tbuckley/cabot-search huggingface dataset:
Does the Na+,K+ pump current undergo remodeling in atrial fibrillation?
Authors: E Carmeliet
Journal: Cardiovascular Research (2003)

energy to transporters that do not use ATP as an energythis issue.source, such as the Na ,Ca exchanger, the Na ,HThe sodium pump current has been the subject of many exchanger, the Na ,K ,2Cl cotransporter, thestudies, but information on human cardiac tissue is lacking.Na ,HCO cotransporter, and the Na ,glucose and 3 1 This gap has been filled by a paper published in this issue Na ,amino acid cotransporters [3]. 1 in which Workman, Kane and Rankin [1] describe the Important biophysical characteristics of the Na pump generating a Na gradient the pump provides potential ATPase.For external K , the K value is much smaller 0.5 than the concentration encountered in the extracellular 1 medium, indicating that the K sensitive site is practically
Effect of infused vasoactive intestinal peptide on airway function in normal subjects.
Authors: J B Palmer, F M Cuss, J B Warren, M Blank, S R Bloom, P J Barnes
Journal: Thorax (1986)

Vasoactive intestinal peptide, one of the putative neurotransmitters of non-adrenergic inhibitory nerves in human airways, is a potent relaxant of human airways in vitro. Previous in vivo studies of infused vasoactive intestinal peptide in asthmatic subjects have shown only a small bronchodilator effect, which may have been secondary to the cardiovascular effects of the peptide. The effect on airway function of infused vasoactive intestinal peptide was studied in normal subjects, who readily develop bronchodilation in response to a beta agonist. Separate experiments were designed to assess whether there is any synergy between this peptide and the beta agonist isoprenaline. Incremental doses of 1, 3, and 6 pmol/kg/min of vasoactive intestinal peptide were infused for 15 minutes. At 6 pmol/kg/min it caused a mean fall in systolic blood pressure from 108 to 88 mm Hg and a rise in heart rate from 71 to 95 beats/min. There was no significant change in specific airways conductance (sGaw) at any dose of vasoactive intestinal peptide. No significant changes were found with placebo. Isoprenaline (400 microgram) given by inhalation at the end of the infusion produced a mean increase in sGaw of 50%. Infused peptide caused no significant change in the cumulative dose-response curve for inhaled isoprenaline. The lack of effect of vasoactive intestinal peptide on airway responses in vivo may be due to rapid enzymatic breakdown of the peptide or to the fact that dosage has to be limited by the cardiovascular effects.
Abstract LB-290: The influence of body size and weight gain on global and gene promoter methylation in a population-based breast cancer study
Authors: Lauren E. McCullough, Jia Chen, Alexandra J. White, Xinran Xu, Yoon Hee Cho, Patrick T. Bradshaw, Sybil M. Eng, Susan L. Teitelbaum, Mary Beth Terry, Gail Garbowski, Alfred I. Neugut, Hanina Hibshoosh, Regina M. Santella, Marilie D. Gammon
Journal: Cancer Research (2014)

Abstract Purpose. Little is known about how modifiable lifestyle factors, influence the epigenome. Elevated body mass index (BMI, weight kg/height m2) and adult weight gain are associated with increased risk of postmenopausal breast cancer, but the underlying mechanisms are not well understood. We hypothesized that these anthropometric factors may modify DNA methylation status by altering sex-steroid hormones levels and inflammatory markers. Methods. Resources from a population-based study (∼650 postmenopausal cases/∼650 postmenopausal controls) were used to construct logistic regression models. We explored potential modification of the global methylation-breast cancer association by BMI and weight gain using two assays: the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) in white blood cell DNA. Additionally, we estimated associations between anthropometrics and promoter methylation status in a panel of 13 breast cancer-related genes using ∼600 breast tumor tissues. Results. We observed a multiplicative interaction between LUMA and BMI (p=0.033) in relation to breast cancer. There was a greater than two-fold risk of postmenopausal breast cancer among women in the highest quartile of LUMA for each strata of BMI: age-adjusted odds ratios (95% confidence intervals) were 2.19(1.37, 3.52), 2.91(1.77, 4.80) and 2.51(1.45, 4.33) for women with BMI&amp;lt;25, BMI25-29.9 and BMI≥30, respectively. The observed estimates did not differ, statistically, across BMI categories. Additionally, we found no interactions with LINE-1 and observed no associations between anthropometrics and promoter methylation status in the genes examined. Conclusions. Our data suggest that the association between BMI, weight gain and postmenopausal breast cancer may arise from mechanisms other than DNA methylation. Citation Format: Lauren E. McCullough, Jia Chen, Alexandra J. White, Xinran Xu, Yoon Hee Cho, Patrick T. Bradshaw, Sybil M. Eng, Susan L. Teitelbaum, Mary Beth Terry, Gail Garbowski, Alfred I. Neugut, Hanina Hibshoosh, Regina M. Santella, Marilie D. Gammon. The influence of body size and weight gain on global and gene promoter methylation in a population-based breast cancer study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-290. doi:10.1158/1538-7445.AM2014-LB-290
Human Enteric Infection with Canine Hookworms
Authors: John Croese
Journal: Annals of Internal Medicine (1994)

Objective: To describe a zoonotic ancylostomiasis (canine), acquired from domestic pets by patients living in developed, urban communities. Design: An 8-year, retrospective case study. Setting: A clinical gastroenterologic practice in Townsville and a university parasitology department in Brisbane, Australia. Patients: Nine patients, each with enteric hookworm infection diagnosed by finding a single organism in situ; five were treated by us, and the rest were referred to us for parasite identification. Measurements: Clinical and demographic data, complete blood examinations, total serum immunoglobulin E assay, and serologic testing with enzyme-linked immunosorbent assay and Western blot using excretory-secretory antigens of Ancylostoma caninum. Gut biopsy specimens were examined histologically, and hookworms were identified using morphologic criteria. Results: The infections in three of the patients were diagnosed during the initial 6 years and six in the last 2 years. All owned a dog and described activity potentially exposing them to infection with canine hookworm larvae. Three patients had a laparotomy for acute abdominal pain, and six had colonoscopies (five with pain and one without symptoms). Six of the nine had blood eosinophilia (mean, 0.97 × 109/L), and five of eight had elevated immunoglobulin E levels (mean level, 756 µg/L); six of eight had eosinophilic inflammation of the gut. In six patients, the worm was identified as A. caninum, whereas in three, damage to the specimen did not allow specific identification; however, they were unlikely to be human parasite species. Although all parasites were in the adult stage, none were sexually mature. Positive serologic findings in seven of the eight patients tested confirmed presence of antibody to the parasite. Conclusions: Human enteric infections with A. caninum are being diagnosed more frequently in northeastern Australia. Although infection may be subclinical, the chief symptom is abdominal pain, sometimes sudden and severe. The pathologic finding is focal or diffuse eosinophilic inflammation caused by a type 1 hypersensitivity response to secreted antigens. Infection by sexually immature worms is scant and nonpatent, indicating poor adaptation to the human host. Serologic testing assists in identification of occult infection. Advanced hygiene and sanitation afford little protection because the parasite reservoir is a large and growing pool of infected domestic pets.
Antagonism of HOX/PBX Dimer Formation Blocks the <i>In vivo</i> Proliferation of Melanoma
Authors: Richard Morgan, Patricia Macanas Pirard, Liesl Shears, Jastinder Sohal, Ruth Pettengell, Hardev S. Pandha
Journal: Cancer Research (2007)

Malignant melanoma is a cancer that arises from melanocyte cells in a complex but well-studied process, and which can only be successfully treated prior to metastasis as it is highly resistant to conventional therapies. A number of recent reports have indicated that members of the HOX family of homeodomain-containing transcription factors are deregulated in melanoma, and may actually be required to maintain proliferation. In this report, we describe the use of a novel, cell-permeable antagonist of the interaction between HOX proteins and PBX, a second homeodomain-containing transcription factor that modifies HOX activity. This antagonist can block the growth of murine B16 cells and trigger apoptosis both in vitro and in vivo when administered to mice with flank tumors.
Experts agree guidelines to ensure responsible use of stem cell treatments
Authors: S. Mayor
Journal: BMJ (2008)

Expert evaluation, independent oversight, and a thorough informed consent process are essential to ensuring responsible use of stem cell treatments in patients, advise guidelines published by the International Society for Stem Cell Research.

The Guidelines for the Clinical Translation of Stem Cells set out a “roadmap” for researchers and doctors on how to move stem cells from the research laboratory into proved treatments for patients. The society, which represents stem cell researchers worldwide, recommends that governments and regulatory bodies adopt and enforce the guidelines to ensure the responsible development of safe and effective stem cell treatments.

“Our guidelines will arm patients and their doctors with the information they need to …
OC-084 The clonal progression of barrett's oesophagus to oesophageal adenocarcinoma
Authors: S Khan, S Zeki, I Mitchell, R Harrison, L Dunn, S Leedham, H Barr, N Shepherd, T Graham, N Wright, S McDonald
Journal: Gut (2012)

<h3>Introduction</h3> Barrett9s oesophagus (BO) is a common premalignant condition, wherein the normal squamous oesophageal epithelium is replaced by a columnar, intestinal phenotype. It is the predominant risk factor for the development of oesophageal adenocarcinoma (OA)<sup>1</sup> which develops through a metaplasia: dysplasia: carcinoma sequence. Initial studies suggested that BO lesions were genetically clonal.<sup>2</sup> However; our group has shown, by gland micro-dissection, that multiple clones are present within BO and it is therefore a genetically heterotypic disease.<sup>3</sup> Furthermore, Maley <i>et al</i><sup>4</sup> have shown that genetic diversity increases the risk of BO progressing to cancer. Here, we demonstrate that although Barrett9s dysplasia is polyclonal, oesophageal adenocarcinomas arising from Barrett9s are typically clonal. <h3>Methods</h3> DNA was macro-dissected from dysplastic and cancerous regions of endoscopic mucosal resection (EMR) and oesophagectomy specimens and screened for mutations in p16<i>INK4A</i>, <i>TP</i>53 and <i>K-RAS</i>. Mutated specimens were serially sectioned; crypts and carcinomas were histologically graded and then micro-dissected using a P.A.L.M. laser capture microscope. DNA was extracted from dissected material and was sequenced for the point mutations identified in the initial screen. <h3>Results</h3> Individual glands from 10 specimens (EMRs and oesophagectomies) were laser captured and sequenced for mutations identified as per above. Seven specimens contained <i>TP53</i> mutations and the three remaining specimens were mutated for p16<i>INK4A</i>. Overall, seven of these specimens contained both mutated and wild type dysplastic glands, with a further one specimen containing three distinct p16<i>INK4A</i>mutation. However, the related cancers from these specimens were monoclonal for a mutated genotype found in the dysplasia. These data show that Barrett9s dysplasia is polyclonal but Barrett9s adenocarcinoma is monoclonal, suggesting that a cellular competition may be involved in the evolution of Barrett9s adenocarcinoma from its surrounding dysplasia. <h3>Conclusion</h3> Barrett9s dysplasia exhibits a mosaic pattern of clones, indicating genetic diversity in Barrett9s dysplasia. Oesophageal adenocarcinomas were monoclonal outgrowths from polyclonal Barrett9s dysplasia. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Jankowski JA</b>, <i>et al. Gastroenterology</i> 2002;<b>122</b>:588–90. 2. <b>Galipeau</b>, <i>et al. J Natl Cancer Inst</i> 1999;<b>91</b>:2087–95. 3. <b>Leedham</b>, <i>et al. Gut</i> 2008;<b>57</b>:1041–8. 4. <b>Maley C</b>, <i>et al. Nature Genetics</i> 2006;<b>38</b>:468–73.
Abstract 304: Comparison of commercially available phospho-AKT [Ser473] antibodies for immunohistochemical biomarker analysis
Authors: Michael Jeffers, Lisa M. Dauffenbach, Ajay Bhargava, Chetan Lathia, Christopher A. Kerfoot
Journal: Cancer Research (2010)

Abstract Immunohistochemical (IHC) analysis of AKT phosphorylation on Ser473 is commonly performed on pre- and post-treatment cancer biopsies as part of pharmacodynamic biomarker assessment for targeted oncology therapeutics. The current study was performed to assess the specificity and sensitivity of four pAKT Ser473 monoclonal antibodies for IHC analysis (clones D9E, 736E11, 587F11 and 14-5). To facilitate this analysis, cancer cell lines with constitutive activation of the PI3K pathway due to mutations in PIK3CA (MCF-7 and MKN-1) or PTEN (MDA-MB-468) were grown in the presence or absence of inhibitors of the PI3K pathway (wortmannin and LY294002). Cell lysates were prepared for analysis via Western blotting and formalin-fixed, paraffin-embedded cell pellets were prepared for analysis via IHC. All antibodies produced a band at 65 kDa, the expected molecular weight for pAKT, when used for Western blot analysis of untreated cell lines and demonstrated a reduction or ablation of this band following treatment of the cell lines with inhibitors of the PI3K pathway. When examined via IHC, antibodies 736E11 and 587F11 demonstrated nuclear and cytoplasmic staining in MCF-7 and MKN-1 cells and membrane staining in MDA-MB-468 cells. These antibodies demonstrated a reduction of staining in all three cell lines treated with PI3K inhibitors, but the reduction was modest in MCF-7 and MKN-1 cells. Clone 587F11 was the least sensitive for IHC. Staining with antibodies 14-5 and D9E was predominantly cytoplasmic or membrane associated, while clone14-5 produced a more punctate appearance. Strong staining was achieved with clone 14-5 and prominent reduction or ablation of staining was observed in all three cell lines treated with PI3K pathway inhibitors. Staining with clone D9E was a little less sensitive than with clone 14-5, but significant reduction or ablation of staining in cell lines treated with PI3K inhibitors was also observed. In summary, clones 14-5 and D9E appear to demonstrate adequate specificity and sensitivity for use in IHC assays. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 304.
Health Effects in Survivors of the Chernobyl Disaster-Reply
Authors: Armin D. Weinberg
Journal: JAMA (1996)

<h3>In Reply.</h3> —Dr Quastel and colleagues are to be commended for establishing a comprehensive research program addressing the Chernobyl health effects among immigrants to Israel. Their findings are similar to those of investigators from Japan, Belarus, Russia, Ukraine, the World Health Organization, the International Atomic Energy Agency, and the International Consortium for Research on the Health Effects of Radiation. The concept of linking the Israeli cancer registry to a registry of immigrants from the affected regions has significant promise. Given that Israel is a geographically small country with an excellent coordinated health care system and resettlement effort, researchers in Israel have a unique opportunity to monitor the long-term effects of previous exposure. While our registry in the United States has only recently begun operating, we hope it too may play a role in tracking the long-term effects and perhaps provide a mechanism for cohort identification for future studies. This is
Decent health care for older people
Authors: J. Morris
Journal: BMJ (2006)

Our population is ageing. The need to pay for decent care for older people becomes more pressing, and last month's Wanless report recommended how to provide long term care fairly.1 But what is decent care? The national standards for the health, treatment, and social care of older people in England—set in 2001 in the national service framework (NSF) for older people—provide a good grounding. Last week the UK national director for older people, Professor Ian Philp, presented the next steps for the framework in the report A New Ambition for Old Age, which examined how the framework is being implemented and announced new aims and targets.2

The national service framework for older people set out eight standards to improve the experiences of older people and their carers who are using health, social care, and other services (box 1). A standard on medicines management followed later. Last week's report added a further 10 programmes for implementing the framework, under three important and timely themes: dignity in care, joined up care, and healthy ageing.



Box 1: National service framework for older people

Standards are focused on



Rooting out age discrimination


Promoting person centred care (including a single assessment process for care records)


Intermediate care


General hospital care


Stroke services


Falls services


Mental health in older people


Promoting health and active life in old age








What has improved since the framework was launched five years ago? A third of older people needing intensive daily help in England now receive this in their own homes rather than in residential care; delayed discharge from acute hospitals has been reduced by more than two thirds; and specialist services for people with stroke and for those prone to falls continue to improve.2 In 2000-1, 12 900 people aged 60 and over who had attended NHS stop smoking services had successfully quit smoking a month later; this total rose to 42 900 in 2003-4. And uptake of influenza immunisation among those aged 65 and over rose from 65% in 2000-1 to 71% in 2003-4.2

Such health gains now need to be built on, however, with campaigns among older people to promote greater physical fitness, reduced obesity, and better management of sensory impairment and incontinence. These campaigns could be run by voluntary organisations such as Age Concern and Help the Aged and be supported by teams in primary and secondary care. Furthermore, many targets set in the overall NHS plan are still directed mainly at younger people and largely ignore the milestones set in the national service framework for older people.

Other national service frameworks were supported with new monies, and despite older people being the prime users of primary care, secondary care, and social services and having benefited from a reduction of four hour waits on trolleys, investments have not been made in more specific services such as general hospital care for older people or an effective continence service.3
Reproductive effects of occupational DDT exposure among male malaria control workers.
Authors: Félix Salazar-García, Esperanza Gallardo-Díaz, Prudencia Cerón-Mireles, Dana Loomis, Victor H Borja-Aburto
Journal: Environmental Health Perspectives (2004)

To assess potential effects of human DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] exposure, we evaluated the reproductive history of 2,033 workers in the antimalaria campaign of Mexico. Data on occupational exposure to DDT and reproductive outcomes were gathered through a questionnaire, and workers provided information about 9,187 pregnancies. We estimated paternal exposure to DDT before each pregnancy using three approaches: a) a dichotomous indicator for pregnancies before and after exposure began, b) a qualitative index of four exposure categories, and c) an estimation of the DDT metabolite DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] accumulated in fat. To assess associations, we used logistic regression models that accounted for correlated observations and adjusted for parents' age at each child's birth, exposure to other pesticides, exposure to chemical substances in other employment, smoking, and alcohol consumption. The odds ratio for birth defects comparing pregnancies after and before the first exposure was 3.77 [95% confidence interval (95% CI), 1.19-9.52]. Compared with the lowest quartile of estimated DDE in fat, the ORs were 2.48 (95% CI, 0.75-8.11), 4.15 (95% CI, 1.38-12.46), and 3.76 (95% CI, 1.23-11.44) for quartiles 2, 3, and 4, equivalent to p,p -DDE in fat of 50, 82, and 298 microg/g fat, respectively. No significant association was found for spontaneous abortion or sex ratio. We found an increased risk of birth defects associated with high occupational exposure to DDT in this group of workers. The significance of this association at lower exposure levels found in the general population remains uncertain.
Electrocardiographic Screening Should Not Be Implemented for Children and Adolescents Between Ages 1 and 19 in the United States
Authors: Richard A. Friedman
Journal: Circulation (2014)

A billion here, a billion there and pretty soon you're talk- ing real money" is a quote attributed to the late Senator Everett Dirksen.Whether or not he actually spoke those words, it is believed that, if he did not, he would have heartily approved having been quoted as such.At this time in American history, this quote as it relates to medical spending is appropriate to the debate.No doubt, this is a complex issue at face value.We have philosophical, ethical, and moral issues surrounding this debate and the 2 types of EBM-evidencebased medicine and emotional-based medicine-as well.Biases and heuristics flavor the decision making and cloud the public policy issues that are central to how we decide what to do and for whom.The role of this column is to present the reader with the information that would allow a prudent practitioner to make an informed decision about whether to advocate for universal screening of children and adolescents with an ECG to prevent sudden cardiac death (SCD).
Surgical Treatment of Minimal Endometriosis
Authors: Joseph C. Gambone, Alan H. DeCherney
Journal: New England Journal of Medicine (1997)

Endometriosis is defined as the presence of glandular and stromal endometrial tissue outside the uterus. It occurs most frequently in the reproductive organs, other pelvic viscera, and the peritoneum and is estimated to be present in 3 to 10 percent of all women of reproductive age. Among those with pelvic pain or infertility, its reported incidence ranges from as low as 20 percent to as high as 90 percent.14 In most studies, however, the diagnosis was not confirmed by biopsy, and there is substantial interobserver variation in visual diagnosis.The current system for staging endometriosis is a revised version . . .