tbuckley/cabot-search huggingface dataset:
Renal acid-base transport: The regulatory role of the inner medullary collecting duct
Authors: J H Schwartz
Journal: Kidney International (1995)

A 36-year-old white woman was referred to Boston City Hospital for evaluation of occasional periods of generalized muscle weakness and shortness of breath for approximately 2 years. Five years previously she had had her first episode of nephrolithiasis and since that time has passed 1 to 2 stones per year. Analysis of three stones indicated that they consisted of calcium phosphate and calcium oxalate. Her serum calcium, 5.1 mEq/liter, and iPTH level, 50 1.dEqIml, were within normal limits. However, her 24-hour urinary excretion of calcium, 550 mg, was elevated. Her renal function has been stable, with plasma creatinine values between 0.7 and 0.9 mg/dl. The only other significant abnormality noted in prior evaluations for these complaints was the finding of mild hyperchioremic metabolic acidosis. The arterial plasma pH was 7.37; serum HC03, between 18—20 mEq/liter; and serum K, 3.1 mEq/liter. During the current evaluation, physical examination was entirely normal. No demonstrable muscle weakness could be elicited. All reflexes were present and equal symmetrically. Electrocardiogram was within normal limits. Laboratory evaluation included: BUN, 16 mg/dl; creatinine, 0.9 mg/dl; calcium, 5.2 mEq/liter; phosphate, 3.8 mg/dl; sodium, 137 mEq/ liter; potassium, 2.6 mEq/liter; chloride, 111 mEq/liter; bicarbonate, 16 mEq/liter; arterial blood pH, 7.36; and arterial blood PCO2, 29 mm Hg. Urinalysis revealed 5—6 red blood cells and 5—10 white blood cells/highpower field; the pH was 6.5. Net acid excretion, 37 mEq/day, was inappropriately low for a systemic acidosis, and potassium excretion was 75 mEq/day despite hypokalemia. An intravenous pyelogram and renal sonograni documented bilateral papillary tubular ectasia and nephrocalcinosis of the papillary collecting duct and were consistent with medullary sponge kidney.
Risk assessment, risk management and risk-based monitoring following a reported accidental release of poliovirus in Belgium, September to November 2014
Authors: Erwin Duizer, Saskia Rutjes, Ana Maria de Roda Husman, Jack Schijven
Journal: Eurosurveillance (2016)

On 6 September 2014, the accidental release of 10 13 infectious wild poliovirus type 3 (WPV3) particles by a vaccine production plant in Belgium was reported. WPV3 was released into the sewage system and discharged directly to a wastewater treatment plant (WWTP) and subsequently into rivers that flowed to the Western Scheldt and the North Sea. No poliovirus was detected in samples from the WWTP, surface waters, mussels or sewage from the Netherlands. Quantitative microbial risk assessment (QMRA) showed that the infection risks resulting from swimming in Belgium waters were above 50% for several days and that the infection risk by consuming shellfish harvested in the eastern part of the Western Scheldt warranted a shellfish cooking advice. We conclude that the reported release of WPV3 has neither resulted in detectable levels of poliovirus in any of the samples nor in poliovirus circulation in the Netherlands. This QMRA showed that relevant data on water flows were not readily available and that prior assumptions on dilution factors were overestimated. A QMRA should have been performed by all vaccine production facilities before starting up large-scale culture of WPV to be able to implement effective interventions when an accident happens.
Abstract LB-261: Mammary tumorigenesis in haploinsufficient Cripto-1 mice.
Authors: Maria Cristina Rangel, Ahmed Raafat, Nadia P. Castro, Malgorzata Klauzinska, Hideaki Karasawa, Alyson Baker, Robert Callahan, David S. Salomon
Journal: Cancer Research (2013)

Abstract The embryonic gene Cripto-1 (Cr-1) is expressed at very low levels in normal adult tissues and detected at high levels in several human tumors. We have previously found that Cr-1 can facilitate the proteolytic intracellular processing of all four Notch receptors. Transgenic mice overexpressing the Notch4 intracellular domain (Int3) in the mammary gland under the control of the whey acidic protein (WAP) promoter rapidly develop mammary hyperplasias and undifferentiated mammary adenocarcinomas in aged nulliparous females and after multiple cycles of pregnancy. Eighty percent of WAP-Int3 females develop mammary tumors by the second pregnancy. To assess the contribution of Cr-1 in the hyperplasias and tumors that arise in transgenic WAP-Int3 mice, we developed a bi-transgenic mouse model lacking one allele of Cr-1, by crossing the knock-in Cr-1/LacZ mice (containing a promoter-less bacterial β-galactosidase gene which disrupts one of the Cr-1 alleles) to WAP-Int3 transgenic mice. We found a 90% reduction in the frequency of mammary hyperplasias in these Cr-1/LacZ/WAP-Int3 mice in comparison to WAP-Int3 mice. Additionally, in the absence of one allele of Cr-1, Int3-induced transformation of mouse mammary epithelial cells was delayed in vivo, and additional cycles of pregnancy were required to observe tumor growth. Notably, only 20% of the Int3/Cr-1 haploinsufficient mice developed mammary tumors by the second pregnancy, as compared to 80% of those mice that preserve two alleles of Cr-1. The few tumors derived from these mice also showed a significantly more differentiated histology in comparison to those tumors that arose from mice preserving both alleles of Cr-1. We are currently generating a mouse model which conditionally lacks the two alleles of Cr-1 in the mammary gland, what should better address our question regarding the functional significance of Cr-1 in the development of Int3-induced mammary tumorigenesis. Citation Format: Maria Cristina Rangel, Ahmed Raafat, Nadia P. Castro, Malgorzata Klauzinska, Hideaki Karasawa, Alyson Baker, Robert Callahan, David S. Salomon. Mammary tumorigenesis in haploinsufficient Cripto-1 mice. [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 LB-261. doi:10.1158/1538-7445.AM2013-LB-261
P576Regulatory analysis of the 4q25 atrial fibrillation risk locus
Authors: L A Aguirre Perez, M E Alonso, C Badia-Careaga, C Arias, A Fernandez-Minan, E Lopez-Jimenez, A Aranega, J L Gomez-Skarmeta, D Franco, M Manzanares
Journal: Cardiovascular Research (2014)

Purpose: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. Recent genome-wide association studies (GWAS) have revealed AF associated variants on chromosome 4q25, in the vicinity of PITX2, which encodes a crucial transcription factor for cardiovascular development. Our aim is to establish whether this region harbours cis-regulatory elements that could be acting on neighbouring genes, such as PITX2. Methods: We tested the regulatory activity of several genomic fragments from 4q25 by transfections assays in cultured cells and transgenic mouse embryos. We also analysed the chromatin architecture of the region by studying physical interactions by means of Chromosome Conformation Capture (3C). Results: We found a genomic fragment of ~7kb containing rs2200733, the most significant variant associated with AF, and sub-fragments of this region, drive reporter expression in HL-1 mouse cardiomyocytes, as well as in the mouse embryo in sites of expression of endogenous Pitx2 in a heterogenous way, such as facial mesenchyme, limb muscles, left gonad and the heart. These fragments are also active in two cell types unrelated to the cardiac lineage (mouse pluripotent P19 cells, and human HEK cells), showing they do not act as classical tissue-specific enhancers, but rather as accessory element that could potentiate the activity of tissue-specific enhancers located elsewhere in the locus. Furthermore, 3C analyses show a complex pattern of long range interactions in the locus, with different regions interacting specifically with the different promoters located there, including the neighbouring Enpep gene. Conclusions: We show that cis-regulatory elements are located in the region of 4q25 associated with an increased risk for AF. These elements establish specific long-distance interactions with various promoters, and therefore could regulate the transcription of these genes. Our results suggest that de-regulation of either one or both PITX2 and ENPEP might have a causal role in the development of AF.
Lack of Correlation between Psychological Factors and Subclinical Coronary Artery Disease
Authors: Patrick G. O'Malley, David L. Jones, Irwin M. Feuerstein, Allen J. Taylor
Journal: New England Journal of Medicine (2000)

The relation between psychological variables and clinically evident coronary artery disease has been studied extensively, although the potential mechanisms of such a relation remain speculative. We studied the relation between multiple psychological variables and subclinical coronary artery disease to assess the possible role of such variables in atherogenesis.We conducted a prospective study of 630 consecutive consenting, active-duty U.S. Army personnel, 39 to 45 years of age, without known coronary artery disease. Each participant was assessed for depression, anxiety, somatization, hostility, and stress. Subclinical coronary artery disease was identified by electron-beam computed tomography.The mean (+/-SD) age of the subjects was 42+/-2 years; 82 percent were male, and 72 percent were white. The prevalence of coronary-artery calcification was 17.6 percent (mean calcification score, 10+/-49). The prevalence of prior or current psychiatric disorders was 12.7 percent. There was no correlation between the coronary-calcification score and the scores measuring depression (r= -0.07, P=0.08), anxiety (r=-0.07, P=0.10), hostility (r=-0.07, P=0.10), or stress (r=-0.002, P=0.96). Somatization (the number and severity of durable physical symptoms) was inversely correlated with calcification scores (r=-0.12, P=0.003), even after we controlled for age and sex. In multivariate logistic-regression models, a somatization score greater than 4 (out of a possible 26) was independently associated with the absence of any coronary-artery calcification (odds ratio, 0.49; 95 percent confidence interval, 0.25 to 0.96).Our data suggest that depression, anxiety, hostility, and stress are not related to coronary-artery calcification and that somatization is associated with the absence of calcification.
Characteristic Colonic Activity With Granulocyte Scintigraphy in Pseudomembranous Colitis
Authors: HANS JACOBSSON, CATARINA Y. BITKOVER, RAGNAR BEFRITS, CATHRINE JONSSON
Journal: Clinical Nuclear Medicine (1998)

A 66-year-old man was treated with several antibiotics to treat septicemia after coronary bypass surgery. To localize an infectious focus, granulocyte scintigraphy was performed 23 days after surgery, showing a dilated colon with activity restricted to the wall. Colonoscopy 6 days later and isolation of toxin from the stool confirmed pseudomembranous colitis, a serious iatrogenic condition requiring specific treatment. Pseudomembranous colitis is caused by toxin from the overgrowth of Clostridium difficile resulting from an imbalance of the intestinal flora caused by the antibiotics. The imaging findngs have not been described previously and may be typical of pseudomembranous colitis.
Abstract LB-200: IL-1beta promotes the development of intestinal epithelial stem cells
Authors: Jishu Shi, Lei Wang, Ziyan Liu, Yijing Li, Loretta Pappan
Journal: Cancer Research (2012)

Abstract Although iflammation has been linked to stem cell-mediated tumorigenesis, the inflammatory factors responsible for the induction of abnormal proliferation of stem cells remain to be identified. Up-regulation of IL-1β has been associated with colon tumor initiation and progression. The objective of this study is to determine whether IL-1β alone may contribute to intestinal stem cells (ISC)-mediated tumorigenesis by promoting the development of ISCs. In a preliminary study, it was shown that rat normal intestinal epithelia cell line IEC-18 cells proliferated as a monolayer culture under serum-free conditions, demonstrating that either IEC-18-ISCs are not active in these conditions or ISCs are absent in IEC-18 cell line. However, we have found that addition of IL-1β to the cell culture medium caused monolayer IEC-18 cells to form spheres with up-regulated expression of stem cell markers including Bmi-1, β-catenin, Lgr5, c-Myc, and Nanog. This shows that IL-1β can induce the development and/or self-renewal of ISCs to form spheres. IL-1β-mediated ISC self-renewal is further demonstrated by a colony-forming assay when IEC-18 cells were cultured in soft agar under serum-free conditions. Interestingly, IL-1β promoted only a relatively small population (about 0.03%) of IEC-18 cells to form colonies, suggesting that the majority of IEC-18 cells are terminally differentiated cells. Furthermore, we have found that, when cultured in collagen-coated plates in serum-free medium, IL-1β-treated IEC-18 cells demonstrated a loss of cell-cell contact inhibition, growth to relatively high cell densities as evidenced by the presence of foci, and up-regulated expression of stem cell markers. Overall, results from our studies provide the first evidence that IL-1β alone can promote the development and self-renewal of ISCs. IL-1β-activated ISCs possess typical characteristics of malignant cells including colony formation in soft agar and loss of cell-cell contact inhibition of growth. Thus, aberrant production of IL-1β in intestinal inflammation may contribute to the initiation and progression of colon cancer by inducing the abnormal development of intestinal epithelial stem cells. 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 LB-200. doi:1538-7445.AM2012-LB-200
OP0098 The detection of a potentially pathogenic subset of HLA-B27 conformers at the cell surface in a rat model of SPA
Authors: K. Mchugh, J. Shaw, S. Kollnberger, L. Utriainen, D. Firmin, S. Milling, C. Renner, P. Bowness
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The MHC class I antigen HLA-B27 (B27) is strongly associated with development of SpA, yet the mechanism by which B27 confers this susceptibility is unclear. B27 exists at the cell surface as fully conformed heterotrimers (B27HT) associated with peptide and b<sub>2</sub>m, but also as peptide-free heavy chain monomers (B27HC) and heavy chain homodimers (B27<sub>2</sub>), which we have shown to interact with innate immune receptors in a distinct manner to B27HT. A pathogenic role for these receptor interactions has been proposed. <h3>Objectives</h3> This study aimed to analyse the expression of these potentially pathogenic aberrant forms of B27 in splenocytes isolated from B27 TG rats through the use of a novel B27-specific monoclonal antibody, HD6. <h3>Methods</h3> Splenic mononuclear cells from age-matched adult (6-9 months) B27 transgenic (TG), B7 TG, and non-transgenic (NT) rats were compared for staining with the monoclonal antibodies HD6, HC-10, HLA-ABC-m1 and an IgG1 isotype control. Staining was also compared in splenocytes isolated from young clinically healthy B27 TG rats (5-10 weeks) with those from the adult B27 TG rats. For further characterisation of the HD6 epitope, splenocytes were cultured with HLA-B27-binding or control peptides prior to FACS analysis. <h3>Results</h3> HD6 staining was consistently seen in the lymphocyte and macrophage/DC populations for adult B27 TG samples. Notably, however, no HD6 staining above background was observed in the granulocyte gate, which was also the case for HC-10. Within the lymphocyte, gate, comparable staining was seen for the CD4+ and CD8+ cell populations. HD6 staining was B27-specific, as B7 TG rat splenocytes consistently failed to stain with HD6, despite similar expression of human MHC class I molecules. Expression of folded HLA-B27 was increased in the older B27 TG rats compared to the younger B27 TG rats, consistent with previous reports, as was expression of free heavy chains. However, very little detectable HD6 staining was observed in cell subsets from the younger rats. HD6 staining was inhibited by incubation of splenocytes with B27-binding peptides. <h3>Conclusions</h3> These data demonstrate cell surface expression of HD6-reactive molecules on a number of cell subsets from HLA-B27 transgenic rats. Moreover, HD6 surface staining is strongly correlated both with the degree of B27 expression and with age. HD6 binding can be inhibited by incubation with B27-binding peptides, suggesting that it detects a population of peptide-free aberrant cell surface B27 conformers. Our data is consistent with the hypothesis that altered immune interactions, as a consequence of the presence of aberrant forms of HLA-B27 at the cell surface, contribute to SpA pathogenesis. <h3>Disclosure of Interest</h3> None Declared
THU0407 Serum ghrelin and obestatin levels in behçet’s disease:
Authors: S.S. Koca, M. Ozgen, R. Dayanan, M. Kara, N. Ilhan, A. Isik
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ghrelin is a potent endogenous orexigenic peptide controlling food intake and energy expenditure.It is produced by inflammatory cells in addition to gastric cells and mediates anti-inflammatory effects. Moreover, increased ghrelin levels have also been reported in a number of inflammatory diseases. <h3>Objectives</h3> To assess serum ghrelin and obestatin levels in patients with Behçet’s disease (BD) and healthy controls (HC). <h3>Methods</h3> Fasting blood samples were obtained from 143 patients with BD (whose mean disease duration of 5.3±6.2 years) and 112 HC. Serum acylated ghrelin (AG), unacylated ghrelin (UAG), total ghrelin (TG), and obestatin levels were measured using commercially available ELISA kits.Appropriate statisticaltests were used to analyze the data. <h3>Results</h3> Whereas serum obestatin level was significantly higher in the BD group than HC group, there was no significant difference in terms of serum ghrelin levels between the groups (Table). In the active BD subgroup (n=67), serum UAG and TG levels were significantly higher (p=0.040 and p=0.039, respectively), while serum AG level was relatively higher (p=0.098), than inactive BD subgroup (n=76). 12.6% of the BD patients and 20.5% of the HC were obese (p=0.086, odds ratio; 0.56, 95% confidence interval; 0.28-1.09). Serum UAG, TG and obestatin levels were significantly lower in obese subgroup than non-obese subgroup of the BD group (p=0.027, p=0.014 and p=0.001, respectively). In the BD group, age and body mass index were negatively correlated with AG (r=-0.199, p=0.017; r=-0.176, p=0.035), UAG (r=-0.246, p=0.003; r=-0.311, p&lt;0.000), TG (r=-0.322, p=0.003; r=-0.346, p=0.001) and obestatin (r=-0.173, p=0.039; r=-0.250, p=0.003) levels, whereas these correlations were not significant in the HC group. <h3>Conclusions</h3> BD, characterized by a triad of recurrent oral and genital ulcers and uveitis, is a systemic vasculitis of unknown etiology. Serum ghrelin levels were high in active but not in inactive BD patients. These results suggest that ghrelin may play a significant role in the activity BD. <h3>References</h3> Baatar D, et al. The effects of ghrelin on inflammation and the immune system. Mol Cell Endocrinol. 2011. Seim I, et al. Ghrelin axis genes, peptides and receptors: recent findings and future challenges. Mol Cell Endocrinol. 2011. Zhou ZY, et al. Cytokines and Behcet’s Disease. Autoimmun Rev. 2012. <h3>Disclosure of Interest</h3> None Declared
PWE-271 Decision analysis using simulation modelling supports local excision in T1 colon cancer
Authors: A Currie, A Askari, C Rao, T Athanasiou, O Faiz, R Kennedy
Journal: Gut (2015)

<h3>Introduction</h3> Population-based bowel cancer screening has resulted in increasing numbers of patients with T1 colonic neoplasia. The need for colectomy in this group is questioned due to the low risk of lymphatic spread and increased treatment morbidity. This study examined the quality-of-life benefits and risks of local excision compared with results after colectomy, for low- and high-risk T1 colonic cancer. <h3>Method</h3> Decision analysis using a Markov simulation model was performed: patients were managed with either local excision (advanced therapeutic endoscopy) or colectomy. Lesions were considered high-risk according to accepted national guidelines. Probabilities and utilities were derived from published data. Hypothetical cohorts of 65- and 80-year-old, fit and unfit patients, with low- or high-risk T1 colonic cancer were studied. The primary outcome was quality-adjusted life expectancy (QALE) in life-years (QALYs). <h3>Results</h3> In low-risk T1 colonic neoplasia, local excision increases QALE by 2.72 QALYS for fit 65-year olds (15.5% increase over surgery) and by 0.93 for unfit 80-year-olds (20.9% increase). For high-risk T1 cancers, the QALE benefit for local excision is 1.82 QALYs for fit 65-year-olds (10.5% improvement) and 0.82 for unfit 80-year-olds (18.6% improvement). In sensitivity analysis, colectomy was only preferred for 65-year-old patients, when risk of recurrence following local excision exceeded 17.3%. <h3>Conclusion</h3> Under a wide range of assumptions, for all patient cohorts, local excision is a reasonable treatment option for both low- and high-risk T1 colonic cancer. Exploration of methods to facilitate local excision of T1 colonic neoplasia appears warranted. <h3>Disclosure of interest</h3> None Declared.
Symptom passing in a transvestite father and three sons
Authors: D W Krueger
Journal: American Journal of Psychiatry (1978)

Three sons of a transvestite father engaged in cross-dressing beginning in early adolescence. The literature suggests that observation may play a role in determining the specificity of the symptoms of conflicted sexual identity. These cases of transvestism in offspring are unusual in that the father played an important role in symptom choice and modeling. It is hoped that in future studies of transvestism in the father will be examined in a more intensive way as a figure with whom an active identification process may evolve.
Newborn Girls Misdiagnosed as Bilaterally Cryptorchid Males
Authors: Virginia V. Weldon, Robert M. Blizzard, Claude J. Migeon
Journal: New England Journal of Medicine (1966)

THERE have previously been reports on a few patients with female pseudohermaphroditism who had complete or nearly complete virilization of the external genitalia and in whom the diagnosis of cryptorchidism in a male was made initially. A majority of these were due to congenital virilizing adrenal hyperplasia, and most patients died during infancy or early childhood. In the past two years 3 apparent males with bilateral cryptorchidism have been referred to the Pediatric Endocrine Clinic of the Johns Hopkins Hospital. All 3 were actually females and had virilizing adrenal hyperplasia of the salt-losing type. Previously, we had seen 2 similar . . .