tbuckley/cabot-search huggingface dataset:
Prognostic Significance of Signet Ring Gastric Cancer
Authors: Sharven Taghavi, Senthil N. Jayarajan, Adam Davey, Alliric I. Willis
Journal: Journal of Clinical Oncology (2012)

Studies in Asia have questioned the dictum that signet ring cell carcinoma (SRC) has a worse prognosis than other forms of gastric cancer. Our study determined differences in presentation and outcomes between SRC and gastric adenocarcinoma (AC) in the United States.The National Cancer Institute Surveillance, Epidemiology, and End Results database was reviewed for SRC and AC from 2004 to 2007.We reviewed 10,246 cases of patients with gastric cancer, including 2,666 of SRC and 7,580 of AC. SRC presented in younger patients (61.9 v 68.7 years; P < .001) and less often in men (52.7% v 68.7%; P < .001). SRC patients were more frequently black (11.3% v 10.9%), Asian (16.4% v 13.2%), American Indian/Alaska Native (0.9% v 0.8%), or Hispanic (23.3% v 14.0%; P < .001). SRC was more likely to be stage T3-4 (45.8% v 33.3%), have lymph node spread (59.7% v 51.8%), and distant metastases (40.2% v 37.6%; P < .001). SRC was more likely to be found in the lower (30.7% v 24.2%) and middle stomach (30.6% v 20.7%; P < .001). Median survival was not different between the two (AC, 14.0 months v SRC, 13.0 months; P = .073). Multivariable analyses demonstrated SRC was not associated with mortality (hazard ratio [HR], 1.05; 95% CI, 0.96 to 1.11; P = .150). Mortality was associated with age (HR, 1.01; 95% CI, 1.01 to 1.02; P < .001), black race (HR, 1.10; 95% CI, 1.01 to 1.20; P = .026), and tumor grade. Variables associated with lower mortality risk included Asian race (HR, 0.83; 95% CI, 0.77 to 0.91; P < .001) and surgery (HR, 0.37; 95% CI, 0.34 to 0.39; P < .001).In the United States, SRC significantly differs from AC in extent of disease at presentation. However, when adjusted for stage, SRC does not portend a worse prognosis.
Active State in the Smooth Muscle of the Rat Portal Vein in Relation to Electrical Activity and Isometric Force
Authors: BÖRJE JOHANSSON
Journal: Circulation Research (1973)

Contractile activity in smooth muscle is usually too variable to permit a meaningful analysis of the time course of the active state. A regular activity of uniform contractions was obtained in the present experiments on isolated rat portal veins by simultaneous increases in the external potassium and calcium concentrations. The contractions were associated with electrical discharges which lasted between 0.8 and 1.5 seconds. The active state during these uniform contractions was determined from the shortening velocities after isotonic releases and from the redevelopment of tension after controlled releases. Results obtained with the two methods agreed satisfactorily. The active state increased over the first 0.4-0.6 seconds. Suggestive evidence of a plateau phase was found in some experiments. The active state clearly began to fall about 1 second after the start of the contraction, and this fall coincided with the fall in the first time derivative of isometric force (dP/dt). The maximal intensity of the active state was, on the average, 173% of the maximal isometric force. During isometric contractions, the series elastic element was stretched by as much as 15% of the total muscle length. Active-state values were therefore corrected for changes in contractile element length. The curve then obtained might represent the time course of the level of activation, reflect variations in internal calcium concentration, and relate to the electrical response. Concepts developed for the mechanics of striated muscle can apparently be applied to propagating vascular smooth muscle, and this applicability might help to clarify electromechanical relations and the actions of vasoactive substances in blood vessels.
Factors responsible for age-related elevation in fasting plasma glucose: a cross-sectional study in Japanese men
Authors: Kentaro Toyoda, Mitsuo Fukushima, Rie Mitsui, Norio Harada, Hidehiko Suzuki, Tomomi Takeda, Ataru Taniguchi, Yoshikatsu Nakai, Toshiko Kawakita, Yuichiro Yamada, Nobuya Inagaki, Yutaka Seino
Journal: Metabolism (2008)
Identification of a novel signal transduction surface molecule on human cytotoxic lymphocytes.
Authors: N M Valiante, G Trinchieri
Journal: The Journal of Experimental Medicine (1993)

In this study, we have used a newly generated monoclonal antibody (mAb C1.7) to identify a novel 38-kD signal-transducing surface molecule (p38) expressed by lymphocyte subsets capable of cell-mediated cytotoxicity. Virtually all CD16+/CD56+ natural killer (NK) cells and approximately half of CD8+ (T cell receptor [TCR] alpha/beta+) T cells and TCR-gamma/delta+ T cells express the p38 surface molecule. Stimulation of p38 on NK cells with mAb C1.7 activated cytotoxicity, induced lymphokine production, and initiated polyphosphoinositol turnover and [Ca2+]i increases. Unlike other NK cell surface molecules that activate cytotoxicity, p38 stimulation did not result in the release of the granule enzyme N-carbobenzoxy-L-thiobenzyl ester-esterase even under conditions in which mAb C1.7 induced NK cell-mediated redirected lysis of Fc gamma R+ target cells. Activated (recombinant interleukin 2 [rIL-2], 5 d) CD8+ T cells mediated non-major histocompatibility complex (MHC)-restricted cytotoxicity, and the CD8+/p38+ subset contained the overwhelming majority of this activity. F(ab')2 fragments of mAb C1.7 inhibited non-MHC-restricted cytotoxicity mediated by resting NK cells and rIL-2-cultured T cells but did not affect spontaneous cytotoxicity mediated by activated, cultured NK cells. Taken as a whole, our results suggest that p38 may have a direct role in the recognition, signal transduction, and/or lytic mechanisms of non-MHC-restricted cytotoxicity.
Histological Course of Nonalcoholic Fatty Liver Disease in Japanese Patients
Authors: Erika Hamaguchi, Toshinari Takamura, Masaru Sakurai, Eishiro Mizukoshi, Yoh Zen, Yumie Takeshita, Seiichiro Kurita, Kuniaki Arai, Tatsuya Yamashita, Motoko Sasaki, Yasuni Nakanuma, Shuichi Kaneko
Journal: Diabetes Care (2009)

OBJECTIVE The goal of this study was to examine whether metabolic abnormalities are responsible for the histological changes observed in Japanese patients with nonalcoholic fatty liver disease (NAFLD) who have undergone serial liver biopsies. RESEARCH DESIGN AND METHODS In total, 39 patients had undergone consecutive liver biopsies. Changes in their clinical data were analyzed, and biopsy specimens were scored histologically for stage. RESULTS The median follow-up time was 2.4 years (range 1.0–8.5). Liver fibrosis had improved in 12 patients (30.7%), progressed in 11 patients (28.2%), and remained unchanged in 16 patients (41%). In a Cox proportional hazard model, decrease in A1C and use of insulin were associated with improvement of liver fibrosis independent of age, sex, and BMI. However, ΔA1C was more strongly associated with the improvement of liver fibrosis than use of insulin after adjustment for each other (χ2; 7.97 vs. 4.58, respectively). CONCLUSIONS Tight glycemic control may prevent histological progression in Japanese patients with NAFLD.
Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo
Authors: Shalin H Naik, Priyanka Sathe, Hae-Young Park, Donald Metcalf, Anna I Proietto, Aleksander Dakic, Sebastian Carotta, Meredith O'Keeffe, Melanie Bahlo, Anthony Papenfuss, Jong-Young Kwak, Li Wu, Ken Shortman
Journal: Nature Immunology (2007)
The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI
Authors: Christina Halsey, Georgina Buck, Sue Richards, Faraneh Vargha-Khadem, Frank Hill, Brenda Gibson
Journal: Journal of Hematology & Oncology (2011)

Abstract Background The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS) directed therapies in childhood acute lymphoblastic leukaemia (ALL). To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1) all patients (n = 555) versus related controls (n = 311), (2) low-risk children (presenting white cell count (WCC) &lt; 50 × 10 9 /l) randomised to intrathecal methotrexate (n = 197) versus intrathecal and high-dose intravenous methotrexate (HDM) (n = 202), and (3) high-risk children (WCC ≥ 50 × 10 9 /l, age ≥ 2 years) randomised to HDM (n = 79) versus cranial irradiation (n = 77). Results There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P &lt; 0.002) with a higher proportion of children with IQs &lt; 80 in the patient groups (13% vs. 5% at 3 years p = 0.003). Conclusion Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes. Trial registration ISRCTN: ISRCTN16757172
Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED‐HF)
Authors: John J.V. McMurray, Inder S. Anand, Rafael Diaz, Aldo P. Maggioni, Christopher O'Connor, Marc A. Pfeffer, Scott D. Solomon, Michal Tendera, Dirk J. van Veldhuisen, Moetaz Albizem, Sunfa Cheng, Debra Scarlata, Karl Swedberg, James B. Young
Journal: European Journal of Heart Failure (2013)
Targeting miR-21 Inhibits<i>In Vitro</i>and<i>In Vivo</i>Multiple Myeloma Cell Growth
Authors: Emanuela Leone, Eugenio Morelli, Maria T. Di Martino, Nicola Amodio, Umberto Foresta, Annamaria Gullà, Marco Rossi, Antonino Neri, Antonio Giordano, Nikhil C. Munshi, Kenneth C. Anderson, Pierosandro Tagliaferri, Pierfrancesco Tassone
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Deregulated expression of miRNAs plays a role in the pathogenesis and progression of multiple myeloma. Among upregulated miRNAs, miR-21 has oncogenic potential and therefore represents an attractive target for the treatment of multiple myeloma. Experimental Design: Here, we investigated the in vitro and in vivo anti-multiple myeloma activity of miR-21 inhibitors. Results: Either transient-enforced expression or lentivirus-based constitutive expression of miR-21 inhibitors triggered significant growth inhibition of primary patient multiple myeloma cells or interleukin-6–dependent/independent multiple myeloma cell lines and overcame the protective activity of human bone marrow stromal cells. Conversely, transfection of miR-21 mimics significantly increased proliferation of multiple myeloma cells, showing its tumor-promoting potential in multiple myeloma. Importantly, upregulation of miR-21 canonical validated targets (PTEN, Rho-B, and BTG2), together with functional impairment of both AKT and extracellular signal–regulated kinase signaling, were achieved by transfection of miR-21 inhibitors into multiple myeloma cells. In vivo delivery of miR-21 inhibitors in severe combined immunodeficient mice bearing human multiple myeloma xenografts expressing miR-21induced significant antitumor activity. Upregulation of PTEN and downregulation of p-AKT were observed in retrieved xenografts following treatment with miR-21 inhibitors. Conclusion: Our findings show the first evidence that in vivo antagonism of miR-21 exerts anti-multiple myeloma activity, providing the rationale for clinical development of miR-21 inhibitors in this still incurable disease. Clin Cancer Res; 19(8); 2096–106. ©2013 AACR.
Defective intracellular transport as a common mechanism limiting expression of inappropriately paired class II major histocompatibility complex alpha/beta chains.
Authors: A J Sant, L R Hendrix, J E Coligan, W L Maloy, R N Germain
Journal: The Journal of Experimental Medicine (1991)

Distinct combinations of class II major histocompatibility complex (MHC) alpha and beta chains show widely varying efficiencies of cell surface expression in transfected cells. Previous studies have analyzed the regions of the class II chains that are critically involved in this phenomenon of variable expression and have shown a predominant effect of the NH2-terminal domains comprising the peptide-binding site. The present experiments attempt to identify the post-translational defects responsible for this variation in surface class II molecule expression for both interisotypic alpha/beta combinations failing to give rise to any detectable cell membrane molecules (e.g., E alpha A beta k) and intraisotypic pairs with inefficient surface expression (e.g., A alpha d A beta k). The results of metabolic labeling and immunoprecipitation experiments using L cell transfectants demonstrate that in both of these cases, the alpha and beta chains form substantial amounts of stable intracellular dimers. However, the isotype- and allele-mismatched combinations do not show the typical post-translational increases in molecular weight that accompany maturation of the N-linked glycans of class II MHC molecules. Studies with endoglycosidase H reveal that no or little progression to endoglycosidase H resistance occurs for these mismatched dimers. These data are consistent with active or passive retention of relatively stable and long-lived mismatched dimers in a pre-medial-Golgi compartment, possibly in the endoplasmic reticulum itself. This retention accounts for the absent or poor surface expression of these alpha/beta combinations, and suggests that conformational effects of the mismatching in the NH2-terminal domain results in a failure of class II molecules to undergo efficient intracellular transport.
Protamines and male infertility
Authors: Rafael Oliva
Journal: Human Reproduction Update (2006)

Protamines are the major nuclear sperm proteins. The human sperm nucleus contains two types of protamine: protamine 1 (P1) encoded by a single-copy gene and the family of protamine 2 (P2) proteins (P2, P3 and P4), all also encoded by a single gene that is transcribed and translated into a precursor protein. The protamines were discovered more than a century ago, but their function is not yet fully understood. In fact, different hypotheses have been proposed: condensation of the sperm nucleus into a compact hydrodynamic shape, protection of the genetic message delivered by the spermatozoa, involvement in the processes maintaining the integrity and repair of DNA during or after the nucleohistone-nucleoprotamine transition and involvement in the epigenetic imprinting of the spermatozoa. Protamines are also one of the most variable proteins found in nature, with data supporting a positive Darwinian selection. Changes in the expression of P1 and P2 protamines have been found to be associated with infertility in man. Mutations in the protamine genes have also been found in some infertile patients. Transgenic mice defective in the expression of protamines also present several structural defects in the sperm nucleus and have variable degrees of infertility. There is also evidence that altered levels of protamines may result in an increased susceptibility to injury in the spermatozoan DNA causing infertility or poor outcomes in assisted reproduction. The present work reviews the articles published to date on the relationship between protamines and infertility.
Characterization of Crohn disease in X-linked inhibitor of apoptosis–deficient male patients and female symptomatic carriers
Authors: Claire Aguilar, Christelle Lenoir, Nathalie Lambert, Bernadette Bègue, Nicole Brousse, Danielle Canioni, Dominique Berrebi, Maryline Roy, Stéphane Gérart, Helen Chapel, Tobias Schwerd, Laurent Siproudhis, Michela Schäppi, Ali Al-Ahmari, Masaaki Mori, Akiko Yamaide, Lionel Galicier, Bénédicte Neven, John Routes, Holm H. Uhlig, Sibylle Koletzko, Smita Patel, Hirokazu Kanegane, Capucine Picard, Alain Fischer, Nadine Cerf Bensussan, Frank Ruemmele, Jean-Pierre Hugot, Sylvain Latour
Journal: Journal of Allergy and Clinical Immunology (2014)
Breast feeding reduces risk of breast cancer recurrence, study finds
Authors: S. Mayor
Journal: BMJ (2015)

Women treated for breast cancer who previously breast fed their babies have a 30% lower risk of recurrence than those who did not, a US study has shown. Breast feeding for six months or more was associated with even greater protection from tumour recurrence.

The study, reported in the Journal of the National Cancer Institute , analysed information on 1636 women with breast cancer from two prospective breast cancer cohorts. …
Residual normality: Friend or foe?
Authors: Michael Thomas, Annette Karmiloff-Smith
Journal: Behavioral and Brain Sciences (2002)

In response to our target article, many of the commentators concentrated on our notion of Residual Normality. In our response, we focus on the questions raised by this idea. However, we also examine broader issues concerning the importance of incorporating a realistic theory of the process of development into explanations of developmental deficits.
Increased Prevalence of Coronary Ectasia in Heterozygous Familial Hypercholesterolemia
Authors: Krishnankutty Sudhir, Thomas A. Ports, Thomas M. Amidon, Jeffrey J. Goldberger, Vikas Bhushan, John P. Kane, Paul Yock, Mary J. Malloy
Journal: Circulation (1995)

Background Although coronary atherosclerosis most commonly produces clinical effects as a result of stenosis, aneurysmal disease also occurs. We have found an increased prevalence of ectasia and aneurysmal disease in familial hypercholesterolemia (FH) suggesting a link between plasma lipoproteins and coronary aneurysms. Methods and Results In 197 asymptomatic subjects with FH, we examined the prevalence of ectasia and its association with coronary risk factors. An ectatic segment was defined as one with a luminal diameter &gt;1.5 times that of the adjacent normal segment, excluding poststenotic dilation. Among subjects with FH, 15% had ectasia compared with 2.5% of an age- and sex-matched control group of 198 subjects without FH pre- senting for coronary angiography ( P &lt;.001). These control patients had significantly more severe coronary atherosclerosis than patients with FH. Ectasia was 3 times more common in men than women ( P &lt;.025). Neither age nor hypertension was predictive. Although in part reflecting the striking sex differential, ectasia was strongly associated with a lower HDL cholesterol level ( P =.003), a higher LDL/HDL ratio ( P =.003), and to a lesser extent, a higher LDL cholesterol level ( P =.07). No association was found with plasma triglycerides or very low-density lipoprotein cholesterol levels. Among FH patients, ectasia was strongly associated with an overall index of occlusive atherosclerotic disease, based on quantitative angiography ( P =.004). Intracoronary ultrasound interrogation of aneurysmal segments revealed circumferential intimal thickening. Conclusions Coronary ectasia is more prevalent in patients with FH than in other patients with coronary atherosclerosis and shows a strong inverse association with HDL cholesterol levels. This suggests that disordered lipoprotein metabolism in FH may predispose patients to aneurysmal coronary artery disease.
Dietary fat intake and risk of stroke in male US healthcare professionals: 14 year prospective cohort study
Authors: K. He
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To examine the association between intake of total fat, specific types of fat, and cholesterol and risk of stroke in men. <b>Design and setting</b> Health professional follow up study with 14 year follow up. <b>Participants</b> 43 732 men aged 40–75 years who were free from cardiovascular diseases and diabetes in 1986. <b>Main outcome measure</b> Relative risk of ischaemic and haemorrhagic stroke according to intake of total fat, cholesterol, and specific types of fat. <b>Results</b> During the 14 year follow up 725 cases of stroke occurred, including 455 ischaemic strokes, 125 haemorrhagic stokes, and 145 strokes of unknown type. After adjustment for age, smoking, and other potential confounders, no evidence was found that the amount or type of dietary fat affects the risk of developing ischaemic or haemorrhagic stroke. Comparing the highest fifth of intake with the lowest fifth, the multivariate relative risk of ischaemic stroke was 0.91 (95% confidence interval 0.65 to 1.28; P for trend = 0.77) for total fat, 1.20 (0.84 to 1.70; P = 0.47) for animal fat, 1.07 (0.77 to 1.47; P = 0.66) for vegetable fat, 1.16 (0.81 to 1.65; P = 0.59) for saturated fat, 0.91 (0.65 to 1.28; P = 0.83) for monounsaturated fat, 0.88 (0.64 to 1.21; P = 0.25) for polyunsaturated fat, 0.87 (0.62 to 1.22; P = 0.42) for <i>trans</i> unsaturated fat, and 1.02 (0.75 to 1.39; P = 0.99) for dietary cholesterol. Intakes of red meats, high fat dairy products, nuts, and eggs were also not appreciably related to risk of stroke. <b>Conclusions</b> These findings do not support associations between intake of total fat, cholesterol, or specific types of fat and risk of stroke in men.
Gene-Environment Interactions in the Development of Type 2 Diabetes: Recent Progress and Continuing Challenges
Authors: Marilyn C. Cornelis, Frank B. Hu
Journal: Annual Review of Nutrition (2012)

Type 2 diabetes (T2D) is thought to arise from the complex interplay of both genetic and environmental factors. Since the advent of genome-wide association studies (GWAS), we have seen considerable progress in our understanding of the role that genetics and gene-environment interactions play in the development of T2D. Recent work suggests that the adverse effect of several T2D loci may be abolished or at least attenuated by higher physical activity levels or healthy lifestyle, whereas low physical activity and dietary factors characterizing a Western dietary pattern may augment it. However, there still remain inconsistencies warranting further investigation. Lack of statistical power and measurement errors for the environmental factors continue to challenge our efforts for characterizing interactions. Although our recent focus on established T2D loci is reasonable, we may be overlooking many other potential loci not captured by recent T2D GWAS. Agnostic approaches to the discovery of gene and environment interactions may address this possibility, but their application to the field is currently limited and still faces conceptual challenges. Nonetheless, continued investment in gene-environment interaction studies through large collaborative efforts holds promise in furthering our understanding of the interplay between genetic and environmental factors.