tbuckley/cabot-search huggingface dataset:
Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras–initiated leukemia
Authors: Mark Y. Chiang, Lanwei Xu, Olga Shestova, Gavin Histen, Sarah L’Heureux, Candice Romany, M. Eden Childs, Phyllis A. Gimotty, Jon C. Aster, Warren S. Pear
Journal: Journal of Clinical Investigation (2008)

Gain-of-function NOTCH1 mutations are found in 50%-70% of human T cell acute lymphoblastic leukemia/lymphoma (T-ALL) cases. Gain-of-function NOTCH1 alleles that initiate strong downstream signals induce leukemia in mice, but it is unknown whether the gain-of-function NOTCH1 mutations most commonly found in individuals with T-ALL generate downstream signals of sufficient strength to induce leukemia. We addressed this question by expressing human gain-of-function NOTCH1 alleles of varying strength in mouse hematopoietic precursors. Uncommon gain-of-function NOTCH1 alleles that initiated strong downstream signals drove ectopic T cell development and induced leukemia efficiently. In contrast, although gain-of-function alleles that initiated only weak downstream signals also induced ectopic T cell development, these more common alleles failed to efficiently initiate leukemia development. However, weak gain-of-function NOTCH1 alleles accelerated the onset of leukemia initiated by constitutively active K-ras and gave rise to tumors that were sensitive to Notch signaling pathway inhibition. These data show that induction of leukemia requires doses of Notch1 greater than those needed for T cell development and that most NOTCH1 mutations found in T-ALL cells do not generate signals of sufficient strength to initiate leukemia development. Furthermore, low, nonleukemogenic levels of Notch1 can complement other leukemogenic events, such as activation of K-ras. Even when Notch1 participates secondarily, the resulting tumors show "addiction" to Notch, providing a further rationale for evaluating Notch signaling pathway inhibitors in leukemia.
Tumor Cytotoxicity of Human Macrophages After Incubation With Synthetic Analogues of 2-Lysophosphatidylcholine2
Authors: Reinhard Andreesen, Jürgen Osterholz, G. Albrecht Luckenbach, Ullrich Costabel, Annegret Schulz, Volker Speth, Paul G. Munder, Georg W. Löhr
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Tumor Cytotoxicity of Human Macrophages After Incubation With Synthetic Analogues of 2-Lysophosphatidylcholine Get access Reinhard Andreesen, Reinhard Andreesen Search for other works by this author on: Oxford Academic PubMed Google Scholar Jürgen Osterholz, Jürgen Osterholz Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Albrecht Luckenbach, G. Albrecht Luckenbach Search for other works by this author on: Oxford Academic PubMed Google Scholar Ullrich Costabel, Ullrich Costabel Search for other works by this author on: Oxford Academic PubMed Google Scholar Annegret Schulz, Annegret Schulz Search for other works by this author on: Oxford Academic PubMed Google Scholar Volker Speth, Volker Speth Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul G. Munder, Paul G. Munder Search for other works by this author on: Oxford Academic PubMed Google Scholar Georg W. Löhr Georg W. Löhr Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 72, Issue 1, January 1984, Pages 53–59, https://doi.org/10.1093/jnci/72.1.53 Published: 01 January 1984 Article history Received: 08 March 1983 Accepted: 26 July 1983 Published: 01 January 1984
Clinical and evolutive patterns of respiratory infections in patients with HIV/AIDS from Timis County, Romania
Authors: Iosif Marincu, Lucian Negrutiu, Stefan Mihaicuta, Ioan Iacobiciu, Nicoleta Bertici, Carmen Ardelean, Ioana Todor, Adriana Neghina, Cristian Oancea, Stefan Frent, Raul Neghina
Journal: European Respiratory Journal (2011)

Background:  Acute respiratory diseases are part of opportunistic infections developed by patients with HIV/AIDS due to immunosuppression. The present study aims evaluating the clinical and evolutive patterns of acute respiratory infections in patients with HIV/AIDS.   Methods:  The authors have retrospectively analyzed 82 patients with HIV/AIDS and acute respiratory diseases admitted at Clinic of Infectious Diseases. The positive diagnosis was based on clinical elements, biological parameters (erythrocyte sedimentation rate, leukocyte count, fibrinogen, C-reactive protein, sputum culture etc) and paraclinic elements (chest radiography, spirometry).   Results:  From the study group, 52 patients with acute respiratory diseases (p=0.04) have been registered: 10 cases (12.19%) had bacterial pneumonia, 8 (9.75%) had interstitial pneumonia, 4 (4.87%) had fungal pneumonia, 8 (9.75%) had acute bronchitis, 11 (13.41%) had influenza, 7 (8.53%) had acute anginas and 4 (4.87%) had pulmonary tuberculosis. The etiological agent has been isolated in 21 cases: 7 with  Streptococcus pneumoniae , 4 with  Staphilococcus aureus , 2 with  Klebsiella pneumoniae , 4 with  Pneumocystis jirovecii  and 4 with  Mycobacterium tuberculosis . In 54 cases, CD4-cell count was less than 200 cells/mm 3  and 28 cases (p=0.01) over 200 cells/mm 3 . Under specific therapy and antiviral treatment, the clinical outcome has been favourable in 50 cases, only 2 cases died with pulmonary tuberculosis.   Conclusion:  The detailed study of the clinical and evolutive patterns of respiratory infections in patients with HIV/AIDS allows timely implementation of specific therapy and prophylaxis in this populational group with multiple risks.
Perceived Mental Stress and Mortality From Cardiovascular Disease Among Japanese Men and Women
Authors: Hiroyasu Iso, Chigusa Date, Akio Yamamoto, Hideaki Toyoshima, Naohito Tanabe, Shogo Kikuchi, Takaaki Kondo, Yoshiyuki Watanabe, Yasuhiko Wada, Teruo Ishibashi, Hiroshi Suzuki, Akio Koizumi, Yutaka Inaba, Akiko Tamakoshi, Yoshiyuki Ohno
Journal: Circulation (2002)

Background— Perceived mental stress has been associated with risk of coronary heart disease (CHD) in white men, but no prospective data are available for other ethnic groups. Methods and Results— From 1988 to 1990, a total of 73 424 Japanese (30 180 men and 43 244 women), aged 40 to 79 years, without a history of stroke, CHD, or cancer completed a lifestyle questionnaire including perception of mental stress under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study). Systematic surveillance was completed until the end of 1997, with a 580 378 person-year follow-up, and the underlying causes of death were determined according to the International Classification of Diseases , 10th revision. For women, there were 316 with total stroke, 113 with CHD, and 643 with total cardiovascular disease (CVD); for men, there were 341, 168, and 778, respectively. Women who reported high stress had a 2-fold higher age-adjusted risk of mortality from total stroke and CHD and 1.5-fold higher risk of total CVD compared with those who reported low stress. Further adjustment for known cardiovascular risk factors and selected psychological variables did not alter the associations materially. The multivariate relative risk for women who perceived high stress versus low stress was 2.24 (95% CI 1.52 to 3.31, P &lt;0.001) for total stroke, 2.28 (95% CI 1.17 to 4.43, P =0.02) for CHD, and 1.64 (95% CI 1.25 to 2.16, P &lt;0.001) for total CVD. For men, these relations were generally weaker but suggestive of myocardial infarction. Conclusions— Perceived mental stress was associated with increased mortality from stroke for women and with CHD for men and women.
Reply to “Letter to the Editor on ‘Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study’”, by V. C. G. Tjan-Heijnen, P. E. Postmus &amp;A. Ardizzoni(Ann Oncol 2002; 13: 485–486)
Authors: P. Bunn
Journal: Annals of Oncology (2002)
Bronchoalveolar lavage fluid findings in patients with chronic hepatitis C virus infection.
Authors: K Kubo, S Yamaguchi, K Fujimoto, M Hanaoka, M Hayasaka, T Honda, T Sodeyama, K Kiyosawa
Journal: Thorax (1996)

BACKGROUND: Hepatitis C virus (HCV) infection has recently been incriminated as an aetiological agent in idiopathic pulmonary fibrosis. This study was performed to determine the cellularity and lymphocyte phenotypes of bronchoalveolar lavage (BAL) fluid in patients with chronic hepatitis C. METHODS: BAL fluid and lavage lymphocyte subsets from 13 patients (10 men) with active chronic hepatitis C, diagnosed by sustained elevated serum glutamic pyruvic transaminase and typical histological findings in the liver, were analysed. Lavage findings in these patients were compared with those from 13 healthy volunteers (eight men) as controls. RESULTS: There was no difference in total cell counts in lavage fluid between the two groups. Lavage lymphocyte and eosinophil numbers were increased in patients with chronic hepatitis C. Surface marker analysis of the lymphocyte populations showed increases in CD2, CD3, CD4, and HLA-DR. CD4/CD8 ratios were not different. CONCLUSIONS: The numbers of lymphocytes and eosinophils in BAL fluid are increased in patients with chronic hepatitis C. These findings suggest that HCV infection may trigger alveolitis.
Functional Genetic Screens Identify Genes Essential for Tumor Cell Survival in Head and Neck and Lung Cancer
Authors: Sanne R. Martens-de Kemp, Remco Nagel, Marijke Stigter-van Walsum, Ida H. van der Meulen, Victor W. van Beusechem, Boudewijn J.M. Braakhuis, Ruud H. Brakenhoff
Journal: Clinical Cancer Research (2013)

Despite continuous improvement of treatment regimes, the mortality rates for non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) remain disappointingly high and novel anticancer agents are urgently awaited.We combined the data from genome-wide siRNA screens on tumor cell lethality in a lung and a head and neck cancer cell line.We identified 71 target genes that seem essential for the survival of both cancer types. We identified a cluster of 20 genes that play an important role during G2-M phase transition, underlining the importance of this cell-cycle checkpoint for tumor cell survival. Five genes from this cluster (CKAP5, KPNB1, RAN, TPX2, and KIF11) were evaluated in more detail and have been shown to be essential for tumor cell survival in both tumor types, but most particularly in HNSCC. Phenotypes that were observed following siRNA-mediated knockdown of KIF11 (kinesin family member 11) were reproduced by inhibition of KIF11 using the small-molecule inhibitor ispinesib (SB-715992). We showed that ispinesib induces a G2 arrest, causes aberrant chromosome segregation, and induces cell death in HNSCC in vitro, whereas primary keratinocytes are less sensitive. Furthermore, growth of HNSCC cells engrafted in immunodeficient mice was significantly inhibited after ispinesib treatment.This study identified a wide array of druggable genes for both lung and head and neck cancer. In particular, multiple genes involved in the G2-M checkpoint were shown to be essential for tumor cell survival, indicating their potential as anticancer targets.
A role for NLRP3 inflammasome in acute myocardial ischaemia-reperfusion injury?
Authors: W. M. C. Jong, C. J. Zuurbier
Journal: Cardiovascular Research (2013)

With much interest we have read the recently published article by Sandanger et al .,1 where NLRP3 mRNA expression was shown to be increased 3–7 days following permanent occlusion of the left anterior descending artery. The increased expression was observed mainly in fibroblasts. The authors also compared hearts from wild-type (WT) C57Bl/6, NLRP3−/−, and ASC−/− mice, using an isolated Langendorff-perfused heart model of acute ischaemia-reperfusion injury. It was reported that deletion of NLRP3 improved cardiac function and reduced infarct size in the isolated heart model. The authors summarized the data and combined the results from the in …
Prolonged self-renewal activity unmasks telomerase control of telomere homeostasis and function of mouse hematopoietic stem cells
Authors: Sanja Sekulovic, Vala Gylfadottir, Irma Vulto, Maura Gasparetto, Yasmine Even, Christy Brookes, Clayton Smith, Connie J. Eaves, Peter M. Lansdorp, Fabio M. Rossi, R. Keith Humphries
Journal: Blood (2011)
Pentagastrin in diffuse oesophageal spasm.
Authors: R M Wexler, M D Kaye
Journal: Gut (1981)

The effect of pentagastrin on oesophageal motility was studied in six subjects with idiopathic diffuse oesophageal spasm (IDOS). Pentagastrin was administered by continuous intravenous infusion in doses of 1 microgram/kg/h, 5 micrograms/kg/h, and 10 micrograms/kg/h. Saline infusion was used as a control. No subject experienced pain during pentagastrin infusion. Two developed dysphagia and repetitive contractions with 'wet' swallows during the saline infusion and the lowest pentagastrin infusion. Contraction amplitude was increased only with 'dry' swallows during the 10 micrograms/kg/h infusion period. Contraction duration was increased with both 'wet' and 'dry' swallows during the 1 microgram/kg/h infusions, and with 'dry' swallows during the 10 micrograms/kg/h infusion. Propagation velocity was not altered by pentagastrin. We conclude that gastrin released physiologically by eating probably does not contribute to symptom production in IDOS. Moreover, it seems unlikely that pentagastrin, at least in these doses, can be exploited for diagnostic purposes.
Epigenetic Silencing of Occludin Promotes Tumorigenic and Metastatic Properties of Cancer Cells via Modulations of Unique Sets of Apoptosis-Associated Genes
Authors: Makoto Osanai, Masaki Murata, Nami Nishikiori, Hideki Chiba, Takashi Kojima, Norimasa Sawada
Journal: Cancer Research (2006)

Abstract Occludin is the first identified integral protein for the tight junction (TJ), and its long COOH-terminal domain is considered to have functions in receiving and transmitting cell survival signals. Loss of TJ-associated molecules, such as occludin, has been correlated with tumor progression in carcinogenesis; however, the precise molecular mechanisms explaining its loss of expression and whether occludin expression has any effects on cancer phenotypes remain to be clarified. Here, we show that forced expression of occludin in cancer cells exhibits enhanced sensitivity to differently acting apoptogenic factors, and thus inhibits the tumorigenicity of transformed cells, via modulation of unique sets of apoptosis-associated genes. In addition, studies using deletion mutants of occludin constructs show that 44 amino acids at the COOH-terminal end play a critical role in modifying the cellular phenotypes. Interestingly, occludin decreases cellular invasiveness and motility, thereby abrogating metastatic potencies of cancer cells. We also found that occludin expression is silenced by CpG island hypermethylation on its promoter region. Synergy with a demethylator and histone deacetylase inhibitor or retinoids that stimulate retinoic acid receptor α induces endogenous occludin, which is sufficient for apoptotic sensitization. Our results show the functional diversity of occludin and suggest that methylator phenotype of occludin provides enhanced tumorigenic, invasive, and metastatic properties of cancer cells, identifying occludin as a likely candidate for a tumor-suppressor gene in certain types of cancer. (Cancer Res 2006; 66(18): 9125-33)
Experimental irritant contact dermatitis due to cumulative epicutaneous exposure to sodium lauryl sulphate and toluene: single and concurrent application
Authors: W. Wigger-Alberti, A. Krebs, P. Elsner
Journal: British Journal of Dermatology (2000)

In clinical practice, cutaneous exposure to a variety of irritants such as surfactants and solvents is frequent. Although the induction of irritant dermatitis by single irritants has been extensively studied in recent years, our knowledge of the effects of simultaneous application of different irritants is limited. Using non-invasive techniques for measurements of transepidermal water loss (TEWL) and skin colour reflectance, we quantified the irritant effects of single and concurrent application of 0.5% sodium lauryl sulphate (SLS) and undiluted toluene (TOL) in vivo. The irritants were applied twice daily for 30 min to the volar forearms of 20 volunteers. Repeated application of SLS and TOL induced an irritant reaction, as indicated by an increase in TEWL and skin redness. In contrast to SLS alone, the application of TOL alone induced only a moderate increase in TEWL, confirming previous results. Concurrent application of SLS/TOL and TOL/SLS induced significantly stronger reactions than those caused by twice daily application of each irritant on its own. Our results demonstrate that a mixed application of an anionic detergent and an organic solvent has an additive effect on skin irritation. It is suggested that pretreatment with SLS causes an increased susceptibility to TOL irritation and vice versa. Thus, the necessity for special precautions against skin absorption of TOL when handling detergents such as SLS is emphasized.
UK government may face legal challenge from Philip Morris over plain cigarette packaging
Authors: A. O'Dowd
Journal: BMJ (2014)

One of the world’s largest tobacco firms is considering legal action against the UK government over its plans to introduce plain packaging for tobacco products.

Philip Morris Ltd, the UK affiliate of Philip Morris International, which produces Marlboro cigarettes among others, raised the possibility of legal action in its response1 to a recent Department of Health consultation2 on regulations that would introduce plain packaging, …
The clinical and metabolic effects of porcine calcitonin on Paget's disease of bone
Authors: Florence Shai, Richard K. Baker, Stanley Wallach
Journal: Journal of Clinical Investigation (1971)

The clinical and metabolic effects of porcine calcitonin were assessed in six patients with Paget's disease and two patients with osteoporosis under metabolic balance conditions. The administration of calcitonin for 4-17 wk resulted in an amelioration of the clinical phenomena associated with Paget's disease, including bone pain, increased skeletal vascularity, congestive heart failure, and neurologic deficits secondary to skeletal impingement. The major metabolic effects of calcitonin in Paget's disease included the induction of positive calcium balance of +50 to +240 mg/day, reduction in hyperphosphatasia and hydroxyprolinuria of 15 to 60%, and a deceleration of radiocalcium turnover by 12 to 46%. Natriuresis, phosphaturia, and reduced urinary calcium excretion were observed, whereas sustained hypocalcemia and hypophosphatemia did not occur. The administration of porcine calcitonin was not associated with adverse objective or subjective reactions, toxic effects, or allergic phenomena. There was no evidence of antibody formation or loss of therapeutic potency. Although the response of individual patients with Paget's disease varied widely, the data indicate that calcitonin, presumably through its skeletal anti-resorptive action, is able to reduce skeletal turnover and volume in Paget's disease, and thereby improve the associated clinical and metabolic abnormalities. Long term therapeutic studies in progress suggest that prolonged periods of control of the generalized condition may be feasible.
Interaction of pentagastrin and the octapeptide of cholecystokinin on the human lower oesophageal sphincter
Authors: R. A. L. Sturdevant, T. Kun
Journal: Gut (1974)

The intravenous infusion of the octapeptide of cholecystokinin inhibited the response of the lower oesophageal sphincter to graded doses of pentagastrin in normal men. The possibility that the effects of these peptides on the lower oesophageal sphincter are only pharmacological and not physiological is discussed.
Immune-mediated pathology in Duchenne muscular dystrophy
Authors: Amy S. Rosenberg, Montserrat Puig, Kanneboyina Nagaraju, Eric P. Hoffman, S. Armando Villalta, V. Ashutosh Rao, Lalage M. Wakefield, Janet Woodcock
Journal: Science Translational Medicine (2015)

Immunopathology contributes to the destruction and fibrosis of muscle in Duchenne muscular dystrophy, reducing the efficacy of dystrophin-replacement therapies.
Oxygen delivery and uptake relationships in patients with aortic stenosis.
Authors: P T Schumacker, J S Soble, T Feldman
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Previous studies have reported finding supply-dependent O2 uptake (VO2) in patients with the adult respiratory distress syndrome, sepsis, chronic obstructive lung disease, sleep apnea, and other cardiopulmonary diseases. A common element among these diverse conditions is the potential to reduce systemic O2 delivery (QO2 = cardiac output.arterial O2 content). The aim of the present study was to determine whether patients with aortic stenosis also exhibit increases in VO2 when O2 delivery is increased after valvuloplasty. Fifty-six patients were studied while breathing room air in the supine position. Expired gases for determination of O2 uptake (VO2 [measured]), cardiac output (thermodilution), arterial and mixed venous blood gases, and hemodynamic measurements were obtained immediately before and within 30 min after aortic valvuloplasty. After valvuloplasty, VO2 (measured) increased from 3.03 +/- 0.51 to 3.24 +/- 0.62 ml/min/kg (p < 0.0001). However, O2 extraction ratio did not change from baseline levels (32.16 +/- 10.1%) after valvuloplasty (32.21 +/- 8.25%, p = not significant). These results could have occurred only if O2 delivery had also increased. Accordingly, Fick-derived Q and corresponding QO2 (Fick) both increased significantly, suggesting the presence of O2 supply-dependent VO2. However, neither Q (thermodilution) nor QO2 (thermodilution) changed significantly, and regression of VO2 (measured) against QO2 (thermodilution) failed to detect a relationship. We conclude that patients with aortic stenosis exhibit increases in O2 delivery and uptake after valvuloplasty, although this may or may not reflect covert tissue hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
The Prospective Contribution of Hostility Characteristics to High Fasting Glucose Levels
Authors: Biing-Jiun Shen, Amanda J. Countryman, Avron Spiro, Raymond Niaura
Journal: Diabetes Care (2008)

To assess whether psychological constructs of hostility, anger, type A behavior pattern, and depressive symptom severity 1) were associated with concurrent and prospective fasting glucose levels and 2) whether this association was moderated by marital status. Participants were 485 healthy men ([mean +/- SD] age 59 +/- 7 years) without a history of heart disease, diabetes, or taking related medications in the Veterans Affairs Normative Aging Study. Their fasting glucose levels between 1986 and 1995 were examined. Hierarchical linear regressions were conducted to investigate whether hostility, anger, type A behavior, and depressive symptoms were associated with concurrent fasting glucose levels as well as fasting glucose 9 years later, controlling for standard sociodemographic and biomedical covariates, including baseline fasting glucose, age, education, marital status, BMI, total cholesterol, and systolic blood pressure. Although none of the psychological variables were associated with concurrent fasting glucose, Cook-Medley hostility (beta = 0.105), anger (beta = 0.091), and type A behavior (beta = 0.152) each were associated with prospective fasting glucose 9 years later, controlling for standard covariates. Depressive symptom severity was not associated with either concurrent or follow-up glucose levels. Further analysis showed that marital status moderated the effects of these characteristics on follow-up fasting glucose such that hostility, anger, and type A behavior were significant only among those who were not married (beta = 0.348, 0.444, 0.439, respectively; all P <0.001). Hostility, anger, and type A behavior appear to be independent risk factors for impaired glucose metabolism among unmarried older men.