tbuckley/cabot-search huggingface dataset:
ON A METHOD OF ISOLATING AND IDENTIFYING BACILLUS TYPHOSUS, BASED ON A STUDY OF BACILLUS TYPHOSUS AND MEMBERS OF THE COLON GROUP IN SEMI-SOLID CULTURE MEDIA
Authors: Philip Hanson Hiss
Journal: The Journal of Experimental Medicine (1897)

Semi-solid culture media, and more especially media rendered semi-solid by temperatures of from 30° to 40° C., seem to have an important bearing in the differentiation of bacterial species, particularly those presenting various degrees of motility. In such media not only the effect of differences in consistence on the motility of an organism may be noted, but the effect produced by various chemicals and nutrient ingredients on the growth and motility may be readily observed. By systematically varying the constituents of such media it has been possible to produce a medium in which the behavior of Bacillus typhosus differentiates it from the various members of the colon group; and also to produce a medium in which the colonies of Bacillus typhosus assume a form which distinguishes them from the colonies of the colon bacilli in plate cultures. Bacillus typhosus alone of all the organisms investigated during these experiments has displayed both the power of giving rise to thread-forming colonies in the plating medium and that of the uniform clouding of the tube medium, hence these two characters may prove to be of great value in the identification of this organism. The practical application of the use of these media has led to the ready detection of Bacillus typhosus and its isolation from the stools of patients suffering from typhoid fever. No suspected water has been subjected to test, but from the investigation of artificially infected tap-water the media here described may be assumed to have an application in the detection of Bacillus typhosus in such waters.
Successful treatment of acute visual loss in Muckle-Wells syndrome with interleukin 1 receptor antagonist
Authors: T Alexander
Journal: Annals of the Rheumatic Diseases (2005)

Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory disease characterised by urticarial skin rash, intermittent fever, arthralgia, and the frequent development of systemic AA amyloidosis. It is caused by mutations in the gene known as NALP3 or CIAS , which encodes a member of the purine superfamily of death domain fold proteins that are implicated in the regulation of inflammation through activation of nuclear factor κB (NF-κB) and regulation of interleukin 1 (IL1) processing.1,2 Over recent years, therapeutic trials with the human recombinant IL1 receptor antagonist anakinra have reported encouraging results in patients with various autoinflammatory syndromes.3,4 We report here the unusual case of acute visual loss in a patient with MWS and its good response to anakinra.

A 70 year old woman with a history …
Defining the Role of Prolactin as an Invasion Suppressor Hormone in Breast Cancer Cells
Authors: Zaynab Nouhi, Naila Chughtai, Strachan Hartley, Eftihia Cocolakis, Jean-Jacques Lebrun, Suhad Ali
Journal: Cancer Research (2006)

Abstract Prolactin hormone (PRL) is well characterized as a terminal differentiation factor for mammary epithelial cells and as an autocrine growth/survival factor in breast cancer cells. However, this function of PRL may not fully signify its role in breast tumorigenesis. Cancer is a complex multistep progressive disease resulting not only from defects in cell growth but also in cell differentiation. Indeed, dedifferentiation of tumor cells is now recognized as a crucial event in invasion and metastasis. PRL plays a critical role in inducing/maintaining differentiation of mammary epithelial cells, suggesting that PRL signaling could serve to inhibit tumor progression. We show here that in breast cancer cells, PRL and Janus-activated kinase 2, a major kinase involved in PRL signaling, play a critical role in regulating epithelial-mesenchymal transformation (EMT), an essential process associated with tumor metastasis. Activation of the PRL receptor (PRLR), achieved by restoring PRL/JAK2 signaling in mesenchymal-like breast cancer cells, MDA-MB-231, suppressed their mesenchymal properties and reduced their invasive behavior. While blocking PRL autocrine function in epithelial-like breast cancer cells, T47D, using pharmacologic and genetic approaches induced mesenchymal-like phenotypic changes and enhanced their invasive propensity. Moreover, our results indicate that blocking PRL signaling led to activation of mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) and transforming growth factor-β/Smad signaling pathways, two major prometastatic pathways. Furthermore, our results indicate that following PRL/JAK2 inhibition, ERK1/2 activation precedes and is required for Smad2 activation and EMT induction in breast cancer cells. Together, these results highlight PRL as a critical regulator of epithelial plasticity and implicate PRL as an invasion suppressor hormone in breast cancer. (Cancer Res 2006; 66(3): 1824-32)
Mini symposium: analysis of therapies for anovulation and miscarriage. Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage
Authors: S Daya
Journal: Human Reproduction Update (1999)

An alloimmune abnormality is believed to be the cause of recurrent miscarriage in couples in whom no other cause can be identified. Because of its immunosuppressive properties, intravenous immunoglobulin (IVIG) is used as a treatment for this disorder. The purpose of this study was to determine whether IVIG improves the chance of successful pregnancy in women with recurrent miscarriage by using individual patient data from efficacy trials. Detailed information on each patient enrolled in these trials was obtained to evaluate the efficacy of IVIG and investigate the effect of clinical variability on pregnancy outcome. Data from 125 patients in the IVIG group and 115 patients in the placebo group were available for analysis. Although the number of previous miscarriages and female age were both negative prognostic factors for successful outcome, there was no significant improvement in successful pregnancy or live birth rate with IVIG. Subgroup analyses indicated that timing of IVIG administration may be important. The results of the present study highlight the importance of stratification for known confounders, so that the role of IVIG can be evaluated in more detail. The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful.
Complexity science: Complexity and clinical care
Authors: T. Wilson, T. Holt, T. Greenhalgh
Journal: BMJ (2001)

This is the second in a series of four articles 

Biological and social systems are inherently complex, so it is hardly surprising that few if any human illnesses can be said to have a single “cause” or “cure.”1 This article applies the principles introduced in the introductory article in this series2 to three specific clinical areas: the control of blood glucose levels in diabetes, the management of diagnostic uncertainty, and health promotion.

A complex adaptive system is a collection of individual agents with freedom to act in ways that are not always totally predictable, and whose actions are interconnected so that the action of one part changes the context for other agents.2 In relation to human health and illness there are several levels of such systems.

For all these reasons neither illness nor human behaviour is predictable and neither can safely be “modelled” in a simple cause and effect system.3 The human body is not a machine and its malfunctioning cannot be adequately analysed by breaking the …
EVERSUN: a phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma
Authors: I.D. Davis, A. Long, S. Yip, D. Espinoza, J.F. Thompson, G. Kichenadasse, M. Harrison, R.M. Lowenthal, N. Pavlakis, A. Azad, G. Kannourakis, C. Steer, D. Goldstein, J. Shapiro, R. Harvie, L. Jovanovic, A.L. Hudson, C.C. Nelson, M.R. Stockler, A. Martin
Journal: Annals of Oncology (2015)
Frontiers in Nephrology
Authors: Mario Gossl, Lilach O. Lerman, Amir Lerman
Journal: Journal of the American Society of Nephrology (2007)

Endothelial dysfunction is an established clinical marker of early coronary artery disease and has been shown to be associated with increased cardiovascular morbidity and mortality. New concepts now extend the view of endothelial dysfunction beyond the traditional involvement of the coronary arterial endothelium alone. Recent research indicates that the coronary vessel wall, especially the vasa vasorum, as well as bone marrow-derived endothelial progenitor cells may be subject to proatherosclerotic changes, even before the development of angiographically evident endothelial dysfunction; therefore, "microvascular endothelial dysfunction," which is composed of dysfunction of the vasa vasorum's endothelium as well as "microcellular endothelial dysfunction," reflecting impaired mobilization and function of endothelial progenitor cells, may precede "macrovascular endothelial dysfunction." Vasa vasorum neovascularization, with endothelial leakage and dysfunction increasing influx of proinflammatory and proatherogenic cellular and noncellular substances into the vessel wall, is proposed as one feature of this new concept. In addition, the role of bone marrow-derived endothelial progenitor cells is discussed as are the potential impact of impaired progenitor cell mobilization, release from the marrow, and function in acute and stable coronary artery disease. Finally, potential future therapies are proposed, focusing on interventions that may prevent or diminish the development of the microvascular and microcellular endothelial dysfunction.
Interrelationship of Serum Lipids with Relative Weight, Blood Glucose, and Physical Activity
Authors: MARIO R. GARCÍA-PALMIERI, RAÚL COSTAS, JOYCE SCHIFFMAN, ANGEL A. COLÓN, RAQUEL TORRES, EMILIO NAZARIO
Journal: Circulation (1972)

Serum cholesterol, serum glyceride, blood glucose, relative weight, physical activity, percent calories from fat, percent calories from carbohydrate, and polyunsaturated/saturated fatty acid (P/S) ratio were determined in 1780 rural and 4023 urban fasting men aged 45-64 years being followed prospectively to ascertain reasons for the low prevalence of coronary heart disease mortality in Puerto Rico as compared to other countries. Lipid and glucose levels and relative weight were higher and physical activity lower in urban men. Glyceride was positively correlated with cholesterol, glucose, and relative weight, and negatively correlated with physical activity. Cholesterol was positively correlated with glyceride, glucose, and relative weight, and not correlated with physical activity. Percent calories from fat and P/S ratio were significantly higher and percent carbohydrates from starch significantly lower in urban men. These variables taken together were not significant in predicting the differences between urban and rural serum cholesterol or glyceride values. Relative weight was the most significant variable in explaining urban-rural differences in serum glyceride and cholesterol levels. These findings confirm the importance of weight control in dietary management for reduction of serum lipids.
Prenatal Features of Ductus Arteriosus Constriction and Restrictive Foramen Ovale in d-Transposition of the Great Arteries
Authors: Yasuki V. Maeno, Steven A. Kamenir, Brian Sinclair, Mary E. van der Velde, Jeffrey F. Smallhorn, Lisa K. Hornberger
Journal: Circulation (1999)

Background —Although most neonates with d-transposition of the great arteries (TGA) have an uncomplicated preoperative course, some with a restrictive foramen ovale (FO), ductus arteriosus (DA) constriction, or pulmonary hypertension may be severely hypoxemic and even die shortly after birth. Our goal was to determine whether prenatal echocardiography can identify these high-risk fetuses with TGA. Methods and Results —We reviewed the prenatal and postnatal echocardiograms and outcomes of 16 fetuses with TGA/intact ventricular septum or small ventricular septal defect. Of the 16 fetuses, 6 prenatally had an abnormal FO (fixed position, flat, and/or redundant septum primum). Five of the 6 had restrictive FO at birth. Five fetuses had DA narrowing at the pulmonary artery end in utero, and 6 had a small DA (diameter z score of &lt;−2.0). Of 4 fetuses with the most diminutive DA, 2 also had an abnormal appearance of the FO, and both died immediately after birth. One other fetus had persistent pulmonary hypertension. Eight fetuses had abnormal Doppler flow pattern in the DA (continuous high-velocity flow, n=1; retrograde diastolic flow, n=7). Conclusions —Abnormal features of the FO, DA, or both are present in fetuses with TGA at high risk for postnatal hypoxemia. These features may result from the abnormal intrauterine hemodynamics in TGA. A combination of restrictive FO and DA constriction in TGA may be associated with early neonatal death.
Impaired vitamin D metabolism with aging in women. Possible role in pathogenesis of senile osteoporosis.
Authors: K S Tsai, H Heath, R Kumar, B L Riggs
Journal: Journal of Clinical Investigation (1984)

Calcium absorption decreases with aging, particularly after age 70 yr. We investigated the possibility that this was due to abnormal vitamin D metabolism by studying 10 normal premenopausal women (group A), 8 normal postmenopausal women within 20 yr of menopause (group B), 10 normal elderly women (group C), and 8 elderly women with hip fracture (group D) whose ages (mean +/- SD) were 37 +/- 4, 61 +/- 6, 78 +/- 4, and 78 +/- 4 yr, respectively. For all subjects, serum 25-hydroxyvitamin D [25(OH)D] did not decrease with age, but serum 1,25-dihydroxyvitamin D [1,25(OH)2D], the physiologically active vitamin D metabolite, was lower (P = 0.01) in the elderly (groups C and D; 20 +/- 3 pg/ml) than in the nonelderly (groups A and B; 35 +/- 4 pg/ml). The increase of serum 1,25(OH)D after a 24-h infusion of bovine parathyroid hormone fragment 1-34, a tropic agent for the enzyme 25(OH)D 1 alpha-hydroxylase, correlated inversely with age (r = -0.58; P less than 0.001) and directly with glomerular filtration rate (r = 0.64; P less than 0.001). The response was more blunted (P = 0.01) in elderly patients with hip fracture (13 +/- 3 pg/ml) than in elderly controls (25 +/- 3 pg/ml). We conclude that an impaired ability of the aging kidney to synthesize 1,25(OH)2D could contribute to the pathogenesis of senile osteoporosis.
Increased release of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha by bronchoalveolar cells lavaged from involved sites in pulmonary tuberculosis.
Authors: K Law, M Weiden, T Harkin, K Tchou-Wong, C Chi, W N Rom
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Mycobacterium tuberculosis and its components have been shown to stimulate mononuclear phagocytes in vitro to release interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Animal models of tuberculosis (TB) also demonstrate the presence of cytokines in granulomas. We hypothesized that bronchoalveolar lavage (BAL) cells from patients with pulmonary TB would have increased spontaneous release of IL-1 beta, IL-6, and TNF-alpha and would have a concomitant alveolitis. We performed BAL on 26 patients with active TB and on six normal volunteers. BAL fluid from radiographically involved and uninvolved sites was evaluated separately for cell types and the spontaneous release of cytokines. The alveolar inflammation in involved sites was characterized by an increase in lymphocytes (miliary TB, 38 +/- 10%; involved sites, 22 +/- 4%; uninvolved sites, 13 +/- 2%; normal, 5 +/- 2%) and neutrophils (involved sites, 21 +/- 7%; uninvolved sites, 3 +/- 2%). There was a significant increase in the spontaneous release of IL-1 beta (501 +/- 280 pg/ml), TNF-alpha (782 +/- 165 pg/ml), and IL-6 (473 +/- 157 pg/ml) from involved sites of TB patients that was 5- to 20-fold greater than uninvolved sites, normal controls, or miliary TB. Northern analysis revealed increased gene expression of IL-1 beta, TNF-alpha, and IL-6 from the involved sites from two patients with TB compared with two negative controls. We conclude that BAL cells, especially alveolar macrophages, are activated in the alveolar inflammation of active TB and spontaneously release increased quantities of IL-1 beta, IL-6, and TNF-alpha, and that these cytokines are likely to be involved in directing granuloma formation and control of M. tuberculosis infection.
PM10 elemental composition and acute respiratory health effects in European children (PEACE project)
Authors: W Roemer, G Hoek, B Brunekreef, J Clench-Aas, B Forsberg, J Pekkanen, A Schutz
Journal: European Respiratory Journal (2000)

The ability of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) to cause respiratory health effects possibly depends on their composition. This study evaluated whether the soluble elemental concentrations in PM10 were related to acute respiratory health effects. The Pollution Effects on Asthmatic Children in Europe (PEACE) study is a multicentre study of the acute effects of PM10 and other air pollution components on the respiratory health of children with chronic respiratory symptoms in urban and suburban panels. Children, 1208, divided among 17 panels were followed for &gt; or =2 months. Exposure to air pollution was monitored on a daily basis. Health status was monitored by twice daily peak expiratory flow (PEF) measurements and a symptom diary. Median concentrations of iron ranged 105-1,110 ng x m(-3) in the urban and 32-517 ng x m(-3) in the suburban locations. The daily concentrations of most elements were not associated with daily variation in PEF, prevalence of respiratory symptoms or bronchodilator use. Silicon and iron concentrations tended to be negatively associated with PEF, and positively associated with the prevalence of phlegm. In two pollutant models, PM10 effect-estimates on phlegm prevalence were reduced and lost significance, whereas the effect-estimates of iron or silicon remained essentially unchanged. The effects of silicon and iron could not be separated. In conclusion, this study provides only weak support for the hypothesis that daily fluctuations in soluble elemental concentrations in ambient particulate matter are responsible for acute health effects.
Idiopathic steatorrhoea with intestinal pseudo-obstruction
Authors: H. A. McClelland, M. J. Lewis, J. M. Naish
Journal: Gut (1962)

This is a case report illustrating a disorder of small intestine motility producing gross muscular hypertrophy and associated with steatorrhoea. The literature is briefly reviewed, and it is suggested that in idiopathic steatorrhoea there is ineffectual peristalsis which leads to stagnation of intestinal contents and hypertrophy of its muscular wall.
Guidelines for the clinical management of familial adenomatous polyposis (FAP)
Authors: H. F. A. Vasen, G. Moslein, A. Alonso, S. Aretz, I. Bernstein, L. Bertario, I. Blanco, S. Bulow, J. Burn, G. Capella, C. Colas, C. Engel, I. Frayling, W. Friedl, F. J. Hes, S. Hodgson, H. Jarvinen, J.-P. Mecklin, P. Moller, T. Myrhoi, F. M. Nagengast, Y. Parc, R. Phillips, S. K. Clark, M. P. de Leon, L. Renkonen-Sinisalo, J. R. Sampson, A. Stormorken, S. Tejpar, H. J. W. Thomas, J. Wijnen
Journal: Gut (2008)

Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken.
Athletic Facial Injuries: Call in Everyone
Authors: Lewis J. Singer
Journal: JAMA (1985)

<h3>To the Editor.—</h3> In the Dec 28, 1984, issue ofThe Journal, Drs Schultz and de Camara<sup>1</sup>described various types of facial athletic injuries, the approach to their diagnosis, and their treatments. Unfortunately, this article did not adequately emphasize the possibility of concurrent eye, ear, nose, and throat, or neurological injuries. As an ophthalmologist, I noted only one mention of concurrent eye injury, which was "to the globe whenever a penetrating eyelid laceration was present." While many athletic-related facial injuries may appear minor, it remains the responsibility of the physician to completely evaluate a patient in a multisystem fashion. Eye injuries can result without external or radiographic evidence of other facial abnormalities. Following a complete history, an eye examination should be performed. The complete eye examination would include visual acuity testing, the evaluation of extraocular movements, pupillary light reflexes, slit-lamp examination, intraocular pressure measurement, and funduscopic evaluation. Evaluations for
Cardiopoietic Factors
Authors: Michela Noseda, Tessa Peterkin, Filipa C. Simões, Roger Patient, Michael D. Schneider
Journal: Circulation Research (2011)

Cardiac muscle creation during embryogenesis requires extracellular instructive signals that are regulated precisely in time and space, intersecting with intracellular genetic programs that confer or fashion the ability of the cells to respond. Unmasking the essential signals for cardiac lineage decisions has paramount importance for cardiac development and regenerative medicine, including the directed differentiation of progenitor and stem cells to a cardiac muscle fate.
Cytokine-like Molecule CCDC134 Contributes to CD8+ T-cell Effector Functions in Cancer Immunotherapy
Authors: Jing Huang, Lin Xiao, Xiaoting Gong, Wenwei Shao, Yanhui Yin, Qinyuan Liao, Yang Meng, Yingmei Zhang, Dalong Ma, Xiaoyan Qiu
Journal: Cancer Research (2014)

CCDC134 is a poorly characterized secreted protein that may act as an immune cytokine. Here, we show that CCDC134 is differentially expressed on resting and activated immune cells and that it promotes CD8(+) T-cell activation, proliferation, and cytotoxicity by augmenting expression of the T-cell effector molecules IFNγ, TNFα, granzyme B, and perforin. CCDC134 facilitated infiltration of CD8(+) T cells with enhanced cytolytic activity into tumors, demonstrating strong antitumor effects in a CD8(+) T-cell-dependent manner. Mechanistically, in CD8(+) T cells, exposure to CCDC134 promoted cell proliferation through the JAK3-STAT5 pathway, a classic feature of many cytokines of the common γ-chain (γ(c)) cytokine receptor family. Overall, our results provide evidence that CCDC134 may serve as a member of the γ(c) cytokine family and illustrate its potent antitumor effects by augmenting CD8(+) T-cell-mediated immunity.