tbuckley/cabot-search huggingface dataset:
Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice
Authors: Kun L. Ma, Xiong Z. Ruan, Stephen H. Powis, Yaxi Chen, John F. Moorhead, Zac Varghese
Journal: Hepatology (2008)

Abstract The prevailing theory in non-alcoholic fatty liver disease (NAFLD) is the “two-hit” hypothesis. The first hit mainly consists of lipid accumulation, and the second is subsequent systemic inflammation. The current study was undertaken to investigate whether inflammatory stress exacerbates lipid accumulation in liver and its underlying mechanisms. We used interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) stimulation in human hepatoblastoma cell line (HepG2) cells and primary hepatocytes in vitro, and casein injection in apolipoprotein E knockout mice in vivo to induce inflammatory stress. The effects of inflammatory stress on cholesterol accumulation were examined by histochemical staining and a quantitative intracellular cholesterol assay. The gene and protein expressions of molecules involved in cholesterol trafficking were examined by real-time polymerase chain reaction (PCR) and western blot. Cytokine production in the plasma of apolipoprotein E knockout mice was measured by enzyme-linked immunosorbent assay. Our results showed that inflammatory stress increased cholesterol accumulation in hepatic cells and in the livers of apolipoprotein E knockout mice. Further analysis showed that inflammatory stress increased the expression of low-density lipoprotein (LDL) receptor (LDLr), sterol regulatory element–binding protein (SREBP) cleavage activating protein (SCAP), and SREBP-2. Confocal microscopy showed that IL-1β increased the translocation of SCAP/SREBP-2 complex from endoplasmic reticulum (ER) to Golgi in HepG2 cells, thereby activating LDLr gene transcription. IL-1β, TNF-α, and systemic inflammation induced by casein injection also inhibited expression of adenosine triphosphate–binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-α (PPAR-α), and liver X receptor-α (LXRα). This inhibitory effect may cause cholesterol efflux reduction. Conclusion : Inflammatory stress up-regulates LDLr-mediated cholesterol influx and down-regulates ABCA1-mediated cholesterol efflux in vivo and in vitro . This may exacerbate the progression of NAFLD by disrupting cholesterol trafficking control, especially during the second hit phase of liver damage. (Hepatology 2008.)
Prevalence of gastrointestinal diseases in two British national birth cohorts
Authors: A G C Ehlin, S M Montgomery, A Ekbom, R E Pounder, A J Wakefield
Journal: Gut (2003)

<b>Background:</b> Few studies have investigated the prevalence of multiple gastrointestinal diseases in the general British population. <b>Aim:</b> To examine the prevalence of Crohn’s disease (CD), ulcerative colitis (UC), irritable bowel syndrome (IBS), gall stones (GS), and peptic ulcer disease (PUD). <b>Subjects:</b> The 1970 British Cohort Study (BCS70) and the National Child Development Study (NCDS) are two one week national birth cohorts born in 1970 and 1958, respectively. All cohort members living in Great Britain were interviewed in 1999/2000. <b>Methods:</b> The prevalence rates of the five diseases were calculated, and associations with sex and childhood social class were investigated using logistic regression. <b>Results:</b> At age 30 years, the prevalence rates per 10 000 (95% confidence interval (CI)) in the 1970 and 1958 cohorts, respectively, were: CD 38 (26–49), 21 (13–30); UC 30 (20–41), 27 (18–37); IBS 826 (775–877), 290 (267–330); GS 88 (71–106), 78 (62–94); and PUD 244 (214–273), 229 (201–256). There was a significantly higher proportion with CD (p=0.023) and IBS (p=0.000) in the 1970 cohort compared with the 1958 cohort at age 30 years. Comparing the cohorts in the 1999/2000 sweep, UC, GS, and PUD were significantly (p=0.001, p=0.000, p=0.000) more common in the 1958 cohort. There was a statistically significant trend for a higher risk of GS with lower social class in both cohorts combined (p=0.027). <b>Conclusion:</b> The study indicates an increasing temporal trend in the prevalence of CD and suggests a period effect in IBS, possibly due to adult life exposures or variation in recognition and diagnosis of IBS.
Centromeres of mammalian chromosomes
Authors: Huntington F. Willard
Journal: Trends in Genetics (1990)

The centromere is the major cis-acting genetic locus involved in chromosome segregation in mitosis and meiosis. The mammalian centromere is characterized by large amounts of tandemly repeated satellite DNA and by a number of specific centromere proteins, at least one of which has been shown to interact directly with centromeric satellite DNA sequences. Although direct functional assays of chromosome segregation are still lacking, the data are most consistent with a structural and possibly functional role for satellite DNA in the mammalian centromere.
Illness as Metaphor; AIDS and its Metaphors
Authors: James Curran
Journal: BMJ (2007)

It is not uncommon for people to write about their experience of experience. After the US writer Susan Sontag underwent chemotherapy for breast cancer, however, she took a different approach. Illness as Metaphor examines in more general than personal terms how society regards illness and being ill, in particular “the punitive or sentimental fantasies concocted about that situation.”

In a sense she still writes from her experience in focusing on descriptions of cancer (with some comparisons with tuberculosis, the disease that killed her father), though drawing examples mainly from Western …
Electrical activation of the expiratory muscles to restore cough.
Authors: A F DiMarco, J R Romaniuk, G S Supinski
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Many patients with spinal cord injury have paralysis of their expiratory muscles and, consequently, lack an effective cough. The purpose of the present study was to evaluate the utility of lower thoracic spinal cord stimulation (SCS) to activate the expiratory muscles. Studies were performed on 15 anesthetized dogs. A quadripolar stimulating electrode (Medtronic Model 3586) was inserted epidurally and on the ventral surface of the lower thoracic spinal cord. Changes in airway pressure, airflow, and internal intercostal and abdominal muscle length were monitored to assess the effects of electrical stimulation. Spinal stimulation applied at the T9-T10 spinal level provided maximal changes in airway pressure generation in preliminary experiments. All subsequent studies were therefore performed with the electrode positioned at this level. The expiratory muscles were stimulated supramaximally over a wide range of lung volumes which were expressed as the corresponding change in airway pressure. The pressure-generating capacity of the expiratory muscles was evaluated by the change in airway pressure produced by SCS during airway occlusion. Peak expiratory airflow was also monitored following release of occlusion. At FRC, deflation (-10 cm H2O) and inflation (+ 30 cm H2O), SCS resulted in positive airway pressures of 44 cm H2O +/- 4 SE, 28 cm H2O +/- 3 SE, and 82 cm H2O +/- 7 SE. The relationship between airway pressure expiratory airflow generation and lung volume was linear (slope = 1.34 +/- 0.04) over the entire vital capacity range. Our results indicate that: (1) a major portion of the expiratory muscles can be activated reproducibly and in concert by electrical stimulation, and (2) this technique may be a clinically useful method of restoring cough in spinal cord injured patients.
Differential gene expression of the three natriuretic peptides and natriuretic peptide receptor subtypes in human liver.
Authors: A M Vollmar, G Paumgartner, A L Gerbes
Journal: Gut (1997)

Various effects of atrial natriuretic peptide (ANP) on the liver have been observed. However, there is limited information about the types of receptors for natriuretic peptides expressed by the human liver.To investigate gene expression of the three NP receptor types (NPR) as well as of the NP in human liver.Presence of mRNA coding for all three NPR and for ANP, brain and C-type natriuretic peptide (BNP, CNP) was investigated by reverse transcription-polymerase chain reaction (RT-PCR). Human liver tissues and hepatocellular carcinoma tissues were examined.Specific PCR products for all three NPR, namely NPR-A, B, and C, could be detected. Moreover, ANP and CNP, but not BNP mRNA was detectable. The concentration of ANP transcripts was up to fivefold higher in hepatocellular carcinoma compared with non-tumorous liver tissue of the same subjects. No difference in the expression of NP receptors relative to GAPDH mRNA of tumorous and non-tumorous tissue was observed except of slightly increased NPR-A transcripts.These data show that NPR transcripts are coexpressed with ANP and CNP mRNA in the human liver. This provides evidence for a local NP system in the human liver.
Does a prescribed treatment match a patient's priorities?
Authors: N. Britten
Journal: BMJ (2003)

Within the past 10 years several studies carried out in different settings have investigated patients' perceptions of prescribed drugs. Most of these studies have been qualitative and relatively small scale. They have all revealed considerable ambivalence about drug taking. This study by Townsend and colleagues confirms the validity of these findings for a community based sample of middle aged people in Scotland with multiple morbidities and provides a rich description of the different aspects of this ambivalence. Most prescribed drugs are taken by elderly people with chronic conditions.

This study also …
Integromic Analysis of Genetic Variation and Gene Expression Identifies Networks for Cardiovascular Disease Phenotypes
Authors: Chen Yao, Brian H. Chen, Roby Joehanes, Burcak Otlu, Xiaoling Zhang, Chunyu Liu, Tianxiao Huan, Oznur Tastan, L. Adrienne Cupples, James B. Meigs, Caroline S. Fox, Jane E. Freedman, Paul Courchesne, Christopher J. O’Donnell, Peter J. Munson, Sunduz Keles, Daniel Levy
Journal: Circulation (2014)

Background— Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown. Methods and Results— We built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P ≤5×10 −8 ) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate &lt;0.05, we identified 370 cis –expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans -eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose, and body mass index) in the same individuals, we found examples in which the expression of eQTL genes was significantly associated with these CVD phenotypes. In addition, mediation tests suggested that a subset of SNPs previously associated with CVD phenotypes in genome-wide association studies may exert their function by altering expression of eQTL genes (eg, LDLR and PCSK7 ), which in turn may promote interindividual variation in phenotypes. Conclusions— Using a network approach to analyze CVD traits, we identified complex networks of SNP-phenotype and SNP-transcript connections. Integrating the CVD network with phenotypic data, we identified biological pathways that may provide insights into potential drug targets for treatment or prevention of CVD.
Blocking effect of verapamil on conduction over a catecholamine-sensitive bypass tract in exercise-induced Wolff-Parkinson-White syndrome
Authors: Yutaka Horio, Koshi Matsuyama, Yasuhiro Morikami, Manabu Rokutanda, Atsumi Hirata, Ken Okumura, Kyoji Takaoka, Hideo Uchida, Kiyotaka Kugiyama, Shukuro Araki
Journal: Journal of the American College of Cardiology (1984)
Men's health: don't blame the victims
Authors: C. Essex
Journal: BMJ (1996)

posts that address problems of inner cities-for example, homelessness and drug misuse.We have been able to extend training based in general practice within the three year scheme when neces- sary.' Research by the South London Organisation of Vocational Training Schemes has shown that many registrars do not feel ready to enter general practice after vocational training (C Vaughan, personal communication).We provide a fourth year of training in the form of a vocational training associate scheme, which addresses registrars' further learning needs while giving them time to gain experience and confidence in practice.This initiative, in its second year, has also been able to support 34 local practices under stress.These changes have allowed us to recruit a full complement of high quality registrars to our schemes and increase the number of locally trained doctors becoming principals in south London.The training issues have become too complex to be solved by appending general practice training to hospital training.We look forward to the results of the evaluation of our innovations.These results will inform the debate about developing excellent training for general practice that will supply highly trained general practitioners for inner cities into the next century.
Pressure amplitude increase on unmatching the aortic-iliac junction of the dog
Authors: D. L. NEWMAN, R. G. GOSLING, N. L. R. BOWDEN, D. H. KING
Journal: Cardiovascular Research (1973)

Pressure pulses were recorded simultaneously at the aortic/external iliac junction and in the abdominal aorta of six normal dogs at a distance 7—10 cm upstream of the junction. The matched abdominal aortic equitrifurcation was then transformed, in vivo, to an unmatched equibifurcation by temporary occlusion of the central branch and the pressure recording procedure repeated. An increase in the oscillatory pressure amplitudes at the junction was observed as a result of the unmatching procedure. At the upstream site the amplitude increase was similar to the junction site for only the first two harmonics of the pressure pulse. These changes were interpreted as being due to increased reflection from the unmatched junction and alteration in the peripherally reflected pressure waves reaching the aorta.
Efficacy and Tolerability of Radiotherapy as Treatment for Bicalutamide-induced Gynaecomastia and Breast Pain in Prostate Cancer
Authors: H. Van Poppel, C.J. Tyrrell, K. Haustermans, P. Van Cangh, F. Keuppens, P. Colombeau, T. Morris, L. Garside
Journal: European Urology (2004)
Psychosocial Risk Factors and Nonfatal Myocardial Infarction
Authors: Nancy J. O’Connor, JoAnn E. Manson, Gerald T. O’Connor, Julie E. Buring
Journal: Circulation (1995)

Background Numerous psychosocial factors have been hypothesized to play a role in coronary heart disease. However, existing studies have yielded inconsistent results. Methods and Results The relations between type A personality as well as suppressed versus expressed anger and risk of nonfatal myocardial infarction (MI) were studied in 340 patients and 340 age-, sex-, and community-matched control subjects. Subjects were interviewed at home to assess behavioral and medical cardiovascular risk factors, and fasting blood samples were obtained. Type A personality was associated with nonfatal MI in crude matched-pair analysis (OR, 1.57; 95% CI, 1.12 to 2.20; P =.008). Adjusting for known cardiovascular risk factors (including treated hypertension, body mass index, treated diabetes, family history of premature MI, physical activity, smoking, alcohol, total calories per day, and saturated fat) did not substantially change the magnitude of the point estimate, although the finding was no longer statistically significant (OR, 1.43; 95% CI, 0.97 to 2.09; P =.069). Further adjustment for lipids, including total cholesterol, total HDL, its subfractions (HDL 2 , HDL 3 ), LDL, VLDL, and triglycerides, markedly attenuated the association (OR, 1.12; 95% CI, 0.66 to 1.90; P =.687), an effect due almost entirely to HDL cholesterol. Suppressed anger was positively but not statistically significantly associated with increased risk of MI in crude matched-pair analysis (OR, 1.33; 95% CI, 0.98 to 1.81; P =.065), in analysis adjusted for behavioral and medical cardiovascular risk factors (OR, 1.26; 95% CI, 0.89 to 1.78; P =.193), or after adjustment for lipids (OR, 1.11; 95% CI, 0.67 to 1.82; P =.695). Conclusions These findings suggest a possible association of type A but not suppressed anger with risk of nonfatal MI that may be mediated by alterations in HDL cholesterol level. If decreases in HDL are not in the same causal pathway, then the apparent association between type A personality and risk of MI is due to confounding, principally by HDL.
An Inhibitor of Histamine Release from Human Leukocytes
Authors: Michael T. Kelly, Arthur White
Journal: Journal of Clinical Investigation (1974)

Lysates of human leukocytes, prepared by ultrasonic disruption, contained heat-labile histamine-releasing factors. An inhibitor of histamine release was generated from such lysates during thermal inactivation of the histamine-releasing activity. Lysates inactivated at 38°C for 60 min produced up to 90% inhibition of histamine release from human leukocytes. Heated lysates produced significant inhibition (P < 0.001) of leukocyte histamine release induced by goat antihuman IgE (51±3% inhibition), compound 48/80 (69±7% inhibition), and fresh leukocyte lysate (63±6% inhibition).
Abstract 3794: Inhibition of prostate cancer bone metastases by the dickkopf-1 neutralizing antibody BHQ880
Authors: Joseph L. Sottnik, Christopher Hall, Andreas Karatsinides, Andrew L. Keller, Seth A. Ettenberg, Evan T. Keller
Journal: Cancer Research (2012)

Abstract Advanced prostate carcinoma (PCa) is usually complicated by the presence of bone metastases. Current therapies targeting bone metastases are suboptimal as the metastases progress in spite of therapy. Accordingly, novel therapeutics are needed to target these lesions. The Wnt inhibitor Dickkopf-1 (DKK-1) appears to play an important role in progression of PCa bone metastases. Overexpression of DKK-1 by PCa promotes tumor growth and bone lysis in laboratory studies and DKK1 is present in clinical PCa bone metastases. Development of a fully humanized anti-DKK-1 neutralizing antibody, BHQ880 (Novartis), provides a potential therapeutic strategy to target PCa bone metastases. The goal of this study was to test if BHQ880 could impact PCa bone metastases. PC-3-luc cells (2.5x105) were injected intratibially into mice. Treatment with anti-DKK-1 or isotype control antibody (n=12 mice per group) was initiated 0, 7, or 14 days post-tumor injection. Mice were treated three times weekly by intraperitoneal injection with 200 μg/mouse (approximately 10 mg/kg) Tumor growth and bone lysis were assessed by weekly bioluminescence and bi-weekly radiography, respectively. All mice were euthanized 31 days post-tumor injection, tumor bearing limbs were formalin fixed and serum was obtained. Tumor bearing limbs were analyzed by dual energy x-ray absorptiometry (DEXA) and histology. Serum was assayed for the bone turnover biomarkers alkaline phosphatase (ALP), osteocalcin (OC), and tartate-resistant acid phosphatase 5b (TRAP5b). BHQ880 was well tolerated with no significant side effects observed. Significant inhibition of tumor growth was observed in mice where treatment was initiated 7 or 14 days post-tumor challenge when established tumors were present. Two mice from the 14-day treatment group had tumor regressions after treatment with BHQ880. Treatment with BHQ880 resulted in decreased bone lysis as determined using DEXA. Furthermore, increased serum concentrations of ALP and OC in mice treated with BHQ880 suggest increased bone production; no significant difference in TRAP5b concentration between treated and untreated mice was found. Treatment with the DKK-1 neutralizing antibody BHQ880 was found to inhibit tumor growth, tumor-induced osteolysis and increase serum bone remodeling markers associated with increased bone production in a murine model of PCa bone metastasis. These data suggest that anti-DKK-1 treatment is a plausible mechanism for inhibition of progression of PCa bone metastases. These data suggest that inhibition of DKK-1 may be an effective strategy to inhibit PCa growth in bone. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3794. doi:1538-7445.AM2012-3794
Changing life expectancy throughout history
Authors: JP Griffin
Journal: Journal of the Royal Society of Medicine (2008)

Rowbotham and Clayton (JRSM 2008;101:454–62) make a very important point when they draw attention to the life expectancy at birth compared to life expectancy at 5+ years of age.1 They state ‘… life expectancy in the mid-Victorian period was not markedly different from what it is today. Once infant mortality is stripped out, life expectancy at 5 years was 75 for men and 73 for women.’ In 1995 Griffin2 produced a comparison of life expectancy of mature men (15+years of age) at different points in history over the last 3000 years ( Table 1).



Table 1

Calculations of life expectancy throughout history



Montagu3 excluded from his calculations any who died violently; no such exclusion was made from any of the other figures presented in Table 1. Montagu noted a dip in life expectancy in Roman figures and attributed this to lead plumbing. The change in life expectancy of mature men has not changed as dramatically over 3000 years as might be expected, although this data must of necessity refer to privileged members of society.

Life expectancy of women at the age of 15 years has however changed dramatically over the last 600 years ( Table 2) and by a decade and a half since the mid-Victorian period. For men, Rowbtham and Clayton have a point but are incorrect as far as women's life expectancy is concerned.



Table 2

Life expectancy of mature women taken from Hollingsworth8 and OPCS data for England and Wales
Breast Cancer Screening with MRI — What Are the Data for Patients at High Risk?
Authors: Laura Liberman
Journal: New England Journal of Medicine (2004)

More than 275,000 women in the United States will receive a diagnosis of breast cancer this year, and 40,110 women will die of the disease.1 Randomized trials have shown that the use of screening mammography in the general population reduces mortality associated with breast cancer by at least 24 percent.2 Cancer is detected in 5 to 7 of every 1000 women on the first screening mammogram and in 2 or 3 of every 1000 women who undergo regular screening mammography. Although the average lifetime risk of breast cancer in an American woman is one in seven,1 the risk increases in . . .
Warnings in Tobacco Advertisements: Marlboro Man vs Surgeon General
Authors: Linda F. Alwitt
Journal: JAMA (1989)

<h3>To the Editor.—</h3> The article by Fischer et al<sup>1</sup>hypothesizes that warnings on cigarette packages are ineffective for adolescents. Although that hypothesis may be supportable, their study does not adequately demonstrate such support. There are several problems with the method and interpretation of results in this study that limit its usefulness. The results are reported out of context. Since there are no control conditions, one cannot tell if the results support the hypothesis. The authors could have collected results for advertisements other than tobacco advertisements for comparison. For assessing eye movements, they could have compared frequency and duration of fixation to other parts of the advertisements besides the warning. As the authors state, the sample size is too small (n = 45) for a study that is supposed to be generalized to all adolescents. The claim that 8% of mean total viewing time was devoted to the warning is more