tbuckley/cabot-search huggingface dataset:
Functional T Cells Targeting NY-ESO-1 or Melan-A Are Predictive for Survival of Patients With Distant Melanoma Metastasis
Authors: Benjamin Weide, Henning Zelba, Evelyna Derhovanessian, Annette Pflugfelder, Thomas K. Eigentler, Anna Maria Di Giacomo, Michele Maio, Erik H.J.G. Aarntzen, I. Jolanda M. de Vries, Antje Sucker, Dirk Schadendorf, Petra Büttner, Claus Garbe, Graham Pawelec
Journal: Journal of Clinical Oncology (2012)

Purpose To analyze the prognostic relevance of circulating T cells responding to NY-ESO-1, Melan-A, MAGE-3, and survivin in patients with melanoma with distant metastasis. Patients and Methods We examined 84 patients with follow-up after analysis (cohort A), 18 long-term survivors with an extraordinarily favorable course of disease before analysis (&gt; 24 months survival after first occurrence of distant metastases; cohort B), and 14 healthy controls. Circulating antigen-reactive T cells were characterized by intracellular cytokine staining after in vitro stimulation. Results In cohort A patients, the presence of T cells responding to peptides from NY-ESO-1, Melan-A, or MAGE-3 and the M category according to the American Joint Committee on Cancer classification were significantly associated with survival. T cells responding to NY-ESO-1 and Melan-A (hazard ratios, 0.29 and 0.18, respectively) remained independent prognostic factors in Cox regression analysis and were superior to the M category in predicting outcome. Median survival of patients possessing T cells responding to NY-ESO-1, Melan-A, or both was 21 months, compared with 6 months for all others. NY-ESO-1–responsive T cells were detected in 70% of cohort A patients surviving &gt; 18 months and in 50% of cohort B patients. Melan-A responses were found in 42% and 47% of patients in cohorts A and B, respectively. In contrast, the proportion was only 22% for NY-ESO-1 and 23% for Melan-A in those who died within 6 months. Conclusion The presence of circulating T cells responding to Melan-A or NY-ESO-1 had strong independent prognostic impact on survival in advanced melanoma. Our findings support the therapeutic relevance of Melan-A and NY-ESO-1 as targets for immunotherapy.
Prospective, Observational Study of Pain and Analgesic Prescribing in Medical Oncology Outpatients With Breast, Colorectal, Lung, or Prostate Cancer
Authors: Michael J. Fisch, Ju-Whei Lee, Matthias Weiss, Lynne I. Wagner, Victor T. Chang, David Cella, Judith B. Manola, Lori M. Minasian, Worta McCaskill-Stevens, Tito R. Mendoza, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2012)

Pain is prevalent among patients with cancer, yet pain management patterns in outpatient oncology are poorly understood.A total of 3,123 ambulatory patients with invasive cancer of the breast, prostate, colon/rectum, or lung were enrolled onto this prospective study regardless of phase of care or stage of disease. At initial assessment and 4 to 5 weeks later, patients completed a 25-item measure of pain, functional interference, and other symptoms. Providers recorded analgesic prescribing. The pain management index was calculated to assess treatment adequacy.Of the 3,023 patients we identified to be at risk for pain, 2,026 (67%) reported having pain or requiring analgesics at initial assessment; of these 2,026 patients, 670 (33%) were receiving inadequate analgesic prescribing. We found no difference in treatment adequacy between the initial and follow-up visits. Multivariable analysis revealed that the odds of a non-Hispanic white patient having inadequate pain treatment were approximately half those of a minority patient after adjusting for other explanatory variables (odds ratio, 0.51; 95% CI, 0.37 to 0.70; P = .002). Other significant predictors of inadequate pain treatment were having a good performance status, being treated at a minority treatment site, and having nonadvanced disease without concurrent treatment.Most outpatients with common solid tumors must confront issues related to pain and the use of analgesics. There is significant disparity in pain treatment adequacy, with the odds of undertreatment twice as high for minority patients. These findings persist over 1 month of follow-up, highlighting the complexity of these problems.
Sexual Dysfunction in Women With the Metabolic Syndrome
Authors: Katherine Esposito, Miryam Ciotola, Raffaele Marfella, Domenico Di Tommaso, Luigi Cobellis, Dario Giugliano
Journal: Diabetes Care (2005)

Female sexual dysfunction is a largely uninvestigated, yet significant, public health problem, with 43% of women complaining of at least one sexual problem (1). Despite the high prevalence, which appears to surpass that of male sexual dysfunction, only recently has there been some focus on the sexual problems of women. We assessed the prevalence of sexual dysfunction in premenopausal women with the metabolic syndrome as compared with the general female population.

Premenopausal women ( n = 100) were enrolled if they had three …
Standard method for developing stroke registers in low-income and middle-income countries: experiences from a feasibility study of a stepwise approach to stroke surveillance (STEPS Stroke)
Authors: T Truelsen, PU Heuschmann, R Bonita, G Arjundas, P Dalal, A Damasceno, D Nagaraja, A Ogunniyi, S Oveisgharan, K Radhakrishnan, VI Skvortsoya, V Stakhovskaya
Journal: The Lancet Neurology (2007)
Impact of Human Immunodeficiency Virus Infection on Cardiovascular Disease in Africa
Authors: Mpiko Ntsekhe, James Hakim
Journal: Circulation (2005)

Background— Human immunodeficiency virus (HIV) infection is the single greatest health challenge facing Africa today. However, the impact of the HIV epidemic on the cardiovascular system in Africans has received scant attention in the world literature. Methods and Results— We searched MEDLINE (January 1, 1980, to December 31, 2004) and reference lists of literature on HIV and the heart in Africa and contacted experts in the field. The search for this review yielded 22 articles involving HIV and the cardiovascular system from 8 countries in Africa. Conclusions— The available information suggests that there are unique features in the etiology, presentation, and spectrum of HIV-associated cardiovascular disorders in people living in Africa. First, pericardial disease may be the initial manifestation of HIV infection in the early stages of the illness. Second, the etiology of cardiac disease tends to reflect the prevalent infectious diseases, such as tuberculosis. Third, unique cardiovascular disorders such as aneurysm of large vessels have been reported in association with HIV infection in several parts of Africa. Finally, the HIV/AIDS pandemic has put pressure on the meager healthcare resources and fragile infrastructure in many African countries, making the diagnosis and treatment of heart disease unrelated to HIV even more difficult.
The Role of Vitamin D in Pregnancy and Lactation: Insights from Animal Models and Clinical Studies
Authors: Christopher S. Kovacs
Journal: Annual Review of Nutrition (2012)

Maternal adaptations during pregnancy and lactation appear to provide calcium to fetus and neonate without relying on vitamin D or calcitriol. Consequently, the blood calcium, calciotropic hormones, and skeleton appear normal at birth in the offspring of mothers who are severely vitamin D deficient or who lack calcitriol or its receptor. It remains unclear whether skeletal or extraskeletal problems will develop postnatally from exposure to vitamin D deficiency in utero. During the neonatal period, calcitriol-stimulated intestinal calcium absorption becomes the dominant mechanism of calcium delivery. The vitamin D-deficient neonate is at risk to develop hypocalcemia, rickets, and possibly extraskeletal disorders (e.g., type 1 diabetes). Breastfed babies are at higher risk of vitamin D deficiency because normally little vitamin D or 25-hydroxyvitamin D passes into breast milk. Dosing recommendations during pregnancy and lactation should ensure that the baby is born vitamin D sufficient and maintained that way during infancy and beyond.
Reduction in IκB Kinase α Expression Promotes the Development of Skin Papillomas and Carcinomas
Authors: Eunmi Park, Feng Zhu, Bigang Liu, Xiaojun Xia, Jianjun Shen, Tracie Bustos, Susan M. Fischer, Yinling Hu
Journal: Cancer Research (2007)

Abstract We reported recently a marked reduction in IκB kinase α (IKKα) expression in a large proportion of human poorly differentiated squamous cell carcinomas (SCC) and the occurrence of Ikkα mutations in human SCCs. In addition, overexpression of IKKα in the epidermis inhibited the development of skin carcinomas and metastases in mice. However, whether a reduction in IKKα expression promotes skin tumor development is currently unknown. Here, we assessed the susceptibility of Ikkα hemizygotes to chemical carcinogen-induced skin carcinogenesis. Ikkα+/− mice developed 2 times more papillomas and 11 times more carcinomas than did Ikkα+/+ mice. The tumors were larger in Ikkα+/− than in Ikkα+/+ mice, but tumor latency was shorter in Ikkα+/− than in Ikkα+/+ mice. Some of the Ikkα+/− papillomas and most Ikkα+/− carcinomas lost the remaining Ikkα wild-type allele. Somatic Ikkα mutations were detected in carcinomas and papillomas. The chemical carcinogen-induced H-Ras mutations were detected in all the tumors. The phorbol ester tumor promoter induced higher mitogenic and angiogenic activities in Ikkα+/− than in Ikkα+/+ skin. These elevated activities were intrinsic to keratinocytes, suggesting that a reduction in IKKα expression provided a selective growth advantage, which cooperated with H-Ras mutations to promote papilloma formation. Furthermore, excessive extracellular signal-regulated kinase and IKK kinase activities were observed in carcinomas compared with those in papillomas. Thus, the combined mitogenic, angiogenic, and IKK activities might contribute to malignant conversion. Our findings provide evidence that a reduction in IKKα expression promotes the development of papillomas and carcinomas and that the integrity of the Ikkα gene is required for suppressing skin carcinogenesis. [Cancer Res 2007;67(19):9158–68]
INTRAUTERINE TRANSFUSION
Authors: J M Bowman, S W Fong, A J Margolis
Journal: JAMA (1966)

The paper, Intra-uterine Transfusion: Fetal Outcome and Complications,1 deserves comment.  The authors carried out 110 transfusions of 73 fetuses using a CO2 method to confirm placement of the catheter tip (or needle) in the peritoneal cavity of the fetus. On two occasions they injected blood into fetal bowel, on another into fetal bladder, and on a fourth into subcutaneous tissue. Such accidents imply that the CO2 method of confirmation of the catheter tip in the peritoneal cavity is not sufficiently accurate.
Antiadhesive properties of a quaternary structure-specific hybridoma antibody against type 1 fimbriae of Escherichia coli.
Authors: S N Abraham, D L Hasty, W A Simpson, E H Beachey
Journal: The Journal of Experimental Medicine (1983)

The relationship between the structure and biological function of type 1 fimbriae of Escherichia coli was investigated using a set of monoclonal antibodies directed against conformation-specific antigenic determinants. Of three monoclonal antibodies tested, only one (clone CD3) prevented adhesion of the vaccine strain to epithelial cells or guinea pig erythrocytes. The antibody produced by CD3, but not that produced by the other two hybridoma clones (AA8 and GG1), precipitated isolated fimbriae by double diffusion in agar gel and was shown to bind in a highly discrete, periodic manner along the length of each of the fimbriae by immunoelectron microscopy. Immunoelectroblots of type 1 fimbrial subunits and polymers electrophoresed in SDS-gels indicated that the antibodies in AA8 and GG1 reacted only with fimbrial monomers (mol wt 17,000), whereas the antibody in CD3 reacted only with polymers of mol wt 102,000 (hexamers) or higher. ELISA inhibition assays demonstrated that dissociated fimbrial subunits lost their reactivity with antibody CD3 but gained reactivity with antibodies AA8 and GG1. Conversely, when allowed to reassemble in vitro in the presence of 5 mM MgCl2, the reassembled fimbriae lost their reactivity with antibodies AA8 and GG1 but regained reactivity with antibody CD3. These results demonstrated that certain antigenic epitopes are dependent on quaternary structural determinants, whereas others are independent of quaternary fimbrial structure and also are inaccessible for antibody binding in fimbriae once they have been assembled. These monoclonal antibodies should prove useful in studies of the structural determinants of the biological function of type 1 fimbriae as well as in studies of fimbrial synthesis, transport, and assembly.
ND6 Gene "Lost" and Found: Evolution of Mitochondrial Gene Rearrangement in Antarctic Notothenioids
Authors: X. Zhuang, C. H. C. Cheng
Journal: Molecular Biology and Evolution (2010)

Evolution of Antarctic notothenioids in the frigid and oxygen-rich Southern Ocean had led to remarkable genomic changes, most notably the gain of novel antifreeze glycoproteins and the loss of oxygen-binding hemoproteins in the icefish family. Recently, the mitochondrial (mt) NADH dehydrogenase subunit 6 (ND6) gene and the adjacent transfer RNA(Glu) (tRNA(Glu)) were also reportedly lost. ND6 protein is crucial for the assembly and function of Complex I of the mt electron transport chain that produces adenosine triphosphate (ATP) essential for life; thus, ND6 absence would be irreconcilable with Antarctic notothenioids being thriving species. Here we report our discovery that the ND6 gene and tRNA(Glu) were not lost but had been translocated to the control region (CR) from their canonical location between ND5 and cytochrome b genes. We characterized the CR and adjacent sequences of 22 notothenioid species representing all eight families of Notothenioidei to elucidate the mechanism and evolutionary history of this mtDNA rearrangement. Species of the three basal non-Antarctic families have the canonical vertebrate mt gene order, whereas species of all five Antarctic families have a rearranged CR bearing the embedded ND6 (ND6(CR)) and tRNA(Glu), with additional copies of tRNA(Thr), tRNA(Pro), and noncoding region in various lineages. We hypothesized that an initial duplication of the canonical mt region from ND6 through CR occurred in the common ancestor to the Antarctic clade, and we deduced the succession of loss or modification of the duplicated region leading to the extant patterns of mt DNA reorganization that is consistent with notothenioid evolutionary history. We verified that the ND6(CR) gene in Antarctic notothenioids is transcribed and therefore functional. However, ND6(CR)-encoded protein sequences differ substantially from basal non-Antarctic notothenioid ND6, and we detected lineage-specific positive selection on the branch leading to the Antarctic clade of ND6(CR) under the branch-site model. Collectively, the novel mt ND6(CR) genotype of the Antarctic radiation represents another major molecular change in Antarctic notothenioid evolution and may reflect an adaptive change conducive to the functioning of the protein (Complex I) machinery of mt respiration in the polar environment, driven by the advent of freezing, oxygen-rich conditions in the Southern Ocean.
Consumption of Black Tea and Cancer Risk: a Prospective Cohort Study
Authors: R. A. Goldbohm, M. G. L. Hertog, H. A. M. Brants, G. van Poppel, P. A. van den Brandt
Journal: JNCI Journal of the National Cancer Institute (1996)

Tea is one of the most frequently consumed beverages in the world. Antioxidant polyphenol compounds (such as catechins and flavonols) are abundantly present in both green and black teas and have been observed to have anticarcinogenic properties in cell and animal model studies. In black tea, however, most of the catechins have been oxidized to forms that may have reduced anticarcinogenic properties. Despite indications from experimental studies that tea may protect against cancer, epidemiologic evidence has been inconclusive.The association between black tea consumption and the subsequent risk of stomach, colorectal, lung, and breast cancers was investigated in The Netherlands Cohort Study on Diet and Cancer among 58,279 men and 62,573 women aged 55-69 years.Subjects in the cohort completed a self-administered questionnaire on dietary habits and other risk factors for cancer at base line in 1986. Follow-up for cancer was done by means of computerized record linkage with all nine regional cancer registries in The Netherlands and the national pathology database. During 4.3 years of follow-up, 200, 650, 764, and 650 cases of stomach, colorectal, lung, and breast cancers were diagnosed, respectively. The questionnaire data of case subjects and those of a random subcohort (n = 3500) were used to calculate rate ratios (RRs) of cancer in categories of consumers of black tea compared with nonconsumers.Tea was not used by 13% of the subjects in the cohort, whereas 37%, 34%, and 16% consumed one to two, three to four, and five or more cups of tea per day, respectively. No association was observed between tea consumption and risk of colorectal cancer: The risk among tea drinkers in each consumption category was similar to that among nondrinkers. The RR of breast cancer among consumers of five or more cups of tea per day was 1.3 (95% confidence interval = 0.9-2.0); no dose-response association was observed. In age- and sex-adjusted analyses, consumption of tea was inversely associated with stomach (two-sided P for trend = .147) and lung (two-sided P for trend < .001) cancers. However, tea drinkers appeared to smoke less and to eat more vegetables and fruits than nondrinkers. When smoking and dietary factors were taken into account, tea in itself did not appear to protect against stomach and lung cancers: The RRs in all consumption categories were close to unity. Analysis of the tea and cancer relationship in a subgroup that included subjects in the lowest two quintiles of consumption of vegetables and fruits also failed to reveal a protective effect of tea consumption on the risk of three cancer types studied (colorectal, lung, and breast cancers).This investigation does not support the hypothesis that consumption of black tea protects against four of the major cancers in humans; a cancer-enhancing effect was not evident, either.
Metabolism of palmitate in isolated working hearts from spontaneously diabetic "BB" Wistar rats.
Authors: G D Lopaschuk, H Tsang
Journal: Circulation Research (1987)

Myocardial fatty acid metabolism was studied in spontaneously-diabetic "BB" Wistar rats. The study involved 4 groups: control Wistar rats, nondiabetic littermates of "BB" Wistar rats, insulin-treated diabetic "BB" rats, and diabetic "BB" rats in which insulin treatment was removed 24 hours prior to study (uncontrolled diabetes). Hearts were perfused for 30 minutes as isolated working hearts in perfusate containing 1.2 mM (1-14C)-palmitate bound to 3% albumin, and 11 mM glucose. Palmitate oxidative rates, calculated as micromoles palmitate oxidized per gram dry weight per minute, were significantly decreased in both diabetic groups (0.447 +/- 0.043 and 0.528 +/- 0.038 in uncontrolled diabetic and treated diabetic versus 0.584 +/- 0.032 and 0.629 +/- 0.033 in nondiabetic littermate and control rats, respectively). This decrease was accompanied, however, by a significant decrease in the heart rate of these 2 groups when compared with control or nondiabetic animals. If the decreased heart function in the diabetic animals was accounted for, no decrease in palmitate oxidative rates occurred, suggesting that fatty acid oxidative metabolism is not impaired in the diabetic myocardium. In the uncontrolled diabetic rats, an increased rate of palmitate incorporation into myocardial triglycerides was seen compared with treated diabetic, nondiabetic littermates, and control rats (8.5 +/- 0.3 mumol/g dry wt/30 min versus 4.8 +/- 0.3, 5.9 +/- 0.7, and 5.7 +/- 0.3, respectively). Myocardial levels of coenzyme A were elevated in the uncontrolled diabetic rats compared with all other groups (647 +/- 25 nmol/g dry wt versus 484 +/- 27, 508 +/- 56, and 534 +/- 9, in treated diabetic, nondiabetic, and control rats, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Effectiveness of β lactam antibiotics compared with antibiotics active against atypical pathogens in non-severe community acquired pneumonia: meta-analysis
Authors: Graham D Mills, Michael R Oehley, Bruce Arrol
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To systematically compare β lactam antibiotics with antibiotics active against atypical pathogens in the management of community acquired pneumonia. <b>Data sources</b> Medline, Embase, Cochrane register of controlled trials, international conference proceedings, drug registration authorities, and pharmaceutical companies. <b>Review methods</b> Double blind randomised controlled monotherapy trials comparing β lactam antibiotics with antibiotics active against atypical pathogens in adults with community acquired pneumonia. Primary outcome was failure to achieve clinical cure or improvement. <b>Results</b> 18 trials totalling 6749 participants were identified, with most patients having mild to moderate community acquired pneumonia. The summary relative risk for treatment failure in all cause community acquired pneumonia showed no advantage of antibiotics active against atypical pathogens over β lactam antibiotics (0.97, 95% confidence interval 0.87 to 1.07). Subgroup analysis was undertaken in those with a specific diagnosis involving atypical pathogens. We found a significantly lower failure rate in patients with <i>Legionella</i> species who were treated with antibiotics active against atypical pathogens (0.40, 0.19 to 0.85). Equivalence was seen for <i>Mycoplasma pneumoniae</i> (0.60, 0.31 to 1.17) and <i>Chlamydia pneumoniae</i> (2.32, 0.67 to 8.03). <b>Conclusions</b> Evidence is lacking that clinical outcomes are improved by using antibiotics active against atypical pathogens in all cause non-severe community acquired pneumonia. Although such antibiotics were superior in the management of patients later shown to have legionella related pneumonia, this pathogen was rarely responsible for pneumonia within the included trials. β lactam agents should remain the antibiotics of initial choice in adults with non-severe community acquired pneumonia.