tbuckley/cabot-search huggingface dataset:
An Odor-Specific Threshold Deficit Implicates Abnormal Intracellular Cyclic AMP Signaling in Schizophrenia
Authors: Bruce I Turetsky, Paul J Moberg
Journal: American Journal of Psychiatry (2008)

Although olfactory deficits are common in schizophrenia, their underlying pathophysiology remains unknown. Recent evidence has suggested that cAMP signaling may be disrupted in schizophrenia. Since cAMP mediates signal transduction in olfactory receptor neurons, this could contribute to the etiology of observed olfactory deficits. This study was designed to test this hypothesis by determining odor detection threshold sensitivities to two odorants that differ in their relative activations of this intracellular cAMP signaling cascade.
Genome-wide Association Study of Susceptibility Loci for Cervical Cancer
Authors: Dan Chen, Ivana Juko-Pecirep, Joanna Hammer, Emma Ivansson, Stefan Enroth, Inger Gustavsson, Lars Feuk, Patrik K.E. Magnusson, James D. McKay, Erik Wilander, Ulf Gyllensten
Journal: JNCI Journal of the National Cancer Institute (2013)

Cervical carcinoma has a heritable genetic component, but the genetic basis of cervical cancer is still not well understood. We performed a genome-wide association study of 731 422 single nucleotide polymorphisms (SNPs) in 1075 cervical cancer case subjects and 4014 control subjects and replicated it in 1140 case subjects and 1058 control subjects. The association between top SNPs and cervical cancer was estimated by odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional logistic regression. All statistical tests were two-sided. Three independent loci in the major histocompatibility complex (MHC) region at 6p21.3 were associated with cervical cancer: the first is adjacent to the MHC class I polypeptide-related sequence A gene (MICA) (rs2516448; OR = 1.42, 95% CI = 1.31 to 1.54; P = 1.6×10−18); the second is between HLA-DRB1 and HLA-DQA1 (rs9272143; OR = 0.67, 95% CI = 0.62 to 0.72; P = 9.3×10−24); and the third is at HLA-DPB2 (rs3117027; OR=1.25, 95% CI = 1.15 to 1.35; P = 4.9×10−8). We also confirmed previously reported associations of B*0702 and DRB1*1501-DQB1*0602 with susceptibility to and DRB1*1301-DQA1*0103-DQB1*0603 with protection against cervical cancer. The three new loci are statistically independent of these specific human leukocyte antigen alleles/haplotypes. MICA encodes a membrane-bound protein that acts as a ligand for NKG2D to activate antitumor effects. The risk allele of rs2516448 is in perfect linkage disequilibrium with a frameshift mutation (A5.1) of MICA, which results in a truncated protein. Functional analysis shows that women carrying this mutation have lower levels of membrane-bound MICA. Three novel loci in the MHC may affect susceptibility to cervical cancer in situ, including the MICA-A5.1 allele that may cause impaired immune activation and increased risk of tumor development.
Solute Transport Across the Peritoneal Membrane
Authors: John K. Leypoldt
Journal: Journal of the American Society of Nephrology (2002)

The current understanding of the transport pathways that govern solute removal during peritoneal dialysis is reviewed. Diffusive transport rates across the peritoneal membrane for small solutes are slow. Even though the rate of diffusive solute transport decreases with increasing molecular size, large molecules (e.g., albumin) are nevertheless removed from the patient during routine peritoneal dialysis. Recent work has confirmed a previous suggestion that diffusive solute transport is limited by the small area of the peritoneal membrane that participates in the transport process. This small functional area is due to either poor contact of the peritoneal membrane with dialysis solution bathing the peritoneal cavity or to the limited surface area of capillaries that perfuse peritoneal tissues. Convective solute transport during peritoneal dialysis is proportional to the transperitoneal ultrafiltration rate but is less than that expected, because of low solute sieving by the peritoneal membrane and fluid absorption from the peritoneal cavity. Low solute sieving across the peritoneal membrane was first identified in 1966, a phenomenon that is now attributed to the presence of water-only transport pathways mediated by aquaporin-1. Fluid absorption from the peritoneal cavity occurs at the same time as transperitoneal ultrafiltration, but the pathways by which these two processes occur simultaneously remain speculative. This review proposes a novel hypothesis, whereby fluid absorption occurs in areas of the peritoneal membrane that are governed by different physical forces than those governing transperitoneal ultrafiltration. Further understanding of the pathways for fluid and solute transport during peritoneal dialysis will permit improvements in the adequacy of the dialysis dose and the more efficacious use of peritoneal dialysis to treat patients with end-stage renal disease.
Plasma surfactant protein levels and clinical outcomes in patients with acute lung injury
Authors: M D Eisner
Journal: Thorax (2003)

Background: Because injury to the alveolar epithelial barrier is a characteristic feature of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), plasma surfactant protein levels may have prognostic value. To test this hypothesis plasma surfactant proteins A and D (SP-A and SP-D) levels were measured in patients with ALI or ARDS enrolled in the NHLBI sponsored multicentre ARDS Network randomised controlled trial of a 6 ml/kg v 12 ml/kg tidal volume strategy. Methods: Data from 565 participants in the clinical trial were used. Plasma levels of SP-A and SP-D were measured at baseline and on day 3 after the start of the mechanical ventilation protocol. The longitudinal impact of baseline plasma surfactant protein levels on clinical outcomes was examined by multivariate analysis, controlling for mechanical ventilation group, APACHE III score, and other clinical covariates. The effect of 6 ml/kg tidal volume ventilation on plasma SP-A and SP-D levels was evaluated using analysis of covariance. Results: Baseline plasma SP-A levels were not related to any clinical outcome. In contrast, higher baseline plasma SP-D levels were associated with a greater risk of death (OR 1.21 per 100 ng/ml increment; 95% CI 1.08 to 1.35), fewer ventilator-free days (mean decrease −0.88 days; p=0.001), and fewer organ failure-free days (mean decrease −1.06 days; p<0.0001). The 6 ml/kg tidal volume strategy had no effect on the rise in plasma SP-A levels (p=0.91) but attenuated the rise in plasma SP-D levels (p=0.0006). Conclusions: Early in the course of ALI/ARDS an increased level of plasma SP-D is associated with a worse clinical outcome. The 6 ml/kg tidal volume strategy attenuated the rise of SP-D early in the clinical course. Taken together, these observations indicate that plasma SP-D, a product of alveolar type II cells, is a valuable biomarker in ALI/ARDS.
Embryonic treatment with xenobiotics disrupts steroid hormone profiles in hatchling red-eared slider turtles (Trachemys scripta elegans).
Authors: E Willingham, T Rhen, J T Sakata, D Crews
Journal: Environmental Health Perspectives (2000)

Many compounds in the environment capable of acting as endocrine disruptors have been assayed for their developmental effects on morphogenesis; however, few studies have addressed how such xenobiotics affect physiology. In the current study we examine the effects of three endocrine-disrupting compounds, chlordane, trans-nonachlor, and the polychlorinated biphenyl (PCB) mixture Aroclor 1242, on the steroid hormone concentrations of red-eared slider turtle (Trachemys scripta elegans) hatchlings treated in ovo. Basal steroid concentrations and steroid concentrations in response to follicle-stimulating hormone were examined in both male and female turtles treated with each of the three compounds. Treated male turtles exposed to Aroclor 1242 or chlordane exhibited significantly lower testosterone concentrations than controls, whereas chlordane-treated females had significantly lower progesterone, testosterone, and 5[alpha]-dihydrotestosterone concentrations relative to controls. The effects of these endocrine disruptors extend beyond embryonic development, altering sex-steroid physiology in exposed animals.
Imaging of Atherosclerosis
Authors: D.R.J. Owen, A.C. Lindsay, R.P. Choudhury, Z.A. Fayad
Journal: Annual Review of Medicine (2010)

It is now well recognized that the atherosclerotic plaques responsible for thrombus formation are not necessarily those that impinge most on the lumen of the vessel. Nevertheless, clinical investigations for atherosclerosis still focus on quantifying the degree of stenosis caused by plaques. Many of the features associated with a high-risk plaque, including a thin fibrous cap, large necrotic core, macrophage infiltration, neovascularization, and intraplaque hemorrhage, can now be probed by novel imaging techniques. Each technique has its own strengths and drawbacks. In this article, we review the various imaging modalities used for the evaluation and quantification of atherosclerosis.
Low-Dose<i>N</i><sup><i>ω</i></sup>-Nitro-<scp>l</scp>-Arginine Methyl Ester Treatment Improves Survival Rate and Decreases Myocardial Injury in a Murine Model of Viral Myocarditis Induced by Coxsackievirus B3
Authors: Shuji Mikami, Seinosuke Kawashima, Kenji Kanazawa, Ken-ichi Hirata, Hak Hotta, Yoshitake Hayashi, Hiroshi Itoh, Mitsuhiro Yokoyama
Journal: Circulation Research (1997)

Abstract Recent reports demonstrated the expression of inducible-type NO synthase in the heart of viral myocarditis. Since NO has multiple biological actions, a substantial amount of NO produced in the diseased heart may act either as a cytotoxic or as a cytoprotective molecule in the process of myocarditis. In the present study, we examined the effect of inhibition of NO synthesis on the mortality and the extent of myocardial injury in a murine model of coxsackievirus B3–induced myocarditis. We fed the infected mice drinking water containing a relatively low concentration (0.37 mmol/L) of N ω -nitro- l -arginine methyl ester (L-NAME) for 14 days after virus inoculation. This dose of L-NAME did not change virus titers in the heart. However, L-NAME–fed mice showed a significant reduction in mortality compared with those fed normal drinking water (nontreated mice). On the contrary, mice given a higher concentration of L-NAME (3.7 mmol/L) exhibited increased mortality. In addition, mice fed a low concentration of L-NAME showed reductions in the severity of heart failure and in the area of myocardial necrosis. Although systemic blood pressure was reduced in nontreated mice, in mice fed a low concentration of L-NAME, it was maintained at a level similar to that in uninfected control mice. L-NAME–treated mice also exhibited a reduction in the degree of inflammatory cell infiltration associated with decreased production of tissue prostaglandin E 2 levels in the heart compared with nontreated mice. Therefore, NO is likely to be involved in the pathogenic mechanisms of myocardial injury and resultant cardiac dysfunction in a murine model of coxsackievirus B3–induced viral myocarditis.
Analysis of Taiwanese ichthyosis vulgaris families further demonstrates differences in<i>FLG</i>mutations between European and Asian populations
Authors: C-K. Hsu, M. Akiyama, I. Nemoto-Hasebe, T. Nomura, A. Sandilands, S-C. Chao, J.Y-Y. Lee, H-M. Sheu, W.H.I. McLean, H. Shimizu
Journal: British Journal of Dermatology (2009)

Background Mutations in the gene encoding filaggrin (FLG) were identified to underlie ichthyosis vulgaris (IV) and also shown to predispose to atopic eczema. Until now, no FLG mutations have been described in the Taiwanese population. Objectives To elucidate filaggrin mutations in the Taiwanese population and further to clarify the population genetics of filaggrin gene mutations in the Asian populations. Methods In the present study, 12 individuals from four unrelated Taiwanese IV families were examined for FLG mutations. We carried out comprehensive sequencing of the entire FLG coding region using an overlapping polymerase chain reaction strategy. Results We identified three FLG mutations in the Taiwanese IV families. One mutation E1795X was a previously unidentified FLG mutation, which might be specific to the Taiwanese. Interestingly, another FLG mutation 3321delA is prevalent in the Japanese population and the other mutation Q2417X was found in the Singaporean Chinese population. No FLG mutation identified in the white European population was found in the Taiwanese population. Conclusions The present findings suggest that the Taiwanese population, as an East Asian group, share FLG mutations with both the Japanese and the Singaporean Chinese population. In addition, these results exemplify differences in the population genetics of filaggrin between Europe and Asia.
Idiopathic Anaphylactoid Reactions
Authors: Scott R. Sale
Journal: JAMA (1981)

Thirty-one patients, aged 6 to 78 years, with anaphylactoid reactions of unknown cause were retrospectively evaluated. All of the patients had life-threatening hypotension, wheezing or upper airway obstruction, and simultaneous angioedema or urticaria. Twenty-six patients also had episodes of angioedema or urticaria alone. In nine patients the initial episode was the most severe. In 16 of 18 patients, medications were effective in controlling or reducing the severity of the symptoms. In ten patients, the reactions were always self-limited and no medications were needed. No deaths occurred in 210 anaphylactoid attacks during 164 patient-years. Remissions lasting more than one year occurred in seven patients. Laboratory studies, food diaries, and skin tests were not helpful in establishing an etiology, although atopy was present in 12 of 15 patients tested.
Different seasons with decreased performance of immunochemical faecal occult blood tests in colorectal cancer screening
Authors: L. G. M. van Rossum, M. G. H. van Oijen
Journal: Gut (2010)

In their paper, Grazzini et al described seasonal influences on the performance of an immunochemical faecal occult blood test (iFOBT) in colorectal cancer screening and concluded that the performance is 17% lower in the hot summer months than in winter.1 We wondered if this would also be true for other countries.

In a previous study in the Netherlands we described lower positivity rates due to prolonged intervals between faecal sampling at home and delivery to the laboratory with the same iFOBT as that used by Grazzini et al .2 We analysed our data for testing in accordance …
Using Transgenic Mice to Analyze the Mechanisms of Progression of Chronic Renal Failure
Authors: FABIOLA TERZI, MARTINE BURTIN, GE[Combining Acute Accent]RARD FRIEDLANDER
Journal: Journal of the American Society of Nephrology (2000)

An understanding of the mechanisms underlying the formation of renal lesions is necessary for the development of strategies aiming to delay the progression of chronic renal failure. The generation of transgenic mice in the past 20 years has contributed significantly to the study of this phenomenon. Overexpression and/or inactivation of single factors in renal tissue demonstrated that molecules such as growth factors, proto-oncogenes, and renin-angiotensin system elements play major roles in renal deterioration. Several mouse models of renal injury have been developed in the past 10 yr. Transgenic mice that exhibit a normal phenotype under physiologic conditions allow analysis of the roles of single factors in the progression of chronic renal failure when renal injury models are used. Using this strategy, it was demonstrated that vascular adaptation, which is a process that involves the endothelin/nitric oxide balance, is essential for the survival of mice after nephron reduction and that the epidermal growth factor/activator protein-1/Bcl-2 pathway is involved in the development of renal lesions after renal injury, possibly via adjustment of the proliferation/apoptosis balance. Moreover, it was demonstrated that selective inhibition of epidermal growth factor signaling in the kidney successfully prevents the progression of chronic renal failure. These results indicate the power of transgenesis for elucidation of the pathogenesis of renal disease.
In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease
Authors: Anna Wieckowska, Nizar N. Zein, Lisa M. Yerian, Rocio A. Lopez, Arthur J. McCullough, Ariel E. Feldstein
Journal: Hepatology (2006)

In patients with nonalcoholic fatty liver disease (NAFLD), a liver biopsy remains the only reliable way to differentiate simple steatosis from nonalcoholic steatohepatitis (NASH). Noninvasive methods are urgently needed. Increasing evidence suggests hepatocyte apoptosis is a key mediator of liver injury in NAFLD. The aim of this study was to quantify hepatocyte apoptosis in plasma from patients with NAFLD and correlate it with histological severity. Plasma was obtained from 44 consecutive patients with suspected NAFLD at the time of liver biopsy. Histology was assessed blindly. Caspase-3-generated cytokeratin-18 fragments were measured in situ via immunohistochemistry and in vivo using a novel enzyme-linked immunosorbent assay. Plasma cytokeratin-18 fragments were markedly increased in patients with NASH compared with patients with simple steatosis or normal biopsies (median [interquartile range]: 765.7 U/L [479.6-991.1], 202.4 U/L [160.4-258.2], 215.5 U/L [150.2-296.2], respectively; P < .001). Cytokeratin-18 fragment levels independently predicted NASH (OR 1.95; 95% CI 1.18-3.22; P = .009 for every 50 U/L increase). A cutoff value of 395 U/L calculated using the receiver operating characteristic curve approach showed a specificity of 99.9%, a sensitivity of 85.7%, and positive and negative predictive values of 99.9% and 85.7%, respectively, for the diagnosis of NASH. In conclusion, these findings strongly suggest that determination of hepatocyte caspase activation in the blood is a strong and independent predictor of NASH in human subjects. These data highlight the potential usefulness of this test as a noninvasive diagnostic means of determining histological disease severity in patients with NAFLD.
Clinical Validity of the Lung Cancer Biomarkers Identified by Bioinformatics Analysis of Public Expression Data
Authors: Bumjin Kim, Hyun Joo Lee, Hye Young Choi, Youngah Shin, Seungyoon Nam, Gilju Seo, Dae-Soon Son, Jisuk Jo, Jaesang Kim, Jinseon Lee, Jhingook Kim, Kwhanmien Kim, Sanghyuk Lee
Journal: Cancer Research (2007)

Abstract Identification of molecular markers often leads to important clinical applications such as early diagnosis, prognosis, and drug targeting. Lung cancer, the leading cause of cancer-related deaths, still lacks reliable molecular markers. We have combined the bioinformatics analysis of the public gene expression data and clinical validation to identify biomarker genes for non–small-cell lung cancer. The serial analysis of gene expression and the expressed sequence tag data were meta-analyzed to produce a list of the differentially expressed genes in lung cancer. Through careful inspection of the predicted genes, we selected 20 genes for experimental validation using semiquantitative reverse transcriptase-PCR. The microdissected clinical specimens used in the study consisted of three groups: lung tissues from benign diseases and the paired (cancer and pathologic normal) tissues from non–small-cell lung cancer patients. After extensive statistical analyses, seven genes (CBLC, CYP24A1, ALDH3A1, AKR1B10, S100P, PLUNC, and LOC147166) were identified as potential diagnostic markers. Quantitative real-time PCR was carried out to additionally assess the value of the seven identified genes leading to the confirmation of at least two genes (CBLC and CYP24A1) as highly probable novel biomarkers. The gene properties of the identified markers, especially their relationship to lung cancer and cell signaling pathway regulation, further suggest their potential value as drug targets as well. [Cancer Res 2007;67(15):7431–8]
USE OF PARTIAL CARDIOPULMONARY BYPASS DURING THE ANHEPATIC PHASE OF ORTHOTOPIC LIVER GRAFTING
Authors: R.Y. Calne, P. Mcmaster, D.P. Smith, G.N. Craddock, Keith Rolles, J.V. Farman, M. Lindop, D.W. Bethune, D. Wheeldon, R. Gill, Roger Williams
Journal: The Lancet (1979)
The MABA approach: a new option to improve bronchodilator therapy
Authors: Mario Cazzola, Jose-Luis Lopez-Campos, Luis Puente-Maestu
Journal: European Respiratory Journal (2013)

MABA agents provide a new approach to dual bronchodilator therapy by combining muscarinic antagonism and beta 2-agonism http://ow.ly/mXXdZRecently, the results of an interesting systematic review have shown that the use of a combination of a longacting b 2 -agonist (LABA) and a long-acting antimuscarinic agent (LAMA), the so called ''dual'' bronchodilator therapy, in stable moderate chronic obstructive pulmonary disease (COPD) patients is potentially a good pharmacological approach for the improvement of symptoms when they are not adequately controlled with tiotropium monotherapy [1].Several studies have demonstrated a superior bronchodilation effect of combining a LABA with a LAMA compared with the individual agents alone, and that these combinations are well tolerated in patients with moderate to severe COPD [2].Published evidence also indicates that ''dual'' bronchodilator therapies induce greater improvements in patientcentred outcomes such as dyspnoea, symptoms, rescue medication use and health-related quality of life than individual drugs used alone [3].Another important problem that we should always consider when we need to prescribe two or more drugs simultaneously to a patient with COPD is represented by the fact that the prescribed number of drugs and
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: P. G. H. Gell, Stewart Sell
Journal: The Journal of Experimental Medicine (1965)

Specific antisera directed against all six of the well characterised allotypic determinants of rabbit IgG (As1, 2, 3, 4, 5, and 6) are capable of inducing blast transformation and DNA synthesis when added to lymphocyte cultures obtained from donor rabbits having the appropriate IgG allotype. Mixtures of antisera directed against two different allotypic determinants induce a "summation" of transformation and DNA synthesis over and above the effect of mixtures of two antisera directed against the same allotypic determinant. This summation effect is observed regardless of whether the antisera which have been mixed are directed against allotypic determinants controlled by the same locus or by different loci. The finding that summation occurs with mixtures of two antisera directed against both the allotypic determinants of a double homozygote rabbit (As1, 6) suggests that lymphocytes from the peripheral blood may be primed to produce only one or the other of the two polypeptide chains of IgG, but not both.