werner Seeger, Friedrich Grimminger
Journal: Annals of Internal Medicine (2002)

Background: Inhalation of the stable prostacyclin analogue iloprost is being studied for treatment of pulmonary hypertension. The selective phosphodiesterase-5 inhibitor sildenafil has been reported to cause pulmonary vasodilatation. Objective: To evaluate the safety and effectiveness of oral sildenafil, alone and in combination with inhaled iloprost, for treatment of pulmonary hypertension. Design: Randomized, controlled, open-label trial. Setting: Intensive care unit. Patients: 30 patients with severe pulmonary arterial hypertension (n = 16), chronic thromboembolic pulmonary hypertension (n = 13), or pulmonary hypertension due to aplasia of the left pulmonary artery (n = 1), all classified as New York Heart Association class III or IV. Intervention: All patients received inhaled nitric oxide and aerosolized iloprost (inhaled dose, 2.8 µg). They were then randomly assigned to receive 12.5 mg of oral sildenafil, 50 mg of sildenafil, 12.5 mg of sildenafil plus inhaled iloprost, or 50 mg of sildenafil plus inhaled iloprost. Measurements: Systemic and pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac output, central venous pressure, peripheral arterial oxygen saturation, and arterial and mixed venous blood gases were measured during right-heart catheterization by using a Swan–Ganz catheter. Results: In rank order of pulmonary vasodilatory potency (maximum reduction of pulmonary vascular resistance and increase in cardiac index), 50 mg of sildenafil plus iloprost was most effective, followed by 12.5 mg of sildenafil plus iloprost. Iloprost alone and 50 mg of sildenafil were almost equally effective but were less potent than the combination regimens, and the least potent treatments were 12.5 mg of sildenafil and nitric oxide. In patients who received 50 mg of sildenafil plus iloprost, the maximum change in pulmonary vasodilatory potency was −44.2% (95% CI, −49.5% to −38.8%), compared with −14.1% (CI, −19.1% to −9.2%) in response to nitric oxide. With administration of 50 mg of sildenafil plus iloprost, the area under the curve for reduction in pulmonary vasodilatory resistance surpassed that of administration of 50 mg of sildenafil alone and iloprost alone combined, the vasodilatory effect lasted longer than 3 hours, and systemic arterial pressure and arterial oxygenation were maintained. No serious adverse events occurred. Conclusion: Although limited by the small sample and lack of long-term observations, the study shows that oral sildenafil is a potent pulmonary vasodilator that acts synergistically with inhaled iloprost to cause strong pulmonary vasodilatation in both severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA)
Authors: Nathan W Levin, Steven Fishbane, Francisco Valdés Cañedo, Steven Zeig, George M Nassar, John E Moran, Giuseppe Villa, Ulrich Beyer, Delphine Oguey
Journal: The Lancet (2007)
Lipid composition of the superficial stratum corneum cells of pig epidermis
Authors: G.M. GRAY, R.J. WHITE, R.H. WILLIAMS, H.J. YARDLEYMRC
Journal: British Journal of Dermatology (1982)

Stratum corneum was removed from the surface of pig skin using a wet brushing technique. The material so obtained was fractionated into cell clumps, discrete cells and fine material by differential filtration through nylon gauzes. Ceramide, cholesterol and free fatty acid accounted for about 95% of the lipid present in each fraction: phospholipid and glycolipid were not detected. Material removed by successive brushings showed no detectable differences in lipid composition.
Preventing the Activation or Cycling of the Rap1 GTPase Alters Adhesion and Cytoskeletal Dynamics and Blocks Metastatic Melanoma Cell Extravasation into the Lungs
Authors: Spencer A. Freeman, Sarah J. McLeod, Janet Dukowski, Pamela Austin, Crystal C.Y. Lee, Brandie Millen-Martin, Paul Kubes, Donna-Marie McCafferty, Michael R. Gold, Calvin D. Roskelley
Journal: Cancer Research (2010)

The Rap1 GTPase is a master regulator of cell adhesion, polarity, and migration. We show that both blocking Rap1 activation and expressing a constitutively active form of Rap1 reduced the ability of B16F1 melanoma cells to extravasate from the microvasculature and form metastatic lesions in the lungs. This correlated with a decreased ability of the tumor cells to undergo transendothelial migration (TEM) in vitro and form dynamic, F-actin-rich pseudopodia that penetrate capillary endothelial walls in vivo. Using multiple tumor cell lines, we show that the inability to form these membrane protrusions, which likely promote TEM and extravasation, can be explained by altered adhesion dynamics and impaired cell polarization that result when Rap1 activation or cycling is perturbed. Thus, targeting Rap1 could be a useful approach for reducing the metastatic dissemination of tumor cells that undergo active TEM.
Combining Transarterial Chemoembolization With Radiofrequency Ablation for Hepatocellular Carcinoma: One Step Forward?
Authors: Andrew X. Zhu, Riad Salem
Journal: Journal of Clinical Oncology (2012)

Managementofhepatocellularcarcinoma(HCC),thesixthmost common cancer and the third most common cause of cancer-related death globally, 1 continues to present many challenges. First, despite the
In utero exposure to cigarette smoking influences lung function at birth
Authors: KC Lodrup Carlsen, JJ Jaakkola, P Nafstad, KH Carlsen
Journal: European Respiratory Journal (1997)

To avoid the possible confounding effects of postnatal exposure to tobacco smoke, we investigated possible effects of uterine tobacco smoke (UTS) exposure upon infant lung function shortly after birth. Infants with no major disease, in one maternity ward in Oslo, Norway, participating in a cohort study established in 1992/1993, were included in the present study (n=803). Exposure information, assessed as maternal active and passive smoking during pregnancy and other personal and environmental factors, was obtained by questionnaire. Tidal flow-volume (TFV) loops (n=802) and compliance (Crs) and resistance (Rrs) of the respiratory system (n=663) were measured at a mean age of 2.7 days. In girls, the TFV ratio (time to reach peak expiratory flow to total expiratory time (tPEF/tE)), and Crs were significantly lower with active as well as passive maternal smoking compared to nonexposure to UTS. Respiratory rate and Rrs were not significantly influenced by UTS exposure. However, in linear regression analysis adjusted for confounding factors (including respiratory rate), tPEF/tE and Crs, but not Rrs, were related to maternal active but not passive daily smoking. One daily cigarette corresponded to a change in tPEF/tE of -0.0021 (95% confidence interval (95% CI) -0.0040 to -0.0002) and a change in Crs of -0.026 mL x cmH2O (95% CI -0.045 to -0.007 mL x cmH2O). The decrease was 0.023 and 0.29, respectively, in infants of an average smoker. Maternal smoking during pregnancy adversely affected tidal flow-volume ratios in healthy newborn babies, as well as the compliance of the respiratory system in girls, independently of the reduced body size also resulting from maternal smoking.
Whole genome sequencing of penicillin-resistant Streptococcus pneumoniae reveals mutations in penicillin-binding proteins and in a putative iron permease
Authors: Fereshteh Fani, Philippe Leprohon, Danielle Légaré, Marc Ouellette
Journal: Genome biology (2011)

Penicillin resistance in Streptococcus pneumoniae is mediated by a mosaic of genes encoding altered penicillin-binding proteins (PBPs). Nonetheless, S. pneumoniae has also developed non-PBP mechanisms implicated in penicillin resistance. In this study, whole genome sequencing of resistant organisms was used to discover mutations implicated in resistance to penicillin.