tbuckley/cabot-search huggingface dataset:
Book Review Infections and Human Cancer (Cancer Surveys. Vol. 33.) Edited by R. Newton, V. Beral, and R.A. Weiss. 396 pp. Plainview, N.Y., Cold Spring Harbor Laboratory Press, 1999. $93. 0-87969-549-8 Microbes and Malignancy: Infection as a cause of human cancers Edited by Julie Parsonnet. 465 pp., illustrated. New York, Oxford University Press, 1999. $75. 0-19-510401-3
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (1999)
Differences in Preferences for Neonatal Outcomes Among Health Care Professionals, Parents, and Adolescents
Authors: Saroj Saigal
Journal: JAMA (1999)

2][3][4][5][6][7][8][9] Both the Canadian Paediatric Society 10 and the American Academy of Pediatrics 11 have issued statements encouraging the involvement of parents in decision making, and in fact, to support the primacy of parental decisions for all infants at the threshold of viability.These statements were developed by health professionals using data on the mortality and morbidity of infants at each gestational age, without explicit consideration of the values and preferences of parents or members of society.In critical care situations involving newborns, parents often assume responsibility for making important lifesustaining decisions, along with neonatologists.Obviously, the preferences of newborns are unknown, and it is assumed that parents will take the best interests of the infant and the family
Innervation of the Systemic Heart of the California Hagfish
Authors: EDWIN F. HIRSCH, MAX JELLINEK, THEODORE COOPER
Journal: Circulation Research (1964)

Large nerves with myelinated fibers and ganglion cells were demonstrated in proximate relationship to the systemic heart of the California hagfish ( Eptatretus stouti ). A system of ganglion cells with fibers is distributed along the aorta, the epicardium, and the endocardium. The myocardium has a plexus of coarse and fine argyrophilic fibers and fibril branches similar to, if not as extensive as, that which occurs in the hearts of fish and amphibians. These details of anatomical structure contradict the original statement by Greene that the heart of the hagfish is aneural, a conclusion which he derived from his inability to obtain a change in the rate and force of cardiac contraction by electric stimulation of the vagus nerve. The high catecholamine content of the cardiac tissues of the California hagfish ( Eptatretus stouti ) is verified. Over 99% was determined to be epinephrine.
Controversial bill to boost US medical research funding is passed in House of Representatives
Authors: Michael McCarthy
Journal: BMJ (2015)

A bill that will substantially boost funding for the US National Institutes of Health (NIH), but which critics have said contains provisions that undermine the US drug approval process, was easily passed in the US House of Representatives on 10 July, in a vote of 344 to 77.

If passed by the Senate in its present form and signed into law, the bill, called the 21st Century Cures Act, would increase funding for the NIH by nearly $9bn (£5.8bn; €8.1bn) over five years.1 An additional $550m would go to the Food and Drug Administration to enable it to streamline and expedite drug and medical device approvals along the lines mandated by the bill.

NIH …
Resolution of Futility by Due Process: Early Experience with the Texas Advance Directives Act
Authors: Robert L. Fine, Thomas Wm. Mayo
Journal: Annals of Internal Medicine (2003)

Every U.S. state has developed legal rules to address end-of-life decision making. No law to date has effectively dealt with medical futilityan issue that has engendered significant debate in the medical and legal literature, many court cases, and a formal opinion from the American Medical Association's Council on Ethical and Judicial Affairs. In 1999, Texas was the first state to adopt a law regulating end-of-life decisions, providing a legislatively sanctioned, extrajudicial, due process mechanism for resolving medical futility disputes and other end-of-life ethical disagreements. After 2 years of practical experience with this law, data collected at a large tertiary care teaching hospital strongly suggest that the law represents a first step toward practical resolution of this controversial area of modern health care. As such, the law may be of interest to practitioners, patients, and legislators elsewhere.
A surrogate hepatitis B virus antigenic epitope represented by a synthetic peptide and an internal image antiidiotype antibody.
Authors: Y M Thanavala, S E Brown, C R Howard, I M Roitt, M W Steward
Journal: The Journal of Experimental Medicine (1986)

The use of molecules that represent single, defined epitopes able to substitute for antigen (i.e. surrogate antigens) offers considerable advantages over the use of native antigen for the precise manipulation of the immune response. We have investigated the immunochemical characteristics of two types of surrogate hepatitis B surface antigen (HBsAg) epitopes: (a) linear and cyclical synthetic peptides representing amino acid residues 139-147, a hydrophilic region corresponding to part of the a determinant of the HBsAg, and (b) four monoclonal antiidiotypes raised against anti-HBs mAb, two of which behave as an internal image of an a determinant. Polyclonal anti-HBs antisera bound the monoclonal antiidiotypes with affinities of the order of 10(8)/M, and to the peptides with greater than 10-fold lower affinities. However, the levels of antibody in the polyclonal antisera for the peptides was greater than for the antiidiotypes. In inhibition RIA, the surrogate antigens show concordance in that the internal image antiidiotypes inhibit the binding of both monoclonal and polyclonal anti-HBs to the linear and cyclical 139-147 peptides. These results imply that surrogate antigens could indeed be useful as potential hepatitis vaccines, but while the antiidiotypes may stimulate B cells of higher affinity, they would react with a more restricted range of B cell reactivities than would the peptides. A future HBV vaccine may thus comprise a synthetic peptide such as cyclical 139-147 or a cluster of monoclonal internal image antiidiotypes.
Hepatitis type A, B, and non-A non-B in fulminant hepatitis.
Authors: L R Mathiesen, P Skinoj, J O Nielsen, R H Purcell, D Wong, L Ranek
Journal: Gut (1980)

Serological investigations for hepatitis B surface and e antigen, antibody to hepatitis B surface, core and e antigen and antibody to hepatitis A virus were carried out in 22 patients with fulminant hepatitis admitted to Medical Department A, Rigshospitalet, Copenhagen, in 1970-77. Nine patients had hepatitis type B and four type A. One patient had evidence of both type A and B infection, whereas the remaining eight patients showed no evidence of type A or B infection. Two of these had been treated with disulfiram and a drug aetiology could not be excluded, but in six patients no known cause of fulminant hepatitis could be determined and these patients were classified as having hepatitis type non-A non-B. The survival rate was not statistically different for patients having type A, B, or non-A non-B hepatitis.
Cofactoring and Dimerization of Proteinase-Activated Receptors
Authors: Huilan Lin, Allen P. Liu, Thomas H. Smith, JoAnn Trejo
Journal: Pharmacological Reviews (2013)

Proteinase-activated receptors (PARs) are G protein–coupled receptors that transmit cellular responses to extracellular proteases and have important functions in vascular physiology, development, inflammation, and cancer progression. The established paradigm for PAR activation involves proteolytic cleavage of the extracellular N terminus, which reveals a new N terminus that functions as a tethered ligand by binding intramolecularly to the receptor to trigger transmembrane signaling. Most cells express more than one PAR, which can influence the mode of PAR activation and signaling. Clear examples include murine PAR3 cofactoring of PAR4 and transactivation of PAR2 by PAR1. Thrombin binds to and cleaves murine PAR3, which facilitates PAR4 cleavage and activation. This process is essential for thrombin signaling and platelet activation, since murine PAR3 cannot signal alone. Although PAR1 and PAR4 are both competent to signal, PAR1 is able to act as a cofactor for PAR4, facilitating more rapid cleavage and activation by thrombin. PAR1 can also facilitate PAR2 activation through a different mechanism. Cleavage of the PAR1 N terminus by thrombin generates a tethered ligand domain that can bind intermolecularly to PAR2 to activate signaling. Thus, PARs can regulate each other's activity by localizing thrombin when in complex with PAR3 and PAR4 or by cleaved PAR1, providing its tethered ligand domain for PAR2 activation. The ability of PARs to cofactor or transactivate other PARs would necessitate that the two receptors be in close proximity, likely in the form of a heterodimer. Here, we discuss the cofactoring and dimerization of PARs and the functional consequences on signaling.
Lung cancer: clinical presentation and specialist referral time
Authors: G. Buccheri, D. Ferrigno
Journal: European Respiratory Journal (2004)

Many textbooks describe symptoms and signs of lung cancer but refer to old series of patients. To update knowledge about lung cancer presentation, a study was carried out on 1,277 consecutive lung cancer patients, who were seen in a single Institution from January 1989 to October 2002. A set of 33 anthropometric, clinical, physical, laboratory, radiological, pathological and follow-up variables was prospectively recorded for all patients. In addition, information was obtained concerning symptoms of alarm ( i.e. potential concern), times to specialist referral and the mix of symptoms at presentation. Patients were carefully followed-up and their subsequent clinical course was recorded. Casual discovery with absence of symptoms occurred more frequently towards the end of the study period and the prevalence of chest pain became less common. No other time-dependent changes were found in the presenting symptoms. Delay in specialist referral was longer when presentation was provoked by cough or by the occurrence of systemic symptoms, such as weight loss, anorexia and asthenia. Referral delay was longer towards the end of the study, perhaps related to an increase in the number of elderly patients with co-morbidities. Both alarm and prevalence symptoms were strong predictors of the clinical outcome, as found in both univariate analysis (favourable: casual discovery and chest infection; unfavourable: chest pain, dyspnoea, systemic symptoms and symptoms of local or systemic dissemination) and in multivariate analysis (favourable: chest infection). Early presentation of lung cancer is characterised by a specific symptomatic pattern. Knowledge of this pattern may help to improve the rate of early diagnosis.
SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo
Authors: Anne-Marie O'Farrell, Tinya J. Abrams, Helene A. Yuen, Theresa J. Ngai, Sharianne G. Louie, Kevin W. H. Yee, Lily M. Wong, Weiru Hong, Leslie B. Lee, Ajia Town, Beverly D. Smolich, William C. Manning, Lesley J. Murray, Michael C. Heinrich, Julie M. Cherrington
Journal: Blood (2003)
Enhanced Survival of Transplanted Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes by the Combination of Cell Sheets With the Pedicled Omental Flap Technique in a Porcine Heart
Authors: Masashi Kawamura, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Kenji Miki, Emiko Ito, Nagako Sougawa, Takuji Kawamura, Takashi Daimon, Tatsuya Shimizu, Teruo Okano, Koichi Toda, Yoshiki Sawa
Journal: Circulation (2013)

Background— Transplantation of cardiomyocytes that are derived from human induced pluripotent stem cell–derived cardiomyocytes (hiPS-CMs) shows promise in generating new functional myocardium in situ, whereas the survival and functionality of the transplanted cells are critical in considering this therapeutic impact. Cell-sheet method has been used to transplant many functional cells; however, potential ischemia might limit cell survival. The omentum, which is known to have rich vasculature, is expected to be a source of blood supply. We hypothesized that transplantation of hiPS-CM cell sheets combined with an omentum flap may deliver a large number of functional hiPS-CMs with enhanced blood supply. Methods and Results— Retrovirally established human iPS cells were treated with Wnt signaling molecules to induce cardiomyogenic differentiation, followed by superparamagnetic iron oxide labeling. Cell sheets were created from the magnetically labeled hiPS-CMs using temperature-responsive dishes and transplanted to porcine hearts with or without the omentum flap (n=8 each). Two months after transplantation, the survival of superparamagnetic iron oxide–labeled hiPS-CMs, assessed by MRI, was significantly greater in mini-pigs with the omentum than in those without it; histologically, vascular density in the transplanted area was significantly greater in mini-pigs with the omentum than in those without it. The transplanted tissues contained abundant cardiac troponin T–positive cells surrounded by vascular-rich structures. Conclusions— The omentum flap enhanced the survival of hiPS-CMs after transplantation via increased angiogenesis, suggesting that this strategy is useful in clinical settings. The combination of hiPS-CMs and the omentum flap may be a promising technique for the development of tissue-engineered vascular-rich new myocardium in vivo.
International Union of Pharmacology. XLIII. Compendium of Voltage-Gated Ion Channels: Transient Receptor Potential Channels
Authors: David E. Clapham, Craig Montell, Guenter Schultz, David Julius
Journal: Pharmacological Reviews (2003)

The transient receptor potential (TRP) proteins are six transmembrane-containing subunits that combine to form cation-selective ion channels. TRP channels are present in yeast, <i>Drosophila, Caenorhabditis elegans</i>, and mammals. They are widely distributed and sense local changes in stimuli ranging from light to temperature and osmolarity. Mammals contain at least 22 distinct genes encoding these ion channels. This summary article presents an overview of the molecular relationships among the TRP channels and a standard nomenclature for them, which is derived from the <i>IUPHAR Compendium of Voltage-Gated Ion Channels.</i>1 The complete Compendium, including data tables for each member of the TRP channel family, can be found at http://www.iuphar-db.org/iuphar-ic/.
PAR-2 Inhibition Reverses Experimental Pulmonary Hypertension
Authors: Grazyna Kwapiszewska, Philipp Markart, Bhola Kumar Dahal, Baktybek Kojonazarov, Leigh Matthew Marsh, Ralph Theo Schermuly, Christian Taube, Andreas Meinhardt, Hossein Ardeschir Ghofrani, Martin Steinhoff, Werner Seeger, Klaus Theo Preissner, Andrea Olschewski, Norbert Weissmann, Malgorzata Wygrecka
Journal: Circulation Research (2012)

A hallmark of the vascular remodeling process underlying pulmonary hypertension (PH) is the aberrant proliferation and migration of pulmonary arterial smooth muscle cells (PASMC). Accumulating evidence suggests that mast cell mediators play a role in the pathogenesis of PH.In the present study we investigated the importance of protease-activated receptor (PAR)-2 and its ligand mast cell tryptase in the development of PH.Our results revealed strong increase in PAR-2 and tryptase expression in the lungs of idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice, and monocrotaline (MCT)-treated rats. Elevated tryptase levels were also detected in plasma samples from IPAH patients. Hypoxia and platelet-derived growth factor (PDGF)-BB upregulated PAR-2 expression in PASMC. This effect was reversed by HIF (hypoxia inducible factor)-1α depletion, PDGF-BB neutralizing antibody, or the PDGF-BB receptor antagonist Imatinib. Attenuation of PAR-2 expression was also observed in smooth muscle cells of pulmonary vessels of mice exposed to hypoxia and rats challenged with MCT in response to Imatinib treatment. Tryptase induced PASMC proliferation and migration as well as enhanced synthesis of fibronectin and matrix metalloproteinase-2 in a PAR-2- and ERK1/2-dependent manner, suggesting that PAR-2-dependent signaling contributes to vascular remodeling by various mechanisms. Furthermore, PAR-2(-/-) mice were protected against hypoxia-induced PH, and PAR-2 antagonist application reversed established PH in the hypoxia mouse model.Our study identified a novel role of PAR-2 in vascular remodeling in the lung. Interference with this pathway may offer novel therapeutic options for the treatment of PH.
Rediscovering the Core of Public Health
Authors: Steven M. Teutsch, Jonathan E. Fielding
Journal: Annual Review of Public Health (2012)

The success of public health has been its ability to understand contemporary health problems, to communicate the needs successfully, to identify solutions, and to implement them through programs and policies. In the past 50 years, those successes can be attributed largely to control of infectious disease, improved maternal and child health, delivery of other personal health care services, and changes in behaviors, particularly smoking. Yet health is primarily a product of our social, cultural, and physical environments. To continue to improve the nation's health and reduce disparities, public health needs to return to its historical roots and engage with other sectors to create healthier communities. To do so requires expanding public health skills in areas such as quantitative policy analysis, communication, and community engagement.
Modification of Collagen IV by Glucose or Methylglyoxal Alters Distinct Mesangial Cell Functions
Authors: Ambra Pozzi, Roy Zent, Sergei Chetyrkin, Corina Borza, Nada Bulus, Peale Chuang, Dong Chen, Billy Hudson, Paul Voziyan
Journal: Journal of the American Society of Nephrology (2009)

Diabetic nephropathy (DN) affects both glomerular cells and the extracellular matrix (ECM), yet the pathogenic mechanisms involving cell-matrix interactions are poorly understood. Glycation alters integrin-dependent cell-ECM interactions, and perturbation of these interactions results in severe renal pathology in diabetic animals. Here, we investigated how chemical modifications of the ECM by hyperglycemia and carbonyl stress, two major features of the diabetic milieu, affect mesangial cell functions. Incubation of collagen IV with pathophysiological levels of either the carbonyl compound methylglyoxal (MGO) or glucose resulted in modification of arginine or lysine residues, respectively. Mouse mesangial cells plated on MGO-modified collagen IV showed decreased adhesion and migration. Cells plated on glucose-modified collagen IV showed reduced proliferation and migration and increased collagen IV production. Inhibiting glucose-mediated oxidative modification of collagen IV lysine residues rescued the alterations in cell growth, migration, and collagen synthesis. We propose that diabetic ECM affects mesangial cell functions via two distinct mechanisms: modification of arginine residues by MGO inhibits cell adhesion, whereas oxidative modification of lysine residues by glucose inhibits cell proliferation and increases collagen IV production. These mechanisms may contribute to mesangial cell hypertrophy and matrix expansion in DN.
Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient
Authors: Ninette Amariglio, Abraham Hirshberg, Bernd W Scheithauer, Yoram Cohen, Ron Loewenthal, Luba Trakhtenbrot, Nurit Paz, Maya Koren-Michowitz, Dalia Waldman, Leonor Leider-Trejo, Amos Toren, Shlomi Constantini, Gideon Rechavi
Journal: PLoS Medicine (2009)

Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells.A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors.This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.
Should we use spirometry in the early detection of COPD?
Authors: P. White
Journal: European Respiratory Journal (2005)

Should we use spirometry in the early detection of COPD?To the Editors:ENRIGHT et al. [1] in the European Respiratory Monograph, promote office spirometry as the way forward in the routine assessment of asthma and chronic obstructive pulmonary disease (COPD), and in the early detection of COPD.They define office spirometry as 'spirometry performed in the primary care setting'.There is an unwelcome ambiguity in their paper when it comes to both of these subjects, and the evidence they use to support their arguments is far from decisive.In the case of the early detection of COPD, the evidence seems to oppose their position.
Targeted therapies to improve CFTR function in cystic fibrosis
Authors: Malcolm Brodlie, Iram J. Haq, Katie Roberts, J. Stuart Elborn
Journal: Genome Medicine (2015)

Cystic fibrosis is the most common genetically determined, life-limiting disorder in populations of European ancestry. The genetic basis of cystic fibrosis is well established to be mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that codes for an apical membrane chloride channel principally expressed by epithelial cells. Conventional approaches to cystic fibrosis care involve a heavy daily burden of supportive treatments to combat lung infection, help clear airway secretions and maintain nutritional status. In 2012, a new era of precision medicine in cystic fibrosis therapeutics began with the licensing of a small molecule, ivacaftor, which successfully targets the underlying defect and improves CFTR function in a subgroup of patients in a genotype-specific manner. Here, we review the three main targeted approaches that have been adopted to improve CFTR function: potentiators, which recover the function of CFTR at the apical surface of epithelial cells that is disrupted in class III and IV genetic mutations; correctors, which improve intracellular processing of CFTR, increasing surface expression, in class II mutations; and production correctors or read-through agents, which promote transcription of CFTR in class I mutations. The further development of such approaches offers great promise for future therapeutic strategies in cystic fibrosis.