tbuckley/cabot-search huggingface dataset:
Novel feedback inhibition of surface antigen synthesis by mammalian target of rapamycin (mTOR) signal and its implication for hepatitis B virus tumorigenesis and therapy
Authors: Chiao-Fang Teng, Han-Chieh Wu, Hung-Wen Tsai, Her-Shyong Shiah, Wenya Huang, Ih-Jen Su
Journal: Hepatology (2011)

Ground glass hepatocytes (GGHs) harboring hepatitis B virus (HBV) pre-S mutants have been recognized as precursor lesions of hepatocellular carcinoma (HCC). Previously, we observed the activation of mammalian target of rapamycin (mTOR) in GGHs and HCCs, together with a decreased expression of HBV surface antigen (HBsAg) in HCC tissues. It is, therefore, hypothesized that the activation of mTOR during HBV tumorigenesis may potentially down-regulate HBsAg expression. In this study, we verified an inverse relationship between the expression of HBsAg and phosphorylated mTOR (p-mTOR) in 13 of 20 paired nontumorous liver and HCC tissues. In vitro , wild-type or mutant pre-S proteins could activate mTOR in the HuH-7 cell line. Interestingly, the up-regulated mTOR, in turn, suppressed HBsAg synthesis at the transcriptional level via the transcription factor, Yin Yang 1 (YY1), which bound to nucleotide 2812-2816 of the pre-S1 promoter. This inhibitory effect by the mTOR signal could be abolished by the knockdown of histone deacetylase 1 (HDAC1). Furthermore, YY1 was physically associated with HDAC1 in a manner dependent on mTOR activation. Collectively, pre-S protein-induced mTOR activation may recruit the YY1-HDAC1 complex to feedback suppress transcription from the pre-S1 promoter. Conclusion: The activation of mTOR signal in GGHs may feedback suppress HBsAg synthesis during HBV tumorigenesis and explain the observed decrease or absence of HBsAg in HCC tissues. Therapy using mTOR inhibitors for HCCs may potentially activate HBV replication in patients with chronic HBV infection. (Hepatology 2011 )
Hypoxic-Ischemia-Related Fetal/Neonatal Complications and Risk of Schizophrenia and Other Nonaffective Psychoses: A 19-Year Longitudinal Study
Authors: Gwen L. Zornberg, Stephen L. Buka, Ming T. Tsuang
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Epidemiologic evidence linking obstetric complications to schizophrenia has been positive but inconclusive. One reason for the lack of conclusive evidence may be the inconsistency in measuring disturbances of fetal/neonatal brain development based on general obstetric markers of maternal health. The authors used data from the National Collaborative Perinatal Project to examine the relationship between schizophrenia and other nonaffective psychoses and a theoretically derived measure of hypoxic-ischemia-related fetal/neonatal complications. METHOD: Six hundred ninety-three men and women (average age 23) born to a community sample of women between 1959 and 1966 were followed up an average of 19 years after early childhood assessments. Subjects with DSM-IV schizophrenia and other nonaffective psychoses were identified using the Diagnostic Interview Schedule and best-estimate consensus diagnoses. RESULTS: Hypoxic-ischemia-related fetal/neonatal complications were associated with a doubling of the risk of developing a psychotic disorder, compared with no relevant complications (6.9% versus 1.4%). When mood disorders were excluded from the group of psychotic diagnoses, the risk of schizophrenia and other nonaffective psychoses associated with hypoxic-ischemia-related fetal/neonatal complications was strikingly elevated, compared with no relevant complications (5.75% versus 0.39%). Nonpsychotic mood disorders were unrelated to these fetal/neonatal complications. Schizophrenia and other nonaffective psychoses were most strongly associated with hypoxic-ischemia-related fetal/neonatal complications of disordered growth and development. CONCLUSIONS: The data show a strikingly elevated, graded, independent risk of schizophrenia and other nonaffective psychoses associated with this classification of antecedent hypoxic-ischemia-related fetal/neonatal complications.
The Role of Lipids in Acute Myocardial Infarction
Authors: DONALD S. FREDRICKSON
Journal: Circulation (1969)

Plasma lipids and lipoproteins usually undergo several phasic changes following myocardial infarction. Within a few hours the free fatty acid (FFA) concentration rises precipitously and may not become normal for 2 days or more. During the first 1 to 3 days, there begins a significant decline in cholesterol and beta lipoproteins. After a possible early decline, the concentrations of very low density lipoproteins and triglycerides begin to climb within the first week and characteristically are considerably above the measured initial levels for weeks thereafter. Beta lipoprotein concentrations return slowly to initial values. The late return of lipids to supranormal levels is probably often an expression of abnormality present before infarction. Some of these oscillations in lipid and lipoprotein concentrations occur after other forms of trauma. Arguments are presented that the early alterations are not attributable to caloric deprivation or anticoagulants and the mechanisms involved are speculated upon.
Cellular mechanisms of muscle injury during exercise
Authors: Michael Kalinski
Journal: British Journal of Sports Medicine (2010)

We will describe the current understanding of the biochemical events following strenuous exercise, associated with overloading of the contractile elements and resulting in injury of skeletal muscle and inflammation. The extent of this damage depends on the mode, intensity, duration of exercise and prior exercise training. As a result of disruption of the muscle cell membrane, myocellular proteins pass through the membrane into the bloodstream. A variety of factors may potentially influence inflammatory responses to muscle damage after eccentric exercise: age, gender, anti-inflammatory drugs. Mild muscle damage stimulates muscle hypertrophy, whereas severe muscle damage can cause injury and may interfere with the training schedules of competitive athletes.
Low-Carbohydrate-Diet Score and the Risk of Coronary Heart Disease in Women
Authors: Thomas L. Halton, Walter C. Willett, Simin Liu, JoAnn E. Manson, Christine M. Albert, Kathryn Rexrode, Frank B. Hu
Journal: New England Journal of Medicine (2006)

Low-carbohydrate diets have been advocated for weight loss and to prevent obesity, but the long-term safety of these diets has not been determined.We evaluated data on 82,802 women in the Nurses' Health Study who had completed a validated food-frequency questionnaire. Data from the questionnaire were used to calculate a low-carbohydrate-diet score, which was based on the percentage of energy as carbohydrate, fat, and protein (a higher score reflects a higher intake of fat and protein and a lower intake of carbohydrate). The association between the low-carbohydrate-diet score and the risk of coronary heart disease was examined.During 20 years of follow-up, we documented 1994 new cases of coronary heart disease. After multivariate adjustment, the relative risk of coronary heart disease comparing highest and lowest deciles of the low-carbohydrate-diet score was 0.94 (95% confidence interval [CI], 0.76 to 1.18; P for trend=0.19). The relative risk comparing highest and lowest deciles of a low-carbohydrate-diet score on the basis of the percentage of energy from carbohydrate, animal protein, and animal fat was 0.94 (95% CI, 0.74 to 1.19; P for trend=0.52), whereas the relative risk on the basis of the percentage of energy from intake of carbohydrates, vegetable protein, and vegetable fat was 0.70 (95% CI, 0.56 to 0.88; P for trend=0.002). A higher glycemic load was strongly associated with an increased risk of coronary heart disease (relative risk comparing highest and lowest deciles, 1.90; 95% CI, 1.15 to 3.15; P for trend=0.003).Our findings suggest that diets lower in carbohydrate and higher in protein and fat are not associated with increased risk of coronary heart disease in women. When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease.
Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth
Authors: Neelesh R. Soman, Steven L. Baldwin, Grace Hu, Jon N. Marsh, Gregory M. Lanza, John E. Heuser, Jeffrey M. Arbeit, Samuel A. Wickline, Paul H. Schlesinger
Journal: Journal of Clinical Investigation (2009)

The in vivo application of cytolytic peptides for cancer therapeutics is hampered by toxicity, nonspecificity, and degradation. We previously developed a specific strategy to synthesize a nanoscale delivery vehicle for cytolytic peptides by incorporating the nonspecific amphipathic cytolytic peptide melittin into the outer lipid monolayer of a perfluorocarbon nanoparticle. Here, we have demonstrated that the favorable pharmacokinetics of this nanocarrier allows accumulation of melittin in murine tumors in vivo and a dramatic reduction in tumor growth without any apparent signs of toxicity. Furthermore, direct assays demonstrated that molecularly targeted nanocarriers selectively delivered melittin to multiple tumor targets, including endothelial and cancer cells, through a hemifusion mechanism. In cells, this hemifusion and transfer process did not disrupt the surface membrane but did trigger apoptosis and in animals caused regression of precancerous dysplastic lesions. Collectively, these data suggest that the ability to restrain the wide-spectrum lytic potential of a potent cytolytic peptide in a nanovehicle, combined with the flexibility of passive or active molecular targeting, represents an innovative molecular design for chemotherapy with broad-spectrum cytolytic peptides for the treatment of cancer at multiple stages.
Bacteriuria and Babies Revisited
Authors: Stephen H. Zinner
Journal: New England Journal of Medicine (1979)

Few issues in infectious disease have produced as much controversy as Kass' observation two decades ago that bacteriuria during pregnancy was associated with low birth weight and increased perinatal morbidity.1 There are several likely reasons for this controversy. First of all, some other studies of bacteriuria during pregnancy did not show an effect on birth weight. In most of these studies, however, the criteria for bacteriuria were not optimal, and the groups were too small to reflect statistically significant differences in the occurrence of two relatively uncommon conditions. Many carefully designed investigations did confirm Kass' observation.2 Another possible explanation for . . .
Localization of F-18 FDG in Nocardia Lung Infection
Authors: Aju Thomas, Amolak Singh, Ben Greenspan
Journal: Clinical Nuclear Medicine (2004)

F-18 FDG is the most commonly used radiotracer for PET. PET has become a very powerful tool for evaluating malignancy. However, localization of FDG is not specific for malignancy, and a number of benign conditions may accumulate FDG. The authors recently encountered a case of pulmonary nocardiosis exhibiting increased uptake of FDG on a PET scan performed to exclude pulmonary malignancy. Markedly increased FDG uptake led to a biopsy that demonstrated Nocardia infection. Localization of FDG in nocardiosis may be regarded as a false-positive case when imaging for malignancy, but can uncover a lethal condition that may otherwise go unnoticed.
Environmental associations with eczema in early life
Authors: J.M. Harris, P. Cullinan, H.C. Williams, P. Mills, S. Moffat, C. White, A.J. Newman Taylor
Journal: British Journal of Dermatology (2001)

Journal Article Environmental associations with eczema in early life Get access J.M. Harris, J.M. Harris Department of Occupational and Environmental Medicine, Imperial College of Science and Technology (National Heart and Lung Institute), 1b Manresa Road, London SW3 6LR, U.K. *Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. J.M.Harris. E‐mail: jessica.harris@ic.ac.uk Search for other works by this author on: Oxford Academic Google Scholar P. Cullinan, P. Cullinan Department of Occupational and Environmental Medicine, Imperial College of Science and Technology (National Heart and Lung Institute), 1b Manresa Road, London SW3 6LR, U.K. *Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar H.C. Williams, H.C. Williams Department of Occupational and Environmental Medicine, Imperial College of Science and Technology (National Heart and Lung Institute), 1b Manresa Road, London SW3 6LR, U.K. *Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. Mills, P. Mills Department of Occupational and Environmental Medicine, Imperial College of Science and Technology (National Heart and Lung Institute), 1b Manresa Road, London SW3 6LR, U.K. *Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Moffat, S. Moffat Department of Occupational and Environmental Medicine, Imperial College of Science and Technology (National Heart and Lung Institute), 1b Manresa Road, London SW3 6LR, U.K. *Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar C. White, C. White Department of Occupational and Environmental Medicine, Imperial College of Science and Technology (National Heart and Lung Institute), 1b Manresa Road, London SW3 6LR, U.K. *Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.J. Newman Taylor A.J. Newman Taylor Department of Occupational and Environmental Medicine, Imperial College of Science and Technology (National Heart and Lung Institute), 1b Manresa Road, London SW3 6LR, U.K. *Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 4, 1 April 2001, Pages 795–802, https://doi.org/10.1046/j.1365-2133.2001.04135.x Published: 01 April 2001
Reddish-purple Areas on the Liver Surface: The Laparoscopic Picture of Peliosis Hepatis
Authors: J.A. Solis-Herruzo, F. Colina, M.T. Muñoz-Yagüe, G. Castellano, J.D. Morillas
Journal: Endoscopy (1983)

Reddish-purple areas occasionally found on the surface of the liver have been related to peliosis hepatis. The purpose of the present study was to determine: 1) the frequency of these changes in a total of 3035 laparoscopies and 2) the histological substrate of these laparoscopical changes. In 20 cases (0.65%), reddish-purple patches of round, triangular, star-shaped or net-work configuration were found on the liver surface. Liver biopsies taken from these areas showed: 1) dilatation of sinusoids; 2) blood-filled cavities, and 3) intralobular hemorrhages. These lesions were frequently combined. In three cases no lesions were found. The presence of these histological lesions was compared with those found in a group serving as controls, in whom no reddish-purple spots were seen at laparoscopy. Our study shows that there is a close statistical relationship (X2: 19.01; p less than 0.001) between the histological and laparoscopic changes. We conclude that: 1) Reddish-purple areas on the liver surface are caused by Peliosis hepatis or are Peliosis hepatis-related lesions, and 2) Peliosis hepatis is not an extremely rare condition in laparoscopy.
In vivo evaluation of chemical biopersistence of man-made mineral fibers.
Authors: A Morgan
Journal: Environmental Health Perspectives (1994)

Techniques developed at the Harwell Laboratory for the determination of the biopersistence of man-made mineral fibers (MMMF) in vivo are described. Results obtained with samples of glass fiber with a range of compositions, and with a sample of rockwool, are summarized. With glass fibers the rate of dissolution of fibers in vivo depends not only on their chemical composition, but also on their length. Certainly, for all fibers exceeding 10 microns in length, the longer the fiber the more rapidly it dissolves. This effect is attributed to differences in the microenvironments to which long and short fibers are exposed. Although this phenomenon appears to operate with all glass fibers, it may not apply to other types of MMMF that dissolve more readily in environments with low pH. Finally, the article examines the validity of the intratracheal method of administration for studying the biopersistence of MMMF in vivo and the use of the rat for this purpose.
Quantitative Associations Between DNA Damage in Human Placenta and Maternal smoking and Birth Weight
Authors: R. B. Everson, E. Randerath, R. M. Santella, T. A. Avitts, I. B. Weinstein, K. Randerath
Journal: JNCI Journal of the National Cancer Institute (1988)

Specimens of human placental DNA were tested for chemical addition products (adducts) by recently developed 32P-postlabeling and immunologic assays, and results were compared with data concerning maternal exposures and birth weight. A total of 7 different adducts were detected in the 53 specimens of human placental tissue examined by the 32P-postlabeling assay. Three of these adducts were found almost exclusively in smokers. Among smokers there were positive dose-response relationships between levels of the smoking-related adducts and biochemical estimates of doses of maternal exposure to cigarette smoke during pregnancy. Levels of 1 adduct found only in smokers appeared to relate directly to amounts of caffeine consumption by the mother. In addition to these relationships with maternal exposures, levels of smoking-related adducts were inversely associated with the birth weight of offspring. Results from this study suggest that even at their current formative stage of development, assays for DNA adducts may help identify determinants of DNA damage to human tissues and improve our ability to demonstrate dose-response relationships for the effects of environmental exposures to potentially carcinogenic agents.The use of P-postlabeling assay to find the determinants of DNA damage demonstrates an innovative approach for measuring toxic end points. This approach begins with estimates of biochemical or molecular damage to tissue and then figures in exposure or susceptibility factors that are associated with the damage. Using this method, researchers studied smoking-related DNA adducts (chemical addition products) and found 7 different DNA adducts in human placental tissue specimens. Maternal smoking during pregnancy was related to 3 of the adducts observed. Levels of adducts were associated with caffeine use, age, race and education of the mother. The intensity of the smoking was determined by three methods: a questionnaire; a biological approach that scored smoking exposure and combined data from questionnaires and assays and a molecular approach that was related to levels of DNA adducts. There was a clear association between birth weight and birth length and levels of adduct that demonstrated that cigarette smoke does cause low birth weight and birth length. Little correlation between levels of tar, nicotine or carbon monoxide and adduct levels was found. The information and study was at an inchoate stage; therefore, further comparison and interpretation are needed to assess the findings.
Consumer-Driven Health Care May Not Be What Patients Need—Caveat Emptor
Authors: Robert A. Berenson
Journal: JAMA (2009)

In addition to policy concerns that consumer-directed health care, based on high deductibles and tax-advantaged health savings accounts will lead patients to forgo needed care and would not reduce costs for those with high annual health care costs, this health reform model poses a major threat to the role of physician-patient trust as a fundamental underpinning of the health care system. Although physicians have deviated from ideals of professionalism in various ways, patients still rely on physicians, as professionals, to serve their patients' best interests. In a commentary in the  Journal of the American Medical Association , Urban Institute Senior Fellow Bob Berenson and Christine Cassel argue that the competitive vision that is core to consumer-driven care would inevitably replace professional ethics with, at best, commercial ethics, a development that should be resisted as health care reform proceeds.
Failure to tackle health inequalities is a false economy, meeting hears
Authors: M. Limb
Journal: BMJ (2013)

England’s new public health bodies should not let the “immense” funding difficulties in local government slow their progress in reducing health inequalities, experts have said.

Jessica Allen, deputy director of University College London’s Institute of Health Equity, said that failure to tackle health inequality was costing the country around £70bn (€82bn; $107bn) a year. This was estimated in productivity losses, lost taxes, higher welfare payments, and additional NHS healthcare costs, she said.

Allen said that the new local health and wellbeing boards in local authorities had to take such factors into account. “When you’re required to reduce health inequalities, look at the cost …
Abstract 3935: International Cancer Genome Consortium (ICGC)
Authors: Thomas J. Hudson, Jennifer L. Jennings
Journal: Cancer Research (2011)

Abstract The International Cancer Genome Consortium (ICGC) is coordinating an extensive research effort to obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in the major forms of cancer. This information will lead to better ways of diagnosing, treating and preventing cancer. The announcement of the ICGC Goals, Structure, Policies and Guidelines to the international scientific community in 2008 enabled funding agencies and research groups to plan their participation within the ICGC. Over 200 authors engaged in ICGC projects published a Nature paper in April 2010. The paper outlines the ethical framework, study design, use of common standards of data collection and analysis and describes how the projects will proceed. As of November 2010, the ICGC has received commitments from funding organizations in Asia, Australia, Europe and North America for the projects listed in the table (below). Over time, additional nations and organizations are anticipated to join the ICGC. Each Cancer Genome Project is expected to involve specimens from approximately 500 patients. Over the next ten years, the ICGC expects to produce comprehensive catalogues of the full range of genetic mutations involved in 50 types of cancer, with key factors being the ability to detect all mutated cancer genes, data at the level of individual DNA bases, application of common standards for pathology and technology and comparison data from matched, non-tumour tissue. The ICGC's informed consent and ethical oversight policies state that cancer patients enrolled in an ICGC-related study should be informed that their participation is voluntary, that their clinical care will not be affected by their participation and that data obtained from analyses using their samples will be made available to the international research community. The genomic analyses of tumors conducted by ICGC members in the U.K. (breast, lung and skin cancer), Japan (liver cancer), and Australia and Canada (pancreatic cancer) are now available on the ICGC website at www.icgc.org. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3935. doi:10.1158/1538-7445.AM2011-3935