tbuckley/cabot-search huggingface dataset:
Immunochemical Evidence for Protein Abnormalities in Platelets from Patients with Glanzmann's Thrombasthenia and Bernard-Soulier Syndrome
Authors: Inger Hagen, Alan Nurden, Ole Jannik Bjerrum, Nils Olav Solum, Jacques Caen
Journal: Journal of Clinical Investigation (1980)

Crossed immunoelectrophoresis of Triton X-100 solubilized proteins from normal and abnormal platelets was performed with rabbit antibodies raised against normal platelets. In Bernard-Soulier platelets protein 13 was not detected, and neither the amphiphilic (probably GP Ib) nor the hydrophilic (glycocalicin) glycocalicin-related proteins were seen when monospecific antiglycocalicin antiserum was used. The most prominent precipitate, 16, and platelet fibrinogen, 24 were not detected in platelets of two patients with type I thrombasthenia, whereas in one patient with type II thrombasthenia fibrinogen was clearly detected, but the amount of protein 16 remained severely reduced. Protein 16 was heavily labeled after lactoperoxidase-catalyzed 125I iodination of normal platelets, and was precipitated by IgG-L, an alloantibody from a polytransfused thrombasthenic patient. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) or protein 16 cut out from immunoplates showed two 125I-labeled glycoprotein bands, which migrate as GP IIb and GP IIIa. SDS-PAGE of 125I-labeled type I thrombasthenic platelets showed no periodic acid-Schiff bands or peaks of radioactivity in the GP IIb and GP IIIa regions, whereas in the GP I region both the periodic acid-Schiff band intensity and the radiolabeling were within the normal range. Autoradiography after crossed immunoelectrophoresis of iodinated thrombasthenic platelets showed that the bulk of radioactivity was bound to protein 17. This glycoprotein, which was also present in normal and Bernard-Soulier platelets, migrates in the GP I region on SDS-PAGE. Thus, the bulk of radioactivity observed in the GP I region after SDS-PAGE is associated with protein 17 and not with glycocalicin.
Cisplatin, gemcitabine and vinorelbine in locally advanced or metastatic non-small-cell lung cancer: A phase I study
Authors: G Frasci, N Panza, P Comella, G P Nicolella, M Natale, C Pacilio, A Gravina, V Caputi, G Botti, G Comella
Journal: Annals of Oncology (1997)
Increased Expression of the Retinoblastoma Gene in Human Colorectal Carcinomas Relative to Normal Colonic Mucosa
Authors: R. Gope, M. A. Christensen, A. Thorson, H. T. Lynch, T. Smyrk, C. Hodgson, D. M. Wildrick, M. L. Gope, B. M. Boman
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Increased Expression of the Retinoblastoma Gene in Human Colorectal Carcinomas Relative to Normal Colonic Mucosa Get access Rajalakshmi Gope, Rajalakshmi Gope Creighton University School of MedicineOmaha, NE Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark A. Christensen, Mark A. Christensen Creighton University School of MedicineOmaha, NE Search for other works by this author on: Oxford Academic PubMed Google Scholar Alan Thorson, Alan Thorson Creighton University School of MedicineOmaha, NE Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry T. Lynch, Henry T. Lynch Creighton University School of MedicineOmaha, NE Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Smyrk, Thomas Smyrk Creighton University School of MedicineOmaha, NE Search for other works by this author on: Oxford Academic PubMed Google Scholar Clague Hodgson, Clague Hodgson Laboratory of Molecular Biology, Ohio Agricultural Research and Development Center, Ohio State UniversityWooster, OH Search for other works by this author on: Oxford Academic PubMed Google Scholar David M. Wildrick, David M. Wildrick Section of Gastrointestinal Oncology and Digestive Diseases, The University of Texas M. D. Anderson Cancer CenterHouston, TX Search for other works by this author on: Oxford Academic PubMed Google Scholar Mohan L. Gope, Mohan L. Gope Creighton University School of MedicineOmaha, NE Search for other works by this author on: Oxford Academic PubMed Google Scholar Bruce M. Boman Bruce M. Boman * Creighton University School of MedicineOmaha, NE *Correspondence to : Bruce M. Boman, M.D., Ph.D., Creighton Cancer Center, Creighton University School of Medicine, Criss III, Rm. 353, 24th at California Sts., Omaha, NE 68178. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 4, 21 February 1990, Pages 310–314, https://doi.org/10.1093/jnci/82.4.310 Published: 21 February 1990 Article history Received: 26 June 1989 Revision received: 10 October 1989 Accepted: 31 October 1989 Published: 21 February 1990
Increasing Negative Lymph Node Count Is Independently Associated With Improved Long-Term Survival in Stage IIIB and IIIC Colon Cancer
Authors: Paul M. Johnson, Geoff A. Porter, Rocco Ricciardi, Nancy N. Baxter
Journal: Journal of Clinical Oncology (2006)

The purpose of this study was to examine the impact of the number of negative lymph nodes on survival in patients with stage III colon cancer.Patients who underwent surgery for stage III colon cancer between January 1988 and December 1997 were identified from the Surveillance, Epidemiology and End Results cancer registry. The number of negative and positive nodes was determined for 20,702 eligible patients. Disease-specific survival was examined by substage according to the number of negative nodes identified. A proportional hazards model was constructed to determine the effect of the number of negative nodes on survival.For stage IIIB and IIIC patients, there was a significant decrease in disease-specific mortality as the number of negative nodes increased; cumulative 5-year cancer mortality was 27% in stage IIIB patients with 13 or more negative nodes identified versus 45% in those with three or fewer negative lymph nodes evaluated (P < .0001). In patients with stage IIIC cancer, those with 13 or more negative nodes had a 5-year mortality of 42% versus 65% in those with three or fewer negative lymph nodes evaluated (P < .0001). There was no association between the number of negative nodes identified and disease-specific survival for patients with stage IIIA disease. After controlling for the number of positive nodes, a higher number of negative nodes was found to be independently associated with improved disease-specific survival.The number of negative nodes is an important independent prognostic factor for patients with stage IIIB and IIIC colon cancer.
OBSERVATIONS ON TISSUE GRAFTS ESTABLISHED IN RABBIT EAR CHAMBERS
Authors: J. B. Hobbs, W. J. Cliff
Journal: The Journal of Experimental Medicine (1971)

An in vivo microscopic and ultrastructural study of tissues transferred to the transparent rabbit ear chamber is presented. Fragments of liver, kidney, thyroid, and myometrium were successfully auto- or allografted into the chamber from donors of all ages and allowed continuous in vivo observation of parenchymal structure and function, as well as of the graft vasculature which plays such an active role during rejection. Circulation was quickly reestablished by anastomosis of graft vessels to those of the ear chamber membrane and only minor reversible parenchymal changes occurred. Both vessels and parenchyma retained the characteristics of the organs of origin on both light and electron microscopy and were observed functioning in vivo for periods up to 1 yr in the case of autografts, and until rejection occurred in allografts. In the latter case, rejection did not occur in tissues obtained from adult and neonatal donors for nearly 3 months, while tissues of fetal origin were generally rejected much earlier. The kidney grafts provide a unique opportunity for a close comparative study of mammalian fetal and adult glomerular blood flow under varying rates of perfusion, and the tubular epithelium could be observed regenerating after initial acute tubular necrosis. Renal tubules from fetal, neonatal, and adult donors were all capable of metaplastic change to form a highly ciliated epithelium. Grafts of these tissues will allow the fine detail of the processes of rejection to be studied continuously in vivo.
TCT-373 Impact of Epicardial Fat Volume on Coronary Artery Disease in Symptomatic Patients with a Zero Calcium Score
Authors: Tsuyoshi Ito, Mitsuyasu Terashima, Kenya Nasu, Masashi Kimura, Yoshihisa Kinoshita, Yasushi Asakura, Etsuo Tsuchikane, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2012)
Chronic Sildenafil Treatment Inhibits Monocrotaline-induced Pulmonary Hypertension in Rats
Authors: Ralph T. Schermuly, Klaus P. Kreisselmeier, Hossein A. Ghofrani, Hüseyin Yilmaz, Ghazwan Butrous, Leander Ermert, Monika Ermert, Norbert Weissmann, Frank Rose, Andreas Guenther, Dieter Walmrath, Werner Seeger, Friedrich Grimminger
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Sildenafil, a phosphodiesterase 5 inhibitor, is currently under investigation for therapy of pulmonary hypertension. This study was designed to investigate chronic effects of sildenafil in monocrotaline (MCT)-induced pulmonary hypertension in rats. Four weeks after a single subcutaneous injection of MCT, the animals displayed nearly threefold elevated pulmonary artery pressure and vascular resistance values, with a concomitant decline in central venous oxygen saturation and arterial oxygenation. Marked right heart hypertrophy was evident, and massive thickening of the precapillary artery smooth muscle layer was histologically apparent. Further deterioration of pulmonary hypertension occurred 6 weeks after MCT injection, with some animals dying during this period because of right heart failure. When chronically administered from Days 14–28, sildenafil significantly increased plasma cyclic guanosine monophosphate and inhibited the development of pulmonary hypertension and right heart hypertrophy, with preservation of gas exchange and systemic arterial pressure. A corresponding efficacy profile was also noted for long-term feeding with sildenafil from Days 28–42. Moreover, the death rate significantly decreased in those animals treated with sildenafil. We conclude that sildenafil attenuates MCT-induced pulmonary hypertension and cor pulmonale in rats.
Low Hemoglobin A1c in Nondiabetic Adults
Authors: Vikas Aggarwal, Andrea L.C. Schneider, Elizabeth Selvin
Journal: Diabetes Care (2012)

To identify predictors of low hemoglobin A(1c) (HbA(1c)) (<5.0%) and to investigate the association of low HbA(1c) with cause-specific mortality and risk of liver disease hospitalization.Prospective cohort study of 13,288 participants in the Atherosclerosis Risk in Communities Study. Logistic regression was used to identify cross-sectional correlates of low HbA(1c), and Cox proportional hazards models were used to estimate the association of low HbA(1c) with cause-specific mortality.Compared with participants with HbA(1c) in the normal range (5.0 to <5.7%), participants with low HbA(1c) were younger, less likely to smoke, had lower BMI, lower white cell count and fibrinogen levels, and lower prevalence of hypercholesterolemia and history of coronary heart disease. However, this group was more likely to have anemia and had a higher mean corpuscular volume. In adjusted Cox models with HbA(1c) of 5.0 to <5.7% as the reference group, HbA(1c) <5.0% was associated with a significantly increased risk of all-cause mortality (hazard ratio [HR]: 1.32, 95% CI: 1.13-1.55) and of cancer death (1.47, 95% CI: 1.16-1.84). We also noted nonsignificant trends toward increased risk of death from cardiovascular causes (1.27, 95% CI: 0.93-1.75) and respiratory causes (1.42, 95% CI: 0.78-2.56). There was a J-shaped association between HbA(1c) and risk of liver disease hospitalization.No single cause of death appeared to drive the association between low HbA(1c) and total mortality. These results add to evidence that low HbA(1c) values may be a generalized marker of mortality risk in the general population.
ATLANTIC DIP: Closing the Loop
Authors: Lisa A. Owens, Gloria Avalos, Breda Kirwan, Louise Carmody, Fidelma Dunne
Journal: Diabetes Care (2012)

Prospective evaluation of pregnancy outcomes in women with pregestational diabetes over 6 years.The ATLANTIC Diabetes in Pregnancy group provides care for women with diabetes throughout pregnancy. In 2007, the group identified that women were poorly prepared for pregnancy and outcomes were suboptimal. A change in practice occurred, offering women specialist-led, hub-and-spoke evidence-based care. We now compare outcomes from 2005 to 2007 with those from 2008 to 2010.There was an increase in the numbers attending preconception care (28-52%, P = 0.01). Glycemic control before and throughout pregnancy improved. There was an overall increase in live births (74-92%, P < 0.001) and decrease in perinatal mortality rate (6.2-0.65%, P < 0.001). There was a decrease in large-for-gestational-age babies in mothers with type 1 diabetes mellitus (30-26%, P = 0.02). Elective caesarean section rates increased, while emergency section rates decreased.Changing the process of clinical care delivery can improve outcomes in women with pregestational diabetes.
Opting in or out of electronic patient records: National clinical leads of Connecting for Health respond
Authors: Gillian Braunold, Mike Pringle, Simon Eccles, Ian Scott, Susan Osborne, Barbara Stuttle
Journal: BMJ (2006)

EDITOR—We as the national clinical leads are concerned that a conflation of issues has clouded the principles in the opt in or opt out debate.1 We believe that patients' clinical information must be appropriately protected. It should be shared with clinicians who genuinely need to know—and no further. Patients may not want some information shared beyond the clinician to whom they have entrusted it.

There is continuing discussion and debate in NHS Connecting for Health and the clinical professions on how best to control access to …
Ca2+/calmodulin-dependent kinase II triggers cell membrane injury by inducing complement factor B gene expression in the mouse heart
Authors: Madhu V. Singh, Ann Kapoun, Linda Higgins, William Kutschke, Joshua M. Thurman, Rong Zhang, Minati Singh, Jinying Yang, Xiaoqun Guan, John S. Lowe, Robert M. Weiss, Kathy Zimmermann, Fiona E. Yull, Timothy S. Blackwell, Peter J. Mohler, Mark E. Anderson
Journal: Journal of Clinical Investigation (2009)

Myocardial Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibition improves cardiac function following myocardial infarction (MI), but the CaMKII-dependent pathways that participate in myocardial stress responses are incompletely understood. To address this issue, we sought to determine the transcriptional consequences of myocardial CaMKII inhibition after MI. We performed gene expression profiling in mouse hearts with cardiomyocyte-delimited transgenic expression of either a CaMKII inhibitory peptide (AC3-I) or a scrambled control peptide (AC3-C) following MI. Of the 8,600 mRNAs examined, 156 were substantially modulated by MI, and nearly half of these showed markedly altered responses to MI with CaMKII inhibition. CaMKII inhibition substantially reduced the MI-triggered upregulation of a constellation of proinflammatory genes. We studied 1 of these proinflammatory genes, complement factor B (Cfb), in detail, because complement proteins secreted by cells other than cardiomyocytes can induce sarcolemmal injury during MI. CFB protein expression in cardiomyocytes was triggered by CaMKII activation of the NF-κB pathway during both MI and exposure to bacterial endotoxin. CaMKII inhibition suppressed NF-κB activity in vitro and in vivo and reduced Cfb expression and sarcolemmal injury. The Cfb–/– mice were partially protected from the adverse consequences of MI. Our findings demonstrate what we believe is a novel target for CaMKII in myocardial injury and suggest that CaMKII is broadly important for the genetic effects of MI in cardiomyocytes.
Quercetin inhibits HGF/c-Met signaling and HGF-stimulated melanoma cell migration and invasion
Authors: Hui-Hui Cao, Chi-Yan Cheng, Tao Su, Xiu-Qiong Fu, Hui Guo, Ting Li, Anfernee Kai-Wing Tse, Hiu-Yee Kwan, Hua Yu, Zhi-Ling Yu
Journal: Molecular Cancer (2015)

Melanoma is notorious for its propensity to metastasize, which makes treatment extremely difficult. Receptor tyrosine kinase c-Met is activated in human melanoma and is involved in melanoma progression and metastasis. Hepatocyte growth factor (HGF)-mediated activation of c-Met signaling has been suggested as a therapeutic target for melanoma metastasis. Quercetin is a dietary flavonoid that exerts anti-metastatic effect in various types of cancer including melanoma. In a previous report, we demonstrated that quercetin inhibited melanoma cell migration and invasion in vitro, and prevented melanoma cell lung metastasis in vivo. In this study, we sought to determine the involvement of HGF/c-Met signaling in the anti-metastatic action of quercetin in melanoma. Transwell chamber assay was conducted to determine the cell migratory and invasive abilities. Western blotting was performed to determine the expression levels and activities of c-Met and its downstream molecules. And immunoblotting was performed in BS3 cross-linked cells to examine the homo-dimerization of c-Met. Quantitative real-time PCR analysis was carried out to evaluate the mRNA expression level of HGF. Transient transfection was used to overexpress PAK or FAK in cell models. Student’s t-test was used in analyzing differences between two groups. Quercetin dose-dependently suppressed HGF-stimulated melanoma cell migration and invasion. Further study indicated that quercetin inhibited c-Met phosphorylation, reduced c-Met homo-dimerization and decreased c-Met protein expression. The effect of quercetin on c-Met expression was associated with a reduced expression of fatty acid synthase. In addition, quercetin suppressed the phosphorylation of c-Met downstream molecules including Gab1 (GRB2-associated-binding protein 1), FAK (Focal Adhesion Kinase) and PAK (p21-activated kinases). More importantly, overexpression of FAK or PAK significantly reduced the inhibitory effect of quercetin on the migration of the melanoma cells. Our findings suggest that suppression of the HGF/c-Met signaling pathway contributes to the anti-metastatic action of quercetin in melanoma.
Spatial Analyses Identify the Geographic Source of Patients at a National Cancer Institute Comprehensive Cancer Center
Authors: Shu-Chih Su, Norma Kanarek, Michael G. Fox, Alla Guseynova, Shirley Crow, Steven Piantadosi
Journal: Clinical Cancer Research (2010)

We examined the geographic distribution of patients to better understand the service area of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, a designated National Cancer Institute (NCI) comprehensive cancer center located in an urban center. Like most NCI cancer centers, the Sidney Kimmel Comprehensive Cancer Center serves a population beyond city limits. Urban cancer centers are expected to serve their immediate neighborhoods and to address disparities in access to specialty care. Our purpose was to learn the extent and nature of the cancer center service area.Statistical clustering of patient residence in the continental United States was assessed for all patients and by gender, cancer site, and race using SaTScan.Primary clusters detected for all cases and demographically and tumor-defined subpopulations were centered at Baltimore City and consisted of adjacent counties in Delaware, Pennsylvania, Virginia, West Virginia, New Jersey and New York, and the District of Columbia. Primary clusters varied in size by race, gender, and cancer site. Spatial analysis can provide insights into the populations served by urban cancer centers, assess centers' performance relative to their communities, and aid in developing a cancer center business plan that recognizes strengths, regional utility, and referral patterns.Today, 62 NCI cancer centers serve a quarter of the U.S. population in their immediate communities. From the Baltimore experience, we might project that the population served by these centers is actually more extensive and varies by patient characteristics, cancer site, and probably cancer center services offered.
Selective Expression and Functions of Interleukin 18 Receptor on T Helper (Th) Type 1 but not Th2 Cells
Authors: Damo Xu, Woon Ling Chan, Bernard P. Leung, David Hunter, Kerstin Schulz, Robert W. Carter, Iain B. McInnes, John H. Robinson, Foo Y. Liew
Journal: The Journal of Experimental Medicine (1998)

Interleukin (IL)-18 induces interferon (IFN)-γ synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12Rβ2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R–derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin–T cell antigen receptor-αβ transgenic mice (D011.10). Anti–IL-18R antibody inhibited IL-18– induced IFN-γ production by Th1 clones in vitro. In vivo, anti–IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-γ and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target.
Vagotomy for peptic ulcer.
Authors: A G Cox, W M Cooke
Journal: BMJ (1970)

JOUtNAand the responses are objective.It has been used in school screening programmes in the United Kingdom and the results reported by Brooks.2Extensive use in Scandinavia, and my own experience, confirms the value of the instrument, the use of which obviates the need for a diagnostic, as opposed to a therapeutic, myringotomy.The advice to prescribe a hearing-aid in cases where repeated myringotomy is re- quired is good only as long as the patient is carefully followed.In the presence of chronic glue ear permanent damage may occur to the tympanic membrane, particularly in its posterior segment, which be- comes thin, loses its middle layer, and becomes flabby.This may eventually be indriven into the sinus tympani and to the mastoid air cells, forming a cholesteatoma.Indeed, this is one of the commoner pathogenetic mechanisms of a cholesteatoma at present.Only a small proportion of child- ren are so involved, but any child with an abnormally thin tympanic membrane should be vigorously treated and observed until complete resolution occurs.Even though this may take several years, it is not safe to dis- charge these children with a hearing-aid.-