tbuckley/cabot-search huggingface dataset:
Reactive pleural inflammation caused by intratracheal instillation of killed microbes
Authors: XY Li, GM Brown, D Lamb, K Donaldson
Journal: European Respiratory Journal (1993)

To investigate the pleural leucocyte response to severe alveolar inflammation, heat-killed Corynebacterium parvum were instilled intratracheally into the lungs of PVG rats and pleural lavage was performed. Polymorphonuclear neutrophils are not normally resident in the pleural space but were found transiently after intratracheal instillation of C. parvum. Macrophages increased gradually in the pleural space following instillation, reaching a peak at day 5. The activity of plasminogen activator inhibitor in the pleural leucocyte supernatants was increased at day 1, but returned to control levels by day 5. The activities of interleukin-1 and tumour necrosis factor secreted by pleural leucocytes were decreased compared with control pleural leucocytes at day 1 and were further reduced at day 5. The analysis of particle translocation showed that intratracheally instilled C. parvum and fluorescent beads with or without C. parvum did not reach the pleural space. We hypothesize that pleural inflammation resulting from C. parvum-induced inflammation in the lung is the result of transfer of a diffusible factor from the adjacent parenchyma.
Dual targeting of the proteasome regulates survival and homing in Waldenström macroglobulinemia
Authors: Aldo M. Roccaro, Xavier Leleu, Antonio Sacco, Xiaoying Jia, Molly Melhem, Anne-Sophie Moreau, Hai T. Ngo, Judith Runnels, Abdelkareem Azab, Feda Azab, Nicholas Burwick, Mena Farag, Steven P. Treon, Michael A. Palladino, Teru Hideshima, Dharminder Chauhan, Kenneth C. Anderson, Irene M. Ghobrial
Journal: Blood (2008)
Effects of Frequent Hemodialysis on Measures of CKD Mineral and Bone Disorder
Authors: John T. Daugirdas, Glenn M. Chertow, Brett Larive, Andreas Pierratos, Tom Greene, Juan Carlos Ayus, Cynthia A. Kendrick, Sam H. James, Brent W. Miller, Gerald Schulman, Isidro B. Salusky, Alan S. Kliger
Journal: Journal of the American Society of Nephrology (2012)

More frequent hemodialysis sessions and longer session lengths may offer improved phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily and Nocturnal Trials to examine the effects of treatment assignment on predialysis serum phosphorus and on prescribed dose of phosphorus binder, expressed relative to calcium carbonate on a weight basis. In the Daily Trial, with prescribed session lengths of 1.5-2.75 hours six times per week, assignment to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95% confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a 1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose at month 12 compared with assignment to conventional hemodialysis. In the Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week, assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95% CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to conventional hemodialysis. Among patients assigned to the group receiving six sessions per week, 73% did not require phosphorus binders at month 12 compared with only 8% of patients assigned to sessions three times per week (P<0.001). At month 12, 42% of patients on nocturnal hemodialysis required the addition of phosphorus into the dialysate to prevent hypophosphatemia. Frequent hemodialysis did not have major effects on calcium or parathyroid hormone concentrations in either trial. In conclusion, frequent hemodialysis facilitates control of hyperphosphatemia and extended session lengths could allow more liberal diets and freedom from phosphorus binders.
Identification of a contractile deficit in adult cardiac myocytes expressing hypertrophic cardiomyopathy–associated mutant troponin T proteins
Authors: Elizabeth M. Rust, Faris P. Albayya, Joseph M. Metzger
Journal: Journal of Clinical Investigation (1999)

The direct effects of expressing hypertrophic cardiomyopathy–associated (HCM-associated) mutant troponin T (TnT) proteins on the force generation of single adult cardiac myocytes have not been established. Replication-defective recombinant adenovirus vectors were generated for gene transfer of HCM-associated I79N and R92Q mutant cardiac TnT cDNAs into fully differentiated adult cardiac myocytes in primary culture. We tested the hypothesis that the mutant TnT proteins would be expressed and incorporated into the cardiac sarcomere and would behave as dominant-negative proteins to directly alter calcium-activated force generation at the level of the single cardiac myocyte. Interestingly, under identical experimental conditions, the ectopic expression of the mutant TnTs was significantly less (∼8% of total) than that obtained with expression of wild-type TnT (∼35%) in the myocytes. Confocal imaging of immunolabeled TnT showed a regular periodic pattern of localization of ectopic mutant TnT that was not different than that in normal controls, suggesting that mutant TnT incorporation had no deleterious effects on sarcomeric architecture. Direct measurements of isometric force production in single cardiac myocytes demonstrated marked desensitization of submaximal calcium-activated tension, with unchanged maximum tension generation in mutant TnT–expressing myocytes compared with control myocytes. Collectively, these results demonstrate an impaired expression of the mutant protein and a disabling of cardiac contraction in the submaximal range of myoplasmic calcium concentrations. Our functional results suggest that development of new pharmacological, chemical, or genetic approaches to sensitize the thin-filament regulatory protein system could ameliorate force deficits associated with expression of I79N and R92Q in adult cardiac myocytes.
Xanthine Oxidoreductase Inhibition Causes Reverse Remodeling in Rats With Dilated Cardiomyopathy
Authors: Khalid M. Minhas, Roberto M. Saraiva, Karl H. Schuleri, Stephanie Lehrke, Meizi Zheng, Anastasios P. Saliaris, Cristine E. Berry, Konrad M. Vandegaer, Dechun Li, Joshua M. Hare
Journal: Circulation Research (2005)

Increased reactive oxygen species (ROS) generation is implicated in cardiac remodeling in heart failure (HF). As xanthine oxidoreductase (XOR) is 1 of the major sources of ROS, we tested whether XOR inhibition could improve cardiac performance and induce reverse remodeling in a model of established HF, the spontaneously hypertensive/HF (SHHF) rat. We randomized Wistar Kyoto (WKY, controls, 18 to 21 months) and SHHF (19 to 21 months) rats to oxypurinol (1 mmol/L; n=4 and n=15, respectively) or placebo (n=3 and n=10, respectively) orally for 4 weeks. At baseline, SHHF rats had decreased fractional shortening (FS) (31±3% versus 67±3% in WKY, P &lt;0.0001) and increased left-ventricular (LV) end-diastolic dimension (9.7±0.2 mm versus 7.0±0.4 mm in WKY, P &lt;0.0001). Whereas placebo and oxypurinol did not change cardiac architecture in WKY, oxypurinol attenuated decreased FS and elevated LV end-diastolic dimension, LV end-systolic dimension, and LV mass in SHHF. Increased myocyte width in SHHF was reduced by oxypurinol. Additionally, fetal gene activation, altered calcium cycling proteins, and upregulated phospho–extracellular signal–regulated kinase were restored toward normal by oxypurinol ( P &lt;0.05 versus placebo-SHHF). Importantly, SHHF rats exhibited increased XOR mRNA expression and activity, and oxypurinol treatment reduced XOR activity and superoxide production toward normal, but not expression. On the other hand, NADPH oxidase activity remained unchanged, despite elevated subunit protein abundance in treated and untreated SHHF rats. Together these data demonstrate that chronic XOR inhibition restores cardiac structure and function and offsets alterations in fetal gene expression/Ca 2+ handling pathways, supporting the idea that inhibiting XOR-derived oxidative stress substantially improves the HF phenotype.
ON SCHAMBERG'S "PECULIAR PROGRESSIVE PIGMENTARY DISEASE OF THE SKIN"
Authors: H.G. ADAMSON
Journal: British Journal of Dermatology (1919)

Journal Article ON SCHAMBERG'S “PECULIAR PROGRESSIVE PIGMENTARY DISEASE OF THE SKIN” Get access H.G. ADAMSON, M.D., F.R.C.P. H.G. ADAMSON, M.D., F.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 31, Issue 4, 1 October 1919, Pages 179–185, https://doi.org/10.1111/j.1365-2133.1919.tb09712.x Published: 01 October 1919
The Global Health System: Actors, Norms, and Expectations in Transition
Authors: Nicole A. Szlezák, Barry R. Bloom, Dean T. Jamison, Gerald T. Keusch, Catherine M. Michaud, Suerie Moon, William C. Clark
Journal: PLoS Medicine (2010)

This is the first in a series of four articles that highlight the changing nature of global health institutions.The Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health care in their societies.
A 50-kDa variant form of human surfactant protein D
Authors: RJ Mason, LD Nielsen, Y Kuroki, E Matsuura, JH Freed, JM Shannon
Journal: European Respiratory Journal (1998)

The dominant form of human surfactant protein D (SP-D) is a multimeric collagenous glycoprotein composed of monomeric subunits that have a molecular mass of 43 kDa under reducing conditions. However, in evaluating monoclonal antibodies to human SP-D, an additional monomeric subunit was identified with a reduced molecular mass of 50 kDa. This 50-kDa variant was detected in approximately half of the samples evaluated and was found in lavage fluid from normal subjects, patients with alveolar proteinosis or idiopathic pulmonary fibrosis and in amniotic fluid. This 50-kDa variant had the same amino-terminal sequence, amino acid composition and apparent size of the carboxy-terminal collagenase-resistant fragment (20 kDa) as the 43-kDa subunit. The major difference was in the amino-terminal portion of the molecule and was due to altered glycosylation, as determined by carbohydrate staining, chemical deglycosylation, treatment with N-glycanase and neuraminidase and reduced signals for threonine at positions 5, 9 and 10 during amino-terminal sequencing. After gel filtration chromatography, the 50-kDa form was not present in the high molecular weight fraction, which is commonly used in purification of SP-D, but was found only in the smaller molecular weight fraction of monomers and trimers of SP-D. In conclusion, the 50 kDa-form of surfactant protein D is produced by post-translational glycosylation and does not form higher ordered oligomers, but its precise physiological function remains to be determined.
Endoscopic Sclerotherapy Compared with Percutaneous Transjugular Intrahepatic Portosystemic Shunt after Initial Sclerotherapy in Patients with Acute Variceal Hemorrhage
Authors: John P. Cello
Journal: Annals of Internal Medicine (1997)

Background: Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency. Objective: To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices. Design: Randomized, controlled clinical trial. Setting: Three teaching hospitals. Patients: 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS. Intervention: Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein. Measurements: Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs. Results: Mean follow-up (± SE) was 567 ± 104 days in the sclerotherapy group and 575 ± 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]). Conclusions: In obliterating varices and reducing rebleeding events from esophageal varices, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant.
Effective Inhibition of the Epidermal Growth Factor/Epidermal Growth Factor Receptor Binding by Anti–Epidermal Growth Factor Antibodies Is Related to Better Survival in Advanced Non–Small-Cell Lung Cancer Patients Treated with the Epidermal Growth Factor Cancer Vaccine
Authors: Beatriz García, Elia Neninger, Ana de la Torre, Idrissa Leonard, Rocío Martínez, Carmen Viada, Gisela González, Zaima Mazorra, Agustín Lage, Tania Crombet
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Epidermal growth factor (EGF) might be a suitable immunotherapeutic target in non–small-cell lung cancer (NSCLC). Our approach consists of active immunotherapy with EGF. The aim of the study is to characterize the humoral response and its effects on signal transduction in relation with the clinical outcome. Experimental Design: Eighty NSCLC patients treated with first-line chemotherapy were randomized to receive the EGF vaccine or supportive care. EGF concentration in sera, anti-EGF antibodies and their capacity to inhibit the binding between EGF/EGF receptor (EGFR), and the EGFR phosphorylation were measured. Results: Seventy-three percent of vaccinated patients developed a good antibody response, whereas none of the controls did. In good antibody-responder patients, self EGF in sera was significantly reduced. In 58% of vaccinated patients, the post-immune sera inhibited EGF/EGFR binding; in the control group, no inhibition occurred. Post-immune sera inhibited the EGFR phosphorylation whereas sera from control patients did not have this capacity. Good antibody-responder patients younger than 60 years had a significantly better survival. A high correlation between anti-EGF antibody titers, EGFR phosphorylation inhibition, and EGF/EGFR binding inhibition was found. There was a significantly better survival for vaccinated patients that showed the higher capacity to inhibit EGF/EGFR binding and for those who showed an immunodominance by the central region of EGF molecule. Conclusions: Immunization with the EGF vaccine induced neutralizing anti-EGF antibodies capable of inhibiting EGFR phosphorylation. There was a significant positive correlation between antibody titers, EGF/EGFR binding inhibition, immunodominance of anti-EGF antibodies, and survival in advanced NSCLC patients.
More Evidence to Support “Outsourcing” of Diabetes Care
Authors: Mayer B. Davidson
Journal: Diabetes Care (2004)

In the January issue of Diabetes Care , there were three articles that provided additional support for “outsourcing” diabetes care to improve outcome measures (1). In the first (2), individual, self-planned, intensive programs were established in 19 community health centers. Most health centers performed at least 30 different interventions during the year. The most common ones were to 1 ) provide a diabetes flow sheet (100%), 2 ) collaborate with community organizations that represented the health center’s population (89%), 3 ) provide a patient self-management or goal sheet to track his or her progress (63%), 4 ) redesign the delivery system to include group cluster visits (63%), and 5 ) use computer information systems to follow-up on examination and laboratory data (37%). A comparison of the results in 989 …
Transcriptional Regulation of a Mesangium-Predominant Gene, Megsin
Authors: Reiko Inagi, Toshio Miyata, Masaomi Nangaku, Hiroshi Ueyama, Ken-ichi Takeyama, Shigeaki Kato, Kiyoshi Kurokawa
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The cDNA of a new human mesangium-predominant gene, megsin, a novel member of the serpin superfamily, has recently been cloned. This study investigates the regulatory mechanisms of megsin gene expression. A genomic clone of the human megsin gene was obtained by screening bacterial artificial chromosome (BAC) library with the megsin cDNA. The analysis for exon-intron junctions of megsin genomic DNA demonstrated that the gene contained 8 exons and 7 introns, spanned 20 kbp, and that the genomic structure of the serpin superfamily was highly conserved. Fluorescence <i>in situ</i> hybridization (FISH) revealed that the megsin gene is localized in chromosome 18q21.3, close to the other serpin genes. The transcriptional start site, located by primer extension analysis, was 391 bp upstream from the start codon. The sequence and reporter analyses on 4021-bp-long 5′-flanking region of megsin gene demonstrated a consensus promoter segment within this region and a relatively strong promoter activity in human mesangial cells and A431, a human tumor cell line recently reported to express a novel serpin identical with megsin. Moreover, this study utilized site-directed and deletion mutagenesis analyses, and electrophoretic mobility shift assay identified one positive regulatory motif, an incomplete activator protein-1 (AP-1) binding motif (CTGATTCAC) within the −120 to −112 region. This cis-acting element in the 5′-flanking region of megsin is involved in the activation of the megsin gene in mesangial cells.
Ethnicity and Peripheral Arterial Disease
Authors: Michael H. Criqui, Veronica Vargas, Julie O. Denenberg, Elena Ho, Matthew Allison, Robert D. Langer, Anthony Gamst, Warner P. Bundens, Arnost Fronek
Journal: Circulation (2005)

Background— Previous studies have indicated higher rates of peripheral arterial disease (PAD) in blacks than in non-Hispanic whites (NHWs), with limited information available for Hispanics and Asians. The reason for the PAD excess in blacks is unclear. Methods and Results— Ethnic-specific PAD prevalence rates were determined in a randomly selected defined population that included 4 ethnic groups; NHWs, blacks, Hispanics, and Asians. A total of 2343 participants aged 29 to 91 years were evaluated. There were 104 cases of PAD (4.4%). In weighted logistic models with NHWs as the reference group and containing demographic factors only, blacks had a higher PAD prevalence than NHWs (OR=2.30, P &lt;0.024), whereas PAD rates in Hispanics and Asians, although somewhat lower, were not significantly different from NHWs. Blacks had significantly more diabetes and hypertension than NHWs and a significantly higher body mass index. Inclusion of these variables and other PAD risk factors in the model did not change the effect size for black ethnicity (OR=2.34, P =0.048). A model containing interaction terms for black ethnicity and each of the other risk factors revealed no significant interaction terms, which indicates no evidence that blacks were more “susceptible” than NHWs to cardiovascular disease risk factors. Conclusions— Black ethnicity was a strong and independent risk factor for PAD, which was not explained by higher levels of diabetes, hypertension, and body mass index. There was no evidence of a greater susceptibility of blacks to cardiovascular disease risk factors as a reason for their higher PAD prevalence. Thus, the excess risk of PAD in blacks remains unexplained and requires further study.
Replicability and Recurrence in the Experimental Evolution of a Group I Ribozyme
Authors: Martin M. Hanczyc, Robert L. Dorit
Journal: Molecular Biology and Evolution (2000)

In order to explore the variety of possible responses available to a ribozyme population evolving a novel phenotype, five Tetrahymena thermophila group I intron ribozyme pools were evolved in parallel for cleavage of a DNA oligonucleotide. These ribozyme populations were propagated under identical conditions and characterized when they reached apparent phenotypic plateaus; the populations that reached the highest plateau showed a near 100-fold improvement in DNA cleavage activity. A detailed characterization of the evolved response in these populations reveals at least two distinct phenotypic trajectories emerging as a result of the imposed selection. Not only do these distinct solutions exhibit differential DNA cleavage activity, but they also exhibit a very different correlation with a related, but unselected, phenotype: RNA cleavage activity. In turn, each of these trajectories is underwritten by differing genotypic profiles. This study underscores the complex network of possible trajectories through sequence space available to an evolving population and uncovers the diversity of solutions that result when the process of experimental evolution is repeated multiple times in a simple, engineered system.
Haptic perception is a dynamic system of cutaneous, proprioceptive, and motor components
Authors: David Travieso, M. Pilar Aivar, Antoni Gomila
Journal: Behavioral and Brain Sciences (2007)

Abstract A general shortcoming of the localist, decompositional, approach to neuroscientific explanation that the target article exemplifies, is that it is incomplete unless supplemented with an account of how the hypothesized subsystems integrate in the normal case. Besides, a number of studies that show that object recognition is proprioception dependent and that cutaneous information affects motor performance make the existence of the proposed subsystems doubtful.
ABVD Alone versus Radiation-Based Therapy in Limited-Stage Hodgkin's Lymphoma
Authors: Ralph M. Meyer, Mary K. Gospodarowicz, Joseph M. Connors, Robert G. Pearcey, Woodrow A. Wells, Jane N. Winter, Sandra J. Horning, A. Rashid Dar, Chaim Shustik, Douglas A. Stewart, Michael Crump, Marina S. Djurfeldt, Bingshu E. Chen, Lois E. Shepherd
Journal: New England Journal of Medicine (2011)

Chemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated with late treatment-related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths.