tbuckley/cabot-search huggingface dataset:
Bridging theory and reality gap
Authors: C. Qiu
Journal: BMJ (2010)

Ritchie and colleagues may be overoptimistic about their programmes to prevent dementia1 given the huge gap between theoretical programmes derived from observational studies and findings from randomised clinical trials.

Indeed, observational studies have frequently shown an association of dementia with several modifiable factors—hypertension, hyperlipidaemia, and diabetes being putative risk factors …
A Quantitative Immunofluorescence Assay (AQUA) Suggests Significant Misclassification (15%) of Estrogen Receptor Status in Breast Cancer.
Authors: A. Welsh, C. Moeder, E. Alarid, D. Rimm
Journal: Cancer Research (2009)

Abstract Introduction: Estrogen Receptor (ER) is arguably the most powerful predictive marker in breast cancer. However, a recent incident in Canada revealed a strikingly high false-negative rate and raised awareness of the current limitations in our measurement of ER. The current clinical standard is both subjective and qualitative. Even though guidelines are about to be issued to standardize this assay, there is very little data on the misclassification rate in current practice in the US.Hypothesis: Our hypothesis is that the use of a quantitative assay for ER on a series of retrospective collections may reveal both the level and significance of the misclassification rate.Method: Cell lines with a range of ER expression levels were analyzed by quantitative western blotting in parallel with IF/AQUA analysis (r2 = 0.865), in order to create standard curves for assessment of absolute ER protein concentration in tissue. The optimized assay was then used to quantify ER protein expression in a large cohort of archival breast cancer samples from Yale (1962-1982, n =617).Results: Using a set of standard curves with recombinant ER and cell line controls, we developed a standardized method for quantifying ER as an absolute concentration (pg ER per μg total protein) in formalin-fixed tissue on TMAs. This ER AQUA assay has a range in sensitivity from 50 pg/μg to 1500pg/μg total protein. Quantification of ER protein expression on the Yale archival cohort revealed a unimodal distribution with 49.8% of cases above the 50pg/ug threshold and thus defined as positive. When compared to pathologist performed conventional ER classification, we found a false negative rate of 6.65% and a false positive rate of 10.2%, for a total misclassification rate of 16.6%. Although no response data is available on that cohort, data is under analysis on 4 other cohorts with endocrine therapy treatment information, including an independent Yale cohort, SWOG 9313, NSABP B14, and the TEAM trial.Conclusion: We have developed a quantitative method to measure absolute levels of ER in breast tissue. Use of this assay on a series of cohorts suggests a misclassification rate in the 15% range. The significance of this level of misclassification with respect to response to endocrine therapy is currently under study. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4068.
Babies born at night have higher risk of encephalopathy, Californian study shows
Authors: J. H. Tanne
Journal: BMJ (2010)

A study of nearly two million babies born at full term in California between 1999 and 2002 showed that those born at night had a higher risk of encephalopathy.

The increase in risk is small, and the causes are not clear, says the study, published in the American Journal of Obstetrics and Gynecology (doi:10.1016/ajog.2010.09.022). The risk of encephalopathy among babies born during the day is about 1.1 per 1000 births, while it is 1.3 per 1000 births among those born at night. The risk is highest for babies born between 10 pm and 4 am. These babies had a 22% higher risk of neonatal encephalopathy than babies born between 7 …
Mulibrey Heart Disease
Authors: Marita Lipsanen-Nyman, Jaakko Perheentupa, Juhani Rapola, Anssi Sovijärvi, Markku Kupari
Journal: Circulation (2003)

Mulibrey nanism is a rare inherited disease characterized by growth failure and multiorgan manifestations, including constrictive pericarditis. Its long-term course, the results of pericardiectomy, and the details of myocardial involvement have not been reported previously.We studied 49 patients (26 men) born before 1985 and followed for up to 25 years. By 1999, 25 patients (51%) had developed congestive heart failure (CHF), 19 (39%) had undergone pericardiectomy for constrictive pericarditis, 10 (22%) had died of cardiac causes, and 5 (10%) had died of noncardiac causes. Of the 19 pericardiectomized patients, 12 derived lasting clinical benefit, whereas 1 patient suffered an early noncardiac death and 6 died later of unrelieved or recurrent CHF. At echocardiography in 34 living patients, left ventricular mass adjusted for body height and weight averaged (+/-SEM) 149+/-5 g in 21 unoperated patients, 144+/-8 g in 13 pericardiectomized patients, and 104+/-7 g in 16 healthy persons matched for age and sex (P=0.000). Autopsies of 11 patients showed fibrotic thickening of the pericardial leaves with myocardial hypertrophy and variable but mostly mild myocardial fibrosis. Endocardial thickening was seen in 3 patients.Constrictive pericarditis, myocardial hypertrophy, and variable myocardial fibrosis constitute the main elements of Mulibrey heart disease. At least one half of patients ultimately develop CHF. Pericardiectomy generally provides clinical benefit, but in approximately one third of patients, CHF may recur because of coexisting myocardial involvement.
Screening for carriers of cystic fibrosis--a general practitioner's perspective.
Authors: M Modell
Journal: BMJ (1993)

The identification of the gene for cystic fibrosis has led to the possibility of population based screening for carriers of cystic fibrosis to identify couples at risk of having an affected child. Pilot studies have shown that screening is feasible and does not cause untoward anxiety, though the uptake of testing varies considerably with the setting and method of invitation. Screening offered at times when individuals (and health professionals) perceive it as directly relevant will probably gradually become established in the United Kingdom. This review examines the role of general practice in genetic carrier screening as exemplified by cystic fibrosis. General practice has a pivotal role from the beginning in providing individuals and couples with information, facilitating testing of patients' relatives and of carriers identified by screening elsewhere (such as antenatal clinics), and offering testing in the context of reproduction. Screening for the cystic fibrosis gene will probably be followed by other genetic screening programmes.
1043-44 Identifying patients at risk for ischemia-driven target vessel revascularization after primary percutaneous coronary intervention: Lessons from the primary angioplasty in myocardial infarction (PAMI) trials
Authors: Rajendra H Mehta, Kishore J Harjai, Judy Boura, William O'Neill, Cindy L Grines
Journal: Journal of the American College of Cardiology (2004)
Purification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes.
Authors: S L Tsai, M H Chen, C T Yeh, C M Chu, A N Lin, F H Chiou, T H Chang, Y F Liaw
Journal: Journal of Clinical Investigation (1996)

In vitro studies in patients with hepatitis B virus (HBV) infection have suggested that hepatocytolysis induced by CD8+ cytotoxic T lymphocytes (CTLs) is the most important effector pathway in eliminating infected cells. The recognition is implicated in the endogenously processed HBV antigens in the context of HLA class I molecules presented on the liver cell membrane. However, the naturally occurring HBV peptide antigens have not yet been demonstrated. We report here that a naturally processed peptide antigen P2 was isolated from HLA class I molecules of HBV-infected liver cell membrane. The P2 peptide exhibited the activity of sensitizing target cells for lysis by CD8+ CTLs. The P2 sequence (YVNVNMGLK) purified from liver tissue was in concordance with that encoded by the viral genome for the HBV nucleocapsid antigen or HBcAg 88-96. P2 peptide could also be isolated from the EBV-transformed B cells that were transfected by HBcAg-expressing vector. The P2 epitope, sharing the HLA-A11 binding motifs, was recognized by HLA-A11-restricted CD8+ CTLs. The data provided direct evidence that, in hepatitis B patients, antigenic peptides of HBV were processed by hepatocytes, presented with the class I MHC molecules, and recognized by CD8+ CTLs.
Nitric oxide formation lowers norepinephrine-induced intrahepatic resistance without major effects on the metabolism in the perfused rat liver
Authors: H Weidenbach, A K Nussler, Z Shu, G Adler, K Beckh
Journal: Hepatology (1997)

Nitric oxide (NO) and norepinephrine are potent vasoactive agents that are involved in the control of portal blood flow. We have studied NO and norepinephrine in a non-recirculated rat liver perfusion to analyze their influence on portal flow and hepatic metabolism. Animals were either pretreated with endotoxin (4 hours; 10 mg/kg intraperitoneally) to activate the inducible NO synthase (NOS2), or used without pretreatment for the constitutive NO synthase (NOS3). In both groups, portal flow, bile flow, bile secretion, and the sinusoidal bile acid uptake were reduced by norepinephrine with a simultaneous increase of glucose and lactate output. The addition of the substrate for NO synthesis, L-arginine (0.5 mmol/L), to the perfusate markedly inhibited the effect of 0.1 micromol/L norepinephrine on portal flow from -2.6 +/- 0.32 to 0.3 +/- 0.1 mL/g/10 min in endotoxin-treated animals, and from -2.9 +/- 0.45 to 0.77 +/- 0.29 mL/g/10 min in the untreated ones. In contrast, neither NO formation after L-arginine supplementation nor inhibition of NO synthesis via the structural analogue (N(G)-monomethyl-L-arginine [L-NMMA]) changed cholestatic and glycogenolytic effects caused by norepinephrine. Only the sinusoidal bile acid uptake was reduced following increased NO formation. Thus, we conclude that endogenous NO formation prevents alpha-catecholaminergic-increased intrahepatic resistance without a major influence on the metabolic effects.
The United States Needs a Health System Like Other Countries
Authors: Michael F. Loudon
Journal: JAMA (1994)

To the Editor.  —Dr Glaser's article 1 on the virtues of a national health system for the United States is but the latest fine example  a superb series that JAMA readers from other countries must surely read with fascination and admiration. His conclusions are clear and compelling.  However, his article contains three important related generalizations, placed for maximum rhetorical effect, two of which are at best misleading and one of which is false.  Glaser states that in other countries... [governments do] not simply dictate to the drug companies, wholesalers, and pharmacists. On the subject of cost control (both global and local) Glaser states, In democratic societies, no single government agency... can fix a limit.... [A] limit cannot be set by a snap of the fingers.... The government of the United Kingdom does dictate to drug companies and distributors. It sets global and regional budgets that impact irrevocably on all
Changes in fibrillation threshold of the heart produced by a beta-sympatholytic agent (practolol), before and after experimental coronary ligation
Authors: G. SCHLEY, W. MEESMANN, A. WILDE, U. WILD
Journal: Cardiovascular Research (1974)

Fibrillation threshold was determined in dogs under piritramide/N2O anaesthesia, by direct electrical stimulation of the myocardium by 50 Hz, AC in pulses of 0·20-0·28 msec during the vulnerable period, before and 3 min after acute ligation of the circumflex ramus of the left coronary artery. Ventricular fibrillation was converted into sinus rhythm after releasing the ligation and defibrillating. The same determinations were then repeated after intravenous administration of 0·5 mg/kg practolol. Fibrillation threshold current following coronary ligation fell on the average from 25·8 mA to 9·3 mA. The threshold current rose on an average, from 30·3 mA to 72·1 mA, after giving practolol. Values after subsequent coronary ligation lay at an average of 54·0 mA, this being approximately five times higher than after circumflex ligation without practolol.
932-85 Altered Muscle Fiber Sarcomeres in Hypertrophic Cardiomyopathy Associated with the 403 Arg-→Gln β-Myosin Heavy Chain Gene Mutation
Authors: Edward B. Lankford, Rhea Levine, Neal D. Epstein, Lameh Fananapazir, H. Lee Sweeney
Journal: Journal of the American College of Cardiology (1995)
Abstract 2514: The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes, in a population of healthy adults in South Australia.
Authors: Visalini Nair-Shalliker, Varinderpal Dhillon, Mark Clements, Bruce K. Armstrong, Michael Fenech
Journal: Cancer Research (2013)

Abstract A positive association between solar UV exposure and micronuclei (MN) frequency (biomarker of chromosome breakage or loss) was previously reported with the effect of solar UV exposure on DNA damage greater when serum vitamin D (25(OH)D) levels were insufficient (&amp;lt;50nmol/L). MN formation can result from global hypomethylation of the DNA repeat sequence, which is suggested to be a significant factor in driving oncogenesis. Therefore the aim was to evaluate the relationship between lymphocytic DNA methylation pattern in LINE-1 repetitive elements and solar UV exposure in 208 male and female participants from South Australia. Possible modifying effects of serum 25(OH)D levels were examined. Personal solar UV exposure was estimated from hours of outdoor exposure over 16 weeks recalled at the time of blood collection. DNA methylation pattern in LINE-1 repetitive elements was assessed in peripheral blood lymphocytes using pyrosequencing. DNA methylation in LINE-1 repetitive elements decreased with increasing sun exposure (% decrease=0.5% per doubling of sun exposure; 95%CI: -0.7-0.2 pvalue=0.00003). There was no correlation between LINE-1 methylation and MN frequency, however for every 1% increase in LINE-1 methylation there was a corresponding 4.3% (95% CI:0.6-8.1 p-value=0.02) increase in nucleoplasmic bridges (biomarker of dicentric chromosome formation) and a 4.3% increase in necrosis (CI:1.9-6.8 p-value=0.0005). This suggests that the reduction in LINE-1 methylation with increased solar exposure may be too small to explain increases in MN frequency and therefore other mechanisms must be considered. There was no clear relationship between 25(OH)D and DNA methylation. In conclusion, the inverse relationship between solar UV radiation and LINE-1 DNA methylation status suggests a role for solar UV exposure in influencing genomic methylation patterns, which in turn appears to be associated with specific biomarkers of cell death (necrosis) and chromosomal stability (NPBs). If this holds true, then the use of LINE-1 hypomethylation, and possibly methylation of other sequences such as Alu repeats, as a biomarker for studying the role of UV in inducing both skin and internal cancers (and other diseases) might deserve further consideration. Citation Format: Visalini Nair-Shalliker, Varinderpal Dhillon, Mark Clements, Bruce K. Armstrong, Michael Fenech. The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes, in a population of healthy adults in South Australia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2514. doi:10.1158/1538-7445.AM2013-2514
Genotype-specific interactions of insulin resistance, steatosis, and fibrosis in chronic hepatitis C
Authors: Ian Homer Y. Cua, Jason M. Hui, James G. Kench, Jacob George
Journal: Hepatology (2008)

Abstract The interaction between insulin resistance (IR), steatosis and genotype to fibrosis in chronic hepatitis C virus (HCV) infection has not been comprehensively assessed. We hypothesized that IR is a key mediator for the development of both steatosis and fibrosis in 346 untreated, nondiabetic patients solely infected with either genotype 1 or 3. We examined for genotype-specific interactions between IR, steatosis and fibrosis by performing subgroup analyses. Because cirrhosis is known to cause IR, we repeated the analysis in a cohort of 313 noncirrhotic HCV-infected patients. We confirmed the impact of IR on fibrosis by analysis of 153 lean subjects in whom any effect of steatosis would be minimized. In HCV genotype 3 patients, increased steatosis was linked to high viral load ( P = 0.001), and was not associated with fibrosis ( P = 0.1). In contrast, body mass index ( P = 0.04) and homeostasis model assessment of insulin resistance (HOMA-IR) ( P = 0.01) contributed directly to steatosis in HCV genotype 1. HOMA-IR rather than steatosis was independently associated with fibrosis for both HCV genotype 1 (OR, 3.22; P = 0.02) and genotype 3 (OR, 3.17; P = 0.04). Exclusion of cirrhotic subjects did not alter the findings with respect to the greater contribution of IR compared to hepatic steatosis, as a predictor of fibrosis ( P = 0.02). Genotype-specific subgroup analyses did not alter this finding. The extent of HOMA-IR remained significantly associated with fibrosis in lean patients, independent of the confounding effect of body mass index on IR (OR, 8.02; P = 0.003). Conclusion: IR is a major independent determinant of fibrosis in chronic HCV infection, regardless of the genotype and the severity of liver damage. (Hepatology 2008.)
β1 Integrin Cytoplasmic Variants Differentially Regulate Expression of the Antiangiogenic Extracellular Matrix Protein Thrombospondin 1
Authors: Hira Lal Goel, Loredana Moro, Joanne E. Murphy-Ullrich, Chung-Cheng Hsieh, Chin-Lee Wu, Zhong Jiang, Lucia R. Languino
Journal: Cancer Research (2009)

Beta(1) integrins play an important role in regulating cell proliferation and survival. Using small interfering RNA or an inhibitory antibody to beta(1), we show here that, in vivo, beta(1) integrins are essential for prostate cancer growth. Among the five known beta(1) integrin cytoplasmic variants, two have been shown to differentially affect prostate cell functions. The beta(1A) variant promotes normal and cancer cell proliferation, whereas the beta(1C) variant, which is down-regulated in prostate cancer, inhibits tumor growth and appears to have a dominant effect on beta(1A). To investigate the mechanism by which beta(1C) inhibits the tumorigenic potential of beta(1A), we analyzed changes in gene expression in cells transfected with either beta(1C) or beta(1A). The results show that beta(1C) expression increases the levels of an extracellular matrix protein, thrombospondin 1 (TSP1), an angiogenesis inhibitor. TSP1 protein levels are increased upon beta(1C) expression in prostate cancer cells as well as in beta(1)-null GD25 cells. We show that TSP1 does not affect proliferation, apoptosis, or anchorage-independent growth of prostate cancer cells. In contrast, the newly synthesized TSP1, secreted by prostate cancer cells expressing beta(1C), prevents proliferation of endothelial cells. In conclusion, our novel findings indicate that expression of the beta(1C) integrin variant in prostate glands prevents cancer progression by up-regulation of TSP1 levels and inhibition of angiogenesis.
The Special Package Evil
Authors: W. C. Wescott
Journal: JAMA (1913)

<h3>To the Editor:</h3> —There is much food for thought in the editorial from the New York<i>Sun</i>(The JournalA. M. A., Oct. 5, 1912, p. 1307) warning the public against physicians who prescribe proprietaries, blaming these physicians for the all-too-prevalent tendency of the public toward self-medication, and lauding the old-fashioned prescription because it at least cannot easily be duplicated. It is but too true that the prescribing of proprietaries fosters self-drugging. When a patient learns that the medicine prescribed is "ready-made" he shrewdly concludes that it was not made for his ailment in particular, but that it must fit a series of similar conditions. Hence, if it is found of value, he will hereafter use it for all symptoms similar to those which caused his physician to prescribe the proprietary. He also will find little difficulty in finding symptoms in the ailments of his friends which will warrant a
Biochemical markers of bone turnover in diagnosis of myeloma bone disease
Authors: Omer Dizdar, Ibrahim Barista, Umut Kalyoncu, Omer Karadag, Gulsen Hascelik, Aysenur Cila, Asli Pinar, Ismail Celik, Ayse Kars, Gulten Tekuzman
Journal: American Journal of Hematology (2006)

Abstract This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein‐1α (MIP‐1α), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty‐five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age‐, sex‐, and bone mineral density‐matched control subjects were enrolled. Levels of MIP‐1α, OPN, carboxy‐terminal telopeptide of Type‐1 collagen (C‐telopeptide or Ctx), deoxypyridinoline (DPD), Type‐1 collagen propeptide (T1Pro), and bone‐specific alkaline phosphatase (BALP) were assessed in both groups. Twenty‐two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP‐1α, and urine DPD were significantly higher in MM patients with bone disease than in controls ( P &lt; 0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls ( P &lt; 0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls ( P &lt; 0.001). The serum OPN and MIP‐1α levels of the patients were significantly correlated with β2‐microglobulin and lactate dehydrogenase levels ( P &lt; 0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP‐1α needs to be further investigated. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
Vaccination scar with soft-tissue atrophy restored by local insulin treatment.
Authors: F K Amroliwalla
Journal: BMJ (1977)

A woman who had a deep scar on her left arm as a result of an influenza vaccination was treated with insulin. Monocomponent porcine insulin was injected into each quadrant of the pit. After 82 days9 treatment her arm appeared normal and has remained so over seven months. Using insulin9s ability to promote fat and protein synthesis is a simple and effective way of treating atrophied scars.
Sixth-nerve Palsy after Lumbar Puncture and Spinal Analgesia
Authors: R. Bryce-Smith, R. R. Macintosh
Journal: BMJ (1951)

BDI JOuHRA275distance.But there seems to be no case in the literature in which receding reduplicated images have been seen.Another unusual feature is that the images are multi- plications of objects actually seen-in the absence of illumination there are no hallucinatory phenomena.As these seizures were also characterized by turning of the head and eyes to the right and smacking of the lips, a left temporo-frontal focus was sought.It is generally cOnsidered that the occurrence of organized visual hallucinations indicates a disturbance in one or other temporal lobe, usually in the dominant hemisphere; and Penfield and Erickson (1941) and Marchand and de Ajuriaguerra (1948) classify seizures characterized thereby in the group of so-called " psychical seizures."In the presFnt case, however, no clinical or electro-