tbuckley/cabot-search huggingface dataset:
Cholesterol Sulfate
Authors: Michael Merten, Jing Fei Dong, Jose A. Lopez, Perumal Thiagarajan
Journal: Circulation (2001)

Background —Cholesterol 3-sulfate is present on a variety of cells and in human LDL, and it has been found in atherosclerotic lesions of human aorta. Its precise biological role has not yet been described. Methods and Results —In this study, we investigated the interaction of platelets with cholesterol sulfate. Platelets adhered in a concentration-dependent and saturable manner to cholesterol sulfate but did not adhere to cholesterol, cholesterol acetate, estrone sulfate, or dehydroepiandrosterone sulfate, suggesting that the specificity of this interaction is determined not only by the cholesterol moiety but also by the sulfate group. This adhesion did not increase after platelet activation, and it was not cation-dependent. Soluble cholesterol sulfate inhibited adhesion in a concentration-dependent manner. However, antibodies against glycoprotein Ib, glycoprotein IIb/IIIa, CD36, P-selectin, von Willebrand factor, or thrombospondin had no significant effect on platelet adhesion to cholesterol sulfate. Perfusion of whole blood in a parallel-plate flow chamber resulted in the rapid and progressive adhesion of platelets to cholesterol sulfate but not to cholesterol acetate or estrone sulfate. Conclusions —Cholesterol sulfate supports platelet adhesion and may be one of the factors determining the prothrombotic potential of atherosclerotic lesions.
BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance
Authors: D.M. Eccles, G. Mitchell, A.N.A. Monteiro, R. Schmutzler, F.J. Couch, A.B. Spurdle, E.B. Gómez-García, R. Driessen, N.M. Lindor, M.J. Blok, P. Moller, M. de la Hoya, T. Pal, S. Domchek, K. Nathanson, C. Van Asperen, O. Diez, K. Rheim, D. Stoppa-Lyonnet, M. Parsons, D. Goldgar
Journal: Annals of Oncology (2015)
Pleiotropic Effects of the Trichloroethylene-Associated P81S VHL Mutation on Metabolism, Apoptosis, and ATM-Mediated DNA Damage Response
Authors: M. C. DeSimone, W. K. Rathmell, D. W. Threadgill
Journal: JNCI Journal of the National Cancer Institute (2013)

The risk relevance of the P81S von Hippel-Lindau (VHL) gene hotspot mutation identified in clear cell renal cell carcinoma from individuals exposed occupationally to trichloroethylene (TCE) is not known. VHL mutations in hereditary VHL syndrome strongly correlate with phenotypic associations, but specific sporadic mutations in VHL that uniquely alter its protein function may provide a selective growth advantage for somatic cells harboring these mutations. VHL deficient ( Vhl-/- ) mouse embryonic stem cells were generated that stably express wild-type, P81S, or R167Q human VHL protein. Under hypoxic conditions, cell lines were examined for hypoxia-inducible transcription factor family (HIF) stabilization and E3-ubiquitin ligase complex interactions. In vivo, teratomas were examined for tumor size, proliferation, apoptosis, and immunohistochemistry and subjected to gene expression analysis. Wild-type, R167Q, and P81S VHL-expressing teratomas were also exposed to 5 Gy ionizing radiation to quantify apoptotic response. Proliferation and apoptosis and teratoma growth were analyzed by either Student t test or analysis of variance with Bonferroni correction. All statistical tests were two-sided. The P81S VHL mutation produces deregulation of HIF factors in cell culture but exhibits a growth advantage in the tumor microenvironment, in part because of suppression of apoptosis (P81S mean = 0.9%, 95% confidence interval = 0.6 to 1.2%; WT mean = 7.6%; 95% confidence interval = 6.4 to 8.8%; P < .001) coupled with sustained proliferation. Transcriptional analysis of P81S teratomas revealed the induction of metabolic pathways, antiapoptotic genes, and global suppression of key DNA damage response genes not observed in VHL wild-type or R167Q mutants. In vivo irradiation exposure showed that P81S mutant is resistant to ionizing radiation–induced apoptosis. The TCE-associated P81S VHL mutation can initiate a unique adaptive response required for selective tumor growth through pleiotropic effects on metabolic diversification, apoptosis suppression, and alteration of the DNA damage response.
Hemoglobin A1c, Fasting Glucose, and Cardiovascular Risk in a Population With High Prevalence of Diabetes
Authors: Hong Wang, Nawar M. Shara, Elisa T. Lee, Richard Devereux, Darren Calhoun, Giovanni de Simone, Jason G. Umans, Barbara V. Howard
Journal: Diabetes Care (2011)

We compared A1C and fasting plasma glucose (FPG) in predicting cardiovascular disease (CVD) in a population with widespread obesity and diabetes.A total of 4,549 American Indian adults underwent the Strong Heart Study (SHS) baseline examination (1989-1991). Data from 3,850 individuals (60% women) with baseline measurements of FPG and A1C and no prevalent CVD were analyzed; 1,386 had known diabetes. CVD events were ascertained over a median of 15 years.A1C ≥6.5% had a 44.3% sensitivity and 98.9% specificity to identify participants with FPG ≥126 mg/dL. Increases in A1C were associated with adverse CVD risk factor profiles; individuals with known diabetes had worse profiles. For A1C <5, 5 to <5.5, 5.5 to <6, 6-6.5, or ≥6.5% or known diabetes, the multivariate-adjusted hazard ratio (HR) [95% CI] for coronary heart disease (CHD) was significant only for individuals with known diabetes (2.76 [2.17-3.51]). Similarly, the adjusted HRs for total CVD were significant only for individuals with A1C ≥6.5% or known diabetes (1.50 [1.10-2.04] and 2.52 [2.06-3.08], respectively). Similar results were observed for FPG.Individuals with known or newly diagnosed diabetes had increased risk for CVD. Although A1C is more convenient than FPG in diagnosing diabetes, neither test adds to conventional CVD risk factors in predicting CHD or total CVD.
Germ Cell Tumors in the Intersex Gonad: Old Paths, New Directions, Moving Frontiers
Authors: Martine Cools, Stenvert L. S. Drop, Katja P. Wolffenbuttel, J. Wolter Oosterhuis, Leendert H. J. Looijenga
Journal: Endocrine Reviews (2006)

The risk for the development of germ cell tumors is an important factor to deal with in the management of patients with disorders of sex development (DSD). However, this risk is often hard to predict. Recently, major progress has been made in identifying gene-products related to germ cell tumor development (testis-specific protein-Y encoded and octamer binding transcription factor 3/4) and in recognizing early changes of germ cells (maturation delay, preneoplastic lesions, and in situ neoplasia). The newly recognized “undifferentiated gonadal tissue” has been identified as a gonadal differentiation pattern bearing a high risk for the development of gonadoblastoma. It is expected that the combination of these findings will allow for estimation of the risk for tumor development in the individual patient (high risk/intermediate risk/low risk). This article reviews the recent literature regarding the prevalence of germ cell tumors in patients with DSD. Some major limitations regarding this topic, including a confusing terminology referring to the different forms of intersex disorders and unclear criteria for the diagnosis of malignant germ cells at an early age (maturation delay vs. early steps in malignant transformation) are discussed. Thereafter, an overview of the recent advances that have been made in our knowledge of germ cell tumor development and the correct diagnosis of early neoplastic lesions in this patient population is provided. A new classification system for patients with DSD is proposed as a tool to refine our insight in the prevalence of germ cell tumors in specific diagnostic groups.
Results of Blood Inflammatory Markers Are Associated More Strongly With Toe-Brachial Index Than With Ankle-Brachial Index in Patients With Type 2 Diabetes
Authors: Yoshimasa Aso, Ki-ichi Okumura, Teruo Inoue, Rika Matsutomo, Noboru Yoshida, Sadao Wakabayashi, Kohzo Takebayashi, Toshihiko Inukai
Journal: Diabetes Care (2004)

OBJECTIVE—Three blood markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin [IL]-6, and fibrinogen) were compared with markers of atherosclerotic cardiovascular disease (CVD) (history of stroke or cardiac ischemia and measured toe-brachial index [TBI]) to determine whether inflammatory markers are associated with atherosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Of 103 patients with type 2 diabetes, 26 had CVD. TBI was plethysmographically determined in both great toes. Serum hsCRP was immunonephelometrically determined. Plasma IL-6 was measured by an enzyme immunoassay. RESULTS—Both ABI and TBI were lower in diabetic patients with CVD than in those without CVD (1.05 ± 0.19 vs. 1.14 ± 0.09, P &amp;lt; 0.05, and 0.75 ± 0.20 vs. 0.95 ± 0.21, P &amp;lt; 0.001, respectively). By linear regression, right TBI but not right ABI showed a significant negative correlation with serum hsCRP (r = −0.372, P &amp;lt; 0.01) and plasma fibrinogen (r = −0.224, P &amp;lt; 0.05). Serum hsCRP was also negatively correlated with lower TBI, but not lower ABI. We found no significant correlation between plasma IL-6 and ABI or TBI. CONCLUSIONS—TBI was strongly associated with CVD, serum hsCRP, and plasma fibrinogen. Of these inflammatory markers, serum hsCRP may be the most promising marker for vascular inflammation.
Two-dimensional ultrasonic tissue characterization: backscatter power, endocardial wall motion, and their phase relationship for normal, ischemic, and infarcted myocardium.
Authors: P J Fitzgerald, M D McDaniel, E L Rolett, J W Strohbehn, D H James
Journal: Circulation (1987)

To understand the possible differences in reflected ultrasonic energy from normal, ischemic, and infarcted myocardium, we studied 20 open-chest dogs with a commercially available two-dimensional ultrasonic scanner. Echocardiographic radiofrequency images of anterior myocardium were obtained serially during complete coronary occlusion for 2 hr (n = 15) or 5 hr (n = 10), or after temporary coronary clamping for 15 min with release for 1 hr (n = 5). We investigated two variables: the cyclic backscatter power and the phase difference among endocardial wall motion (EWM), cyclic backscatter power (BSP), and left ventricular pressure (LVP). The cyclic BSP decreased from a control (nonischemic) level of 5.1 +/- 0.8 to 2.3 +/- 0.7 dB during ischemia (up to 30 min after coronary ligation). The phase difference between the EWM and BSP progressed from a control (nonischemic) value of 38 +/- 20 to 115 +/- 23 degrees during ischemia. For the infarction period (2 to 5 hr after coronary ligation), the cyclic BSP progressively returned toward baseline control levels to 4.0 +/- 1.2 dB, but the phase had increased further to 170 +/- 28 degrees. The reperfusion study showed a similar decrease in cyclic BSP and an increase in phase after arterial clamping and both returned to near-normal nonischemic values upon arterial release. Simultaneous LVP recordings were performed to assess the phase contribution of endocardial dyskinesis to the total phase difference measurement. At 5 hr the dyskinesis had contributed 46% to the total phase difference, while the backscatter power contributed 54%. However, the EWM contribution occurred immediately while BSP contribution changed progressively during the 5 hr study period.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevention of Transition From Incipient to Overt Nephropathy With Telmisartan in Patients With Type 2 Diabetes
Authors: Hirofumi Makino, Masakazu Haneda, Tetsuya Babazono, Tatsumi Moriya, Sadayoshi Ito, Yasuhiko Iwamoto, Ryuzo Kawamori, Masahiro Takeuchi, Shigehiro Katayama
Journal: Diabetes Care (2007)

To date, evidence for long-term renoprotection with angiotensin receptor blockers (ARBs) has come almost exclusively from Caucasian patients (1–3), despite Japanese people being at high risk of diabetic nephropathy and very susceptible to end-stage renal disease (4–6). We conducted the INNOVATION Study (Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy) to evaluate the efficacy of an ARB in preventing transition from microalbuminuria to overt nephropathy in Japanese patients (7). This study is the first large-scale clinical study to investigate prevention of overt diabetic nephropathy using an ARB in normotensive and hypertensive Japanese patients with type 2 diabetes.

The randomized, multicenter, double-blind, placebo-controlled trial was performed in patients aged from 30 to 74 years with type 2 diabetes and urinary albumin-to-creatinine ratio (UACR) 100–300 mg/g and serum creatinine <1.5 mg/dl (men) and <1.3 mg/dl (women). Exclusion criteria included type 1 diabetes, age of diabetes onset <30 years, seated systolic blood pressure (SBP)/diastolic blood pressure (DBP) ≥180/100 mmHg, and definable chronic kidney disease …
Asthma, rhinitis and air pollution: is traffic to blame?
Authors: B. Brunekreef, J. Sunyer
Journal: European Respiratory Journal (2003)

This issue of the European Respiratory Journal contains two papers that contribute to a growing body of evidence incriminating traffic fumes in respiratory disease.NICOLAI et al. [1] report a cross-sectional study that finds significant associations between traffic counts and exposure to trafficrelated air pollution on the one hand and current asthma, wheeze and cough on the other.In a sub-group of children exposed to environmental tobacco smoke, traffic counts are also related to allergic sensitisation.LEE et al.[2] report a large questionnaire survey from Taiwan, in which a composite measure of exposure to traffic-related air pollution is found to be associated with physician-diagnosed allergic rhinitis.A parallel analysis reported previously [3] found a similar association between traffic-related air pollution and physiciandiagnosed as well as questionnaire-reported asthma.How do these studies relate to earlier work on air pollution and childhood respiratory illness?How do they relate to earlier work on traffic-related pollution?Large-scale, cross-sectional studies on air pollution and respiratory outcomes in children have been reported from the USA [4], Switzerland [5], Canada [6] and Austria [7].The US and Swiss studies found associations between some air pollutants (especially fine particles) and cough and bronchitis symptoms, the Canadian study found no relationships and the Austrian study documented associations between nitrogen dioxide (NO 2 ; described as a marker for traffic-related air pollution) and asthma, wheeze and cough.East/West comparisons have generally highlighted high bronchitis and cough prevalence in the East, which were ascribed to "classical" pollution, consisting of sulphur dioxide (SO 2 ) and particles [8], with higher rhinitis in the West.A recent study from California, USA, found an association between wheeze prevalence and the air pollution components, acid and NO 2 .Taken together, these findings suggest that society is witnessing a transition from classical pollution, dominated by SO 2 and particles generated by coal and oil combustion, with the effects primarily on cough and bronchitis, to pollution mixtures dominated by traffic exhausts represented by NO 2 , with effects on wheeze and perhaps asthma prevalence.It is important to look at what precisely is the definition of asthma in some of these studies.The paper by NICOLAI et al.[1] defines asthma as a report by parents that a doctor has diagnosed asthma at least once or that a doctor has diagnosed asthmatic, spastic or obstructive bronchitis more than once.This definition therefore includes, to some extent, symptoms that may be bronchitic rather than asthmatic."Current asthma" is then defined as a combination of asthma and wheeze symptoms occurring in the past year.The study
Molecular and cellular mechanisms of cardiotoxicity.
Authors: Y J Kang
Journal: Environmental Health Perspectives (2001)

Cardiotoxicity resulting from detrimental environmental insults has been recognized for a long time. However, extensive studies of the mechanisms involved had not been undertaken until recent years. Advances in molecular biology provide powerful tools and make such studies possible. We are gathering information about cellular events, signaling pathways, and molecular mechanisms of myocardial toxicologic responses to environmental toxicants and pollutants. Severe acute toxic insults cause cardiac cell death instantly. In the early response to mild environmental stimuli, biochemical changes such as alterations in calcium homeostasis occur. These may lead to cardiac arrhythmia, which most often is reversible. Prolonged stimuli activate transcription factors such as activator protein-1 through elevation of intracellular calcium and the subsequent activation of calcineurin. Upregulation by activated transcription factors of hypertrophic genes results in heart hypertrophy, which is a short-term adaptive response to detrimental factors. However, further development of hypertrophy will lead to severe and irreversible cardiomyopathy, and eventually heart failure. From cardiac hypertrophy to heart failure, myocardial cells undergo extensive biochemical and molecular changes. Cardiac hypertrophy causes tissue hypoperfusion, which activates compensatory mechanisms such as production of angiotensin II and norepinephrine. Both further stimulate cardiac hypertrophy and, importantly, activate counterregulatory mechanisms including overexpression of atrial natriuretic peptide and b-type natriuretic peptide, and production of cytokines such as tumor necrosis factor-alpha. This counterregulation leads to myocardial remodeling as well as cell death through apoptosis and necrosis. Cell death through activation of mitochondrial factors and other pathways constitutes an important cellular mechanism of heart failure. Our current knowledge of cardiotoxicity is limited. Further extensive studies are warranted for a comprehensive understanding of this field.
The Evidence for the Effectiveness of Medical Nutrition Therapy in Diabetes Management
Authors: Joyce Green Pastors, Hope Warshaw, Anne Daly, Marion Franz, Karmeen Kulkarni
Journal: Diabetes Care (2002)

Numerous advances in diabetes management and medical nutrition therapy (MNT) for individuals with diabetes make this an exciting time. Historically, a challenge to proving the benefit of MNT has been the lack of clinical and behavioral research. In recent years, however, evidence-based outcomes research that documents the clinical effectiveness of MNT in diabetes has been reported.

The term “medical nutrition therapy” was introduced in 1994 by the American Dietetic Association to better articulate the nutrition therapy process. It is defined as the use of specific nutrition services to treat an illness, injury, or condition and involves two phases: 1 ) assessment of the nutritional status of the client and 2 ) treatment, which includes nutrition therapy, counseling, and the use of specialized nutrition supplements (1). MNT for diabetes incorporates a process that, when implemented correctly, includes: 1 ) an assessment of the patient’s nutrition and diabetes self-management knowledge and skills; 2 ) identification and negotiation of individually designed nutrition goals ; 3 ) nutrition intervention involving a careful match of both a meal-planning approach and educational materials to the patient’s needs, with flexibility in mind to have the plan be implemented by the patient; and 4) evaluation of outcomes and ongoing monitoring. These four steps are necessary to assist patients in acquiring and maintaining the knowledge, skills, attitudes, behaviors, and commitment to successfully meet the challenges of daily diabetes self-management (2).

The primary purpose of this article is to review the evidence for the effectiveness of MNT in diabetes, both as an independent variable and in combination with other components of diabetes self-management training (DSMT). In addition, the recent studies that have demonstrated the effectiveness of lifestyle intervention, which included MNT, in preventing type 2 diabetes will be highlighted. Evidence from several studies that supports the cost-effectiveness of MNT in diabetes will also be …
Monogenic Diabetes in the Young, Pharmacogenetics and Relevance to Multifactorial Forms of Type 2 Diabetes
Authors: Martine Vaxillaire, Philippe Froguel
Journal: Endocrine Reviews (2008)

Abstract Most valuable breakthroughs in the genetics of type 2 diabetes for the past two decades have arisen from candidate gene studies and familial linkage analysis of maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes typically occurring before 25 years of age caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but presents genetic, metabolic and clinical heterogeneity. MODY can result from mutations in at least six different genes encoding the glucose sensor enzyme glucokinase and transcription factors that participate in a regulatory network essential for adult β-cell function. Additional genes have been described in other discrete phenotypes or syndromic forms of diabetes. Whereas common variants in the MODY genes contribute very modestly to type 2 diabetes susceptibility in adults, major findings emerging from the advent of genome-wide association studies will deliver an increasing number of genes and new pathways for the pathological events of the disease.
Interrater Agreement Among Psychiatrists in Psychiatric Emergency Assessments
Authors: Bruce B. Way, Michael H. Allen, Jeryl L. Mumpower, Thomas R. Stewart, Steven M. Banks
Journal: American Journal of Psychiatry (1998)

The authors' purpose in this study was to investigate the interrater agreement among psychiatrists in psychiatric emergency service settings. The interrater reliability of many of the key concepts in psychiatric emergency service settings has not been studied.Videotapes of 30 psychiatric emergency service patient assessment interviews conducted by psychiatrists were shown to eight experienced psychiatric emergency service psychiatrists. The eight psychiatrists rated each videotape on dimensions such as severity of depression and psychosis and recommended a disposition for each patient. Interrater reliability was then explored.The level of agreement (intraclass correlation coefficient) among the reviewing psychiatrists was higher for psychosis and substance abuse but lower for psychopathology, impulse control problems, danger to self, and disposition. The reviewers' disposition recommendations did not match well with the assessing psychiatrist's actual disposition, but comparisons with actual practice should be considered only suggestive.Psychiatric emergency service assessments need improvement. This may be accomplished by exploring the underlying structure of psychiatric emergency service concepts, the creation and validation of structured assessment tools, and the creation of practice guidelines.