tbuckley/cabot-search huggingface dataset:
Assessment of Cardiac Dysfunction in a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel, With or Without Trastuzumab As Adjuvant Therapy in Node-Positive, Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: NSABP B-31
Authors: Elizabeth Tan-Chiu, Greg Yothers, Edward Romond, Charles E. Geyer, Michael Ewer, Deborah Keefe, Richard P. Shannon, Sandra M. Swain, Ann Brown, Louis Fehrenbacher, Victor G. Vogel, Thomas E. Seay, Priya Rastogi, Eleftherios P. Mamounas, Norman Wolmark, John Bryant
Journal: Journal of Clinical Oncology (2005)

Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) -positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines.National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms.Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients; 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for > or = 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity.Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CD. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy.
Biomarkers of human exposure to pesticides.
Authors: W A Anwar
Journal: Environmental Health Perspectives (1997)

For centuries, several hundred pesticides have been used to control insects. These pesticides differ greatly in their mode of action, uptake by the body, metabolism, elimination from the body, and toxicity to humans. Potential exposure from the environment can be estimated by environmental monitoring. Actual exposure (uptake) is measured by the biological monitoring of human tissues and body fluids. Biomarkers are used to detect the effects of pesticides before adverse clinical health effects occur. Pesticides and their metabolites are measured in biological samples, serum, fat, urine, blood, or breast milk by the usual analytical techniques. Biochemical responses to environmental chemicals provide a measure of toxic effect. A widely used biochemical biomarker, cholinesterase depression, measures exposure to organophosphorus insecticides. Techniques that measure DNA damage (e.g., detection of DNA adducts) provide a powerful tool in measuring environmental effects. Adducts to hemoglobin have been detected with several pesticides. Determination of chromosomal aberration rates in cultured lymphocytes is an established method of monitoring populations occupationally or environmentally exposed to known or suspected mutagenic-carcinogenic agents. There are several studies on the cytogenetic effects of work with pesticide formulations. The majority of these studies report increases in the frequency of chromosomal aberrations and/or sister chromatid exchanges among the exposed workers. Biomarkers will have a major impact on the study of environmental risk factors. The basic aim of scientists exploring these issues is to determine the nature and consequences of genetic change or variation, with the ultimate purpose of predicting or preventing disease.
Effect of Mitral Valvulotomy on Tricuspid Insufficiency Associated with Mitral Stenosis
Authors: PIER FEDERICO ANGELINO, BENIAMINO LO BUE, VALERIA LEVI
Journal: Circulation (1959)

Twenty patients, affected by mitral disease associated with tricuspid insufficiency and selected for mitral commissurotomy on the basis of clinical evidence of advanced heart disease, have been studied before and after surgery. The further course of the disease could be related to various clinical and pathophysiologic conditions, the importance of which in the selection of patients is stressed.
1172 ANTIVIRAL ACTIVITY AND RESISTANCE PROFILE OF THE NOVEL HCV NS5A INHIBITOR GS-5885
Authors: G. Cheng, B. Peng, A. Corsa, M. Yu, M. Nash, Y.-J. Lee, Y. Xu, T. Kirschberg, Y. Tian, J. Taylor, J.O. Link, W. Delaney
Journal: Journal of Hepatology (2012)
Rehabilitation Following Cardiac Surgery
Authors: R. NEWELL FINCHUM
Journal: Circulation (1971)

Of 120 vocational rehabilitation clients having cardiac surgery between July, 1966 and December, 1968, seven were lost to follow-up, and the operative and late mortality totaled 14%. Ninety-six patients were seen for voluntary outpatient evaluation with a mean postoperative evaluation time of 22 months. Two-thirds of the patients had acquired heart disease and were in functional class III or IV preoperatively. After surgery 76 were in functional class I or II with 20 in functional class III. The electrocardiogram and radiographic heart size had returned toward normal in over 50%, and 76% of those having preoperative exercise tests demonstrated improved exercise capacity postoperatively. The rehabilitation effort was successful in 83% of those surviving surgery and 77% of the entire series. Medical and surgical physical factors were found to be more important than psychosocial factors in determining the vocational outcome after surgery. The duration of unemployment was the most important preoperative variable in predicting the rehabilitation result. The importance of medical follow-up after cardiac surgery is emphasized by the detection of a significant number of residual medical problems.
Gastric T lymphocyte responses to Helicobacter pylori in patients with H pylori colonisation.
Authors: X J Fan, A Chua, C N Shahi, J McDevitt, P W Keeling, D Kelleher
Journal: Gut (1994)

Helicobacter pylori has been identified as a dominant factor in the pathogenesis of duodenal ulcer. The aim of this study was to examine peripheral blood and gastric lymphocyte proliferation and cytokine production in patients with H pylori colonisation. Sixty five dyspeptic patients attending for endoscopy were studied; 35 of these were H pylori positive and 30 H pylori negative as assessed by culture, histology, and rapid urease test. H pylori antigen was capable of stimulating peripheral blood lymphocyte proliferative responses even in H pylori negative patients. Peripheral blood lymphocyte proliferative responses to H pylori (but not to purified protein derivative or phythaemagglutinin) were significantly lower in H pylori positive than H pylori negative patients. Similarly, antigen specific proliferative responses and interferon gamma production by gastric lamina propria lymphocytes were also depressed in H pylori positive patients compared with H pylori negative patients. CD8 and CD22 positive lamina propria lymphocytes were increased in H pylori positive patients. These data show that antigen specific responses to H pylori are significantly lower in H pylori positive patients and could indicate activation of antigen specific suppression.
Impairment of jejunal absorption rate of carnosine by glycylglycine in man in vivo.
Authors: G C Cook
Journal: Gut (1976)

Using a double-lumen tube jejunal perfusion system in vivo, the mutual effects of carnosine (beta-alanyl-L-histidine) and glycylglycine on their respective absorption rates have been studied in six Zambian African adults. Data on the effect of the constituent amino-acids of carnosine on glycylglycine absorption rate have similarly been obtained. The solutions infused in each subject contained (A) carnosine (50 mmol l.-1), (B) carnosine (50 mmol l.-1) and glycylglycine (50 mmol l.-1), (C) glycylglycine (50 mmol l.-1), and (D) glycylglycine (50 mmol l.-1), L-histidine (50 mmol l.-1) and beta-alanine (50 mmol l.-1). Glycylglycine produced a significant impairment in the mean rate of histidine absorption from carnosine (P less than 0-01). However, carnosine did not have a significant effect on the mean rate of glycine absorption from glycylglycine. Mean rate of histidine absorption from solution D was significantly higher than that from solution A (P less than 0-01). Mean rate of glycine absorption from glycylglycine was not significantly different during infusion of solutions B, C, and D. The results are consistent with the concept that carnosine on glycylglycine is probably because the affinity of mechanism; the lack of influence of carnosine on glycylglycine is probably because the affinity of carnosine for the dipeptide uptake mechanism is relatively low. A gross difference has been shown between mean absorption rate of histidine from free L-histidine (solution D) (25-8 mmol h-1) and when it is given in the form of carnosine in the presence of another dipeptide (solution B) (8-7 mmol h-1); that emphasizes the complexity of amino acid and peptide interaction during absorption, which must be important in nutrition.
Defective bronchus-associated lymphoid tissue in long-term surviving rat lung allografts.
Authors: J B Winter, J Prop, M Groen, A H Petersen, T Uyama, B Meedendorp, C R Wildevuur
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

In a previous study we found that a local immune response did not develop in the bronchus-associated lymphoid tissue (BALT) of infected rat allografts. We hypothesized that the BALT in rat lung allografts was damaged after allotransplantation. Therefore, we investigated three prerequisites for a normal function of the BALT, i.e., its structure, the uptake of antigens, and the lymphocyte migration to the BALT in three groups of rats (n = 10 each): (1) Brown Norway(BN)-to-Lewis (LEW) allografts; (2) LEW-to-LEW isografts; and (3) normal LEW rats. All rats were immunosuppressed with CsA (injected on days 2 and 3). Six mo after transplantation the structure of the BALT and the uptake of intrabronchially injected carbon particles in the BALT were determined histologically; the migration of intravenously injected, fluoroscein-isothiocyanate labeled lymphocytes to the BALT was determined immunohistochemically. In the allografts the BALT was defective in all three investigated aspects. It was reduced in size and lymphocyte density and was largely replaced by fibrous tissue. Twenty-four h after administration no carbon particles and only a few labeled lymphocytes were found in the BALT. In contrast, in the syngeneically transplanted and nontransplanted lungs the BALT consisted of a large and dense collection of lymphocytes. In these BALTs large numbers of carbon particles and labeled lymphocytes were found. In conclusion, after allogeneic transplantation the BALT in the lung becomes defective in structure and function. The BALT is most likely damaged by rejection, since the BALT is syngeneic lung transplants was perfectly normal.
Effect of preoperative lactulose on posthaemorrhoidectomy pain.
Authors: C D Johnson
Journal: BMJ (1987)

<h3>Abstract</h3> <b>Objective:</b> To describe the epidemiology of HIV-1 infection in pregnant women in the United Kingdom. <b>Design:</b> Serial unlinked serosurveillance for HIV-1 in neonatal specimens and surveillance through registers of diagnosed maternal and paediatric infections from reporting by obstetricians, paediatricians, and microbiologists. <b>Setting:</b> United Kingdom, 1988-96. <b>Subjects:</b> Pregnant women proceeding to live births and their children <b>Main outcome measures:</b> Time trends in prevalence of HIV-1 seropositivity in newborn infants (as a proxy for infection in mothers); the proportions of mothers with diagnosed HIV-1 infections, and their characteristics. <b>Results:</b> HIV-1 prevalence among mothers in London rose sixfold between 1988 and 1996 (0.19% of women tested; 1 in 520 in 1996). Apart from in Edinburgh and Dundee, levels remained low in Scotland (0.025%; 1 in 3970) and elsewhere in the United Kingdom (0.016%; 1 in 1930). Over a third of births to infected mothers in 1996 occurred outside London. In London the reported infections were predominantly among black African women, whereas in Scotland most were associated with drug injecting. The contribution of reported infection among African women increased over time as that of drug injecting declined. In Scotland 51% of mothers9 infections were diagnosed before the birth. In England, despite a national policy initiative in 1992 to increase the antenatal detection rate of HIV, no improvement in detection was observed, and in 1996 only 15% of previously unrecognised HIV infections were diagnosed during pregnancy. <b>Conclusions:</b> HIV-1 infection affects mothers throughout the United Kingdom but is most common in London. Levels of diagnosis in pregnant women have not improved. Surveillance data can monitor effectively the impact of initiatives to reduce preventable HIV-1 infections in children. <h3>Key messages</h3> HIV-1 infections among pregnant women are commonest in London but they are found in all parts of the United Kingdom Black African ethnic group or a history of drug injecting are important risk factors, but HIV-1 infection occurs among women without either characteristic Identification of HIV infection in pregnant women, if combined with uptake of interventions, reduces the risk of mother to child transmission HIV testing should be universally available in all antenatal clinics without any obstacle All pregnant women in London should be offered and recommended HIV testing; elsewhere, HIV testing should be offered and recommended to those with risk characteristics
The Metabolism of Insecticides: The Role of Monooxygenase Enzymes
Authors: A P Kulkarni, E Hodgson
Journal: The Annual Review of Pharmacology and Toxicology (1984)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies
Authors: M COHEN, X YANG, J DOWNEY
Journal: Cardiovascular Research (2005)

Ischemic preconditioning is a powerful infarct-sparing intervention. Intensive investigations have revealed many of the signaling steps used to elicit this protection. One of the steps involves activation of nitric oxide synthase (NOS) by phosphorylation, with the production of NO and subsequent activation of guanylyl cyclase, production of cGMP, activation of protein kinase G, opening of mitochondrial KATP channels, and generation of reactive oxygen species. The latter act as second messengers to activate critical kinase cascades that trigger entrance into the preconditioned state. Thus, NO exposure before ischemia can act as a powerful preconditioning mimetic. Elevating NO just prior to or at reperfusion can still be an effective cardioprotective strategy. Activation of NOS or production of NO can be done pharmacologically with exogenous agents to trigger this cascade. Many of these strategies are already available and safe.
Dimethylthiourea, an oxygen radical scavenger, protects isolated cardiac myocytes from hypoxic injury by inhibition of Na(+)-Ca2+ exchange and not by its antioxidant effects.
Authors: R C Ziegelstein, J L Zweier, E D Mellits, A Younes, E G Lakatta, M D Stern, H S Silverman
Journal: Circulation Research (1992)

Myocardial reoxygenation injury may be attenuated by oxygen free radical scavengers, arguing for a role of oxygen radicals in this process. To determine whether free radical scavengers affect reoxygenation injury in isolated cardiac myocytes, resting rat ventricular myocytes were exposed to hypoxic (PO2 less than 0.02 mm Hg) glucose-free buffer alone (n = 50) or with the addition of the oxygen radical scavengers 1,3-dimethyl-2-thiourea (DMTU, 25 mM, n = 46), human recombinant superoxide dismutase (SOD, 1,000 units/ml, n = 40), or the combination of these agents (n = 41). All cells responded by undergoing contracture to a rigor form. Hypoxia was then continued for a second period (T2), the duration of which correlates inversely with survival. After reoxygenation, cells either retained their rectangular shape (survival) or hypercontracted to a rounded form (death). For the group of cells with a T2 period greater than 30 minutes, no cell exposed to buffer alone (n = 20) or to SOD (n = 16) survived, in contrast to 15 of 24 (63%) cells exposed to DMTU. The addition of SOD to DMTU offered no advantage to DMTU alone. The protective effect of DMTU was not observed when it was added at reoxygenation, suggesting that this agent has an important effect during the hypoxic period when intracellular Ca2+ is known to rise, most likely because of the reversal of Na(+)-Ca2+ exchange. Therefore, the effects of DMTU on Ca2+ regulation (indexed by indo-1 fluorescence) during hypoxia were studied. DMTU significantly blunted the [Ca2+] rise during the hypoxic period.(ABSTRACT TRUNCATED AT 250 WORDS)
The Accumulation of Deleterious Mutations as a Consequence of Domestication and Improvement in Sunflowers and Other Compositae Crops
Authors: Sebastien Renaut, Loren H. Rieseberg
Journal: Molecular Biology and Evolution (2015)

For populations to maintain optimal fitness, harmful mutations must be efficiently purged from the genome. Yet, under circumstances that diminish the effectiveness of natural selection, such as the process of plant and animal domestication, deleterious mutations are predicted to accumulate. Here, we compared the load of deleterious mutations in 21 accessions from natural populations and 19 domesticated accessions of the common sunflower using whole-transcriptome single nucleotide polymorphism data. Although we find that genetic diversity has been greatly reduced during domestication, the remaining mutations were disproportionally biased toward nonsynonymous substitutions. Bioinformatically predicted deleterious mutations affecting protein function were especially strongly over-represented. We also identify similar patterns in two other domesticated species of the sunflower family (globe artichoke and cardoon), indicating that this phenomenon is not due to idiosyncrasies of sunflower domestication or the sunflower genome. Finally, we provide unequivocal evidence that deleterious mutations accumulate in low recombining regions of the genome, due to the reduced efficacy of purifying selection. These results represent a conundrum for crop improvement efforts. Although the elimination of harmful mutations should be a long-term goal of plant and animal breeding programs, it will be difficult to weed them out because of limited recombination.
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans
Authors: Sekar Kathiresan, Olle Melander, Candace Guiducci, Aarti Surti, Noël P Burtt, Mark J Rieder, Gregory M Cooper, Charlotta Roos, Benjamin F Voight, Aki S Havulinna, Björn Wahlstrand, Thomas Hedner, Dolores Corella, E Shyong Tai, Jose M Ordovas, Göran Berglund, Erkki Vartiainen, Pekka Jousilahti, Bo Hedblad, Marja-Riitta Taskinen, Christopher Newton-Cheh, Veikko Salomaa, Leena Peltonen, Leif Groop, David M Altshuler, Marju Orho-Melander
Journal: Nature Genetics (2008)
A Strategy to Control Transmission of<i>Schistosoma japonicum</i>in China
Authors: Long-De Wang, Hong-Gen Chen, Jia-Gang Guo, Xiao-Jun Zeng, Xian-Lin Hong, Ji-Jie Xiong, Xiao-Hua Wu, Xian-Hong Wang, Li-Ying Wang, Gang Xia, Yang Hao, Daniel P. Chin, Xiao-Nong Zhou
Journal: New England Journal of Medicine (2009)

Schistosoma japonicum causes an infection involving humans, livestock, and snails and is a significant cause of morbidity in China.We evaluated a comprehensive control strategy in two intervention villages and two control villages along Poyang Lake in the southeastern province of Jiangxi, where annual synchronous chemotherapy is routinely used. New interventions, implemented from 2005 through 2007, included removing cattle from snail-infested grasslands, providing farmers with mechanized farm equipment, improving sanitation by supplying tap water and building lavatories and latrines, providing boats with fecal-matter containers, and implementing an intensive health-education program. During the intervention period, we observed changes in S. japonicum infection in humans, measured the rate of infection in snails, and tested the infectivity of lake water in mice.After three transmission seasons, the rate of infection in humans decreased to less than 1.0% in the intervention villages, from 11.3% to 0.7% in one village and from 4.0% to 0.9% in the other (P<0.001 for both comparisons). The rate of infection in humans in control villages fluctuated but remained at baseline levels. In intervention villages, the percentage of sampling sites with infected snails decreased from 2.2% to 0.1% in one grassland area and from 0.3% to no infection in the other (P<0.001 for both comparisons). The rate of infection in mice after exposure to lake water decreased from 79% to no infection (P<0.001).A comprehensive control strategy based on interventions to reduce the rate of transmission of S. japonicum infection from cattle and humans to snails was highly effective. These interventions have been adopted as the national strategy to control schistosomiasis in China.