tbuckley/cabot-search huggingface dataset:
Bone Morphogenetic Protein 7 in the Development and Treatment of Bone Metastases from Breast Cancer
Authors: Jeroen T. Buijs, Nico V. Henriquez, Petra G.M. van Overveld, Geertje van der Horst, Ivo Que, Ruth Schwaninger, Cyrill Rentsch, Peter ten Dijke, Anne-Marie Cleton-Jansen, Keltouma Driouch, Rosette Lidereau, Richard Bachelier, Slobodan Vukicevic, Philippe Clézardin, Socrates E. Papapoulos, Marco G. Cecchini, Clemens W.G.M. Löwik, Gabri van der Pluijm
Journal: Cancer Research (2007)

Abstract Bone morphogenetic protein 7 (BMP7) counteracts the physiological epithelial-to-mesenchymal transition (EMT), a process that is indicative of epithelial plasticity. Because EMT is involved in cancer, we investigated whether BMP7 plays a role in breast cancer growth and metastasis. In this study, we show that decreased BMP7 expression in primary breast cancer is significantly associated with the formation of clinically overt bone metastases in patients with ≥10 years of follow-up. In line with these clinical observations, BMP7 expression is inversely related to tumorigenicity and invasive behavior of human breast cancer cell lines. Moreover, BMP7 decreased the expression of vimentin, a mesenchymal marker associated with invasiveness and poor prognosis, in human MDA-MB-231 (MDA-231)-B/Luc+ breast cancer cells under basal and transforming growth factor-β (TGF-β)–stimulated conditions. In addition, exogenous addition of BMP7 to TGF-β–stimulated MDA-231 cells inhibited Smad-mediated TGF-β signaling. Furthermore, in a well-established bone metastasis model using whole-body bioluminescent reporter imaging, stable overexpression of BMP7 in MDA-231 cells inhibited de novo formation and progression of osteolytic bone metastases and, hence, their metastatic capability. In line with these observations, daily i.v. administration of BMP7 (100 μg/kg/d) significantly inhibited orthotopic and intrabone growth of MDA-231-B/Luc+ cells in nude mice. Our data suggest that decreased BMP7 expression during carcinogenesis in the human breast contributes to the acquisition of a bone metastatic phenotype. Because exogenous BMP7 can still counteract the breast cancer growth at the primary site and in bone, BMP7 may represent a novel therapeutic molecule for repression of local and bone metastatic growth of breast cancer. [Cancer Res 2007;67(18):8742–51]
PTH-116 Point Of Care Testing For Adult Coeliac Disease: A Potential Role In Endoscopy
Authors: S Wong, PD Mooney, M Kurien, AJ Johnston, A Avgerinos, M Hadjivassiliou, DS Sanders
Journal: Gut (2014)

<h3>Introduction</h3> Endoscopic markers of coeliac disease (CD) lack sensitivity; therefore many centres take routine duodenal biopsies or have a low threshold for biopsy, ensuring high detection rates. Newly available, point of care tests (POCT) provide rapid findings unlike conventional serological markers, potentially reducing the need for duodenal biopsies. This study evaluates a new POCT (Simtomax) which detects IgA and IgG deamidated gliadin peptide (DGP) with comparisons made to conventional serological markers and histology. <h3>Methods</h3> Patients referred for a gastroscopy to a specialist CD list were prospectively recruited between March and November 2013. Patients were excluded if they were on a gluten free diet at the time of the test or if they had previously been diagnosed with seronegative villous atrophy. All patients had a duodenal biopsy as the gold standard for detecting CD. Concurrently serological testing for IgA tissue transglutaminase (TTG), endomysial antibody (EMA), total immunoglobulin A level and the DGP based rapid test was performed. Sensitivity, specificity, positive predictive (PPV) and negative predictive values (NPV) were calculated. <h3>Results</h3> 354 patients met the inclusion criteria (45.8% male mean age 53.3 +18.5). Of these, 52 (14.7% 11.2 – 18.9) had newly diagnosed CD and 302 were controls with a normal duodenal biopsy. The sensitivity, specificity, PPV and NPV for the POCT were 94, 83, 49 and 99% respectively. This compares with results for TTG of 92, 88, 57, 99 and EMA of 88, 97, 85, and 98% respectively. In a second cohort, 43 patients with known CD for re-assessment were recruited (20.9% male, mean age 49.4 +16.6). 16 (37% 23 -53) of these 16 patients (37%) had persistent villous atrophy despite a gluten free diet. POCT compared to histology showed sensitivity of 88% and specificity 41%. tTG showed sensitivity and specificity of 63 and 70% respectively and EMA 56 and 78% respectively. However agreement between histology and POCT was poor with concordance between results in only 60% (κ=0.274). tTG and EMA were marginally better with κ=0.321 and κ=0.345 respectively. <h3>Conclusion</h3> This is the first study to prospectively demonstrate the value of a novel POCT for adult CD in endoscopy compared to the gold standard of histology. The sensitivity and specificity of the POCT is comparable to conventional serology. Simtomax could be used to appropriately identify patients requiring a duodenal biopsy within the endoscopic setting. This strategy may be cost effective by reducing the number of routine duodenal biopsies taken. Further work is required to clarify the role of POCT for the assessment of histological remission in patients with known CD. <h3>Disclosure of Interest</h3> None Declared.
Cross Talk Between Angiotensin AT <sub>1</sub> and α <sub>1</sub> -Adrenergic Receptors
Authors: Hong-Tai Li, Carlin S. Long, Mary O. Gray, D. Gregg Rokosh, Norman Y. Honbo, Joel S. Karliner
Journal: Circulation Research (1997)

Abstract Signaling mediated by the angiotensin (Ang) II and α 1 -adrenergic receptor (α 1 -AR) pathways is important for cardiovascular homeostasis. However, it is unknown whether Ang II has any direct effect on α 1 -AR expression and signaling in cardiac myocytes. In the present study, we determined α 1 -AR subtype mRNA levels by RNase protection; receptor density by competition binding with 5-methylurapidil; and α 1 -AR mediated c- fos expression by Northern blot analysis. We found that Ang II had no effect on α 1b - and α 1d -AR mRNA levels but decreased the α 1a -AR mRNA level in a time- and dose-dependent manner. The maximal effect occurred at 6 hours with 100 nmol/L Ang II (40.0±8.2% reduction, n=4, P &lt;.01). The decrease in α 1a -AR mRNA level induced by Ang II is mediated by the Ang II AT 1 receptor subtype and is associated with decreased stability of α 1a -AR mRNA. Corresponding to the changes in the α 1a -AR mRNA level, Ang II (100 nmol/L, 24 hours) reduced the density of high-affinity sites for 5-methylurapidil (α 1A -AR) by 29% (56.5±6.4 versus 79.0±11.6 fmol/mg protein, n=4, P &lt;.05). α 1 -AR stimulated c- fos induction, which could be blocked by 5-methylurapidil but not by chloroethylclonidine, was attenuated by Ang II preincubation (100 nmol/L, 24 hours). We conclude that there is previously undescribed cross talk between AT 1 receptors and α 1 -ARs. Ang II selectively downregulates α 1a -AR subtype mRNA and its corresponding receptor as well as α 1a -AR mediated expression of the immediate-early gene c- fos in cardiac myocytes.
Isocyanate asthma: respiratory symptoms due to 1,5-naphthylene di-isocyanate.
Authors: M G Harries, P S Burge, M Samson, A J Taylor, J Pepys
Journal: Thorax (1979)

Occupationally related asthma developing in three patients due specifically to exposure to 1,5-naphthylene di-isocyanate (NDI), a hot curing agent used in manufacturing rubber, has been confirmed for the first time using bronchial provocation testing. This substance has been thought to be safer than toluene di-isocyanate (TDI) and diphenylmethane di-isocyanate (MDI) because of its relatively high melting point (120 degrees C). Each patient worked in the same factory and the circumstances of exposure were similar. Provocation testing was also performed with TDI in concentrations up to 0.018 parts per million (ppm) and MDI in concentrations up to 0.02 ppm, to which the patients had been exposed in the past, but no reactions were elicited. None of the patients had increased bronchial reactivity judged by histamine lability and exercise testing. Each patient was advised to give up his job, but two of the three could not find alternative employment and remained exposed. Three-year follow-up shows that airways narrowing has persisted in those who have remained exposed.
Pancreatic and salivary amylase/creatinine clearance ratios in normal subjects and in patients with chronic pancreatitis.
Authors: J E Hegarty, M D O'Donnell, K F McGeeney, O Fitzgerald
Journal: Gut (1978)

The clearance of pancreatic and salivary amylase relative to creatinine was measured in 26 control subjects and 22 patients with chronic pancreatitis. Control values for pancreatic amylase clearance (+/- SD) were 2.64 +/- 0.86% compared with 1.54 +/- 0.95% for salivary amylase. In chronic pancreatitis, pancreatic amylase clearance ratios were significantly higher than controls (P less than 0.0005, mean 4.09 +/- 1.63 SD). The difference in clearance rate of salivary amylase did not reach a level of significance when compared with the control group. Twelve of the 22 patients showed pancreatic amylase clearance values above the normal limit of 4.4, while only five were abnormal when the clearance of total amylase was measured. The patients also showed statistically higher (P less than 0.0005) levels of serum salivary amylase when compared with 69 control sera. No such difference was found for the pancreatic component of serum amylase. Comparison of beta2-microglobulin clearance values showed no statistical difference between patients and controls.
Identification and characterization of the monoblast in mononuclear phagocyte colonies grown in vitro.
Authors: T J Goud, C Schotte, R van Furth
Journal: The Journal of Experimental Medicine (1975)

A liquid culture technique for growing mononuclear phagocyte colonies on a glass surface is described. This useful and reliable technique made it possible to study immature mononuclear phagocytes. In the mononuclear phagocyte colonies the cells grow separate from each other in a single layer. Three types of cells are recognized in these colonies, namely nondividing macrophages, and proliferating promonocytes and monoblasts. The macrophage and the promonocyte exhibit the typical characteristics previously demonstrated by the other methods, whereas the monoblast could only be fully characterized by the present liquid culture method. This proliferating cell (labeling index with [3H]thymidine, 92-96%) is almost round (diameters, 10 X 10 mum), has only a small rim of strongly basophilic cytoplasm, almost devoid of granules, and shows a certain degree of ruffling of the cell surface. The monoblast is positive for esterase with alpha-naphthyl butyrate as substrate (91%), for peroxidase (78% in the peroxidase-positive colonies), and lysozyme (43%). The monoblast is able to pinocytize dextran sulphate (15-20%) and to phagocytize opsonized bacteria (20-30%), latex particles (47%), and IgG-coated red cells (96%). IgG receptors (94%) and complement receptors (16%) are present at the cell surface. In these respects the monoblast has the typical characteristics of the mononuclear phagocytes, but its properties show it to be a more immature cell type than the promonocyte. On the basis of these criteria and the sequence of appearance of the different cell types during incubation and during the development of the individual mononuclear phagocyte colony, monoblasts being present before promonocytes appear in the colony, it is concluded that the monoblast is the precursor of the promonocyte. In these cultures granulocyte colonies are also formed, consisting of myeloblasts, (pro)myelocytes, stabs, and polymorphonuclear neutrophils. Besides the typically tight structure of this kind of colony, the granulocytic cells themselves are quite distinct from the mononuclear phagocytes by their morphology, cytochemical characteristics (e.g. all negative for esterase with alpha-naphthyl butyrate, but 96% positive with N-acetyl DL-alanyl 1-naphthylester), functional characteristics (pinocytic index 13-21%; phagocytic index; for opsonized bacteria 15-36%, for latex particles 10%, and for IgG-coated red cells 0%), and their very small number of IgG receptors and lack of complement receptors. On the basis of these criteria, these granulocytic cells are easily distinguished from the immature cells of the mononuclear phagocyte colonies. The present study confirms the conclusion that the mononuclear phagocytes are a separate cell line, quite distinct from the granulocytic series, since even the most immature cells so far identified--the monoblast and the myeloblast--have quite different characteristics.
Atrial natriuretic peptide in chronic heart failure in the rat: a correlation with ventricular dysfunction.
Authors: K Tsunoda, G P Hodsman, E Sumithran, C I Johnston
Journal: Circulation Research (1986)

To assess the relation between atrial natriuretic peptide and ventricular dysfunction, we simultaneously measured both atrial and plasma immunoreactive atrial natriuretic peptide concentrations in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. When compared to controls (n = 39), rats with infarction (n = 16) had markedly elevated plasma immunoreactive atrial natriuretic peptide concentrations (1205.8 +/- 180.9 vs. 126.7 +/- 8.9 pg/ml, p less than 0.001) and reduced immunoreactive atrial natriuretic peptide concentrations in right and left atria (31.4 +/- 4.6 vs. 61.2 +/- 3.2 ng/mg, p less than 0.001; 14.9 +/- 2.2 vs. 32.7 +/- 2.4 ng/mg, p less than 0.001, respectively). Right ventricular weight increased in proportion to infarct size, and both were correlated with plasma immunoreactive atrial natriuretic peptide levels (r = 0.825, p less than 0.001 and r = 0.816, p less than 0.001, respectively). Right atrial immunoreactive atrial natriuretic peptide content was significantly higher than left in both controls and rats with infarction. Both right and left atrial immunoreactive atrial natriuretic peptide concentrations were negatively correlated with both right ventricular weight as well as plasma immunoreactive atrial natriuretic peptide concentrations (right atrium: r = -0.816, p less than 0.001, r = -0.708, p less than 0.01; left atrium: r = -0.687, p less than 0.01, r = -0.644, p less than 0.01, respectively). These results suggest that chronic stimulation of atrial natriuretic peptide release from both atria is associated with increased turnover and depleted stores of atrial natriuretic peptide in atria in proportion to the severity of heart failure. It also suggests that plasma atrial natriuretic peptide levels may be used as a reliable index of cardiac decompensation in chronic heart failure.
Interleukin‐1β modulation using a genetically engineered antibody prevents adverse cardiac remodelling following acute myocardial infarction in the mouse
Authors: Antonio Abbate, Benjamin W. Van Tassell, Ignacio M. Seropian, Stefano Toldo, Roshanak Robati, Amit Varma, Fadi N. Salloum, Lisa Smithson, Charles A. Dinarello
Journal: European Journal of Heart Failure (2010)
Effects of weight changes produced by exercise, food restriction, or overeating on body composition
Authors: Lawrence B. Oscai, John O. Holloszy
Journal: Journal of Clinical Investigation (1969)

The body weight of rats was reduced by exercise or by restriction of food intake over a period of 18 wk. Body composition was studied to determine if exercise protects against the loss of lean tissue that can occur as a result of a negative caloric balance. Rats weighing 706 +/-14 g were divided into four groups matched for weight. A baseline group was killed at the beginning of the study. An exercising group, fed ad lib., was subjected to a program of swimming. A sedentary, free-eating group was provided with food ad lib. Two sedentary, paired-weight subgroups were calorie restricted so that they lost weight at the same rate as the exercisers. The protein intake of one paired-weight subgroup was matched with that of the exercising group. The other sedentary, paired-weight animals ate the standard diet. There was no significant difference in body composition between the two sedentary, paired-weight subgroups which were, therefore, pooled for comparison with the other groups. The exercisers lost 182+/-19 g as a result of both an increase in caloric expenditure and a decrease in appetite. The sedentary, food-restricted animals lost an average of 182+/-18 g. The sedentary, free-eating animals gained 118+/-13 g. The carcasses of the exercised animals contained significantly less fat and more lean tissue than those of the sedentary, paired-weight animals, providing evidence for a fat mobilizing and protein conserving effect of exercise. The composition of the body substance lost by the exercising animals was 78% fat, 5% protein, 1% minerals, and 16% water, compared to 62% fat, 11% protein, 1% minerals, and 26% water for the sedentary, food-restricted rats. Fat accounted for 87% and water for 10% of the weight gained by the sedentary, free-eating animals.
IL-7 inhibits fibroblast TGF-β production and signaling in pulmonary fibrosis
Authors: Min Huang, Sherven Sharma, Li X. Zhu, Michael P. Keane, Jie Luo, Ling Zhang, Marie D. Burdick, Ying Q. Lin, Mariam Dohadwala, Brian Gardner, Raj K. Batra, Robert M. Strieter, Steven M. Dubinett
Journal: Journal of Clinical Investigation (2002)

Based on studies by our group and others, we hypothesized that IL-7 may possess antifibrotic activities in an IFN-gamma-dependent and independent manner. Here, we have evaluated the antifibrotic therapeutic potential of IL-7 in both in vitro and in vivo pulmonary fibrosis models. IL-7 inhibited both TGF-beta production and signaling in fibroblasts and required an intact JAK1/STAT1 signal transduction pathway. IL-7-mediated inhibition of TGF-beta signaling was found to be associated with an increase in Smad7, a major inhibitory regulator in the SMAD family. In the presence of IL-7, Smad7 dominant negative fibroblasts restored TGF-beta-induced collagen synthesis, indicating that an IL-7-mediated increase in Smad7 suppressed TGF-beta signaling. Consistent with these in vitro findings, recombinant IL-7 decreased bleomycin-induced pulmonary fibrosis in vivo, independent of IFN-gamma. The antifibrotic activities of IL-7 merit further basic and clinical investigation for the treatment of pulmonary fibrosis.
Lesbian couples requesting donor insemination: an update of the knowledge with regard to lesbian mother families
Authors: P. Baetens
Journal: Human Reproduction Update (2001)

Although a variety of ways exist of becoming a lesbian mother, an increasing number of lesbian couples have began to visit fertility centres requesting donor insemination (DI). The practice of inseminating lesbian couples remains a controversial issue within the reproductive medicine world. Lesbian mothers offer their children a familial context, which differs on a number of important characteristics from the traditional heterosexual family. In lesbian families, a father has been absent right from the start, and the child is raised by two mothers. The present article reviews whether there is any theoretical and/or empirical evidence for the most common assumptions with regard to lesbian motherhood. It also reports on a number of studies in which the practice of counselling lesbian couples is discussed. Although many important research questions have yet to be addressed, none of the investigations carried out so far could identify an adverse effect of lesbian motherhood on child development. Counselling lesbian couples for DI should aim to provide information about the practical aspects of the treatment. The requests of lesbian couples, however, differ substantially from those of single mothers and heterosexual couples. Counsellors should respect these differences and focus upon the specific living conditions of lesbian families.
Selection, training, and support of relief workers: an occupational health issue
Authors: M. McCall, P. Salama
Journal: BMJ (1999)

> Courage rather than cowardice, compassionate human concern of one for the other; and resilience in the face of overwhelming stress.1 Many of today's violent conflicts can be characterised as “complex humanitarian emergencies.” Complex humanitarian emergencies are defined by Leaning as “Crises in life support and security that threaten large civilian populations with suffering and death and impose severe constraints on those who would seek to offer help.”2 Lauttze interprets these emergencies as “complicated disaster situations that have political, military and humanitarian dimensions and are often associated with natural disasters, especially drought.”3 Kosovo, Rwanda, Sudan, and Afghanistan are recent examples. The rapid growth, in capacity and number, of humanitarian relief organisations in response to complex humanitarian emergencies has created concern about the professionalism of their relief workers. The risk to the psychological wellbeing of relief workers caused by exposure to traumatic events is a particular worry and has been studied little.4 Research on the psychological sequelae to trauma has focused on primary victims,5–7 domestic rescue workers, 8 9 military personnel,10 and psychologists.11 Complex humanitarian emergencies may generate more stress among relief workers than “natural” disasters for several reasons. Firstly, an element of physical insecurity, with the risk of violent personal assault or injury, is increasingly present.12 Secondly, work in these situations necessarily involves moral and ethical dilemmas—for example, negotiating with warlords; witnessing human rights abuses, but being constrained from responding by operational considerations; and concern that humanitarian aid may perpetuate conflicts.13–16 Finally, caring for people with serious injuries caused by violence, witnessing unnatural deaths, and handling dead bodies or body parts are highly traumatic experiences in themselves.17 #### Summary points
Identification of a Novel Germ Line Variant Hotspot Mutant p53-R175L in Pediatric Adrenal Cortical Carcinoma
Authors: Alina Nico West, Raul C. Ribeiro, Jesse Jenkins, Carlos Rodriguez-Galindo, Bonald C. Figueiredo, Richard Kriwacki, Gerard P. Zambetti
Journal: Cancer Research (2006)

Abstract Hotspot mutations in the p53 tumor suppressor gene result in the disruption of DNA contact points or alter the overall structure of the protein to prevent DNA binding. When inherited, hotspot mutants are associated with Li-Fraumeni syndrome (LFS), a familial cancer predisposition. One of the most common hotspot mutations occurs at codon 175, resulting in an arginine to histidine substitution. We have identified a novel germ line variant of the 175 mutant (Arg to Leu; R175L) in a pediatric patient who developed adrenal cortical carcinoma. Surprisingly, the family is not tumor prone or associated with LFS. In vitro, the R175L mutant displayed an attenuated tumor suppressor activity in the regulation of transcription, colony formation, and apoptosis when compared with wild-type p53 and the R175H mutant. These findings suggest that p53-R175L retains sufficient activity to suppress LFS, but not adrenal cortical carcinoma. Therefore, not all hotspot mutants are functionally equivalent and the biochemical nature of the mutant may significantly influence clinical outcome. The implications of these results for genetic counseling are discussed. (Cancer Res 2006; 66(10): 5056-62)