tbuckley/cabot-search huggingface dataset:
Risk Factors for Chronic Kidney Disease
Authors: Melanie K. Haroun, Bernard G. Jaar, Sandra C. Hoffman, George W. Comstock, Michael J. Klag, Josef Coresh
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Chronic kidney disease (CKD) is an increasing cause of morbidity and mortality in the United States. Prospective data on risk factors for CKD are limited to men, and few studies examine the importance of smoking. The authors performed a community-based, prospective observational study of 20-yr duration to examine the association between hypertension and smoking on the future risk of CKD in 23,534 men and women in Washington County, Maryland. CKD was identified as end-stage renal disease in the Health Care Financing Administration database or kidney disease listed on the death certificate. All cases were confirmed as CKD by medical chart review. Adjusted relative hazards of CKD were modeled using Cox proportional hazards regression including age as the time variable and baseline BP, cigarette smoking, gender, and diabetes status as risk factors. The adjusted hazard ratio (95% confidence interval) of developing CKD among women was 2.5 (0.05 to 12.0) for normal BP, 3.0 (0.6 to 14.4) for high-normal BP, 3.8 (0.8 to 17.2) for stage 1 hypertension, 6.3 (1.3 to 29.0) for stage 2 hypertension, and 8.8 (1.8 to 43.0) for stages 3 or 4 hypertension compared with individuals with optimal BP. In men, the relationship was similar but somewhat weaker than in women, with corresponding hazard ratios of 1.4 (0.2 to 12.1), 3.3 (0.4 to 25.6), 3.0 (0.4 to 22.2), 5.7 (0.8 to 43.0), and 9.7 (1.2 to 75.6), respectively. Current cigarette smoking was also significantly associated with risk of CKD in both men and women (hazard ratio in women 2.9 [1.7 to 5.0] and in men 2.4 [1.5 to 4.0]). A large proportion of the attributable risk of CKD in this population was associated with stage 1 hypertension (23%) and cigarette smoking (31%). In conclusion, CKD risk shows strong graded relationships to the sixth report of the Joint National Committee (JNC-VI) on Prevention, Detection Evaluation and Treatment of High BP criteria for BP, to diabetes, and to current cigarette smoking that are at least as strong in women as in men. E-mail: coresh@jhu.edu
OC-083 Faecal Occult Blood test Analysis in the United Kingdom Bowel Cancer Screening Programme
Authors: J Geraghty, J Snowball, P Butler, S Sarkar, R Blanks, S Halloran, C Rees
Journal: Gut (2013)

<h3>Introduction</h3> Increased vascularity of colorectal neoplasia creates bleeding detected by Faecal Occult Blood tests (FOBt). As bleeding is sporadic &amp; unevenly distributed within stools, multiple testing may be required. UK bowel cancer screening programme (BCSP) kits contain 6 windows &amp; subjects returning 5 or 6 positive results are termed “Abnormal” &amp; referred to colonoscopy. If 1–4 windows are positive, the result is initially “Unclear” &amp; 2 further kits are submitted, further positivity leads to colonoscopy (“Weak positive”). If no further blood is detected, subjects are deemed ”Normal” &amp; retested in 2 years. <h3>Aim</h3> to study FOBt positivity in detail &amp; whether particular patterns are associated with neoplasia rates that indicate the screening algorithm should be changed. <h3>Methods</h3> We selected all subjects from one hub completing 2 screening episodes between 2007–9. Each episode included up to 3 kits and 18 windows. 95 possible combinations were identified. The number of positive windows compared to the total in a given episode was expressed as a “positivity ratio”, ranging from 0–100%. Each combination leading to colonoscopy was analysed. Abnormal (83–100% positivity) &amp; Unclear (11–83% positivity) groups were matched to neoplasia detection rates. Subjects with cancer detected in episode 2 following an Unclear result in episode 1, had their episode 1 pattern analysed. <h3>Results</h3> FOBt from 284,387 subjects resulted in 4,000 colonoscopies, diagnosing 286 cancers. The overall cancer rate was 7.1% &amp; adenoma rate 39.9%. The cancer rate was 21.3% in the Abnormal group and 5.8% in the Weak positive group. Cancer detection increased from 1.9–24.5% in linear correlation with increasing positivity of windows, ranging from 11–83% of windows positive. Equivalent percentage positivity rates may or may not lead to colonoscopy depending on the particular pattern. A combination of 4 positive windows in kit 1 followed by 2 normal kits (4NN) equates to a positivity rate of 22% &amp; is currently categorised in the Normal group &amp; doesn’t lead to colonoscopy. Other combinations with 22% window positivity do lead to colonoscopy &amp; a cancer detection rate of 3%. There were 260 subjects with a 4NN combination in episode 1 not leading to colonoscopy &amp; 5 of these subsequently had cancers detected following different combinations in episode 2. <h3>Conclusion</h3> This study demonstrates higher ratios of positive windows; detect higher rates of cancer. At present, in the UK some subjects with 11% positive windows proceed to colonoscopy, while others with a rate of 22% (all at kit 1) do not. Based on these findings, further work examining the entire BCSP population, including the costs &amp; benefits of changing the algorithm is in progress. <h3>Disclosure of Interest</h3> None Declared
Protein Kinase C-δ and Mitogen-Activated Protein/Extracellular Signal–Regulated Kinase-1 Control GLI Activation in Hedgehog Signaling
Authors: Natalia A. Riobo, Gwendolyn M. Haines, Charles P. Emerson
Journal: Cancer Research (2006)

Abstract One third of all lethal cancers are associated with excessive activation of the Hedgehog (HH) pathway by mutations of its signaling components or by increased responsiveness of cells to the HH ligand. HH signaling through the GLI transcription factors leads to increased cell proliferation by up-regulation of the extracellular regulated kinase (ERK) pathway and by expression of S phase cyclins. In this study, we have tested the hypothesis that the HH pathway can integrate ERK signaling to modulate the activity of GLI. Using NIH 3T3 cells, we show that phorbol esters, acting through protein kinase C-δ (PKCδ) and mitogen-activated protein/extracellular signal–regulated kinase-1 (MEK-1), fully stimulate the transcriptional activity of endogenous and overexpressed GLI proteins, as assessed by GLI-luciferase reporter assays, and induce the expression of endogenous GLI1 and PTCH-1 target genes, as assessed by reverse transcription-PCR. Moreover, activation of GLI elicited by Sonic Hedgehog also requires PKCδ and MEK-1 function. Remarkably, coexpression of activated MEK-1 and GLI1 or GLI2 induced a 10-fold synergistic increase in GLI-luciferase activity that was totally blocked by PD98059. The NH2-terminal region of GLI1 (amino acids 1-130) is required for sensing the ERK pathway, as deletion of this domain produces active GLI1 protein with greatly reduced response to activation by MEK-1. Basic fibroblast growth factor activation of the ERK pathway also stimulated GLI1 activity through its NH2-terminal domain. Our results identify PKCδ and MEK-1 as essential, positive regulators of GLI-mediated HH signaling. Furthermore, our findings suggest that tumors with deregulated HH and ERK synergize to stimulate cell proliferation pathways. (Cancer Res 2006; 66(2): 839-45)
Heparin-binding defective lipoprotein lipase is unstable and causes abnormalities in lipid delivery to tissues
Authors: E. Peer Lutz, Martin Merkel, Yuko Kako, Kristan Melford, Herbert Radner, Jan L. Breslow, André Bensadoun, Ira J. Goldberg
Journal: Journal of Clinical Investigation (2001)

Lipoprotein lipase (LpL) binding to heparan sulfate proteoglycans (HSPGs) is hypothesized to stabilize the enzyme, localize LpL in specific capillary beds, and route lipoprotein lipids to the underlying tissues. To test these hypotheses in vivo, we created mice expressing a human LpL minigene (hLpLHBM) carrying a mutated heparin-binding site. Three basic amino acids in the carboxyl terminal region of LpL were mutated, yielding an active enzyme with reduced heparin binding. Mice expressing hLpLHBM accumulated inactive human LpL (hLpL) protein in preheparin blood. hLpLHBM rapidly lost activity during a 37°C incubation, confirming a requirement for heparin binding to stabilize LpL. Nevertheless, expression of hLpLHBM prevented the neonatal demise of LpL knockout mice. On the LpL-deficient background hLpLHBM expression led to defective targeting of lipids to tissues. Compared with mice expressing native hLpL in the muscle, hLpLHBM transgenic mice had increased postprandial FFAs, decreased lipid uptake in muscle tissue, and increased lipid uptake in kidneys. Thus, heparin association is required for LpL stability and normal physiologic functions. These experiments confirm in vivo that association with HSPGs can provide a means to maintain proteins in their stable conformations and to anchor them at sites where their activity is required.
Aromatase Cytochrome P450, The Enzyme Responsible for Estrogen Biosynthesis*
Authors: EVAN R. SIMPSON, MALA S. MAHENDROO, GARY D. MEANS, MICHAEL W. KILGORE, MARGARET M. HINSHELWOOD, SANDRA GRAHAM-LORENCE, BILAL AMARNEH, YUJI ITO, CAROLYN R. FISHER, M. DODSON MICHAEL, CAROLE R. MENDELSON, SERDAR E. BULUN
Journal: Endocrine Reviews (1994)

THE biosynthesis of estrogens appears to occur throughout the entire vertebrate phylum including mammals, birds, reptiles, amphibians, teleost and elasmobranch fish, and Agnatha (hagfish and lampreys) (1–3). It has also been described in the protochordate Amphioxus (4). To our knowledge, estrogen biosynthesis has not been reported in nonvertebrate animal phyla. In most vertebrate species that have been examined, aromatase expression occurs in the gonads and in the brain. This is true of the fish and avian species that have been examined as well as most mammals such as rodents. In many species estrogen biosynthesis in the brain has been implicated in sex-related behavior such as mating responses, and frequently a marked sexually dimorphic difference has been demonstrated. This is true, for example, in avian species in which the song of the male is important in courtship behavior (5). In the case of humans and a number of higher primates, there is a more extensive tissue distribution of estrogen biosynthesis, since this also occurs in the placenta of the developing fetus as well as in the adipose tissue of the adult.
Inferring Genealogical Processes from Patterns of Bronze-Age and Modern DNA Variation in Sardinia
Authors: S. Ghirotto, S. Mona, A. Benazzo, F. Paparazzo, D. Caramelli, G. Barbujani
Journal: Molecular Biology and Evolution (2009)

The ancient inhabitants of a region are often regarded as ancestral, and hence genetically related, to the modern dwellers (for instance, in studies of admixture), but so far, this assumption has not been tested empirically using ancient DNA data. We studied mitochondrial DNA (mtDNA) variation in Sardinia, across a time span of 2,500 years, comparing 23 Bronze-Age (nuragic) mtDNA sequences with those of 254 modern individuals from two regions, Ogliastra (a likely genetic isolate) and Gallura, and considering the possible impact of gene flow from mainland Italy. To understand the genealogical relationships between past and present populations, we developed seven explicit demographic models; we tested whether these models can account for the levels and patterns of genetic diversity in the data and which one does it best. Extensive simulation based on a serial coalescent algorithm allowed us to compare the posterior probability of each model and estimate the relevant evolutionary (mutation and migration rates) and demographic (effective population sizes, times since population splits) parameters, by approximate Bayesian computations. We then validated the analyses by investigating how well parameters estimated from the simulated data can reproduce the observed data set. We show that a direct genealogical continuity between Bronze-Age Sardinians and the current people of Ogliastra, but not Gallura, has a much higher probability than any alternative scenarios and that genetic diversity in Gallura evolved largely independently, owing in part to gene flow from the mainland.
A cytotoxic analysis of antiseptic medication on skin substitutes and autograft
Authors: Q. le Duc, M. Breetveld, E. Middelkoop, R.J. Scheper, M.M.W. Ulrich, S. Gibbs
Journal: British Journal of Dermatology (2007)

There is an increasing demand for the clinical application of human skin substitutes (HSSs) for treating ulcers, burns and surgical wounds. Due to this increasing demand and due to the simultaneous requirement for the administration of topical antiseptic medications, there is a need to determine potential cytotoxic effects of these medications on HSSs compared with autograft skin.To perform such an evaluation.Two different HSSs were used (autologous reconstructed epidermis on fibroblast-populated human dermis and allogeneic reconstructed epidermis on a fibroblast-populated rat collagen gel) and were compared with conventional full-thickness autograft. Twelve different antiseptics were applied topically to the stratum corneum in vitro for 24 h. The degree of cytotoxicity was analysed as detrimental changes in histology, metabolic activity (MTT assay) and RNA staining of tissue sections.The antiseptic medications tested showed different degrees of cytotoxicity. Acticoat, Aquacel Ag, Dermacyn, Fucidin, 0.5% silver nitrate solution and chlorhexidine digluconate were not cytotoxic for either HSS or autograft, and can therefore be used as required. Flamazine and zinc oxide cream resulted in moderate cytotoxicity. However, application of Betadine((R)), cerium-silver sulfadiazine cream, silver sulfadiazine cream with 1% acetic acid and Furacine resulted in a substantial decrease in cell viability and a detrimental effect on tissue histology when applied to autograft and especially to HSS.Due to the potential cytotoxic effect of some antiseptics on HSS, it is advised that clinicians balance the cytotoxicity of the medication, its antiseptic properties and the severity of colonization in choosing which one to apply.
Hemidystonia With One Eye-of-the-Tiger Sign
Authors: Sanjay Pandey, Debra L. Byler, Mark Hallett
Journal: JAMA Neurology (2014)

Awomaninher lateteenspresentedwithdystonicposturingofher left hand for 2 years and left foot for 3months. Dystonic posturing of her hand had started when she was 8 months pregnant, and it slowly worsened to involve her left lower limb, leading to difficulty in walking (Video). She was evaluated for left hemidystonia. Fluid-attenuated inversion recovery (FLAIR)magnetic resonance images (MRIs) of the brain gave the appearance of the eyeof-the-tiger sign in the right basal ganglia similar to what would be seenwithaneuroferritinopathy,butsusceptibility-weighted imaging revealed evidence of hemosiderin indicative of an old hemorrhagic infarct (Figure). The results ofmagnetic resonanceangiography for evaluation of intracranial vessels were normal. Mutation analysis for pantothenate kinase 2 was negative. Antinuclear antibody and anti–double-stranded DNAwere negative.
Protective Helmets and Traumatic Epilepsy
Authors: W. B. Jennett
Journal: BMJ (1967)

cutaneous involvement.This applies particularly to infants with a history of oral, cutaneous, or gastrointestinal candidiasis, as well as to patients with debilitating diseases predisposing to candidal infection (diabetes -mellitus, leukaemia, etc.).Such patients fre- quently receive prolonged antibiotic therapy, and the combination of nystatin with tetra- cycline is prudent here in order to pre- vent systemic candidal dissemination from :gastrointestinal foci.Systemic candidiasis is
Antinuclear antibody with distinct specificity for polymyositis.
Authors: J F Wolfe, E Adelstein, G C Sharp
Journal: Journal of Clinical Investigation (1977)

In the course of studying antinuclear antibodies in the rheumatic diseases, a new precipitin reaction (provisionally referred to as PM-1) was observed between calf thymus nuclear extract and polymyositis sera. Objectives of this study were to further define the immunologic nature of this reaction and to determine its specificity for polymyositis. Immunodiffusion studies using calf thymus nuclear extract revealed the PM-1 precipitin line in 17 of 28 patients with polymyositis. This reaction was not produced by sera of 460 patients with other diseases. Enzyme and heat treatments of the nuclear extract showed that PM-1 was distinct from native DNA, ribonucleoprotein, and Sm antigens. Fractionation of PM-1-positive serum by 30% ammonium sulphate and Sephadex G-200 chromatography revealed that the factor producing the PM-1 precipitin reaction was in a serum fraction which showed only IgG by immunoelectrphoresis against anti-whole human serum. Because of the apparent strong specificity, the PM-1 system may represent a marker antibody for polymyositis.
Salivary eicosanoid concentration in patients with Sjogren's syndrome.
Authors: M Tishler, I Yaron, A Raz, F A Meyer, M Yaron
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To investigate eicosanoid concentrations in the saliva of patients with primary Sjögren9s syndrome (SS). METHODS: Whole mixed saliva of 36 subjects was assayed for eicosanoid concentrations using a radioimmunoassay. Patients with primary SS having positive lip biopsy served as the study group; their results were compared with data from patients with dry mouth and negative lip biopsy (dry mouth group), and with a group of normal healthy controls. RESULTS: Concentrations of thromboxane B2 were significantly (p &lt; 0.01) increased in 18 patients with primary SS compared with 10 patients with dry mouth and eight healthy normal controls (1.95 (SD 0.51) ng/ml saliva compared with 0.52 (0.1) ng/ml and 0.3 (0.1) ng/ml, respectively). Similarly, prostaglandin E2 concentrations were also significantly increased (p &lt; 0.01) in 11 patients with primary SS compared with five patients with dry mouth and eight normal controls (3.75 (0.82) ng/ml saliva compared with 0.32 (0.1) ng/ml and 0.41 (0.1) ng/ml, respectively). CONCLUSION: Salivary concentrations of eicosanoids are significantly increased in patients with primary SS, and this may prove helpful in the diagnosis of this disease.
Genetic Causes of Hearing Loss
Authors: P J Willems
Journal: New England Journal of Medicine (2000)

Hearing loss is the most common sensory defect in humans, affecting normal communication in 10 percent of people aged 65 years or older. In most cases, hearing loss is a multifactorial disorder caused by both genetic and environmental factors. However, single-gene mutations can lead to hearing loss. In these cases, hearing loss is a monogenic disorder with an autosomal dominant, autosomal recessive, X-linked, or mitochondrial mode of inheritance. These monogenic forms of hearing loss can be syndromic (characterized by hearing loss in combination with other abnormalities) or nonsyndromic (with only hearing loss). This review focuses on nonsyndromic hearing loss, since . . .
Magnetically Labeled Cells with Surface‐Modified Fe<sub>3</sub>O<sub>4</sub> Spherical and Rod‐Shaped Magnetic Nanoparticles for Tissue Engineering Applications
Authors: Sara Gil, Clara R. Correia, João F. Mano
Journal: Advanced Healthcare Materials (2015)

Magnetically targeted cells with internalized magnetic nanoparticles (MNPs) could allow the success of cell transplantation and cell‐based therapies, overcoming low cell retention that occurs when delivering cells by intravenous or local injection. Upon magnetization, these cells could then accumulate and stimulate the regeneration of the tissue in situ. Magnetic targeting of cells requires a detailed knowledge between interactions of engineered nanomaterials and cells, in particular the influence of shape and surface functionalization of MNPs. For the first time, cellular internalization of amino surface‐modified iron oxide nanoparticles of two different shapes (nanospheres or nanorods) is studied. MNPs show high cellular uptake and labeled cells could exhibit a strong reaction with external magnetic fields. Compared to nanorods, nanospheres show better internalization efficiency, and labeled cells exhibit strong transportation reaction with external magnetic fields. Contiguous viable cell‐sheets are developed by magnetic‐force‐based tissue engineering. The results confirm that the developed magnetic‐responsive nano‐biomaterials have potential applicability in tissue engineering or cellular therapies.
Sequence-based prediction of protein-protein interactions by means of codon usage
Authors: Hamed Shateri Najafabadi, Reza Salavati
Journal: Genome biology (2008)

Abstract We introduce a novel approach to predict interaction of two proteins solely by analyzing their coding sequences. We found that similarity in codon usage is a strong predictor of protein-protein interactions and, for high specificity values, is as sensitive as the most powerful current prediction methods. Furthermore, combining codon usage with other predictors results in a 75% increase in sensitivity at a precision of 50%, compared to prediction without considering codon usage.
Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13
Authors: Todd A. Fehniger, John C. Byrd, Guido Marcucci, Camille N. Abboud, Cheryl Kefauver, Jacqueline E. Payton, Ravi Vij, William Blum
Journal: Blood (2008)
Naturally Occurring Human Antiglobulins with Specificity for γE
Authors: Ralph C. Williams, Robert W. Griffiths, Jean D. Emmons, Richard C. Field
Journal: Journal of Clinical Investigation (1972)

Human sera have been examined for antibodies with specific reactivity for gammaE using the tanned cell hemagglutination test. Cells tanned with three different gammaE myeloma proteins provided a reproducible test system. Inhibition of agglutination reactions by gammaE proteins, but not by gammaG, gammaA, gammaM, or gammaD confirmed the specificity of these reactions. 8.5% of 304 serial serum samples obtained from miscellaneous hospitalized patients showed clear-cut anti-gamma-globulins with specificity for gammaE. In most of these instances no definite clinical history of concomitant allergic disorders could be obtained. 53% of 73 patients with well-established allergic disorders (hay fever, extrinsic asthma) showed serum anti-gamma-globulins with reactivity for gammaE. Some patients studied before and after desensitization to Bermuda grass allergen showed an increase in titer or a conversion from negative to positive reactions for anti-gammaE antibodies following several month courses of progressive desensitization. Gradient and gel filtration studies indicated that anti-gammaE globulins were 19S gammaM in all instances. No clear correlation was noted between quantitative serum gammaE levels and titer of anti-gammaE antibodies.19S serum fractions with anti-gammaE antibody activity did not release histamine from normal human peripheral blood leukocytes, whereas specific rabbit anti-gammaE antisera consistently induced leukocytic histamine release. Moreover, macroglobulin fractions with anti-gammaE activity did not block allergen-specific leukocyte histamine release induced by in vitro leukocyte challenge with allergens such as Bermuda grass and leukocytes from allergic donors. In some instances 19S human serum fractions with anti-gammaE activity appeared to potentiate histamine release when incubated concomitantly with specific allergen and leukocytes from allergic individuals.