tbuckley/cabot-search huggingface dataset:
Vitamin E Supplementation and Immune Response in Elderly Patients
Authors: Håkan Melhus
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Pak and Rac GTPases promote oncogenic KIT–induced neoplasms
Authors: Holly Martin, Raghuveer Singh Mali, Peilin Ma, Anindya Chatterjee, Baskar Ramdas, Emily Sims, Veerendra Munugalavadla, Joydeep Ghosh, Ray R. Mattingly, Valeria Visconte, Ramon V. Tiu, Cornelis P. Vlaar, Suranganie Dharmawardhane, Reuben Kapur
Journal: Journal of Clinical Investigation (2013)

An acquired somatic mutation at codon 816 in the KIT receptor tyrosine kinase is associated with poor prognosis in patients with systemic mastocytosis and acute myeloid leukemia (AML). Treatment of leukemic cells bearing this mutation with an allosteric inhibitor of p21-activated kinase (Pak) or its genetic inactivation results in growth repression due to enhanced apoptosis. Inhibition of the upstream effector Rac abrogates the oncogene-induced growth and activity of Pak. Although both Rac1 and Rac2 are constitutively activated via the guanine nucleotide exchange factor (GEF) Vav1, loss of Rac1 or Rac2 alone moderately corrected the growth of KIT-bearing leukemic cells, whereas the combined loss resulted in 75% growth repression. In vivo, the inhibition of Vav or Rac or Pak delayed the onset of myeloproliferative neoplasms (MPNs) and corrected the associated pathology in mice. To assess the role of Rac GEFs in oncogene-induced transformation, we used an inhibitor of Rac, EHop-016, which specifically targets Vav1 and found that EHop-016 was a potent inhibitor of human and murine leukemic cell growth. These studies identify Pak and Rac GTPases, including Vav1, as potential therapeutic targets in MPN and AML involving an oncogenic form of KIT.
Fat absorption in germ-free and conventional rats artificially deprived of bile secretion.
Authors: Y Demarne, T Corring, A Pihet, E Sacquet
Journal: Gut (1982)

Bile duct ligation was performed in germ-free and conventional rats in order to study the effects of bile deprivation on the absorption of dietary lipids and the excretion of faecal lipids in the presence or the absence of gastrointestinal flora. The main consequence of bile duct ligation in conventional rats was decrease of about 50% in the apparent absorption of dietary lipids (peanut oil). In germ-free rats, absorption decreased by only about 25%. In conventional as well as in germ-free controls, faecal lipids were mainly excreted as compounds directly soluble in organic solvents that is, free fatty acids, triglycerides, partial glycerides, cholesterol, cholesterol esters. Deprivation of bile secretion significantly increased the faecal excretion of 'insoluble' compounds-that is, calcium soaps-both in germ-free and conventional rats. Free fatty acids and sterol esters were the two main class of soluble faecal lipids both in germ-free and conventional rats deprived of bile secretion. Faecal excretion of triglycerides remained low in germ-free as well as in conventional animals. No significant difference of fatty acid absorption was observed between germ-free and conventional controls. Deprivation of bile secretion resulted in a significant decrease in the absorption of all fatty acids in germ-free as well as in conventional animals. However, the decrease was larger for saturated fatty acids-that is, 16:0 or 18:0- than for unsaturated fatty acids-that is, 18:1 or 18:2. The absorption of all fatty acids, except linoleic acid (18:2), was significantly lower in conventional rats artificially deprived of bile secretion than in their germ-free counterparts. Evidence was given for a negative digestive balance of stearic acid (18:0) in bile deprived conventional animals. This observation was correlated with a very efficient biohydrogenation of dietary unsaturated fatty acids as revealed by radio gas chromatography of faecal acids in bile deprived conventional rats fed a diet containing 1-14C oleic acid (18:1) as homogeneous triglycerides. Nevertheless, biohydrogenation of unsaturated dietary fatty acids by the gastrointestinal flora was not considered to be the only factor involved in the origin of the difference of fat absorption between bile deprived germ-free and conventional animals.
Effect of Exercise on Serum Estrogens in Postmenopausal Women
Authors: Anne McTiernan, Shelley S. Tworoger, Cornelia M. Ulrich, Yutaka Yasui, Melinda L. Irwin, Kumar B. Rajan, Bess Sorensen, Rebecca E. Rudolph, Deborah Bowen, Frank Z. Stanczyk, John D. Potter, Robert S. Schwartz
Journal: Cancer Research (2004)

Abstract Elevated circulating estrogens and a sedentary lifestyle increase risk for breast cancer. The effect of exercise on circulating estrogens in sedentary postmenopausal women is unknown. The objective of this study was to examine the effects of a 12-month moderate-intensity exercise intervention on serum estrogens. We randomly assigned 173 sedentary, overweight (body mass index &amp;gt; 24.0 kg/m2, body fat &amp;gt; 33%), postmenopausal women, ages 50–75 years, not using hormone therapy, living in the Seattle, Washington, area for the next year, and willing to be randomly assigned to an exercise intervention or stretching control group. The exercise intervention included facility and home-based exercise (45 min, 5 days/week moderate intensity sports/recreational exercise). A total of 170 (98.3%) women completed the study with exercisers averaging 171 min/week of exercise. After 3 months, exercisers experienced declines in estrone, estradiol, and free estradiol of 3.8, 7.7, and 8.2%, respectively, versus no change or increased concentrations in controls (P = 0.03, 0.07, and 0.02, respectively). At 12 months, the direction of effect remained the same, although the differences were no longer statistically significant. The effect was limited to women who lost body fat: women whose percentage of body fat [by dual energy x-ray absortiometry (DEXA)] decreased by ≥2% had statistically significant (comparing exercisers versus controls) decreases at 12 months of 11.9, 13.7, and 16.7% for serum estrone, estradiol, and free estradiol, respectively. We concluded that a 12-month moderate-intensity exercise intervention in postmenopausal women resulted in significant decreases in serum estrogens. The association between increased physical activity and reduced risk for postmenopausal breast cancer may be partly explained by effects on serum estrogens.
High-Dose Etoposide: From Phase I to a Component of Curative Therapy
Authors: Steven N. Wolff, John D. Hainsworth, F. Anthony Greco
Journal: Journal of Clinical Oncology (2008)

In 1983, we reported in Journal of Clinical Oncology 1 a phase I high-dose escalation study of the chemotherapeutic agent etoposide.By reinfusing autologous bone marrow to assure hematopoietic recovery, we were able to identify the nonmyeloid dose-limiting toxicity of this agent.At the same time, other chemotherapy agents were similarly studied, based on the concept that high-dose therapy might be superior treatment for cancers that were not successfully treated with standard-dose cytotoxic therapy. [2]3][4][5][6][7][8] The results of these singleagent studies led to the development of the combination regimens that today remain integral to high-dose anticancer therapy.The intravenous infusion of marrow-derived hematopoietic stem cells to facilitate marrow ablative cytotoxic therapy was under intense investigation in the 1980s.The fundamentals of such therapy were pioneered, during the previous decade, by Nobel laureate E. Donnell Thomas, MD, and George Santos, MD. 9 They hypothesized that supra-maximal therapy could overcome resistance to standarddose therapy and began to unravel the immunologic aspects of allogeneic graft-versus-host disease.Patients with resistant acute leukemia were initially treated, using fresh allogeneic marrow and cytotoxic therapy consisting of total whole-body irradiation (TBI) with cyclophosphamide or busulfan with cyclophosphamide.These therapies provided two predominant functions: (1) profound immunosuppression to allow engraftment of allogeneic cells and (2) cytoreduction to eradicate leukemia refractory to standard-dose treatment.Despite substantial toxicity, a minority of patients with otherwise incurable acute leukemia achieved long-term complete remission.Autologous cryopreserved marrow-derived stem-cell transplantation was similarly developed to allow patients to donate their own stem cells, thus avoiding the allogeneic consequences of graft-versushost disease.The first reports of cryopreserved autologous transplantation, in the 1980s, used large aliquots of marrow aspirates as the cell source with adequate marrow recovery and cure of some patients with resistant lymphoma. 10,11 In this era, improvements in supportive care
The influence of negative illness cognitions and neuroticism on subjective symptoms and mood in rheumatoid arthritis
Authors: L-O Persson
Journal: Annals of the Rheumatic Diseases (2002)

It was hypothesised that negative RA related illness cognitions are strongly related to the neuroticism trait and act as a common factor behind other self reported subjective symptoms (pain and ADL status), mood, and positive RA related illness cognitions; but are unrelated to objective indices of impairment (disease duration, C reactive protein (CRP), and joint stiffness).To examine the relative influence of negative illness cognitions and neuroticism versus degree of impairment on subjective symptoms, positive illness cognitions, and mood in rheumatoid arthritis (RA).Structural equation modelling analyses (LISREL) were performed on two independent samples of patients with RA consisting of 212 outpatients and 105 inpatients, respectively.The hypotheses were largely confirmed. Firstly, negative RA cognitions were found to be dependent on neuroticism. Secondly, negative RA cognitions had a strong and dominating influence on all other self reported data. Subjective symptoms were equally well explained by negative RA cognitions as by degree of impairment. No relations were found between negative RA cognitions (or neuroticism) and degree of impairment.The findings suggest that neuroticism, recognised as a relatively stable personality trait, strongly influences self rated symptoms and wellbeing in RA. This has important clinical implications concerning the use of standardised self rating questionnaires commonly used to assess illness status in RA and the long term effectiveness of psychological interventions and patient training courses in RA rehabilitation.
Prevention of irinotecan plus5-fluorouracil/leucovorin-induced diarrhoea by oral administration of neomycin plus bacitracin in first-line treatment of advanced colorectal cancer
Authors: A. Alimonti, F. Satta, I. Pavese, E. Burattini, V. Zoffoli, A. Vecchione
Journal: Annals of Oncology (2003)
Metabolic properties of IgG subclasses in man
Authors: Andreas Morell, William D. Terry, Thomas A. Waldmann
Journal: Journal of Clinical Investigation (1970)

Metabolic properties of the four subclasses of human IgG were investigated by performing 47 turnover studies in individuals with normal IgG serum concentrations, as well as in patients with an increased level of one of the subclasses. Studies in 12 subjects with normal IgG serum concentration showed that the average biologic half-life of G(1), G(2), and G(4) was 21 days, while that of G(3) was only 7.1 days. Fractional catabolic rates of G(1), G(2), and G(4) were 6.9 to 8% of the intravascular pool per day. G(3), however, had a higher fractional catabolic rate, amounting to 16.8% of the intravascular pool per day. Distribution of the subclasses was such that the intravascular compartment contained 51-54% of the total body pools of G(1), G(2), and G(4), but 64% of the total body pool of G(3).The short survival and high fractional catabolic rate of G(3) is an inherent property of these molecules, and is not due to denaturation during isolation and radiolabeling. This was demonstrated by studies of a patient with a serum G(3)-myeloma protein. The survival of her own protein, separately labeled either in vivo with guanidoarginine-(14)C or in vitro with (125)I, was determined in the patient. Survivals of the in vivo and in vitro labeled proteins were identical.G(1) and G(3) serum concentrations and synthetic rates were determined. The mean serum concentration of G(1) was 6.8 mg/ml and that of G(3) was 0.7 mg/ml, while their synthetic rates were 25.4 and 3.4 mg/kg per day respectively. The low serum concentration of IgG(2) thus results from a combination of high catabolic and low synthetic rates. Studies in 10 patients with multiple myeloma showed that an elevated serum concentration of any IgG subclass was associated with shortened biologic half-life and increased fractional catabolic rate of all subclasses. The implications of this concentration-catabolism relationship are discussed. The serum concentration of nonmyeloma IgG was usually low in myeloma patients and the synthesis of nonmyeloma IgG was somewhat decreased, suggesting that low serum concentrations of nonmyeloma IgG result from decreased synthesis, as well as from an increased fractional catabolic rate.
Improvement of Staging by Combining Tumor and Treatment Parameters: The Value for Prognostication in Rectal Cancer
Authors: Marleen J.E.M. Gosens, J. Han J.M. van Krieken, Corrie A.M. Marijnen, Elma Meershoek-Klein Kranenbarg, Hein Putter, Harm J. Rutten, Krzysztof Bujko, Cornelis J.H. van de Velde, Iris D. Nagtegaal
Journal: Clinical Gastroenterology and Hepatology (2007)

<b>Background & Aims:</b> Staging of cancer is based on the TNM system. This valuable system takes only tumor-related parameters into account, but in the era of refined surgery and preoperative therapy treatment-related factors are of equal importance. By using rectal cancer as a model we explored the hypothesis that a combination of tumor- and treatment-related parameters will result in improved prognostication. <b>Methods:</b> Standardized clinicopathologic and histologic factors considered predictive for survival were studied in eligible patients treated in a trial for rectal cancer (n = 1324). These factors were analyzed in relation to survival using log-rank tests, Kaplan–Meier curves, and Cox regression both individually and in combination, the latter including TNM staging. A second data set from an independent trial (n = 316) was used for data validation. <b>Results:</b> Multivariate analysis identified nodal status (<i>P</i> = .001) and circumferential margin (<i>P</i> = .001) involvement as the most important prognostic factors for survival. The combination of these factors formed an improved staging system (node status and circumferential margin [NCRM]) compared with the present TNM staging with respect to 5-year cancer-specific survival. The results were confirmed in our independent patient population. <b>Conclusions:</b> NCRM staging of rectal cancer results in a broad range of survival rates and favorable patient grouping. Our data give strong evidence that a staging system combing tumor- and treatment-related factors provides better prognostic information than the classic TNM system, which is based solely on tumor-related factors. Similar results might be obtained in other types of cancer in which quality of treatment is important for outcome.
Leading Causes of Death in the United States
Authors: E. F. Tierney
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<i>CCR</i>20th Anniversary Commentary: From Regulatory T Cells to Checkpoint Monoclonal Antibodies—Immuno-oncology Advances Clinical Cancer Research
Authors: Dominik Wolf, Anna Maria Wolf
Journal: Clinical Cancer Research (2015)

Abstract Immune escape is a hallmark of cancer development and metastasis. Regulatory T cells (Treg) are potent inhibitors of cancer immune surveillance but also prevent inflammation-driven tumorigenesis. The study by Wolf and colleagues, which was published in the February 2003 issue of Clinical Cancer Research, showed the expansion of Treg in solid cancer patients, providing a deeper understanding of cancer immune escape mechanisms that later set the stage for the development of scientific breakthroughs in cancer immunotherapy. Clin Cancer Res; 21(12); 2657–9. ©2015 AACR. See related article by Wolf et al., Clin Cancer Res 2003;9(2) Feb 2003;606–12
Clinical and immunologic aspects of egg donation pregnancies: a systematic review
Authors: M. L. P. van der Hoorn, E. E. L. O. Lashley, D. W. Bianchi, F. H. J. Claas, C. M. C. Schonkeren, S. A. Scherjon
Journal: Human Reproduction Update (2010)

Egg donation (ED) makes it possible for subfertile women to conceive. Pregnancies achieved using ED with unrelated donors are unique, since the entire fetal genome is allogeneic to the mother. The aims of this review were to evaluate the consequences of ED pregnancies and to place them in the special context of their atypical immunologic relationships.This review comprised an online search of English language publications listed in Pubmed/Medline, up to 29 January 2010. Seventy-nine papers met inclusion criteria. Using the literature and the authors' own experience, the relevant data on pregnancy outcome and complications, placental pathology and immunology were evaluated.Multiple studies document that ED pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. The incidence of other perinatal complications, such as intrauterine growth restriction, prematurity and congenital malformations, is comparable to conventional IVF. During pregnancy, both local and systemic immunologic changes occur and in ED pregnancies these changes are more pronounced. There is almost no information in the literature on the long-term complications of ED pregnancies for the mother.ED pregnancies have a higher risk of maternal morbidity. Owing to the high degree of antigenic dissimilarity, ED pregnancies represent an interesting model to study complex immunologic interactions, as the fully allogeneic fetus is not rejected but tolerated by the pregnant woman. Knowledge of the immune system in ED pregnancies has broader significance, as it may also give insight into immunologic aspects of tolerance in solid organ transplantation.
Contextual Synthetic Lethality of Cancer Cell Kill Based on the Tumor Microenvironment
Authors: Norman Chan, Isabel M. Pires, Zuzana Bencokova, Carla Coackley, Kaisa R. Luoto, Nirmal Bhogal, Minalini Lakshman, Ponnari Gottipati, F. Javier Oliver, Thomas Helleday, Ester M. Hammond, Robert G. Bristow
Journal: Cancer Research (2010)

Abstract Acute and chronic hypoxia exists within the three-dimensional microenvironment of solid tumors and drives therapy resistance, genetic instability, and metastasis. Replicating cells exposed to either severe acute hypoxia (16 hours with 0.02% O2) followed by reoxygenation or moderate chronic hypoxia (72 hours with 0.2% O2) treatments have decreased homologous recombination (HR) protein expression and function. As HR defects are synthetically lethal with poly(ADP-ribose) polymerase 1 (PARP1) inhibition, we evaluated the sensitivity of repair-defective hypoxic cells to PARP inhibition. Although PARP inhibition itself did not affect HR expression or function, we observed increased clonogenic killing in HR-deficient hypoxic cells following chemical inhibition of PARP1. This effect was partially reversible by RAD51 overexpression. PARP1−/− murine embryonic fibroblasts (MEF) showed a proliferative disadvantage under hypoxic gassing when compared with PARP1+/+ MEFs. PARP-inhibited hypoxic cells accumulated γH2AX and 53BP1 foci as a consequence of altered DNA replication firing during S phase–specific cell killing. In support of this proposed mode of action, PARP inhibitor–treated xenografts displayed increased γH2AX and cleaved caspase-3 expression in RAD51-deficient hypoxic subregions in vivo, which was associated with decreased ex vivo clonogenic survival following experimental radiotherapy. This is the first report of selective cell killing of HR-defective hypoxic cells in vivo as a consequence of microenvironment-mediated “contextual synthetic lethality.” As all solid tumors contain aggressive hypoxic cells, this may broaden the clinical utility of PARP and DNA repair inhibition, either alone or in combination with radiotherapy and chemotherapy, even in tumor cells lacking synthetically lethal, genetic mutations. Cancer Res; 70(20); 8045–54. ©2010 AACR.
The Use of Radiolabelled 18-F-2-Deoxy-2-Fluro-Glucose (18-FDG) in Combined Positron Emission Tomography-Computed Tomography (PET-CT) to Evaluate Infection: Lessons Learned from a Case Series of 23 Patients with Chronic Granulomatous Disease (CGD)
Authors: Amanda K. Rudman Spergel, Clara C. Chen, Cheryl Ann Beegle, Patricia Littel, Mary Garofalo, Sandra Anaya-O'Brien, Martha Marquesen, Ulas Bagci, Daniel J. Mollura, John I. Gallin, Harry L. Malech
Journal: Journal of Allergy and Clinical Immunology (2015)
A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells
Authors: Ju-Seog Lee, Jeonghoon Heo, Louis Libbrecht, In-Sun Chu, Pal Kaposi-Novak, Diego F Calvisi, Arsen Mikaelyan, Lewis R Roberts, Anthony J Demetris, Zongtang Sun, Frederik Nevens, Tania Roskams, Snorri S Thorgeirsson
Journal: Nature Medicine (2006)