tbuckley/cabot-search huggingface dataset:
Identification of HLA-DR1 beta chain residues critical for binding staphylococcal enterotoxins A and E.
Authors: D R Karp, E O Long
Journal: The Journal of Experimental Medicine (1992)

Superantigens are thought to make external contacts with major histocompatibility complex (MHC) class II molecules and with the V beta portion of a T cell antigen receptor (TCR), thereby stimulating entire families of T cells. The precise mapping of superantigen binding sites on class II molecules may provide valuable information on how TCR and MHC molecules interact. Two bacterial superantigens, staphylococcal enterotoxins A and E (SEA/SEE) bind well to most HLA-DR alleles, but poorly to HLA-DRw53. The sequences responsible for this binding were localized to the putative alpha helix of the DR beta chain by measuring toxin binding to a panel of chimeric class II molecules expressed on transfected cells. Binding of SEA/SEE to the DRw14 (Dw9) molecule suggested that the conserved histidine 81 in the beta chain of most DR molecules was important, whereas the tyrosine 81 in the DRw53 beta chain was detrimental for high-affinity binding. To prove this, reciprocal point mutations were introduced in the DR1 and DRw53 beta chains. Mutation of histidine 81 in the DR1 beta chain to tyrosine reduced SEA/SEE binding, but did not prevent recognition of two DR1-restricted peptides by six of eight antigen-specific T cell lines. Conversely, introduction to histidine at position 81 in the DRw53 beta chain restored normal levels of SEA/SEE binding. These data suggest that a binding site of SEA and SEE lies on the outer face of the beta chain alpha helix, pointing away from the antigen-binding groove.
Results of Initial Low-Dose Computed Tomographic Screening for Lung Cancer
Authors: Timothy R Church, William C Black, Denise R Aberle, Christine D Berg, Kathy L Clingan, Fenghai Duan, Richard M Fagerstrom, Ilana F Gareen, David S Gierada, Gordon C Jones, Irene Mahon, Pamela M Marcus, JoRean D Sicks, Amanda Jain, Sarah Baum
Journal: New England Journal of Medicine (2013)

Lung cancer is the largest contributor to mortality from cancer. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) rather than with chest radiography reduced mortality from lung cancer. We describe the screening, diagnosis, and limited treatment results from the initial round of screening in the NLST to inform and improve lung-cancer-screening programs.
Human angiogenic cell precursors restore function in the infarcted rat heart: A comparison of cell delivery routes
Authors: Zhuo Sun, Jun Wu, Hiroko Fujii, Jiang Wu, Shu‐Hong Li, Svetlana Porozov, Adina Belleli, Valentin Fulga, Yael Porat, Ren‐Ke Li
Journal: European Journal of Heart Failure (2008)
Overexpression of the Cellular DEK Protein Promotes Epithelial Transformation <i>In vitro</i> and <i>In vivo</i>
Authors: Trisha M. Wise-Draper, Rachael A. Mintz-Cole, Teresa A. Morris, David S. Simpson, Kathryn A. Wikenheiser-Brokamp, Mark A. Currier, Timothy P. Cripe, Gerard C. Grosveld, Susanne I. Wells
Journal: Cancer Research (2009)

High levels of expression of the human DEK gene have been correlated with numerous human malignancies. Intracellular DEK functions have been described in vitro and include DNA supercoiling, DNA replication, RNA splicing, and transcription. We have shown that DEK also suppresses cellular senescence, apoptosis, and differentiation, thus promoting cell growth and survival in monolayer and organotypic epithelial raft models. Such functions are likely to contribute to cancer, but direct evidence to implicate DEK as an oncogene has remained elusive. Here, we show that in line with an early role in tumorigenesis, murine papilloma formation in a classical chemical carcinogenesis model was reduced in DEK knockout mice. Additionally, human papillomavirus E6/E7, hRas, and DEK cooperated in the transformation of keratinocytes in soft agar and xenograft establishment, thus also implicating DEK in tumor promotion at later stages. Finally, adenoviral DEK depletion via short hairpin RNA expression resulted in cell death in human tumor cells in vitro and in vivo, but did not significantly affect differentiated epithelial cells. Taken together, our data uncover oncogenic DEK activities as postulated from its frequent up-regulation in human malignancies, and suggest that the targeted suppression of DEK may become a strategic approach to the treatment of cancer.
Efficacy and Safety of Besifloxacin Ophthalmic Suspension 0.6% Compared with Moxifloxacin Ophthalmic Solution 0.5% for Treating Bacterial Conjunctivitis
Authors: Marguerite B. McDonald, Eugene E. Protzko, Lynne S. Brunner, Timothy W. Morris, Wolfgang Haas, Michael R. Paterno, Timothy L. Comstock, Dale W. Usner
Journal: Ophthalmology (2009)
Primary Pulmonary Hypertension: An Unusual Case Associated with Extrahepatic Portal Hypertension
Authors: Mark D. Cohen, Lewis J. Rubin, Wayne E. Taylor, Jennifer A. Cuthbert
Journal: Hepatology (1983)

A patient with both extrahepatic portal hypertension and primary pulmonary hypertension is reported. The pulmonary hypertension developed without a surgical portal-systemic shunt, and at autopsy there was no evidence of a large spontaneous shunt. This association of pulmonary arterial hypertension and portal venous hypertension without either intrinsic liver disease or a large portal-systemic anastomosis has not been reported previously. Our case supports the concept that portal hypertension with its attendant portal-systemic collateral circulation may be the major predisposing cause of pulmonary hypertension both in intrinsic liver disease and extrahepatic portal vein obstruction.
Human Epidermal Growth Factor Receptor 2 Regulates Angiopoietin-2 Expression in Breast Cancer via AKT and Mitogen-Activated Protein Kinase Pathways
Authors: Guilian Niu, W. Bradford Carter
Journal: Cancer Research (2007)

Abstract Abnormal activation of human epidermal growth factor receptor 2 (HER2; ErbB-2) in breast tumors results in increased metastasis and angiogenesis, as well as reduced survival. Here, we show that angiopoietin-2 (Ang-2) expression correlates with HER2 activity in human breast cancer cell lines. Inhibiting HER2 activity with anti-HER2 monoclonal antibody trastuzumab (Herceptin) or HER2 short interfering RNA in tumor cells down-regulates Ang-2 expression. Consistent with the important roles of AKT and mitogen-activated protein kinase in the HER2 signaling pathway, AKT and ERK mitogen-activated protein kinase (MAPK) kinase activity is necessary for Ang-2 up-regulation by HER2. Moreover, overexpression of HER2 protein up-regulates Ang-2 expression. Heregulin-β1–induced Ang-2 up-regulation is abrogated when AKT and ERK kinase activity are blocked. Immunohistochemical analysis of HER2 and Ang-2 proteins in human breast carcinomas shows that Ang-2 expression in breast cancer correlates with HER2 expression. These studies provide evidence that the Ang-2 gene is regulated by HER2 activity in breast cancer, and propose an additional mechanism for HER2 contributing to tumor angiogenesis and metastasis. [Cancer Res 2007;67(4):1487–93]
Covered Versus Uncovered Wallstent for Malignant Extrahepatic Biliary Obstruction: A Cohort Comparative Analysis
Authors: Do Hyun Park, Myung–Hwan Kim, Jung Sik Choi, Sang Soo Lee, Dong Wan Seo, Ji Hye Kim, Jimin Han, Jong Cheol Kim, Eun Kwang Choi, Sung Koo Lee
Journal: Clinical Gastroenterology and Hepatology (2006)
Absent/reduced glucose transporter-1 protein expression in infantile subglottic haemangiomas
Authors: D.J. Purvis, J.I. Harper, B.E. Hartley, N.J. Sebire
Journal: British Journal of Dermatology (2006)

Background Positive immunohistochemical staining for glucose transporter-1 protein (GLUT1) is a characteristic of cutaneous infantile haemangiomas. Objectives To examine GLUT1 expression in subglottic haemangiomas. Methods Review of clinical notes and biopsy tissue with immunostaining for GLUT1 in 14 patients with subglottic haemangiomas. Results GLUT1 immunostaining was negative in 11 cases, and focally positive in three. No subglottic haemangiomas demonstrated the intense diffuse positive GLUT1 staining seen in cutaneous infantile haemangiomas. Five patients had cutaneous as well as subglottic haemangiomas, one of whom had a GLUT1-negative subglottic haemangioma and a GLUT1-positive cutaneous haemangioma of the lip. Conclusions Subglottic haemangiomas appear immunohistochemically different from cutaneous infantile haemangiomas, which may reflect differences in endothelial cell differentiation or underlying aetiology.
Cellular Distribution and Function of Soluble Guanylyl Cyclase in Rat Kidney and Liver
Authors: FRANZISKA THEILIG, MAGDALENA BOSTANJOGLO, HERMANN PAVENSTÄDT, CLEMENS GRUPP, GUDRUN HOLLAND, ILKA SLOSAREK, AXEL M. GRESSNER, MICHAEL RUSSWURM, DORIS KOESLING, SEBASTIAN BACHMANN
Journal: Journal of the American Society of Nephrology (2001)

Soluble guanylyl cyclase (sGC) catalyzes the biosynthesis of cGMP in response to binding of L-arginine-derived nitric oxide (NO). Functionally, the NO-sGC-cGMP signaling pathway in kidney and liver has been associated with regional hemodynamics and the regulation of glomerular parameters. The distribution of the ubiquitous sGC isoform α1β1 sGC was studied with a novel, highly specific antibody against the β1 subunit. In parallel, the presence of mRNA encoding both subunits was investigated by using in situ hybridization and reverse transcription-PCR assays. The NO-induced, sGC-dependent accumulation of cGMP in cytosolic extracts of tissues and cells was measured in vitro. Renal glomerular arterioles, including the renin-producing granular cells, mesangium, and descending vasa recta, as well as cortical and medullary interstitial fibroblasts, expressed sGC. Stimulation of isolated mesangial cells, renal fibroblasts, and hepatic Ito cells with a NO donor resulted in markedly increased cytosolic cGMP levels. This assessment of sGC expression and activity in vascular and interstitial cells of kidney and liver may have implications for understanding the role of local cGMP signaling cascades.
No Association Between Hepatitis B and Pancreatic Cancer in a Prospective Study in Korea
Authors: Amy Berrington de Gonzalez, Sun-Ha Jee, Eric A. Engels
Journal: Journal of Clinical Oncology (2008)

data on HBsAg were missing for 68% of the study population.Fourth, no information was provided regarding the laboratory methodology used for HBsAg testing, or whether the HBsAg-positive results were
Enhanced Pulmonary and Systemic Response to Endotoxin in Transgenic Sickle Mice
Authors: J. David Holtzclaw, Daniel Jack, Samuel M. Aguayo, James R. Eckman, Jesse Roman, Lewis L. Hsu
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Some suggest that sickle cell disease (SCD) is associated with a "proinflammatory state" that predisposes patients to acute chest syndrome in the setting of triggering factors. Conflicting data emerged when inflammation markers in SCD were compared with healthy individuals. Therefore, we examined transgenic sickle and control mice at baseline and with endotoxin (LPS) intraperitoneal injection to determine whether a proinflammatory state truly exists. At baseline, sickle mice had elevated levels of circulating leukocytes and soluble vascular cell adhesion molecule 1 (sVCAM-1). No other differences were observed at baseline or in response to saline. However, LPS challenge was associated with significant increases in mortality (p<0.05), airway tone (p<0.03), serum and bronchoalveolar lavage levels of cytokines tumor necrosis factor-alpha (p<0.03), interleukin-1beta (p<0.02), and sVCAM-1 (p<0.01) in sickle mice compared with control subjects. Furthermore, 4 hours after LPS, microarray analysis identified 413 genes differentially expressed in the sickle mice (n=5) compared with only 7 in the control subjects (n=5). No difference in lung parenchyma was observed by light microscopy. This enhanced response to LPS suggests that the sickle red blood cell confers a subclinical "proinflammatory state." This enhanced response to inflammatory insult, particularly by adhesion molecules such as sVCAM-1, could play a role in the increased susceptibility to pulmonary dysfunction that has been observed clinically in SCD.
Change of enzyme properties caused by cross-linking treatment of human erythrocytes
Authors: M. Ikawa, A. Yoshida
Journal: American Journal of Hematology (1982)

Abstract Aragon et al [4] reported that rat erythrocytes can be cross‐linked and permeabilized without significant inactivation or alteration of several enzymes in the glycolytic pathway. If this is the case, in situ kinetic analysis of the red cell enzymes in normal human red cells and abnormal red cells associated with hemolytic problems could be performed. However, we found that the treatment of human red cells with several bifunctional cross‐linking reagents under various conditions always caused a certain extent of inactivation and a change in kinetic properties of glucose‐6‐phosphate dehydrogenase, 6‐phosphogluconate dehydrogenase, and lactate dehydrogenase. Thus, the cross‐linking and permeabilization method, as it stands, is not satisfactory for in situ kinetic analysis of red cell enzymes.
Biobanking Comes of Age: The Transition to Biospecimen Science
Authors: Jim Vaught
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Biobanking involves the collection, processing, storage, and distribution of biological specimens and the policies and procedures necessary to accomplish those aims successfully. Although biobanking may also involve collections for environmental studies or museum archives, most efforts to standardize biobanking practices have been directed toward human biomedical research. Initially focused primarily on collecting samples for diagnostic purposes in pathology settings, biobanks have evolved into complex organizations engaged in advancing personalized (or precision) medicine and translational research. This evolution has involved the development of biobanking best practices and the transformation of a field driven by empirical approaches into the emerging area of biospecimen science. It has become increasingly important to develop evidence-based practices for collecting biospecimens and data that can be shared with confidence with international collaborators. Aside from these technical approaches, other factors play crucial roles, such as ethical and regulatory issues, business planning and sustainability, and approaches to data collection and sharing.
Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade
Authors: Jianhui Ma, Yan Meng, David J. Kwiatkowski, Xinxin Chen, Haiyong Peng, Qian Sun, Xiaojun Zha, Fang Wang, Ying Wang, Yanling Jing, Shu Zhang, Rongrong Chen, Lianmei Wang, Erxi Wu, Guifang Cai, Izabela Malinowska-Kolodziej, Qi Liao, Yuqin Liu, Yi Zhao, Qiang Sun, Kaifeng Xu, Jianwu Dai, Jiahuai Han, Lizi Wu, Robert Chunhua Zhao, Huangxuan Shen, Hongbing Zhang
Journal: Journal of Clinical Investigation (2010)

The receptor tyrosine kinase/PI3K/AKT/mammalian target of rapamycin (RTK/PI3K/AKT/mTOR) pathway is frequently altered in cancer, but the underlying mechanism leading to tumorigenesis by activated mTOR remains less clear. Here we show that mTOR is a positive regulator of Notch signaling in mouse and human cells, acting through induction of the STAT3/p63/Jagged signaling cascade. Furthermore, in response to differential cues from mTOR, we found that Notch served as a molecular switch to shift the balance between cell proliferation and differentiation. We determined that hyperactive mTOR signaling impaired cell differentiation of murine embryonic fibroblasts via potentiation of Notch signaling. Elevated mTOR signaling strongly correlated with enhanced Notch signaling in poorly differentiated but not in well-differentiated human breast cancers. Both human lung lymphangioleiomyomatosis (LAM) and mouse kidney tumors with hyperactive mTOR due to tumor suppressor TSC1 or TSC2 deficiency exhibited enhanced STAT3/p63/Notch signaling. Furthermore, tumorigenic potential of cells with uncontrolled mTOR signaling was suppressed by Notch inhibition. Our data therefore suggest that perturbation of cell differentiation by augmented Notch signaling might be responsible for the underdifferentiated phenotype displayed by certain tumors with an aberrantly activated RTK/PI3K/AKT/mTOR pathway. Additionally, the STAT3/p63/Notch axis may be a useful target for the treatment of cancers exhibiting hyperactive mTOR signaling.
Three types of blood group I specificity among monoclonal anti-I autoantibodies revealed by analogues of a branched erythrocyte glycolipid.
Authors: T Feizi, R A Childs, K Watanabe, S I Hakomori
Journal: The Journal of Experimental Medicine (1979)

Blood group I activities of the purified glycosphingolipid lacto-N-iso-octaosyl ceramide (Fromula: see text) and 8 of its analogues have been evaluated with 11 anti-I sera including 5 anti-I sera previously tested. All but one of the antisera were inhibited by the lacto-N-iso-octaosyl structure. Three types of I-specificity could be distinguished although none of the anti-I sera was identical in its inhibition patterns with the nine glycophingolipid analogues. The anti-I sera Ma and Woj represent the first type and require an intact Galbeta1 leads to 4GlcNAcbeta1 leads to 6 chain, the anti-I sera Step, Gra, Ver, and Ful represent the second type which requires Galbeta1 leads to 4GlcNAcbeta1 leads to 3 chain with branching, and the anti-I sera Phi, Da, Sch, and Low belong to the third type which requires both branches to be intact. Anti-I antibodies varry in their ability to react with their antigenic determinants in the presence of external substitutions with alpha-linked galactose or sialic acid.
257 SORAFENIB VERSUS RADIOEMBOLIZATION WITH Y90: CLINICAL EVALUATION AND SURVIVAL IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA AND CIRRHOSIS
Authors: S. Gaia, M. Tabone, A. Cantamessa, D. Campion, P. Carucci, M. Grosso, A. Risso, P.R. Brunocilla, A. Calvo, F. Brunello, M. Rizzetto
Journal: Journal of Hepatology (2013)
Concanavalin A?induced T-cell?Mediated hepatic injury in mice: The role of tumor necrosis factor*1
Authors: Florian Gantner, Marcel Leist, I Ansgar Wilhelm Lohse, Paul Georg Germann, Gisa Tiegs
Journal: Hepatology (1995)

Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent hepatic injury in mice. T lymphocytes were previously identified as effector cells of concanavalin A—induced liver injury. Here we report that hepatic injury is characterized by apoptotic cell death. On concanavalin A challenge, the cytokines tumor necrosis factor-α (TNFα), interleukin-2, granulocyte macrophage-colony stimulating factor, and interferon-γ were detectable in the circulation of the mice. Pretreatment of mice with anti-mouse TNF-α antiserum protected them from concanavalin A-induced liver injury. Nude mice failed to release TNF-α or interleukin-2 after concanavalin A challenge and were protected from liver injury. Lymph node cell transfer from responder mice to resistant nude mice resulted in susceptibility of the latter towards concanavalin A, i.e., to induction of cytokine release and hepatotoxicity. These experiments suggest that immunocompetent T cells play a pivotal role in concanavalin A—stimulated TNF-α release in vivo. After intravenous administration of fluorescein isothiocyanate-labeled concanavalin A to mice, the most fluorescence was found within the liver. In vitro, concanavalin A stimulation of separate cultures of mouse lymph node cells or nonparenchymal liver cells induced the release of minute amounts of TNF, whereas stimulation of cocultures of these cells resulted in production of substantial amounts of TNF-α. These findings may explain the hepatotropic effect of concanavalin A. In conclusion, T-cell-dependent concanavalin A-induced apoptotic liver injury in mice is related to immunological and cytokinemediated disorders and possibly to autoreactive hepatic processes.
A Multifaceted Intervention to Implement Guidelines and Improve Admission Paediatric Care in Kenyan District Hospitals: A Cluster Randomised Trial
Authors: Philip Ayieko, Stephen Ntoburi, John Wagai, Charles Opondo, Newton Opiyo, Santau Migiro, Annah Wamae, Wycliffe Mogoa, Fred Were, Aggrey Wasunna, Greg Fegan, Grace Irimu, Mike English
Journal: PLoS Medicine (2011)

In developing countries referral of severely ill children from primary care to district hospitals is common, but hospital care is often of poor quality. However, strategies to change multiple paediatric care practices in rural hospitals have rarely been evaluated.This cluster randomized trial was conducted in eight rural Kenyan district hospitals, four of which were randomly assigned to a full intervention aimed at improving quality of clinical care (evidence-based guidelines, training, job aides, local facilitation, supervision, and face-to-face feedback; n = 4) and the remaining four to control intervention (guidelines, didactic training, job aides, and written feedback; n = 4). Prespecified structure, process, and outcome indicators were measured at baseline and during three and five 6-monthly surveys in control and intervention hospitals, respectively. Primary outcomes were process of care measures, assessed at 18 months postbaseline. In both groups performance improved from baseline. Completion of admission assessment tasks was higher in intervention sites at 18 months (mean = 0.94 versus 0.65, adjusted difference 0.54 [95% confidence interval 0.05-0.29]). Uptake of guideline recommended therapeutic practices was also higher within intervention hospitals: adoption of once daily gentamicin (89.2% versus 74.4%; 17.1% [8.04%-26.1%]); loading dose quinine (91.9% versus 66.7%, 26.3% [-3.66% to 56.3%]); and adequate prescriptions of intravenous fluids for severe dehydration (67.2% versus 40.6%; 29.9% [10.9%-48.9%]). The proportion of children receiving inappropriate doses of drugs in intervention hospitals was lower (quinine dose >40 mg/kg/day; 1.0% versus 7.5%; -6.5% [-12.9% to 0.20%]), and inadequate gentamicin dose (2.2% versus 9.0%; -6.8% [-11.9% to -1.6%]).Specific efforts are needed to improve hospital care in developing countries. A full, multifaceted intervention was associated with greater changes in practice spanning multiple, high mortality conditions in rural Kenyan hospitals than a partial intervention, providing one model for bridging the evidence to practice gap and improving admission care in similar settings.
Vasectomy and Increased Risk of Prostate Cancer
Authors: Jeffrey A. Perlman
Journal: JAMA (1993)

To the Editor.  —Giovannucci et al 1,2 reported associations between prostate cancer and vasectomy from two cohort studies inThe Journal. 3 The publication of two positive articles from Harvard University left many physicians resigned to a vasectomy risk for prostatic carcinoma. Young families now need to be informed when making permanent contraceptive choices; however, a recent National Institutes of Health panel 4 stated that there is insufficient basis for changing current practices and that screening for prostate cancer need not be different for sterilized men.  This position may not change very soon. Given past contraceptive safety study history, weak associations between contraception and cancer may require 50 or more observational studies before a causal link, if any, can be established. This is supported by contradictory negative findings in other existing investigations and, among weakly positive studies such as those from Harvard, inconsistent findings among subgroups. 4 Among the recent weakly
Glucose Levels at the Site of Subcutaneous Insulin Administration and Their Relationship to Plasma Levels
Authors: Stefan Lindpointner, Stefan Korsatko, Gerd Köhler, Hans Köhler, Roland Schaller, Lukas Schaupp, Martin Ellmerer, Thomas R. Pieber, Werner Regittnig
Journal: Diabetes Care (2010)

To examine insulin's effect on the tissue glucose concentration at the site of subcutaneous insulin administration.