tbuckley/cabot-search huggingface dataset:
Reducing inequalities in health will need a long timeframe, MPs are told
Authors: Adrian O’Dowd
Journal: BMJ (2008)

Government targets to reduce health inequalities in England might be measuring the wrong things, and the means to tackle the problem will emerge only over a long period, MPs have been told.

Public health experts told MPs on the parliamentary select committee on health last week, as part of its inquiry into health inequalities, why they thought so little progress had been made so far.

MPs asked why health inequalities have continued to grow, despite government efforts in its 2003 strategy Tackling Inequalities: A Programme for Action and despite GPs achieving health targets set out in their contract. …
Multicentre surveillance of prevalence of the 23S rRNA A2058G and A2059G point mutations and molecular subtypes of Treponema pallidum in Taiwan, 2009–2013
Authors: B.-R. Wu, C.-J. Yang, M.-S. Tsai, K.-Y. Lee, N.-Y. Lee, W.-C. Huang, H. Wu, C.-H. Lee, T.-C. Chen, W.-C. Ko, H.-H. Lin, P.-L. Lu, Y.-H. Chen, W.-C. Liu, S.-P. Yang, P.-Y. Wu, Y.-C. Su, C.-C. Hung, S.-Y. Chang
Journal: Clinical Microbiology and Infection (2014)
Osteo-Arthritis. A Handbook for Patients
Authors: Douglas Hubble
Journal: Annals of the Rheumatic Diseases (1956)

Continental treatment differs in certain respects from British practice, and more emphasis, for instance, is placed on spas.Also the patient abroad seems to associate radio-activity, in some vague manner, with the treatment of rheumatism-a habit of thought which is not discouraged.In fact, it may be said that, if dreams are the product of experience in the waking hours, the reviewer of continental medical literature is likely to have his slumbers disturbed by visions of petrol-pumps labelled "Fill up here with Thorium-X" and high voltage machines advertising "Emanations without Examina- tions"; in Great Britain, on the other hand, the public is becoming radiation-conscious, experts are questioning the desirability of certain diagnostic-radiology pro- cedures, and there is even heart-searching over the possibility that a proportion of cases of ankylosing spondylitis treated by deep x-rays may develop leukaemia in later years.The authors have provided an adequate alphabetical index but have deliberately curtailed the bibliography and quoted French references wherever possible; this measure of economy may be not unconnected with the cost of publication in France which, to judge by the price of the volume, is considerably higher than in England.
Animal fur and asthma: an indoor farmyard phenomenon?
Authors: Julian Crane
Journal: European Respiratory Journal (2015)

The relationships between allergen exposure, sensitisation and the development of allergic disease have, since their first description, been complicated, often counterintuitive, and rarely straightforward. Ever since Charles Blackley put himself through a private medical education in order to study his own severe "summer catarrh", allergens and their human targets have been behaving oddly. Blackley [1] suggested a hypothesis (circa 1870s) that his summer catarrh or hay fever might be associated with exposure to seasonal grass pollens (the current belief at the time was that it was caused by increased temperatures in summer). He confirmed his hypothesis in a series of elegant and painstaking experiments, often on himself. At a time when hay fever was distinctly uncommon, he headed to local farming communities around the rapidly developing city of Manchester, to study probable sufferers. To his surprise, the very people exposed relentlessly to grass pollens in their daily working lives rarely reported hay fever symptoms. It might be argued that with this observation he also suggested the earliest stirrings of what would become part of the hygiene hypothesis, namely that people who live on farms get less allergic disease. How do animal furs protect children from asthma and allergy? Is it time to trial furs and other farm type exposures? <http://ow.ly/Nce0O>
The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology
Authors: Jason A. Chen, Olga Peñagarikano, T. Grant Belgard, Vivek Swarup, Daniel H. Geschwind
Journal: Annual Review of Pathology Mechanisms of Disease (2015)

Autism spectrum disorder (ASD) is defined by impaired social interaction and communication accompanied by stereotyped behaviors and restricted interests. Although ASD is common, its genetic and clinical features are highly heterogeneous. A number of recent breakthroughs have dramatically advanced our understanding of ASD from the standpoint of human genetics and neuropathology. These studies highlight the period of fetal development and the processes of chromatin structure, synaptic function, and neuron-glial signaling. The initial efforts to systematically integrate findings of multiple levels of genomic data and studies of mouse models have yielded new clues regarding ASD pathophysiology. This early work points to an emerging convergence of disease mechanisms in this complex and etiologically heterogeneous disorder.
A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer
Authors: L.K Borysiewicz, A Fiander, M Nimako, S Man, G.W.G Wilkinson, D Westmoreland, A.S Evans, M Adams, S.N Stacey, M.E.G Boursnell, E Rutherford, J.K Hickling, S.C Inglis
Journal: The Lancet (1996)
Inborn resistance of mice to myxoviruses: macrophages express phenotype in vitro.
Authors: J Lindenmann, E Deuel, S Fanconi, O Haller
Journal: The Journal of Experimental Medicine (1978)

A strain of avian influenza A virus was adapted to grow in mouse peritoneal macrophages in vitro. The adapted strain, called M-TUR, induced a marked cytopathic effect in macrophages from susceptible mice. Mice homozygous (A2G) or heterozygous (F1 hybrids between A2G and several susceptible strains) for the gene Mx, shown previously to induce a high level of resistance towards lethal challenge by a number of myxoviruses in vivo, yielded peritoneal macrophages which were not affected by M-TUR. Peritoneal macrophages could be classified as resistant or susceptible to M-TUR without sacrificing the cell donor. Backcrosses were arranged between (A2G X A/J)F1 and A/J mice. 64 backcross animals could be tested individually both for resistance of their macrophages in vitro after challenge with M-TUR, and for resistance of the whole animal in vivo after challenge with NWS (a neurotropic variant of human influenza A virus). Macrophages from 36 backcross mice were classified as susceptible, and all of these mice died after challenge. Macrophages from 28 mice were classified as resistant, and 26 mice survived challenge. We conclude that resistance of macrophages and resistance of the whole animal are two facets of the same phenomenon.
Hepatitis C Virus Seromarkers and Subsequent Risk of Hepatocellular Carcinoma: Long-Term Predictors From a Community-Based Cohort Study
Authors: Lee Mei-Hsuan, Hwai-I Yang, Sheng-Nan Lu, Chin-Lan Jen, Shiou-Hwei Yeh, Chun-Jen Liu, Pei-Jer Chen, San-Lin You, Li-Yu Wang, Wei J. Chen, Chien-Jen Chen
Journal: Journal of Clinical Oncology (2010)

Hepatitis C virus (HCV) contributes to one third of hepatocellular carcinoma cases worldwide. Long-term predictors for HCV-related hepatocellular carcinoma are essential for early intervention. Serum HCV RNA and ALT levels and HCV genotype were assessed for their predictability of hepatocellular carcinoma risk.A prospective cohort of 925 participants positive for antibodies against HCV and age 30 to 65 years was recruited and followed from 1991 to 2006. Serum HCV RNA and ALT levels and HCV genotypes at enrollment and during follow-up were examined. Newly developed hepatocellular carcinoma was identified by health examination and computerized linkage with national cancer registration and death certification profiles. Multivariate adjusted hazard ratios with 95% CIs were estimated using Cox regression models.Fifty-five participants newly developed hepatocellular carcinoma during 8,476 person-years of follow-up, giving an incidence rate of 648.9 per 100,000 person-years. The cumulative hepatocellular carcinoma risk increased from 1.1% for HCV RNA seronegative status to 6.4% for low HCV RNA levels and to 14.7% for high HCV RNA levels (P < .001). The cumulative risk also increased with elevated serum ALT levels from 1.7% for persistently ≤ 15 U/L to 4.2% for ever more than 15 U/L but never more than 45 U/L and to 13.8% for ALT ever ≥ 45 U/L (P < .001). Having HCV genotype 1 was associated with a higher cumulative hepatocellular carcinoma risk (12.6%) than not having HCV genotype 1 (4.5%; P < .001).Elevated serum levels of HCV RNA and ALT and HCV genotype 1 infection are independent risk predictors of hepatocellular carcinoma. These findings have strong implications for the management of chronic HCV.
Evaluation of efficacy of liver transplantation in alcoholic cirrhosis by a case-control study and simulated controls
Authors: Thierry Poynard, Philippe Barthelemy, Serge Fratte, Karim Boudjema, Michel Doffoel, Clare Vanlemmens, JeanPhilippe Miguet, Georges Mantion, Michel Messner, Bernard Launois, Sylvie Naveau, JeanClaude Chaput, None for a Multi-centre group
Journal: The Lancet (1994)
Serum HER2 levels are increased in patients with chronic heart failure
Authors: Patrick J. Perik, Elisabeth G.E. de Vries, Jourik A. Gietema, Winette T.A. van der Graaf, Tom D.J. Smilde, Dirk T. Sleijfer, Dirk J. van Veldhuisen
Journal: European Journal of Heart Failure (2006)
Peeling the Onion: Ribosomes Are Ancient Molecular Fossils
Authors: C. Hsiao, S. Mohan, B. K. Kalahar, L. D. Williams
Journal: Molecular Biology and Evolution (2009)

We describe a method to establish chronologies of ancient ribosomal evolution. The method uses structure-based and sequence-based comparison of the large subunits (LSUs) of Haloarcula marismortui and Thermus thermophilus. These are the highest resolution ribosome structures available and represent disparate regions of the evolutionary tree. We have sectioned the superimposed LSUs into concentric shells, like an onion, using the site of peptidyl transfer as the origin (the PT-origin). This spherical approximation combined with a shell-by-shell comparison captures significant information along the evolutionary time line revealing, for example, that sequence and conformational similarity of the 23S rRNAs are greatest near the PT-origin and diverge smoothly with distance from it. The results suggest that the conformation and interactions of both RNA and protein can be described as changing, in an observable manner, over evolutionary time. The tendency of macromolecules to assume regular secondary structural elements such as A-form helices with Watson–Crick base pairs (RNA) and α-helices and β-sheets (protein) is low at early time points but increases as time progresses. The conformations of ribosomal protein components near the PT-origin suggest that they may be molecular fossils of the peptide ancestors of ribosomal proteins. Their abbreviated length may have proscribed formation of secondary structure, which is indeed nearly absent from the region of the LSU nearest the PT-origin. Formation and evolution of the early PT center may have involved Mg2+-mediated assembly of at least partially single-stranded RNA oligomers or polymers. As one moves from center to periphery, proteins appear to replace magnesium ions. The LSU is known to have undergone large-scale conformation changes upon assembly. The T. thermophilus LSU analyzed here is part of a fully assembled ribosome, whereas the H. marismortui LSU analyzed here is dissociated from other ribosomal components. Large-scale conformational differences in the 23S rRNAs are evident from superimposition and prevent structural alignment of some portions of the rRNAs, including the L1 stalk.
Evidence Suggesting a Multigenic Origin of Membranous Septal Defect in Rats
Authors: MORJORIE HOPKINS FOX
Journal: Circulation Research (1969)

The study was designed to assess the relative importance of parity, parental age and the fetal genome in the etiology of congenital interventricular septal defects in a subline of Long-Evans rats with a high incidence of malformation (25%). Analysis of successive litters produced in 27 full sibships indicated that parity and parental aging had no consistently significant influence on the incidence of defects. Relatively consistent litter incidences within sibships but highly significant differences in the mean litter incidences of the different sibships support the hypothesis that the fetal genome is of primary etiologic importance. Analysis of the half-sibships produced by 12 males in sequential matings with different young virgin females indicated that neither paternal age nor a parental age differential significantly influenced the incidence of defects. Highly significant differences between the half-sibships in respect to mean litter incidences of malformation were attributable to highly significant differences between sires, significant differences between dams and considerable within litter variation. Analysis of the parental-offspring distribution of defects rules out the possibility of fully penetrant unifactorial inheritance but suggests that ventricular anomalies are transmitted in accordance with a polygenic, quasi-continuous inheritance pattern.
Rationale and design of a randomised, controlled, multicenter trial investigating the effects of selective serotonin re‐uptake inhibition on morbidity, mortality and mood in depressed heart failure patients (MOOD‐HF)
Authors: Christiane E. Angermann, Götz Gelbrich, Stefan Störk, Andreas Fallgatter, Jürgen Deckert, Hermann Faller, Georg Ertl
Journal: European Journal of Heart Failure (2007)
DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and tumor cell survival in diffuse large B cell lymphoma
Authors: Corina A. Schmid, Mark D. Robinson, Nicole A. Scheifinger, Sebastian Müller, Sergio Cogliatti, Alexandar Tzankov, Anne Müller
Journal: The Journal of Experimental Medicine (2015)

The epigenetic dysregulation of tumor suppressor genes is an important driver of human carcinogenesis. We have combined genome-wide DNA methylation analyses and gene expression profiling after pharmacological DNA demethylation with functional screening to identify novel tumor suppressors in diffuse large B cell lymphoma (DLBCL). We find that a CpG island in the promoter of the dual-specificity phosphatase DUSP4 is aberrantly methylated in nodal and extranodal DLBCL, irrespective of ABC or GCB subtype, resulting in loss of DUSP4 expression in 75% of &amp;gt;200 examined cases. The DUSP4 genomic locus is further deleted in up to 13% of aggressive B cell lymphomas, and the lack of DUSP4 is a negative prognostic factor in three independent cohorts of DLBCL patients. Ectopic expression of wild-type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N-terminal kinase (JNK) and induces apoptosis in DLBCL cells. Pharmacological or dominant-negative JNK inhibition restricts DLBCL survival in vitro and in vivo and synergizes strongly with the Bruton’s tyrosine kinase inhibitor ibrutinib. Our results indicate that DLBCL cells depend on JNK signaling for survival. This finding provides a mechanistic basis for the clinical development of JNK inhibitors in DLBCL, ideally in synthetic lethal combinations with inhibitors of chronic active B cell receptor signaling.
Adenine nucleotide metabolism and compartmentalization in isolated adult rat heart cells.
Authors: T Geisbuhler, R A Altschuld, R W Trewyn, A Z Ansel, K Lamka, G P Brierley
Journal: Circulation Research (1984)

The metabolism and intracellular compartmentalization of adenine nucleotides in a preparation of adult rat heart myocytes showing good morphology, viability, and tolerance to calcium ion has been examined by high performance liquid chromatography. These myocytes contain an average of 23 nmol adenine nucleotide per milligram protein which is about 60% of the adenine nucleotide content of intact rat heart tissue. The loss of adenine nucleotide occurs during the incubation and washing steps that increase the yield of viable cells, rather than during the collagenase perfusion. An analysis of cellular compartments shows that the adenine nucleotide of the cell consists of 17 nmol adenine nucleotide in the cytosol, 5 nmol in the mitochondria, and 1.3 nmol adenosine diphosphate bound to myofibrils per milligram cell protein. Myocytes lose both adenosine triphosphate and adenine nucleotide when incubated anaerobically in the absence of glucose, and the lost adenine nucleotide can be accounted for as increased inosine, adenosine, and inosine monophosphate. Myocytes that contain less than 0.1 nmol of cytosol adenosine triphosphate per milligram cell protein maintain an intact sarcolemma, but are unable to carry out anaerobic glycolysis. Reoxygenation of anaerobic cells results in restoration of energy charge and a net resynthesis of about 2 nmol adenine nucleotide per milligram protein. Adenosine and inosine monophosphate decrease on reaeration of anaerobic cells, whereas inosine levels increase. When iodoacetate is added to block glycolysis, the decline in adenine nucleotide and production of inosine monophosphate are accelerated and there is no resynthesis of adenine nucleotide when anaerobic cells are reoxygenated . Large accumulations of inosine monophosphate are also seen in myocytes treated with an uncoupler of oxidative phosphorylation.
Beyond the "ABC approach"
Authors: A. Singh
Journal: European Respiratory Journal (2007)

To the Editors: 

I read with interest the recent review by Celli and Barnes 1, wherein the authors have beautifully discussed the aetiology, cellular and molecular mechanisms, management and new definition of exacerbations of chronic obstructive pulmonary disease (COPD).

In the management of acute exacerbations of COPD they have discussed the role of three classes of drugs …
Skeletal effects of selective oestrogen receptor modulators (SERMs)
Authors: J. L. D. Diez
Journal: Human Reproduction Update (2000)

Women suffer a higher incidence of osteoporosis than men, in part due to oestrogen deficiency after menopause. In fact, the administration of oestrogen to post-menopausal women is associated with a decrease of bone resorption. Tamoxifen is a widely used selective oestrogen receptor modulator in women with breast cancer, which has been shown an agonistic profile in bone. However, tamoxifen seems less effective than oestradiol as an anti-resorptive agent and has no effect when the endogenous production of oestrogen is normal. Additionally, tamoxifen exhibits agonistic activity on the endometrium and has been suggested an oncogenic potential on that tissue. Raloxifene, a selective oestrogen receptor modulator from the benzothiophene family, behaves also as an agonist on the bone in both laboratory and clinical studies. Ongoing clinical trials confirm a protective effect of raloxifene similar to oestrogens. The Multiple Outcome of Raloxifene Evaluation (MORE) study is a prospective, randomized trial which, in a recent 2 year interim analysis, has shown that women suffering from osteoporosis receiving raloxifene had 42% fewer vertebral fractures than women receiving a placebo.
CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide.
Authors: R R Ingalls, D T Golenbock
Journal: The Journal of Experimental Medicine (1995)

CD11c/CD18 is a member of the leukocyte integrin family, heterodimeric adhesion molecules that interact with a diverse repertoire of ligands, including bacterial lipopolysaccharide (LPS). Their role as signal transducing receptors remains uncertain. We used a heterologous expression system to determine if CD11c/CD18 was capable of initiating signal transduction in response to LPS-binding, as assessed by the induced translocation of nuclear factor-kappa B. We have previously reported that Chinese hamster ovary (CHO)-K1 fibroblasts, normally unresponsive to LPS, acquire serum-dependent macrophage-like responses to LPS when transfected with CD14 (Golenbock, D.T., Y. Liu, F. Millham, M. Freeman, and R. Zoeller. 1993. J. Biol. Chem. 268:22055-22059), a known LPS receptor. In contrast, CHO cells acquired serum-independent responses to Gram-negative bacteria and LPS when transfected with CD11c/CD18 (CHO/CD11c). In comparison to CHO cells transfected with CD14 (CHO/CD14), responses in CHO/CD11c cells were slower, required higher endotoxin concentrations for maximal response, and were not inhibited by the presence of antibodies to CD14. CD11c/CD18 is, thus, the second phagocyte receptor, in addition to CD14, which has been shown to have the capacity to activate cells after binding to LPS. The function of this receptor in normal phagocytes may be limited to the recognition of LPS in infected tissues, where LPS-CD14 interactions are not favored because of the absence of serum proteins.
Reflex cardiovascular and respiratory effects of serotonin in conscious and anesthetized dogs.
Authors: I H Zucker, K G Cornish
Journal: Circulation Research (1980)

Cardiovascular and respiratory effects of intra-left atrial or intra-left ventricular injection of serotonin were studied in conscious dogs (n = 8), anesthetized closed-chest dogs (n = 13) and anesthetized open-chest dogs (n = 9). Serotonin (50-200 microgram), injected as a bolus, resulted in an initial bradycardia and hypotension followed by a delayed tachycardia and hypertension in the conscious dogs. The hypertension was seen as an increase of 21.5 +/- 2.7 (mean +/ SE) mm Hg from a control pressure of 102.5 +/- 1.9 mm Hg, whereas the initial decrease in pressure was 22.6 +/- 1.9 mm Hg. The tachycardia was 23.3 +/- 3.9 beats/min above a control heart rate of 104.9 +/- 3.9 beats/min whereas the bradycardia was 58.5 +/- 3.7 beats/min below control. There was a significant attenuation of the hypotension in both groups of anesthetized dogs. In fact, no hypotension was elicited in the open-chest anesthetized dogs. Open-chest anesthetized dogs showed only a hypertensive response (mean increase 67.2 +/- 5.5 mm Hg). Stimulation of respiration was seen in all groups of dogs. In conscious dogs there was a 214.8 +/- 15.4% increase in respiratory depth and a 20.8 +/- 3.1 breaths/min increase in respiratory rate. Atropine significantly reduced the bradycardia and abolished the hypotension in conscious dogs. Bilateral cervical vagotomy did not abolish the response in open-chest anesthetized dogs. We conclude that the so-called "hypertensive coronary chemoreflex" is altered dramatically by the state of the preparation and by anesthesia.