tbuckley/cabot-search huggingface dataset:
Myocardial infarction in young patients: an analysis by age subsets.
Authors: B D Hoit, E A Gilpin, H Henning, A A Maisel, H Dittrich, J Carlisle, J Ross
Journal: Circulation (1986)

We examined, in age subsets, 2643 patients with acute myocardial infarction. Clinical features and 1 year morbidity and mortality were compared in 203 young patients (less than 45 years), 1671 patients 46 to 70 years old, and 769 elderly patients (greater than 70 years). Ninety-two percent of young patients were men, and a family history of premature coronary artery disease was more common in young patients (41% compared with 28% of middle-aged and 12% of elderly patients). More young patients were currently smoking cigarettes (82% compared with 56% of middle-aged and 24% of elderly patients), and only 8% of young patients had never smoked. Previous myocardial infarction and history of angina pectoris or congestive heart failure were less common (p less than .001) in the young patients than in middle-aged and elderly patients. In-hospital mortality was only 2.5% for young patients, compared with 9.0% in middle-aged and 21.4% in elderly patients (both p less than .001). Postdischarge 1 year mortality was also strikingly low in young patients, at 2.6% compared with 10.3% in middle-aged and 24.4% in elderly patients. The incidence of reinfarction during the 1 year of follow-up was similar in all subsets. The statistical significance of 65 variables as predictors of 1 year mortality and reinfarction was tested and the following found to be significant (p less than .05): hospital discharge on antiarrhythmic drugs, digoxin, or diuretics; history of previous myocardial infarction or congestive heart failure; chest x-ray findings of heart failure; low ejection fraction; and atrial fibrillation. Thus, young patients entering the hospital have an excellent 1 year prognosis, but those with prior infarction in whom there are selected abnormal findings at hospital discharge comprise a subgroup that may benefit from early aggressive management.
Genetics and pulmonary medicine bullet 3: Genetic susceptibility to tuberculosis in human populations
Authors: R. Bellamy
Journal: Thorax (1998)

Prior to the discovery of the tubercle bacillus, the observation that tuberculosis frequently occurred in many members of the same family convinced physicians that it was a hereditary disease.1 However, in 1882 when Robert Koch demonstrated that tuberculosis was caused by a microorganism,2attention turned to the importance of the pathogen and the genetic constitution of the host was largely ignored. It is estimated that only 10% of those who become infected with Mycobacterium tuberculosis will ever develop clinical disease,3 and in only a few cases is there an obvious identifiable risk factor such as diabetes, advanced age, alcohol abuse, HIV infection, or corticosteroid usage. Why then do some people succumb to the disease when most of the population can successfully fight off the tubercle bacillus? Clearly, although M tuberculosis is necessary, it is not sufficient. Determining why only some individuals are susceptible to tuberculosis is important as this will give us insight into which components of disease pathogenesis are important and hopefully assist the development of new treatment or prevention strategies.

It is a common misapprehension that death from multifactorial diseases such as cancer and cardiovascular problems are influenced by genetic factors, but that death from infection is due to a bad environment or simply bad luck. In fact, a study of 960 adoptees in Denmark concluded that the genetic component of susceptibility to premature death from infectious diseases is greater than for cancer or cardiovascular causes.4 In 1949 the pioneering geneticist J B S Haldane recognised that infectious diseases have been the main agent of natural selection during the past 5000 years.5 Organisms which are widespread in the human population and which exert a high mortality will exert the most pronounced evolutionary effects.6 In the early part of the 19th century it …
The anatomy of the sinus of Valsalva
Authors: K. Reid
Journal: Thorax (1970)

The anatomy of the aortic root has been studied in different species, and common structural features of importance have been detailed. The findings confirm the universal presence of a well-marked ridge limiting the distal extent of the aortic sinuses. Redefining the sinuses in this way shows that normally the coronary ostia lie within the sinus proximal to the ridge and it appears that their position relative to the ridge is related to an animal9s fleetness. Aortic cusps in the fresh state have no recoil tendency to bring them into apposition but lie in a collapsed open position. It is suggested that prosthetic outflow valves should imitate the normal valve in this important respect.
Decreased natural killer cell activity in generalized pustular psoriasis (von Zumbusch type)
Authors: M. KAMIŃSKI, A. SZMURŁO, MARIA PAWIŃSKA, STEFANIA JABLOŃSKA
Journal: British Journal of Dermatology (2006)

Mononuclear cells isolated from the peripheral blood of four untreated patients with pustular psoriasis (von Zumbusch type) displayed greatly diminished natural killer cell activity against K-562 erythroleukaemic target cells in a 51Cr release assay when compared with mononuclear cells from healthy controls.
The evolution of malignant and reactive γδ + T cell clones in a relapse T-ALL case after allogeneic stem cell transplantation
Authors: Shaohua Chen, Xin Huang, Haitao Zheng, Suxia Geng, Xiuli Wu, Lijian Yang, Jianyu Weng, Xin Du, Yangqiu Li
Journal: Molecular Cancer (2013)

Abstract Background To improve the outcome of patients with T-cell acute lymphoblastic leukemia (T-ALL), characterization of the biological features of T-ALL blast cells and the immune status of patients with T-ALL is needed to identify specific therapeutic strategies. Findings Using a novel approach based on the combination of fine-tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR), we molecularly identified a malignant γδ + T cell clone with a Vδ5Dδ2Jδ1 rearrangement that was paired with a T cell receptor (TCR) VγI and comprised a Vγ1Vδ5 T cell clone in a relapse T-ALL patient. This malignant Vδ5 T cell clone disappeared after chemotherapy, but the clone was detected again when disease relapsed post allogeneic hematopoietic stem cell transplantation (allo-HSCT) at 100 weeks. Using PCR and GeneScan analyses, the distribution and clonality of the TCR Vγ and Vδ subfamilies were examined before and after allo-HSCT in the patient. A reactive T cell clone with a Vδ4Dδ3Jδ1 rearrangement was identified in all samples taken at different time points (i.e., 4, 8, 68, 100 and 108 weeks after allo-HSCT). The expression of this Vδ4+ T cell clone was higher in the patient during complete remission (CR) post allo-HSCT and at disease relapse. Conclusions This study established a sensitive methodology to detect T cell subclones, which may be used to monitor minimal residual disease and immune reconstitution.
Serum albumin and mortality
Authors: PeterB. Soeters, MaartenF. Von Meyenfeldt, WilhelmusJ.H.J. Meijerink, ElisabethW.H.M. Fredrix, EmielF.M. Wouters, AnnemieM.W.J. Schols, W.R. Williams, Anna Pawlowicz, Brian Davies, Michel De Lor Geril, Jeanne Guidollet, Serge Renaud, P. Gosling, D.G. Beevers, G.E. Goode, N.C. Hickey, W.A. Littler, C.P. Shearman, J.J. Sheridan, J.N.W. West, R. Grimble, B. Darne, P. Ducimetière, L. Guize, RichardG. Stevens, BaruchS. Blumberg
Journal: The Lancet (1990)
Negative Regulation of YAP by LATS1 Underscores Evolutionary Conservation of the <i>Drosophila Hippo</i> Pathway
Authors: Jianmin Zhang, Gromoslaw A. Smolen, Daniel A. Haber
Journal: Cancer Research (2008)

The Hippo pathway defines a novel signaling cascade regulating cell proliferation and survival in Drosophila, which involves the negative regulation of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal amplification locus in mouse and human cancers, and that it mediates dramatic transforming activity in MCF10A primary mammary epithelial cells. Here, we show that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 phenocopies YAP overexpression. Because this effect can be suppressed by simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 in mammalian cells. Expression profiling of genes induced by ectopic expression of YAP or by knockdown of LATS1 reveals a subset of potential Hippo pathway targets implicated in epithelial-to-mesenchymal transition, suggesting that this is a key feature of YAP signaling in mammalian cells.
The New Era of Drug Therapy for Obesity: The Evidence and the Expectations
Authors: Ben J. Jones, Stephen R. Bloom
Journal: Drugs (2015)

There is an urgent need for effective pharmacological therapies to help tackle the growing obesity epidemic and the healthcare crisis it poses. The past 3 years have seen approval of a number of novel anti-obesity drugs. The majority of these influence hypothalamic appetite pathways via dopaminergic or serotoninergic signalling. Some are combination therapies, allowing lower doses to minimize the potential for off-target effects. An alternative approach is to mimic endogenous satiety signals using long-lasting forms of peripheral appetite-suppressing hormones. There is also considerable interest in targeting thermogenesis by brown adipose tissue to increase resting energy expenditure. Obesity pharmacotherapy has seen several false dawns, but improved understanding of the pathways regulating energy balance, and better-designed trials, give many greater confidence that recently approved agents will be both efficacious and safe. Nevertheless, a number of issues from preclinical and clinical development continue to attract debate, and additional large-scale trials are still required to address areas of uncertainty.
Arsenic trioxide improves hematopoiesis in refractory severe aplastic anemia
Authors: Ning Li, Yongping Song, Jian Zhou, Baijun Fang
Journal: Journal of Hematology & Oncology (2012)

Abstract We investigated the efficacy of arsenic trioxide (ATO) in patients with refractory severe aplastic anemia (SAA). A total of 5 consecutive adults were enrolled. The patients received ATO at a dose of 0.15 mg/kg intravenously daily for 5 days every week for 8 weeks. If necessary, a second course was performed after an interval of one week. All patients achieved clinically significant responses to ATO. The overall complete response rate and overall response rate at 17 weeks were 60% (3/5) and 100%(5/5), respectively. So treatment with ATO may be a feasible approach in patients with refractory SAA.
ADAM9 Promotes Lung Cancer Metastases to Brain by a Plasminogen Activator-Based Pathway
Authors: Chen-Yuan Lin, Hung-Jen Chen, Cheng-Chung Huang, Liang-Chuan Lai, Tzu-Pin Lu, Guan-Chin Tseng, Ting-Ting Kuo, Qian-Yu Kuok, Jennifer L. Hsu, Shian-Ying Sung, Mien-Chie Hung, Yuh-Pyng Sher
Journal: Cancer Research (2014)

Abstract The transmembrane cell adhesion protein ADAM9 has been implicated in cancer cell migration and lung cancer metastasis to the brain, but the underpinning mechanisms are unclear and clinical support has been lacking. Here, we demonstrate that ADAM9 enhances the ability of tissue plasminogen activator (tPA) to cleave and stimulate the function of the promigratory protein CDCP1 to promote lung metastasis. Blocking this mechanism of cancer cell migration prolonged survival in tumor-bearing mice and cooperated with dexamethasone and dasatinib (a dual Src/Abl kinase inhibitor) treatment to enhance cytotoxic treatment. In clinical specimens, high levels of ADAM9 and CDCP1 correlated with poor prognosis and high risk of mortality in patients with lung cancer. Moreover, ADAM9 levels in brain metastases derived from lung tumors were relatively higher than the levels observed in primary lung tumors. Our results show how ADAM9 regulates lung cancer metastasis to the brain by facilitating the tPA-mediated cleavage of CDCP1, with potential implications to target this network as a strategy to prevent or treat brain metastatic disease. Cancer Res; 74(18); 5229–43. ©2014 AACR.
Biologic Correlates of 18Fluorodeoxyglucose Uptake in Human Breast Cancer Measured by Positron Emission Tomography
Authors: R. Bos
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Variable uptake of the glucose analog 18fluorodeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared 18FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms. PATIENTS AND METHODS: Preoperative 18FDG-PET scans were performed in 55 patients. 18FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1α); vascular endothelial growth factor (VEGF165); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed. RESULTS: There were positive correlations between 18FDG uptake and Glut-1 expression (P < .001), MAI (P = .001), amount of necrosis (P = .010), number of tumor cells/volume (P = .009), expression of HK I (P = .019), number of lymphocytes (P = .032), and microvessel density (r = .373; P = .005). HIF-1α, VEGF165, HK II, HK III, and macrophages showed no univariate correlation with 18FDG. In logistic regression, however, HIF-1α and HK II added value to MAI and Glut-1. CONCLUSION: 18FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of 18FDG into the cell, HK for entering 18FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1α for upregulating Glut-1. Together, these features explain why breast cancers vary in 18FDG uptake and elucidate the low uptake in lobular breast cancer.
Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain
Authors: Yi Dai, Shenglan Wang, Makoto Tominaga, Satoshi Yamamoto, Tetsuo Fukuoka, Tomohiro Higashi, Kimiko Kobayashi, Koichi Obata, Hiroki Yamanaka, Koichi Noguchi
Journal: Journal of Clinical Investigation (2007)

Proinflammatory agents trypsin and mast cell tryptase cleave and activate PAR2, which is expressed on sensory nerves to cause neurogenic inflammation. Transient receptor potential A1 (TRPA1) is an excitatory ion channel on primary sensory nerves of pain pathway. Here, we show that a functional interaction of PAR2 and TRPA1 in dorsal root ganglion (DRG) neurons could contribute to the sensation of inflammatory pain. Frequent colocalization of TRPA1 with PAR2 was found in rat DRG neurons. PAR2 activation increased the TRPA1 currents evoked by its agonists in HEK293 cells transfected with TRPA1, as well as DRG neurons. Application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP(2)) suppressed this potentiation. Decrease of plasma membrane PIP(2) levels through antibody sequestration or PLC-mediated hydrolysis mimicked the potentiating effects of PAR2 activation at the cellular level. Thus, the increased TRPA1 sensitivity may have been due to activation of PLC, which releases the inhibition of TRPA1 from plasma membrane PIP(2). These results identify for the first time to our knowledge a sensitization mechanism of TRPA1 and a novel mechanism through which trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation.
Lysis of Fresh Human Tumor Cells by Autologous Large Granular Lymphocytes and T-Lymphocytes: Two Distinct Killing Activities Induced by Coculture With Autologous Tumor&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Atsushi Uchida, Michael Moore
Journal: JNCI Journal of the National Cancer Institute (1984)

The specific and natural killer (NK)-restricted nature of autologous tumor killing by blood lymphocytes was studied in patients with carcinomatous pleural effusions. Large granular lymphocytes (LGL) and small T-lymphocytes were isolated by centrifugation on discontinuous Percoll density gradients. Tumor cells freshly isolated from pleural effusions of cancer patients were classified according to their susceptibility to purified LGL from normal donors in a 4-hour 51Cr release assay. Of 15 NK-sensitive tumors, 14 were lysed by fresh autologous LGL, whereas only 2 were killed by T-cells. Neither LGL nor T-cells were cytotoxic to NK-resistant autologous tumor. LGL and T-cells were then cultured in vitro with autologous tumor cells for 6 days. In 13 of 15 autologous mixed lymphocyte-tumor cultures (MLTC) NK-sensitive tumor-cultured LGL maintained their autotumor killing activity, whereas LGL cultured alone lost the activity. Depletion of high-affinity sheep erythrocyte-rosetting cells from Percoll-purified LGL resulted in an enrichment of effector cells. LGL from autologous MLTC were able to kill NK-susceptible allogeneic effusion tumor and K562 as were fresh LGL. No lysis of NK-resistant autologous tumor was observed with cultured LGL. In contrast, activation of T-cells in autologous MLTC resulted in the generation of autotumor killer cells in 10 of 15 NK-sensitive and 3 of 6 NK-resistant tumor samples. However, cultured T-cells were incapable of killing allogeneic tumor and K562. In autologous MLTC T-cells proliferated in response to autologous tumor, whereas no proliferation was observed in the culture of LGL. The enrichment of blasts from cultured T-cells on discontinuous Percoll gradients induced an augmentation of autotumor cytotoxicity, with no reactivity in blast-depleted, small, resting T-lymphocytes. These results indicated that 2 distinct types of autotumor-recognizing lymphocytes, LGL and T-cells, are present in the peripheral blood of cancer patients.
Hospitals put into special measures in 2013 have cut their mortality
Authors: G. Iacobucci
Journal: BMJ (2015)

The ancient auriferous gravels that helped spawn the California Gold Rush have figured prominently in investigations of the Cenozoic history of the Sierra Nevada. These fluvial sediments, scattered throughout the northern half of the range, are the remnants of much larger deposits that accumulated throughout the Eocene and Early Oligocene. In this study, we present a reconstruction of the original extent of the gravels developed according to a few simple rules. This reconstruction suggests that large swaths of the northern Sierra Nevada were once buried under broad alluvial plains, a result consistent with previous work. The reconstruction also supports the hypothesis that the gravels accumulated behind high ridges along the Sierra Nevada foothills, with the Yuba River providing an important outlet. Moreover, gravel deposits on two high peaks indicate that the gravels may have buried the Feather River watershed up to the modern crest of the range. Finally, on the basis of our reconstruction, we estimate that the total volume of the gravels was, at a minimum, ∼200 km<sup>3</sup>.
High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase
Authors: Takuji Ishimoto, Miguel A. Lanaspa, Christopher J. Rivard, Carlos A. Roncal-Jimenez, David J. Orlicky, Christina Cicerchi, Rachel H. McMahan, Manal F. Abdelmalek, Hugo R. Rosen, Matthew R. Jackman, Paul S. MacLean, Christine P. Diggle, Aruna Asipu, Shinichiro Inaba, Tomoki Kosugi, Waichi Sato, Shoichi Maruyama, Laura G. Sánchez-Lozada, Yuri Y. Sautin, James O. Hill, David T. Bonthron, Richard J. Johnson
Journal: Hepatology (2013)

Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease. Here we tested the hypothesis that fructose may interact with a high-fat diet to induce fatty liver, and to determine if this was dependent on a key enzyme in fructose metabolism, fructokinase. Wild-type or fructokinase knockout mice were fed a low-fat (11%), high-fat (36%), or high-fat (36%) and high-sucrose (30%) diet for 15 weeks. Both wild-type and fructokinase knockout mice developed obesity with mild hepatic steatosis and no evidence of hepatic inflammation on a high-fat diet compared to a low-fat diet. In contrast, wild-type mice fed a high-fat and high-sucrose diet developed more severe hepatic steatosis with low-grade inflammation and fibrosis, as noted by increased CD68, tumor necrosis factor alpha, monocyte chemoattractant protein-1, alpha-smooth muscle actin, and collagen I and TIMP1 expression. These changes were prevented in the fructokinase knockout mice. Conclusion: An additive effect of high-fat and high-sucrose diet on the development of hepatic steatosis exists. Further, the combination of sucrose with high-fat diet may induce steatohepatitis. The protection in fructokinase knockout mice suggests a key role for fructose (from sucrose) in this development of steatohepatitis. These studies emphasize the important role of fructose in the development of fatty liver and nonalcoholic steatohepatitis. (Hepatology 2013;58:1632–1643)
Epidermal growth factor receptor gene copy number, K-ras mutation and pathological response to preoperative cetuximab, 5-FU and radiation therapy in locally advanced rectal cancer
Authors: C. Bengala, S. Bettelli, F. Bertolini, S. Salvi, S. Chiara, C. Sonaglio, L. Losi, N. Bigiani, G. Sartori, C. Dealis, N. Malavasi, R. D'Amico, G. Luppi, B. Gatteschi, A. Maiorana, P.F. Conte
Journal: Annals of Oncology (2008)
GPs’ income fell 3% in a year, UK data show
Authors: Abi Rimmer
Journal: BMJ (2015)

GPs’ average income before tax in 2013-14 was £90 200 (€124 000; $140 000), a 3% decrease on the 2012-13 figure, shows an analysis by the NHS Health and Social Care Information Centre.1 The figures relate to UK GPs on the general medical services (GMS) contract and the primary medical services (PMS) contract and to salaried GPs.

The average taxable income of contractor GPs working under a GMS or PMS contract in the United Kingdom was £99 800 in 2013-14. This was a …
Thorax in the 1960s
Authors: A J Robertson
Journal: Thorax (2006)

At the Spring meeting of the Thoracic Society in 1970, I summarised some of the work done after receiving over 700 papers, of which 53% had come from the UK and 45% from 40 different countries. About 40% of all papers were rejected, the acceptance rate being 64% for those from the UK and 56% for those from elsewhere. I do not think we ever refused anything which should have been taken, although we had almost certainly taken some which we should not have accepted.

In those 10 years our circulation rose by over 40%; two thirds were exported and nearly one third of our issues went to the United States. I introduced abstracts at the beginning …