tbuckley/cabot-search huggingface dataset:
Low-Level Environmental Lead Exposure and Children’s Intellectual Function: An International Pooled Analysis
Authors: Bruce P. Lanphear, Richard Hornung, Jane Khoury, Kimberly Yolton, Peter Baghurst, David C. Bellinger, Richard L. Canfield, Kim N. Dietrich, Robert Bornschein, Tom Greene, Stephen J. Rothenberg, Herbert L. Needleman, Lourdes Schnaas, Gail Wasserman, Joseph Graziano, Russell Roberts
Journal: Environmental Health Perspectives (2005)

Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.
Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80.
Authors: S H Lee, P M Starkey, S Gordon
Journal: The Journal of Experimental Medicine (1985)

We have estimated the macrophage content of different tissues of the normal adult mouse using F4/80, a highly specific antigen marker for mature mouse macrophages. An absorption indirect binding assay was used to quantitate F4/80 antigen against a calibration standard made from the J774.2 macrophage-like cell line. The richest sources of tissue F4/80 antigen were found to be bone marrow, spleen, cervical and mesenteric lymph nodes, large bowel, liver, kidneys, and small bowel. The organs that have the highest total F4/80 antigen content are the liver, large bowel, small bowel, bone marrow, spleen, cervical and mesenteric lymph nodes, and kidney. We conclude that the mononuclear phagocyte system is mainly distributed in the gastrointestinal tract and liver, followed by hemopoietic and lymphoid tissues.
Investigation of Colonic and Whole-Gut Transit With Wireless Motility Capsule and Radiopaque Markers in Constipation
Authors: Satish S.C. Rao, Braden Kuo, Richard W. McCallum, William D. Chey, John K. DiBaise, William L. Hasler, Kenneth L. Koch, Jeffrey M. Lackner, Carrie Miller, Richard Saad, Jack R. Semler, Michael D. Sitrin, Gregory E. Wilding, Henry P. Parkman
Journal: Clinical Gastroenterology and Hepatology (2009)
Malignant and premalignant lesions of the penis
Authors: M. Arya, J. Kalsi, J. Kelly, A. Muneer
Journal: BMJ (2013)

<h3>Introduction</h3> Derangements in myocardial energetics are thought to play an important role in the pathophysiology of several cardiac diseases. Myocardial energetics can non-invasively be assessed by measuring the phosphocreatine-to-adenosine triphosphate ratio (PCr/ATP) using 31Phosphorus magnetic resonance spectroscopy (31P-MRS). Here we compare cardiac PCr/ATP across a spectrum of metabolic cardiac pathologies. MethodsUsing a 3D chemical shift imaging sequence and surface coil we recorded PCr/ATP in 433 participants: athletes (n=17), healthy controls with normal weight (n=148), overweight (n=67) and with obesity (n=73), diabetes (n=23), heart failure with preserved ejection fraction (HFpEF) (n=33), heart failure with reduced ejection fraction (HFrEF) (n=63) and amyloid (n=9). <h3>Results</h3> A spectrum of myocardial PCr/ATP exists ranging from normal in athletes (2.23 ± 0.28) and those with normal weight (2.05 ± 0.38) to severely impaired in those with cardiac amyloid (1.34 ± 0.19, Figure 1). Despite normal systolic function (all LVEF &gt;57%) those living with obesity and diabetes have lower PCr/ATP than normal (all p&lt;0.001). In all groups with HF, regardless of aetiology, myocardial energetics were impaired (all p&lt;0.001). Across the whole cohort PCr/ATP was negatively correlated with body mass index (r -0.28, p &lt;0.001), age (r -0.34, p&lt;0.001) and LV mass (r -0.1, p&lt;0.001). PCr/ATP was not related to systolic or diastolic blood pressure in these cohorts. <h3>Conclusions</h3> Despite normal systolic function, overweight, obesity and diabetes are associated with lower PCr/ATP ratios than normal weight controls. These changes in myocardial energetics appear to exist on a spectrum with further derangement present in overt cardiac pathology. Derangements in myocardial energetics are present in myocardial pathologies independent of underlying aetiology and thus may represent a viable therapeutic target in several conditions. <h3>Conflict of Interest</h3> None
Restoration of E2F Expression Rescues Vascular Endothelial Cells From Tumor Necrosis Factor-α–Induced Apoptosis
Authors: Ioakim Spyridopoulos, Nicole Principe, Kevin L. Krasinski, Shu-hua Xu, Marianne Kearney, Meredith Magner, Jeffrey M. Isner, Douglas W. Losordo
Journal: Circulation (1998)

Normally, quiescent endothelial cells (EC) line the inner surface of arteries and protect against thrombosis and neointimal growth. A variety of noxious stimuli, including balloon angioplasty, may compromise EC integrity, thereby initiating proliferation and triggering the local release of cytokines, including tumor necrosis factor-alpha (TNF-alpha).In vivo blockade of TNF-alpha using a soluble receptor molecule results in accelerated reendothelialization at sites of balloon angioplasty, suggesting an important physiological role of TNF-alpha in attenuating regrowth of endothelium after balloon angioplasty. Our studies reveal that TNF-alpha, an apoptosis-inducing cytokine, induces G1 cell-cycle arrest in proliferating EC. Quiescent EC are relatively immune to TNF-induced apoptosis versus proliferating EC, which display repression of the E2F transcription factor coincident with TNF-induced apoptosis and cell-cycle arrest. We also show that in this setting, E2F overexpression exerts a survival effect in proliferating EC and restores cell-cycle progression, in direct contrast to results of prior reports, which revealed that deregulated expression of E2F in normally cycling cells induces apoptosis.These data demonstrate that TNF-induced apoptosis is highly dependent on cell-cycle activity and that E2F can function as survival factor under certain conditions.
Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution
Authors: Agnar Helgason, Snæbjörn Pálsson, Gudmar Thorleifsson, Struan F A Grant, Valur Emilsson, Steinunn Gunnarsdottir, Adebowale Adeyemo, Yuanxiu Chen, Guanjie Chen, Inga Reynisdottir, Rafn Benediktsson, Anke Hinney, Torben Hansen, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Helmut Schäfer, Mezbah Faruque, Ayo Doumatey, Jie Zhou, Robert L Wilensky, Muredach P Reilly, Daniel J Rader, Yu Bagger, Claus Christiansen, Gunnar Sigurdsson, Johannes Hebebrand, Oluf Pedersen, Unnur Thorsteinsdottir, Jeffrey R Gulcher, Augustine Kong, Charles Rotimi, Kári Stefánsson
Journal: Nature Genetics (2007)
p73 Loss Triggers Conversion to Squamous Cell Carcinoma Reversible upon Reconstitution with TAp73α
Authors: Jodi Johnson, James Lagowski, Alexandra Sundberg, Sarah Lawson, Yuangang Liu, Molly Kulesz-Martin
Journal: Cancer Research (2007)

The expression level of the p53 family member, p73, is frequently deregulated in human epithelial cancers, correlating with tumor invasiveness, therapeutic resistance, and poor patient prognosis. However, the question remains whether p73 contributes directly to the process of malignant conversion or whether aberrant p73 expression represents a later selective event to maintain tumor viability. We explored the role of p73 in malignant conversion in a clonal model of epidermal carcinogenesis. Whether sporadic or small interfering RNA (siRNA) induced, loss of p73 in initiated p53+/+ keratinocytes leads to loss of cellular responsiveness to DNA damage by ionizing radiation (IR) and conversion to squamous cell carcinoma (SCC). Reconstitution of TAp73alpha but not DeltaNp73alpha reduced tumorigenicity in vivo, but did not restore cellular sensitivity to IR, uncoupling p73-mediated DNA damage response from its tumor-suppressive role. These studies provide direct evidence that loss of p73 can contribute to malignant conversion and support a role for TAp73alpha in tumor suppression of SCC. The results support the activation of TAp73alpha as a rational mechanism for cancer therapy in solid tumors of the epithelium.
Patients with ankylosing spondylitis have been breast fed less often than healthy controls: a case–control retrospective study
Authors: J Montoya, N B Matta, P Suchon, M C Guzian, N C Lambert, J P Mattei, S Guis, M Breban, J Roudier, N Balandraud
Journal: Annals of the Rheumatic Diseases (2015)

Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and pelvis of young adults. On the HLA-B27 genetic background, the occurrence of AS is influenced by the intestinal microbiota. The goal of our study was to test whether breast feeding, which influences microbiota, can prevent the development of AS.First, 203 patients with HLA-B27-positive AS fulfilling the modified New York criteria were recruited in the Department of Rheumatology, Ste Marguerite hospital in Marseilles. A total of 293 healthy siblings were also recruited to make up a control group within the same families. Second, 280 healthy controls, and 100 patients with rheumatoid arthritis and their siblings were recruited. The data collected were age, gender, number of brothers and sisters, age at disease onset, type and duration of feeding (breast or bottle).Patients with AS had been breast fed less often than healthy controls. In families where children were breast fed, the patients with AS were less often breast fed than their healthy siblings (57% vs 72%), giving an OR for AS onset of 0.53 (95% CI (0.36 to 0.77), p value=0.0009). Breast feeding reduced familial prevalence of AS. The frequency of breast feeding was similar in the AS siblings and in the 280 unrelated controls. However, patients with AS were less often breast fed compared with the 280 unrelated controls (OR 0.6, 95% CI (0.42 to 0.89), p<0.01).Our study suggests a breastfeeding-induced protective effect on the occurrence of AS. To our knowledge, this is the first study of breastfeeding history in patients with AS.
Impaired Cerebral Vasoreactivity and Risk of Stroke in Patients With Asymptomatic Carotid Artery Stenosis
Authors: Mauro Silvestrini
Journal: JAMA (2000)

Standards for treating patients with asymptomatic carotid artery stenosis have been difficult to establish because of the lack of evidence for factors influencing these patients' prognoses. However, preliminary evidence suggests that an alteration in cerebral hemodynamic function may play a relevant role in the occurrence of stroke in patients with carotid artery disease.To investigate the relationship between cerebrovascular reactivity to hypercapnia and cerebrovascular events in patients with severe unilateral asymptomatic carotid artery stenosis.Prospective, blinded longitudinal study conducted in an outpatient neurovascular department in Italy between June 1996 and April 1998, with a median follow-up of 28.5 months.Ninety-four patients with asymptomatic carotid artery stenosis of at least 70% (74 men; mean age, 71 years).Subsequent occurrence of cerebral ischemic events (transient ischemic attack or stroke) or death, analyzed by cerebrovascular reactivity to hypercapnia (measured by transcranial Doppler ultrasonography and calculated by the breath-holding index values in the middle cerebral arteries).The overall annual rate for all ischemic events was 7.9%. Seventeen patients (18%) had ischemic events, all but 1 of which were ipsilateral to the carotid artery stenosis. Among factors considered, only lower breath-holding index values in the middle cerebral artery ipsilateral to carotid artery stenosis were significantly associated with the risk of an event (hazard ratio, 0.09; 95% confidence interval, 0.02-0.38; P=.001, by multivariate analysis). Based on data from previously studied healthy subjects, the cutoff of the breath-holding index for distinguishing between impaired and normal cerebrovascular reactivity was determined to be 0.69. Using this cutoff, the annual ipsilateral ischemic event risk was 4.1% in patients with normal and 13.9% in those with impaired breath-holding index values.These results suggest a link between impaired cerebrovascular reactivity and the risk of ischemic events ipsilateral to severe asymptomatic carotid stenosis.
High prevalence of ESBL-producing Enterobacteriaceae carriage in Dutch community patients with gastrointestinal complaints
Authors: E.A. Reuland, I.T.M.A. Overdevest, N. al Naiemi, J.S. Kalpoe, M.C. Rijnsburger, S.A. Raadsen, I. Ligtenberg-Burgman, K.W. van der Zwaluw, M. Heck, P.H.M. Savelkoul, J.A.J.W. Kluytmans, C.M.J.E. Vandenbroucke-Grauls
Journal: Clinical Microbiology and Infection (2012)
Nomogram to predict the presence of EGFR activating mutation in lung adenocarcinoma
Authors: N. Girard, C.S. Sima, D.M. Jackman, L.V. Sequist, H. Chen, J.C-H. Yang, H. Ji, B. Waltman, R. Rosell, M. Taron, M.F. Zakowski, M. Ladanyi, G. Riely, W. Pao
Journal: European Respiratory Journal (2011)

Epidermal growth factor receptor ( EGFR ) tumour genotyping is crucial to guide treatment decisions regarding the use of EGFR tyrosine kinase inhibitors in nonsmall cell lung cancer (NSCLC). However, some patients may not be able to obtain tumour testing, either because tissue is limited and/or tests are not routinely offered. Here, we aimed to build a model-based nomogram to allow for prediction of the presence of EGFR mutations in NSCLC. We retrospectively collected clinical and pathological data on 3,006 patients with NSCLC who had their tumours genotyped for EGFR mutations at five institutions worldwide. Variables of interest were integrated in a multivariate logistic regression model. In the 2,392 non-Asian patients with lung adenocarcinomas, the most important predictors of harbouring EGFR mutation were: lower tobacco smoking exposure (OR 0.41, 95% CI 0.37–0.46), longer time interval between smoking cessation and diagnosis (OR 2.19, 95% CI 1.71–2.80), advanced stage (OR 1.58, 95% CI 1.18–2.13), and papillary (OR 4.57, 95% CI 3.14–6.66) or bronchioloalveolar (OR 2.84, 95% CI 1.98–4.06) histologically predominant subtype. A nomogram was established and showed excellent discriminating accuracy: the concordance index on an independent validation dataset was 0.84. As clinical practices transition to incorporating genotyping as part of routine care, this nomogram could be highly useful to predict the presence of EGFR mutations in lung adenocarcinoma in non-Asian patients when mutational profiling is not available or possible.
Reducing sugary drink intake is linked to raised HDL cholesterol levels
Authors: Jacqui Wise
Journal: BMJ (2015)

Children who reduce their consumption of sugar sweetened drinks by just one serving a week see improvements in their high density lipoprotein (HDL) cholesterol levels, a study published in the Journal of Nutrition has found.1

The US study used data from a multiethnic sample of 613 children aged 8 to 15 who were enrolled in a randomised double blind vitamin D supplementation trial. They self reported their intake of sugar sweetened beverages and had their fasting blood lipid …
Genetic Ablation of CCAAT/Enhancer Binding Protein α in Epidermis Reveals Its Role in Suppression of Epithelial Tumorigenesis
Authors: Kari D. Loomis, Songyun Zhu, Kyungsil Yoon, Peter F. Johnson, Robert C. Smart
Journal: Cancer Research (2007)

Abstract CCAAT/enhancer binding protein α (C/EBPα) is a basic leucine zipper transcription factor that inhibits cell cycle progression and regulates differentiation in various cell types. C/EBPα is inactivated by mutation in acute myeloid leukemia (AML) and is considered a human tumor suppressor in AML. Although C/EBPα mutations have not been observed in malignancies other than AML, greatly diminished expression of C/EBPα occurs in numerous human epithelial cancers including lung, liver, endometrial, skin, and breast, suggesting a possible tumor suppressor function. However, direct evidence for C/EBPα as an epithelial tumor suppressor is lacking due to the absence of C/EBPα mutations in epithelial tumors and the lethal effect of C/EBPα deletion in mouse model systems. To examine the function of C/EBPα in epithelial tumor development, an epidermal-specific C/EBPα knockout mouse was generated. The epidermal-specific C/EBPα knockout mice survived and displayed no detectable abnormalities in epidermal keratinocyte proliferation, differentiation, or apoptosis, showing that C/EBPα is dispensable for normal epidermal homeostasis. In spite of this, the epidermal-specific C/EBPα knockout mice were highly susceptible to skin tumor development involving oncogenic Ras. These mice displayed decreased tumor latency and striking increases in tumor incidence, multiplicity, growth rate, and the rate of malignant progression. Mice hemizygous for C/EBPα displayed an intermediate-enhanced tumor phenotype. Our results suggest that decreased expression of C/EBPα contributes to deregulation of tumor cell proliferation. C/EBPα had been proposed to block cell cycle progression through inhibition of E2F activity. We observed that C/EBPα blocked Ras-induced and epidermal growth factor–induced E2F activity in keratinocytes and also blocked Ras-induced cell transformation and cell cycle progression. Our study shows that C/EBPα is dispensable for epidermal homeostasis and provides genetic evidence that C/EBPα is a suppressor of epithelial tumorigenesis. [Cancer Res 2007;67(14):6768–76]
Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1–dependent microvascular degeneration
Authors: Elsa Kermorvant-Duchemin, Florian Sennlaub, Mirna Sirinyan, Sonia Brault, Gregor Andelfinger, Amna Kooli, Stéphane Germain, Huy Ong, Pedro d'Orleans-Juste, Fernand Gobeil, Tang Zhu, Chantal Boisvert, Pierre Hardy, Kavita Jain, J Russel Falck, Michael Balazy, Sylvain Chemtob
Journal: Nature Medicine (2005)
Cyclosporin in the treatment of corticosteroid resistant autoimmune chronic active hepatitis.
Authors: L D Jackson, E Song
Journal: Gut (1995)

A 17 year old Asian patient with autoimmune chronic active hepatitis resistant to treatment with high dose corticosteroids and azathioprine was given cyclosporin at a dose of 5 mg/kg/day. Within two weeks of starting the cyclosporin treatment a favourable clinical and biochemical response was obtained and by one month serum aminotransferase activities were within normal limits. An attempted reduction in the daily dose of cyclosporin resulted in a relapse of the patient9s disease. Remission was again attained by returning the dose of cyclosporin to 5 mg/kg/day. No significant side effects of the treatment have been shown. Cyclosporin seems to have a role in the treatment of corticosteroid resistant autoimmune chronic active hepatitis and its further evaluation is warranted.
Conducting Clinical Research Using Crowdsourced Convenience Samples
Authors: Jesse Chandler, Danielle Shapiro
Journal: Annual Review of Clinical Psychology (2016)

Crowdsourcing has had a dramatic impact on the speed and scale at which scientific research can be conducted. Clinical scientists have particularly benefited from readily available research study participants and streamlined recruiting and payment systems afforded by Amazon Mechanical Turk (MTurk), a popular labor market for crowdsourcing workers. MTurk has been used in this capacity for more than five years. The popularity and novelty of the platform have spurred numerous methodological investigations, making it the most studied nonprobability sample available to researchers. This article summarizes what is known about MTurk sample composition and data quality with an emphasis on findings relevant to clinical psychological research. It then addresses methodological issues with using MTurk--many of which are common to other nonprobability samples but unfamiliar to clinical science researchers--and suggests concrete steps to avoid these issues or minimize their impact.
IMMUNOPHARMACOLOGY OF RAPAMYCIN
Authors: Robert T. Abraham, Gregory J. Wiederrecht
Journal: Annual Review of Immunology (1996)

▪ Abstract The potent immunosuppressive drugs FK506 and rapamycin interfere with signal transduction pathways required for T cell activation and growth. The distinct inhibitory effects of these drugs on the T cell activation program are mediated through the formation of pharmacologically active complexes with members of a family of intracellular receptors termed the FK506 binding proteins (FKBPs). The FKBP12 · FK506 complex specifically binds to and inhibits calcineurin, a signaling protein required for transcriptional activation of the interleukin (IL)-2 gene in response to T cell antigen receptor engagement. The FKBP12 · rapamycin complex interacts with a recently defined target protein termed the mammalian target of rapamycin (mTOR). Accumulating data suggest that mTOR functions in a previously unrecognized signal transduction pathway required for the progression of IL-2-stimulated T cells from G 1 into the S phase of the cell cycle. Here we review the immunopharmacology of rapamycin, with particular emphasis on the characterization of mTOR.
B-lymphocyte heterogeneity: development and characterization of an alloantiserum which distinguishes B-lymphocyte differentiation alloantigens.
Authors: A Ahmed, I Scher, S O Sharrow, A H Smith, W E Paul, D H Sachs, K W Sell
Journal: The Journal of Experimental Medicine (1977)

CBA/N mice and F1 male mice, which are hemizygous for the CBA/N X chromosome, have an immune defect which is associated with the absence (deficiency) of a subpopulation of mature or late developing B lymphocytes. This characteristic was utilized to develop an antiserum that was specific for this subclass of B cells. C57BL/L mice were immunized with DBA/2 spleen calls, and the resulting antisera was absorbed with lymphoid cells derived from immunologically abnormal (CBA/N female X DBA/2 male)F1 male mice. The absorbed antisera was cytotoxic for a subpopulation of lymphocytes that was present in the spleens of adult DBA/2 and (CBA/N female X DBA/2 male)F1 female mice. The cells killed by the absorbed antisera were Ig-bearing, complement receptor-bearing B lymphocytes, which had a low-to-intermediate density of total surface Ig. Moreover, the cells remaining after treatment of adult (CBA/N female X DBA/2 male)F1 female spleen cells with the absorbed antisera and C had a high ratio of surface IgM to IgD. The development of this cytotoxic alloantisera, which is specific for a late developing (mature) subpopulation of B lymphocytes, will allow the functional characterization of subclasses of B lymphocytes.