tbuckley/cabot-search huggingface dataset:
THERAPY OF INFECTION WITH PNEUMONIA VIRUS OF MICE (PVM)
Authors: Harold S. Ginsberg, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1951)

Inhibition of the multiplication of PVM by the capsular polysaccharide of Friedländer bacillus, type B, is associated with restriction in the development of pneumonia induced with the virus in the mouse lung. The extent of the pneumonic process appears to be a function of the degree of viral multiplication; the greater the inhibition of multiplication, the less extensive is the pneumonia and the more probable is the recovery of animals treated with the polysaccharide. Effective therapy of pneumonia induced in mice with PVM is obtained with a single injection of 0.02 mg. of the substance given intranasally either 2 or 3 days after inoculation. Under appropriate conditions, treated animals recover completely from a viral infection which is, in control animals, uniformly fatal. The polysaccharide produces inhibition if given in the first two-thirds of the latent period of the multiplication cycle, i.e., within 10 hours, but is ineffective when given at 12 hours or later. However, the second cycle and subsequent cycles are inhibited irrespective of the time the substance is injected during the first cycle of multiplication. The findings are discussed in relation to a theory regarding the mechanism of action of the polysaccharide.
Preliminary Investigation of the Clinical Significance of Detecting Circulating Tumor Cells Enriched from Lung Cancer Patients
Authors: Chi Wu, Huaijie Hao, Longyun Li, Xiaoyun Zhou, Zijian Guo, Li Zhang, Xiaotong Zhang, Wei Zhong, Huiqin Guo, Ross Macrae Bremner, Ping Lin
Journal: Journal of Thoracic Oncology (2009)
Medical Education in Sheffield in the Queen's Reign
Authors: S. Snell
Journal: BMJ (1897)

c 29 climbing difficulties can be partly overcome by the use of suitable gearing, and the heating effects in the engine by the use of water circulation.But all these means add to the weight, cost, and complexity of the mechanism, which as at present constructed can only be worked and repaired by a skilled mechanic.STEAM.Our only other available source of power is steam.A steam engine is free from all the risks and difficulties involved in a gas or oil engine, but the weight of the mechanism and fuel is a serious drawback.But here means exist of overcoming these disadvantages.Fuel can be carried in a liquid form, the working parts can be reduced in weight by the use of steel tube framing, and finally the use of the Serpollet boiler, which is light, a rapid steam producer, and self-cleansing seems to point to a practicable solution of the many diffi- culties which stand, in the way of the use of that at first sight most fascinating dynamic agent-oil.
Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease
Authors: Daniel M. Forton, Howard C. Thomas, Christine A. Murphy, Joanna M. Allsop, Graham R. Foster, Janice Main, Keith A. Wesnes, Simon D. Taylor-Robinson
Journal: Hepatology (2002)

Patients with chronic hepatitis C virus (HCV) infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. Several studies have shown that patients exhibit low quality-of-life scores that are independent of disease severity. We therefore considered whether HCV infection has a direct effect on the central nervous system, resulting in cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV were tested with a computer-based cognitive assessment battery and also completed depression, fatigue, and quality-of-life questionnaires. The HCV-infected patients were impaired on more cognitive tasks than the HCV-cleared group (mean [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P = .02). A factor analysis showed impairments in power of concentration and speed of working memory, independent of a history of intravenous drug usage (IVDU), depression, fatigue, or symptom severity. A subgroup of 17 HCV-infected patients also underwent cerebral proton magnetic resonance spectroscopy ( 1 H MRS). The choline/creatine ratio was elevated in the basal ganglia and white matter in this group. Patients who were impaired on 2 or more tasks in the battery had a higher mean choline/creatine ratio compared with the unimpaired patients. In conclusion, these preliminary results demonstrate cognitive impairment that is unaccounted for by depression, fatigue, or a history of IVDU in patients with histologically mild HCV infection. The findings on MRS suggest that a biological cause underlies this abnormality.
Intracranial tuberculosis resembling Hand-Schuller-Christian disease.
Authors: P B Cotton, M L Thomas
Journal: BMJ (1971)

thromboplastin or other substances from the ioc sac into the maternal circulation, resulting in the connuous consmption of fibrinogen The increased incidce of oic fluid embolism with intrauterine death of the fetus may be due to the increased friability of the membranes, which are therefore more likely to split or tear, thus creating favourable condi- tions for amniotic fluid infusion during labour and delivery.We should like to thank Professor Stallworthy for pernmission to usw the clinical material, and Dr. Phizackerley, department of biochemistry, for his advice.
Six hospitals are named as "outliers" for mortality rates
Authors: N. Hawkes
Journal: BMJ (2014)

Six hospitals in England have been identified as posing a greater than average risk of death to the patients they treat. 

The data, which cover the two year period between July 2011 and June 2013 and are published by the Health and Social Care Information Centre,1 show that four foundation trusts—Mid Cheshire, Colchester, Aintree, and Blackpool—were mortality “outliers,” along with two trusts that have not gained foundation status, East Lancashire and Wye Valley.

The centre uses a measure called the summary hospital level mortality indicator (SHMI) to compare death rates for both elective and emergency admissions. Being recorded as an outlier in a single year …
BASAL-CELL CARCINOMA..
Authors: D. I. McCALLUM, P. D. C. Kinmont
Journal: British Journal of Dermatology (1966)

Journal Article BASAL‐CELL CARCINOMA.: An Analysis of Cases Seen at a Combined Clinic Get access D. I. McCALLUM, D. I. McCALLUM Consultant Dermatologist, Nottingham General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar P. D. C. Kinmont P. D. C. Kinmont Consultant Dermatologist, Derbyshire Royal Infirmary, Derby Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 78, Issue 3, 1 March 1966, Pages 141–146, https://doi.org/10.1111/j.1365-2133.1966.tb12190.x Published: 01 March 1966
Elevated hepatocyte levels of the Forkhead box A2 (HNF-3β) transcription factor cause postnatal steatosis and mitochondrial damage
Authors: Douglas E. Hughes, Donna Beer Stolz, Songtao Yu, Yongjun Tan, Janardan K. Reddy, Simon C. Watkins, Anna Mae Diehl, Robert H. Costa
Journal: Hepatology (2003)

The Forkhead box (Fox) transcription factor Foxa2 (HNF–3β) and related family members Foxa1 (HNF–3α) and Foxa3 (HNF–3γ) act in concert with other hepatocyte nuclear factors (HNF) to coordinately regulate liver–specific gene expression. To circumvent the hepatic functional redundancy of the Foxa proteins, we used the T–77 transgenic (TG) mouse line in which the -3–kb transthyretin (TTR) promoter functioned to increase hepatocyte expression of the Foxa2 cDNA. Adult TG mice exhibited reduced hepatic glycogen and progressive liver injury, but maintained normal serum levels of glucose, insulin, and glucagon. In this study, we further characterized the postnatal liver defect in TTR–FoxA2 TG mice. The postnatal TG mice displayed significant reduction in serum glucose levels and in hepatocyte glycogen storage without increased serum levels of ketone bodies and free fatty acid suggesting that they are not undergoing a starvation response. We show that TG liver developed a substantial transient steatosis, which reached a maximum at postnatal day 5 and is associated with increased expression of hepatic genes involved in fatty acid and triglyceride synthesis, lipid β–oxidation, and amino acid biosynthesis. Furthermore, transmission electron microscopy analysis of postnatal TG liver revealed extensive mitochondrial membrane damage, which is likely due to reactive oxygen species generated from lipid β–oxidation. In conclusion, our model proposes that in response to reduction in hepatocyte glycogen storage, the TTR–Foxa2 TG mice survive by maintaining sufficient serum levels of glucose through gluconeogenesis using deaminated amino acids with dicarboxylate products of peroxisomal lipid β–oxidation shuttled through the tricarboxylic acid cycle.
The Brain Machine: The Development of Neurophysiological Thought
Authors: Paul Grobstein
Journal: JAMA (1986)

That neuroscience is currently in a phase of rapid progress and high visibility must be obvious to anyone with professional interests in the biomedical sciences. What may be less evident, except perhaps to those immersed in the field, is that neuroscience has acquired something of a schizophrenic character, with rapid movement in two quite different directions. One direction involves the exploitation of revolutionary advances in molecular and cellular biology to generate, at a rate and precision of detail previously inconceivable, new information about the elements that make up the nervous system. The other, inevitably less concerned with cellular and subcellular phenomena, consists of a new burst of progress in the age-old task of finding rigorous and productive ways to describe and investigate the most complex and sophisticated aspects of brain function. One direction of movement encourages an increasing alliance between neuroscientists and cell and molecular biologists. The other, in contrast,
Determination of bisphenol A and related aromatic compounds released from bis-GMA-based composites and sealants by high performance liquid chromatography.
Authors: R Pulgar, M F Olea-Serrano, A Novillo-Fertrell, A Rivas, P Pazos, V Pedraza, J M Navajas, N Olea
Journal: Environmental Health Perspectives (2000)

Most of the composites and sealants used in dentistry are based on bisphenol A diglycidylether methacrylate (Bis-GMA). Reports revealed that in situ polymerization is not complete and that free monomers can be detected by different analytic methods. Concerns about the estrogenicity of bisphenol A (BPA) and other aromatic components leached from commercial products have been expressed. We studied biphenolic components eluted from seven composites and one sealant before and after in vitro polymerization using HPLC and gas chromatography/mass spectrometry and we investigated how pH modifications affect the leaching of these components. We found BPA (maximal amount 1.8 microg/mg dental material), its dimethacrylate derivative (Bis-DMA, 1.15 microg/mg), bisphenol A diglycidylether (6. 1 microg/mg), Bis-GMA (2.0 microg/mg), and ethoxylate and propoxylate of bisphenol A in media in which samples of different commercial products were maintained under controlled pH and temperature conditions. Our results confirm the leaching of estrogenic monomers into the environment by Bis-GMA-based composites and sealants in concentrations at which biologic effects have been demonstrated in in vivo experimental models. The main issue with implications for patient care and dentist responsibility is to further determine the clinical relevance of this estrogenic exposure.
Drinking water contaminants and adverse pregnancy outcomes: a review.
Authors: Frank Bove, Youn Shim, Perri Zeitz
Journal: Environmental Health Perspectives (2002)

Concern for exposures to drinking water contaminants and their effects on adverse birth outcomes has prompted several studies evaluating chlorination disinfection by-products and chlorinated solvents. Some of these contaminants are found to be teratogenic in animal studies. This review evaluates 14 studies on chlorination disinfection by-products such as trihalomethanes (THMs) and five studies on chlorinated solvents such as trichloroethylene (TCE). The adverse birth outcomes discussed in this review include small for gestational age (SGA), low birth weight, preterm birth, birth defects, spontaneous abortions, and fetal deaths. Because of heterogeneities across the studies in the characterization of birth outcomes, the assessment and categorization of exposures, and the levels and mixtures of contaminants, a qualitative review was conducted. Generally, the chief bias in these studies was exposure misclassification that most likely underestimated the risk, as well as distorted exposure-response relationships. The general lack of confounding bias by risk factors resulted from these factors not being associated with drinking water exposures. The studies of THMs and adverse birth outcomes provide moderate evidence for associations with SGA, neural tube defects (NTDs), and spontaneous abortions. Because fewer studies have been conducted for the chlorinated solvents than for THMs, the evidence for associations is less clear. Nevertheless, the findings of excess NTDs, oral clefts, cardiac defects, and choanal atresia in studies that evaluated TCE-contaminated drinking water deserve follow-up.
Am I My Parents' Keeper? An Essay on Justice Between the Young and the Old
Authors: William J. Bicknell
Journal: JAMA (1988)

This is a fine book. Professor Daniels helps us step back from the noise, polemic, and confusing detail that characterize much of today's debate on the cost, content, and distribution of health services. The title is a bit of a misnomer. This is far more than a book for those with an interest in the problems of aging. It concerns the fair allocation of resources to health and human services. As Daniels states, "This book is primarily concerned with the just design of social institutions.... It is a philosophical essay, not a detailed analysis of policy options." The arguments brought to bear are just as applicable to the needs of the mentally impaired, disabled young adults, or frail older persons. Daniels develops a powerful rationale for looking at resource allocation from the perspective of fairness across an entire life span rather than as an issue of competition between age cohorts.
Relationship of Amount of Cigarette Smoking to Coronary Heart Disease Mortality Rates in Men
Authors: ROBERT W. BUECHLEY, ROBERT M. DRAKE, LESTER BRESLOW
Journal: Circulation (1958)

Seven out of 8 previous reports indicate a relationship between morbidity or mortality from coronary heart disease and amount of cigarette smoking. Data from 2 California study groups, longshoremen and respondents to a household sample health survey, are presented to show similar relationships. In 4 studies showing mortality, the coronary heart disease death rates for men, in various age groups from 40 to 70 years, who smoked a pack of cigarettes or more per day, generally exceeded the corresponding rates for nonsmokers by from 1 to 7 deaths per thousand per year.
Increasing Melanoma Cell Death Using Inhibitors of Protein Disulfide Isomerases to Abrogate Survival Responses to Endoplasmic Reticulum Stress
Authors: Penny E. Lovat, Marco Corazzari, Jane L. Armstrong, Shaun Martin, Vittoria Pagliarini, David Hill, Anna M. Brown, Mauro Piacentini, Mark A. Birch-Machin, Christopher P.F. Redfern
Journal: Cancer Research (2008)

Abstract Exploiting vulnerabilities in the intracellular signaling pathways of tumor cells is a key strategy for the development of new drugs. The activation of cellular stress responses mediated by the endoplasmic reticulum (ER) allows cancer cells to survive outside their normal environment. Many proteins that protect cells against ER stress are active as protein disulfide isomerases (PDI) and the aim of this study was to test the hypothesis that apoptosis in response to ER stress can be increased by inhibiting PDI activity. We show that the novel chemotherapeutic drugs fenretinide and velcade induce ER stress–mediated apoptosis in melanoma cells. Both stress response and apoptosis were enhanced by the PDI inhibitor bacitracin. Overexpression of the main cellular PDI, procollagen-proline, 2-oxoglutarate-4-dioxygenase β subunit (P4HB), resulted in increased PDI activity and abrogated the apoptosis-enhancing effect of bacitracin. In contrast, overexpression of a mutant P4HB lacking PDI activity did not increase cellular PDI activity or block the effects of bacitracin. These results show that inhibition of PDI activity increases apoptosis in response to agents which induce ER stress and suggest that the development of potent, small-molecule PDI inhibitors has significant potential as a powerful tool for enhancing the efficacy of chemotherapy in melanoma. [Cancer Res 2008;68(13):5363–8]
Generalized Anxiety Disorder
Authors: Jeremy DeMartini, Gayatri Patel, Tonya L. Fancher
Journal: Annals of Internal Medicine (2019)

Generalized anxiety disorder (GAD) is a common and disabling illness that is often underdiagnosed and undertreated. Patients with GAD are at increased risk for suicide as well as cardiovascular-related events and death. Most patients can be diagnosed and managed by primary care physicians. Symptoms include chronic, pervasive anxiety and worry accompanied by nonspecific physical and psychological symptoms (restlessness, fatigue, difficulty concentrating, irritability, muscle tension, or sleep disturbances). Effective treatments include psychotherapy (often cognitive behavioral therapy) and pharmacotherapy, such as selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors.
Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling
Authors: Yeonseok Chung, Seon Hee Chang, Gustavo J. Martinez, Xuexian O. Yang, Roza Nurieva, Hong Soon Kang, Li Ma, Stephanie S. Watowich, Anton M. Jetten, Qiang Tian, Chen Dong
Journal: Immunity (2009)
Abstract A12: Combined EZH2 and PI3K inhibition as a novel therapy for treatment of castration resistant prostate cancer
Authors: Miriam Enos
Journal: Cancer Research (2013)

Abstract Prostate cancer is the most frequently diagnosed non-dermatological malignancy in North American men. Presently, preventative testing and castration therapies are the only measures that effectively decrease mortality. However, these therapies are not effective in the case of the advanced disease, for which there is still no cure. As such, there is an unmet medical need to develop more effective therapies for castration-resistant, metastatic tumors. Surprisingly, there are but a few things known about the signals that drive and maintain advanced disease. The PI3K/AKT signaling pathway is frequently deregulated in human malignancies and is activated in a majority of advanced stage carcinomas of the prostate. More recently, a member of PRC2 complex, EZH2, has been reported to be a marker and driver of late stage disease. Based on this knowledge about the key disregulated signaling pathways in prostate cancer, we decided to explore them as potential therapeutic avenues. We found that both genetic and biochemical inhibition of EZH2 results in reduced proliferation and transformation in soft agar. Similarly, treating cells with a PI3K specific inhibitor, GDC- 0941 produces only a cytostatic effect, an observation that is supported by a body of literature suggesting that GDC-0941 is ineffective as a mono-therapy drug. To this end we decided to explore the combination of both EZH2 and PI3K inhibitors and have found that simultaneous suppression of these two important oncogenic signals, kills androgen-dependent (AD) and independent (AI) prostate cancer cells in vitro and in vivo. Knock-down of another member of PRC2 complex, SUZ12, phenocopies this cytotoxicity when combined with PI3K inhibitor, suggesting that EZH2 role is PRC2-dependent. These preliminary data suggest specific cooperation of EZH2 and PI3K/AKT signaling pathways in assuring cell survival and maintenance of tumorigenicity in prostate cancer cells. Currently we are exploring the potential downstream effectors that could be responsible for the synergy that we observe upon combination treatment. Citation Format: Miriam Enos. Combined EZH2 and PI3K inhibition as a novel therapy for treatment of castration resistant prostate cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A12.
ERK1/2 mitogen-activated protein kinase selectively mediates IL-13-induced lung inflammation and remodeling in vivo
Authors: P. J. Lee
Journal: Journal of Clinical Investigation (2005)

IL-13 dysregulation plays a critical role in the pathogenesis of a variety of inflammatory and remodeling diseases. In these settings, STAT6 is believed to be the canonical signaling molecule mediating the tissue effects of IL-13. Signaling cascades involving MAPKs have been linked to inflammation and remodeling. We hypothesized that MAPKs play critical roles in effector responses induced by IL-13 in the lung. We found that Tg IL-13 expression in the lung led to potent activation of ERK1/2 but not JNK1/2 or p38. ERK1/2 activation also occurred in mice with null mutations of STAT6. Systemic administration of the MAPK/ERK kinase 1 (MEK1) inhibitor PD98059 or use of Tg mice in which a dominant-negative MEK1 construct was expressed inhibited IL-13–induced inflammation and alveolar remodeling. There were associated decreases in IL-13–induced chemokines (MIP-1α/CCL-3, MIP-1β/CCL-4, MIP-2/CXCL-1, RANTES/CCL-5), MMP-2, -9, -12, and -14, and cathepsin B and increased levels of α1-antitrypsin. IL-13–induced tissue and molecular responses were noted that were equally and differentially dependent on ERK1/2 and STAT6 signaling. Thus, ERK1/2 is activated by IL-13 in the lung in a STAT6-independent manner where it contributes to IL-13–induced inflammation and remodeling and is required for optimal IL-13 stimulation of specific chemokines and proteases as well as the inhibition of specific antiproteases. ERK1/2 regulators may be useful in the treatment of IL-13–induced diseases and disorders.