tbuckley/cabot-search huggingface dataset:
The Assessment of SpondyloArthritis international Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general
Authors: M. Rudwaleit, D. van der Heijde, R. Landewe, N. Akkoc, J. Brandt, C. T. Chou, M. Dougados, F. Huang, J. Gu, Y. Kirazli, F. Van den Bosch, I. Olivieri, E. Roussou, S. Scarpato, I. J. Sorensen, R. Valle-Onate, U. Weber, J. Wei, J. Sieper
Journal: Annals of the Rheumatic Diseases (2010)

Distinguishing true cellulitis from its many imitators is challenging but critical if we are to avoid unnecessary use of antibiotics and delays in treatment. Common imitators of cellulitis are stasis dermatitis, lipodermatosclerosis, contact dermatitis, lymphedema, eosinophilic cellulitis, and papular urticaria. Specific criteria do not exist for the diagnosis of cellulitis, but the alert physician can find clues in the history and physical examination that point toward cellulitis.
Biomaterial Strategies for Immunomodulation
Authors: Nathan A. Hotaling, Li Tang, Darrell J. Irvine, Julia E. Babensee
Journal: Annual Review of Biomedical Engineering (2015)

Strategies to enhance, suppress, or qualitatively shape the immune response are of importance for diverse biomedical applications, such as the development of new vaccines, treatments for autoimmune diseases and allergies, strategies for regenerative medicine, and immunotherapies for cancer. However, the intricate cellular and molecular signals regulating the immune system are major hurdles to predictably manipulating the immune response and developing safe and effective therapies. To meet this challenge, biomaterials are being developed that control how, where, and when immune cells are stimulated in vivo, and that can finely control their differentiation in vitro. We review recent advances in the field of biomaterials for immunomodulation, focusing particularly on designing biomaterials to provide controlled immunostimulation, targeting drugs and vaccines to lymphoid organs, and serving as scaffolds to organize immune cells and emulate lymphoid tissues. These ongoing efforts highlight the many ways in which biomaterials can be brought to bear to engineer the immune system.
Airway goblet cell mucin: its structure and regulation of secretion
Authors: KC Kim, K McCracken, BC Lee, CY Shin, MJ Jo, CJ Lee, KH Ko
Journal: European Respiratory Journal (1997)

Mucociliary clearance is a major function of the airway epithelium. This important function depends both on the physicochemical properties of the airway mucus and on the activity of the cilia. The former, in turn, is dependent mainly on the quality and quantity of mucous glycoproteins or mucins, which are produced by two different cell types, namely, goblet cells of the epithelium and mucous cells of the submucosal gland. Neither the structural nor the functional differences of mucins produced by these two cell types are yet known. The availability of primary airway epithelial cell culture systems, however, has made it possible to study the structure and regulation of airway goblet cells to some extent. The epithelial mucins are extremely hydrophobic and are associated with various macromolecules, the quality and quantity of which may also affect the physicochemical properties of the mucus. Secretion of epithelial mucins is stimulated by various factors, including a number of inflammatory agents. The recent progress in mucin molecular biological research will allow us to identify different mucin core proteins produced by those different cell types, and, hopefully, the differential functions of these mucins in health and disease.
Induction of autophagy, a promising approach for treating liver injury
Authors: Wen-Xing Ding
Journal: Hepatology (2013)

Recent investigations have demonstrated a complex interrelationship between autophagy and cell death. A common mechanism of cell death in liver injury is tumor necrosis factor (TNF) cytotoxicity. To better delineate the in vivo function of autophagy in cell death, we examined the role of autophagy in TNF-induced hepatic injury. Atg7Δhep mice with a hepatocyte-specific knockout of the autophagy gene atg7 were generated and cotreated with D-galactosamine (GalN) and lipopolysaccharide (LPS). GalN/LPS-treated Atg7Δhep mice had increased serum alanine aminotransferase levels, histological injury, numbers of TUNEL (terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling)-positive cells and mortality as compared with littermate controls. Loss of hepatocyte autophagy similarly sensitized to GalN/TNF liver injury. GalN/LPS injury in knockout animals did not result from altered production of TNF or other cytokines. Atg7Δhep mice had accelerated activation of the mitochondrial death pathway and caspase-3 and −7 cleavage. Increased cell death did not occur from direct mitochondrial toxicity or a lack of mitophagy, but rather from increased activation of initiator caspase-8 causing Bid cleavage. GalN blocked LPS induction of hepatic autophagy, and increased autophagy from beclin 1 overexpression prevented GalN/LPS injury. Autophagy, therefore, mediates cellular resistance to TNF toxicity in vivo by blocking activation of caspase-8 and the mitochondrial death pathway, suggesting that autophagy is a therapeutic target in TNF-dependent tissue injury.
Abstract 4969: Hypo adenosine-to-inosine editing of microRNA-455 promotes melanoma metastasis
Authors: Einav Shoshan, Aaron Mobley, Russell Braeuer, Takafumi Kamiya, Li Huang, Mayra Vasquez, Lee H. Jeong, Sun Jim kim, George Calin, Anil Sood, Gal Markel, Isaiah Fidler, Menashe Bar-Eli
Journal: Cancer Research (2014)

Abstract We have previously reported that activation of CREB in metastatic melanoma cells resulted in reduced expression of adenosine deaminase acting on RNA 1 (ADAR1), an RNA editing enzyme. We hypothesized that disruption of A-to-I editing of microRNAs alters expression of genes regulating melanoma progression. By sequencing miRs in primary vs. metastatic melanoma cells, we show that the overall microRNA editing frequencies were reduced in metastatic melanoma cells. Specifically, we found A-to-I editing in two sites of miR-455 in non-metastatic melanoma cells with accumulation of unedited miR-455 in metastatic melanoma cells. Using two animal models, we demonstrated that the unedited miR-455 promoted melanoma growth and metastasis, while the edited form suppressed these features. Unedited miR-455 promotes melanoma progression via suppression of the tumor suppressor cytoplasmic polyadenilation element binding protein (CPEB1). Thus, miR-455 A-to-I editing alters the selection of its target genes and directs its function to inhibit melanoma growth and metastasis. Taken together, our results provide a previously undescribed mechanism (microRNA editing) contributing to melanoma progression. Citation Format: Einav Shoshan, Aaron Mobley, Russell Braeuer, Takafumi Kamiya, Li Huang, Mayra Vasquez, Lee Ho Jeong, Sun Jim kim, George Calin, Anil Sood, Gal Markel, Isaiah Fidler, Menashe Bar-Eli. Hypo adenosine-to-inosine editing of microRNA-455 promotes melanoma metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4969. doi:10.1158/1538-7445.AM2014-4969
Reliable High-Throughput Genotyping and Loss-of-Heterozygosity Detection in Formalin-Fixed, Paraffin-Embedded Tumors Using Single Nucleotide Polymorphism Arrays
Authors: Esther H. Lips, Jan Willem F. Dierssen, Ronald van Eijk, Jan Oosting, Paul H.C. Eilers, Rob A.E.M. Tollenaar, Eelco J. de Graaf, Ruben van't Slot, Cisca Wijmenga, Hans Morreau, Tom van Wezel
Journal: Cancer Research (2005)

Abstract Most human cancers show genetic instabilities leading to allelic imbalances, including loss of heterozygosity (LOH). Single nucleotide polymorphism (SNP) arrays can be used to detect LOH. Currently, these arrays require intact genomic DNA as obtained from frozen tissue; however, for most cancer cases, only low-quality DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is available. In this study, we tested Illumina BeadArrays to genotype FFPE tissue and detect LOH/allelic imbalances in matched colorectal tumor and normal tissue. Genotypes were compared between leukocyte and FFPE normal tissue as well as between frozen and FFPE tumor tissue. Identical genotypes and LOH profiles were obtained from normal and tumor isolates. LOH was mainly observed on chromosomes 4, 5q, 12q, 14q, 15q, 17p, 18, and 20p, which are commonly detected regions in colorectal cancer. LOH profiles of the BeadArrays were compared with profiles obtained by Affymetrix GeneChip 10K arrays, showing identical LOH patterns. These data show that genome-wide genotyping of FFPE tissue with the BeadArray gives reliable results and is a powerful technique for LOH analysis.
Fatty Liver, Insulin Resistance, and Features of Metabolic Syndrome
Authors: Ki-Chul Sung, Sarah H. Wild, Hyon Joo Kwag, Christopher D. Byrne
Journal: Diabetes Care (2012)

Nonalcoholic fatty liver disease (NAFLD) coexists with insulin resistance (IR), but it is uncertain whether NAFLD and IR contribute independently to atherosclerosis. We tested whether fatty liver, IR, and metabolic syndrome (MetS) features (waist, glucose, triglyceride, HDL cholesterol [HDL-C], and blood pressure) were associated with a marker of atherosclerosis (coronary artery calcium [CAC] score >0), independently of cardiovascular risk factors and cardiovascular disease (CVD).
RESPIRATORY RESPONSE OF PSYCHONEUROTIC PATIENTS TO IDEATIONAL AND TO SENSORY STIMULI
Authors: JACOB E. FINESINGER, SARAH G. MAZICK
Journal: American Journal of Psychiatry (1940)

1. A series of experiments was carried out on a group of psychoneurotic patients and of normal controls, in which was studied the effect on the respiration of the administration of a painful stimulus and of its subsequent recall. The changes in minute respiratory volume are reported as an index of respiratory response. 2. Of 32 experiments on 27 psychoneurotic patients (Group I) with diagnoses of hysteria, anxiety neurosis and phobia, an increase in minute respiratory volume appeared during the painful period in 79 per cent of the experiments, and during the period of recall in 77 per cent of the experiments. The increase obtained for both periods, especially for the pain period, was on the average significantly greater than the variability of this group of patients as shown in a preliminary period. 3. Of 14 similar experiments on 12 psychoneurotic patients (Group II) with diagnoses of hypochondriasis, compulsion neurosis, reactive depression, questionable schizophrenia, the changes in minute respiratory volume during the periods of pain and recall were not significantly greater than could be expected from the variability of this group during the preliminary period. Furthermore there were almost as many cases showing a decrease as showing an increase. 4. In 24 similar experiments on 15 control subjects, an increase for the periods of pain and recall appeared in about 80 per cent of the cases. The increase found was greater than the variability of this group during the preliminary period. 5. The response of the three groups of subjects to a painful stimulus and its recall appeared to be closely parallel to the response to an unpleasant ideational stimulus as previously reported.
Treatment-Specific Risks of Second Malignancies and Cardiovascular Disease in 5-Year Survivors of Testicular Cancer
Authors: Alexandra W. van den Belt-Dusebout, Ronald de Wit, Jourik A. Gietema, Simon Horenblas, Marieke W.J. Louwman, Jacques G. Ribot, Harald J. Hoekstra, Gabey M. Ouwens, Berthe M.P. Aleman, Flora E. van Leeuwen
Journal: Journal of Clinical Oncology (2007)

Purpose To compare radiotherapy and chemotherapy effects on long-term risks of second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) in testicular cancer (TC) survivors. Patients and Methods In our nationwide cohort comprising 2,707 5-year TC survivors, incidences of SMNs and CVDs were compared with general-population rates by calculating standardized incidence ratios (SIRs) and absolute excess risks (AERs). Treatment effects on risks of SMN and CVD were quantified in multivariable Cox regression and competing risks analyses. Results After a median follow-up time of 17.6 years, 270 TC survivors developed SMNs. The SIR of SMN overall was 1.7 (95% CI, 1.5 to 1.9), with an AER of 32.3 excess occurrences per 10,000 person-years. SMN risk was 2.6-fold (95% CI, 1.7- to 4.0-fold) increased after subdiaphragmatic radiotherapy and 2.1-fold (95% CI, 1.4- to 3.1-fold) increased after chemotherapy, compared with surgery only. Subdiaphragmatic radiotherapy increased the risk of a major late complication (SMN or CVD) 1.8-fold (95% CI, 1.3- to 2.4-fold), chemotherapy increased the risk of a major late complication 1.9-fold (95% CI, 1.4- to 2.5-fold), and smoking increased the risk of a major late complication 1.7-fold (95% CI, 1.4- to 2.1-fold), compared with surgery only. The median survival time was 1.4 years after SMN and 4.7 years after CVD. Conclusion Radiotherapy and chemotherapy increased the risk of developing SMN or CVD to a similar extent as smoking. Subdiaphragmatic radiotherapy strongly increases the risk of SMNs but not of CVD, whereas chemotherapy increases the risks of both SMNs and CVDs. Prolonged follow-up after chemotherapy is needed to reliably compare the late complications of radiotherapy and chemotherapy after 20 years.
Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA
Authors: S.M. Swain, J. Baselga, D. Miles, Y.-H. Im, C. Quah, L.F. Lee, J. Cortés
Journal: Annals of Oncology (2014)

BackgroundResults from the phase III trial CLEOPATRA in human epidermal growth factor receptor 2-positive first-line metastatic breast cancer demonstrated significant improvements in progression-free and overall survival with pertuzumab, trastuzumab, and docetaxel over placebo, trastuzumab, and docetaxel. We carried out exploratory analyses of the incidence and time to development of central nervous system (CNS) metastases in patients from CLEOPATRA.Patients and methodsPatients received pertuzumab/placebo: 840 mg in cycle 1, then 420 mg; trastuzumab: 8 mg/kg in cycle 1, then 6 mg/kg; docetaxel: initiated at 75 mg/m2. Study drugs were administered i.v. every 3 weeks. The log-rank test was used for between-arm comparisons of time to CNS metastases as first site of disease progression and overall survival in patients with CNS metastases as first site of disease progression. The Kaplan–Meier approach was used to estimate median time to CNS metastases as first site of disease progression and median overall survival.ResultsThe incidence of CNS metastases as first site of disease progression was similar between arms; placebo arm: 51 of 406 (12.6%), pertuzumab arm: 55 of 402 (13.7%). Median time to development of CNS metastases as first site of disease progression was 11.9 months in the placebo arm and 15.0 months in the pertuzumab arm; hazard ratio (HR) = 0.58, 95% confidence interval (CI) 0.39–0.85, P = 0.0049. Overall survival in patients who developed CNS metastases as first site of disease progression showed a trend in favor of pertuzumab, trastuzumab, and docetaxel; HR = 0.66, 95% CI 0.39–1.11. Median overall survival was 26.3 versus 34.4 months in the placebo and pertuzumab arms, respectively. Treatment comparison of the survival curves was not statistically significant for the log-rank test (P = 0.1139), but significant for the Wilcoxon test (P = 0.0449).ConclusionsWhile the incidence of CNS metastases was similar between arms, our results suggest that pertuzumab, trastuzumab, and docetaxel delays the onset of CNS disease compared with placebo, trastuzumab, and docetaxel.ClinicalTrials.govNCT00567190.
FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting
Authors: Mara Riminucci, Michael T. Collins, Neal S. Fedarko, Natasha Cherman, Alessandro Corsi, Kenneth E. White, Steven Waguespack, Anurag Gupta, Tamara Hannon, Michael J. Econs, Paolo Bianco, Pamela Gehron Robey
Journal: Journal of Clinical Investigation (2003)

FGF-23, a novel member of the FGF family, is the product of the gene mutated in autosomal dominant hypophosphatemic rickets (ADHR). FGF-23 has been proposed as a circulating factor causing renal phosphate wasting not only in ADHR (as a result of inadequate degradation), but also in tumor-induced osteomalacia (as a result of excess synthesis by tumor cells). Renal phosphate wasting occurs in approximately 50% of patients with McCune-Albright syndrome (MAS) and fibrous dysplasia of bone (FD), which result from postzygotic mutations of the GNAS1 gene. We found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro. In situ hybridization analysis of FGF-23 mRNA expression identified “fibrous” cells, osteogenic cells, and cells associated with microvascular walls as specific cellular sources of FGF-23 in FD. Serum levels of FGF-23 were increased in FD/MAS patients compared with normal age-matched controls and significantly higher in FD/MAS patients with renal phosphate wasting compared with those without, and correlated with disease burden bone turnover markers commonly used to assess disease activity. Production of FGF-23 by FD tissue may play an important role in the renal phosphate–wasting syndrome associated with FD/MAS.
Hepatitis C-associated hepatocellular carcinoma
Authors: Fuad Hasan, Lennox J. Jeffers, Maria De Medina, Rajender K. Reddy, Talley Parker, Eugene R. Schiff, Michael Houghton, Quilim Choo, George Kuo
Journal: Hepatology (1990)

In the United States, a large percentage of patients with hepatocellular carcinoma are serologically negative for hepatitis B. We conducted a retrospective study to determine the prevalence of hepatitis C antibody in the sera of 59 patients with hepatocellular carcinoma who were HBsAg-negative and had no evidence of alcoholic liver disease, primary biliary cirrhosis, autoimmune hepatitis, hemochromatosis or alpha 1-antitrypsin deficiency. Twenty patients (34%) were hepatitis C antibody-positive and hepatitis B core antibody-negative. All twenty patients had underlying cirrhosis, and seven (35%) had histories of transfusions. Eleven (19%) additional patients were also hepatitis C antibody-positive but were hepatitis B core antibody-positive as well. Twenty-one (36%) patients were both hepatitis C antibody- and hepatitis B core antibody-negative and seven (12%) were hepatitis C antibody-negative but hepatitis B core antibody-positive. The prevalence of hepatitis C antibody was also determined among three other population groups serving as controls and found to be 14% in 28 HbsAg-positive patients with hepatocellular carcinoma, 44% in 76 patients with cryptogenic cirrhosis and 0.5% in 200 consecutive volunteer blood donors. We conclude that hepatitis C antibody is prevalent among patients with hepatocellular carcinoma and may therefore be a common causative agent of this disease. A significant number of patients with and without cirrhosis, negative for hepatitis C antibody and hepatitis B core antibody, remain without a discernible cause for this malignancy. Perhaps a second- or third-generation test will detect hepatitis C antibody in some of these patients.
Interrelationships of Cardiac Output, Blood Pressure, and Peripheral Resistance during Normal Respiration in Normotensive and Hypertensive Individuals
Authors: ARNOLD H. WILLIAMS, ARTHUR L. GROPPER
Journal: Circulation (1951)

The effects of normal respiration upon the heart, blood pressure, and peripheral circulation were studied in normotensive and hypertensive subjects. Changes of right and left ventricular output were measured by the ballistocardiogram and the pressure-pulse method of Remington, peripheral blood flow by plethysmographs. The central and peripheral changes were interrelated and evidence is presented that the latter are chiefly due to the effects of intrathoracic pressure upon cardiac filling.
Expression of a Peroxisome Proliferator-Activated Receptor γ1 Splice Variant that Was Identified in Human Lung Cancers Suppresses Cell Death Induced by Cisplatin and Oxidative Stress
Authors: Hyo Jung Kim, Jin-Yong Hwang, Hyun Jun Kim, Wan Sung Choi, Jae Heun Lee, Hye Jung Kim, Ki Churl Chang, Toru Nishinaka, Chihiro Yabe-Nishimura, Han Geuk Seo
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The activation of peroxisome proliferator-activated receptor γ (PPARγ) has been implicated in the inhibition of tumor progression in lung cancers through the induction of differentiation and apoptosis. Recently, we identified a novel splice variant of human PPARγ1 (hPPARγ1) that exhibits dominant-negative activity in human tumor-derived cell lines. This study aimed to examine the expression and pathophysiologic roles of a truncated splice variant of hPPARγ1 (hPPARγ1tr) in primary human lung cancer tissues. Experimental Design: The expression and localization of hPPARγ1tr was surveyed in human primary lung cancer tissues using immunohistochemistry and Western blot analysis. Using transfectants stably expressing wild-type hPPARγ1 (hPPARγ1wt) and hPPARγ1tr, we also analyzed the pathophysiologic roles of hPPARγ1tr. Results: We showed that PPARγ is expressed predominantly in the nucleus of nontumorous tissues, whereas it is present in both the nucleus and the cytoplasm of tumorous tissues in squamous cell carcinoma (SCC) of the lung. Western blot analysis confirmed the presence of PPARγ1tr in primary lung SCC tissue but not in nontumorous tissue. Expression of PPARγ1tr in Chinese hamster ovary cells attenuated their susceptibility to cell death induced by oxidative stress or cisplatin, whereas their susceptibility was completely recovered by down-regulation of PPARγ1tr with small interfering RNA. Conclusions: hPPARγ1tr is expressed strongly in tumorous tissues of primary human lung SCC and its overexpression renders transfected cells more resistant to chemotherapeutic drug- and chemical-induced cell death. These data suggest that the decreased drug sensitivity of PPARγ1tr-expressing cells may be associated with increased tumor aggressiveness and poor clinical prognosis of patients.
Relationship between posterior pharyngeal pouch and hiatus hernia
Authors: T. B. Smiley, P. K. Caves, D. C. Porter
Journal: Thorax (1970)

The formation of posterior pharyngeal pouches is generally attributed to dysfunction of the cricopharyngeal sphincter. The reason for this dysfunction and its exact nature have not been established. Observations in the Royal Victoria Hospital, Belfast, suggested that an association exists between pharyngeal pouch and hiatus hernia. Barium studies performed in patients with a pharyngeal pouch using a described technique demonstrated the presence of a hiatus hernia in 32 out of 34 patients. Illustrative case histories and a review of published work on cricopharyngeal function are provided to support our conclusions that gastro-oesophageal reflux is the primary factor leading to cricopharyngeal dysfunction, with the formation of a pharyngeal pouch in some cases. Several possible criticisms of this theory are discussed and the need for further investigation in patients with a pharyngeal pouch is emphasized. The management of patients with a pharyngeal pouch and hiatus hernia is briefly outlined.