tbuckley/cabot-search huggingface dataset:
Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities
Authors: Enrico Silini, Fulvia Bono, Agostino Cividini, Antonella Cerino, Savino Bruno, Sonia Rossi, Giovanni Belloni, Bruno Brugnetti, Emilio Civardi, Laura Salvaneschi, Mario U. Mondelli
Journal: Hepatology (1995)

Hepatitis C virus (HCV) infection persists for an indefinite length of time in a major proportion of patients, inducing chronic liver lesions that evolve to cirrhosis and hepatocellular carcinoma (HCC) in approximately 20% of cases. We studied HCV viremia and genotypes by reverse transcription-polymerase chain reaction (RT-PCR) in 341 consecutive anti-HCV-positive patients. Of these, 167 patients had persistently normal or near normal alanine aminotransferase (ALT) levels (fluctuations < or = 5 IU above the upper limit of normal); the remaining 174 patients presented with elevated ALT and histological evidence of chronic liver disease. Seventy percent of patients with normal ALT values had circulating HCV RNA despite the absence of biochemical indicators of liver damage and mild histological forms of chronic hepatitis were detected in most patients who underwent liver biopsy. Isolated genotype III infection was significantly more prevalent in this patient group with respect to control patients with abnormal ALT values (70% vs. 39%; P < .001). Conversely, isolated genotype II was more frequently found in patients with elevated ALT values and evidence of chronic liver disease (45% vs. 23%; P < .01) and it was progressively more represented in advanced liver disease, such as cirrhosis and HCC. Virological features of HCV infection might be associated with different clinical manifestations, suggesting a potential prognostic significance on disease outcome.
Functional Recapitulation of Smooth Muscle Cells Via Induced Pluripotent Stem Cells From Human Aortic Smooth Muscle Cells
Authors: Tae-Hee Lee, Sun-Hwa Song, Koung Li Kim, Ji-Yeun Yi, Ga-Hee Shin, Ji Yeon Kim, Jihoon Kim, Yong-Mahn Han, Sang Hun Lee, Suk-Ho Lee, Sung Han Shim, Wonhee Suh
Journal: Circulation Research (2009)

Generation of induced pluripotent stem (iPS) cells has been intensively studied by a variety of reprogramming methods, but the molecular and functional properties of the cells differentiated from iPS cells have not been well characterized.To address this issue, we generated iPS cells from human aortic vascular smooth muscle cells (HASMCs) using lentiviral transduction of defined transcription factors and differentiated these iPS cells back into smooth muscle cells (SMCs).Established iPS cells were shown to possess properties equivalent to human embryonic stem cells, in terms of the cell surface markers, global mRNA and microRNA expression patterns, epigenetic status of OCT4, REX1, and NANOG promoters, and in vitro/in vivo pluripotency. The cells were differentiated into SMCs to enable a direct, comparative analysis with HASMCs, from which the iPS cells originated. We observed that iPS cell-derived SMCs were very similar to parental HASMCs in gene expression patterns, epigenetic modifications of pluripotency-related genes, and in vitro functional properties. However, the iPS cells still expressed a significant amount of lentiviral transgenes (OCT4 and LIN28) because of partial gene silencing.Our study reports, for the first time, the generation of iPS cells from HASMCs and their differentiation into SMCs. Moreover, a parallel comparative analysis of human iPS cell-derived SMCs and parental HASMCs revealed that iPS-derived cells possessed representative molecular and in vitro functional characteristics of parental HASMCs, suggesting that iPS cells hold great promise as an autologous cell source for patient-specific cell therapy.
Laminar Shear Stress and 3′ Polyadenylation of eNOS mRNA
Authors: Martina Weber, Curt H. Hagedorn, David G. Harrison, Charles D. Searles
Journal: Circulation Research (2005)

The 3′ poly(A) tail is important in messenger RNA stability and translational efficiency. In somatic tissues, 3′ polyadenylation of mRNAs has been thought to largely be a constitutively active process. We have reported that laminar shear stress causes a brief increase in endothelial nitric oxide synthase (eNOS) transcription, followed by a prolonged increase in eNOS mRNA stability. We sought to determine whether shear stress and other stimuli affected eNOS 3′ polyadenylation in endothelial cells. Under basal (static) conditions, eNOS mRNA possessed short 3′ poly(A) tails of &lt;25 nt. In contrast, laminar shear stress increased expression of eNOS transcripts with long poly(A) tails. ENOS transcripts with longer poly(A) tails had prolonged half-lives (6 hours in static cells versus 18 hours in sheared cells). Polysome analysis revealed that eNOS mRNA from sheared cells was shifted into more translationally active polysome fractions compared with eNOS mRNA from static cells. Shear-induced lengthening of the eNOS 3′ poly(A) tail was the result of increased nuclear polyadenylation. Furthermore, hydrogen peroxide and HMG Co-A reductase inhibitors, other stimuli known to modulate eNOS expression posttranscriptionally, also induced eNOS 3′ poly(A) tail lengthening. These results support the concept that shear stress modulates eNOS mRNA stability and translation via increased 3′ polyadenylation. We suggest that mRNA 3′ polyadenylation is a posttranscriptional mechanism used by endothelial cells to regulate gene expression.
Partitioning the Variation in Mammalian Substitution Rates
Authors: Nick G. C. Smith, Adam Eyre-Walker
Journal: Molecular Biology and Evolution (2003)

We have used analysis of variance to partition the variation in synonymous and amino acid substitution rates between three effects (gene, lineage, and a gene-by-lineage interaction) in mammalian nuclear and mitochondrial genes. We find that gene effects are stronger for amino acid substitution rates than for synonymous substitution rates and that lineage effects are stronger for synonymous substitution rates than for amino acid substitution rates. Gene-by-lineage interactions, equivalent to overdispersion corrected for lineage effects, are found in amino acid substitutions but not in synonymous substitutions. The variance in the ratio of amino acid and synonymous substitution rates is dominated by gene effects, but there is also a significant gene-by-lineage interaction.
Antitussive effect of (-) menthol mediated by nasal trigeminal TRPM8 receptors
Authors: Jana Plevkova, Brendan J. Canning, Ivan Poliacek, Mariana Brozmanova, Milos Tatar
Journal: European Respiratory Journal (2011)

(-) Menthol, main component of the peppermint is exploited in many over-the-counter drugs for common cold and cough. It has been reported that (-) menthol has antitussive effect in humans and animals. However, there are conflicting evidences against that statement and also case reports of respiratory failure induced by menthol in kids. Based on the recent data about the distribution of the TRPM8 – menthol receptors expressing neurons in the upper airways, and their low proportion within the vagal nerves in lower airways we suppose, that effect of (-) menthol on cough could be mediated by TRPM8 expressed on nasal afferents. To test this hypothesis a segmental airway challenges with (-) menthol were performed in anaesthetized guinea pigs (nose, trachea and lower airways were separately treated by menthol) and under such set up citric acid cough dose response curves (DRC) were constructed according the method described by  Canning et al .,  2006.  The DRC were compared to control provocations. The (-) menthol applied topically to the trachea does not influence cough significantly. (-) menthol vapors applied directly to lower airways via cannula resulted to the tendency to facilitate cough, with visible signs of increased mucus output, loaded breathing and wheezing. The antitussive effect of menthol was observed only in the group treated by nasal (-) menthol vapors, which reduced cough response to CA significantly comparing to control response p   Our results correspond with the data describing the TRPM8 distribution in the respiratory tract, and may contribute to explanation of adverse effects induced by menthol inhalation in kids. Supported:VEGA 1/0031/11.
The Safety and Efficacy of Zidovudine (AZT) in the Treatment of Subjects with Mildly Symptomatic Human Immunodeficiency Virus Type 1 (HIV) Infection
Authors: Margaret A. Fischl
Journal: Annals of Internal Medicine (1990)

To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection.A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts.Multicenter trial at AIDS Clinical Trial units.Seven hundred eleven subjects with mildly symptomatic HIV infection.Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months.Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively.Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.
Antigen recognition. IV. Discrimination by antigen-binding immunocompetent B cells between immunity and tolerance is determined by adherent cells.
Authors: E Diener, N Kraft, K C Lee, C Shiozawa
Journal: The Journal of Experimental Medicine (1976)

Mouse spleen cells capable of specifically binding intrinsically tritium-labeled polymerized flagellin (POL) (labeling by biosynthesis of flagellar protein) via IgM receptors were found to comprise a distinct population of about 20-50 cells per 10(6) lymphocytes. Evidence is presented that the majority of mouse spleen cells binding tritium-labeled POL undergoes blastogenesis after antigen capping, antigen shedding, and receptor reformation. Under conditions of tolerance induction in vitro, however, loss of antigen from the cell surface was inhibited. Such inhibition of antigen redistribution and shedding was reversed by a short pulse of colchicine and new antigen receptors were formed. In spite of this, colchicine had no effect on the tolerant state. However, tolerance could be broken, regardless of presence or absence of the alkaloid, with radioresistant theta-negative accessory (A) cells (adherent cells) from normal but not from tolerant spleen cell populations. "Tolerant" A cells, although they were incapable of cooperating in a response to POL, were capable of participating in a response to a second unrelated antigen. It is concluded that tolerance to POL in vitro is induced by mechanisms other than the physical blocking of bone marrow-derived (B) cell receptors by antigen. Most likely, the discrimination by the B cell between a tolerogenic and immunogenic signal is mediated by A cells.
Nylon Flock–Associated Interstitial Lung Disease
Authors: WILLIAM L. ESCHENBACHER, KATHLEEN KREISS, M. DIANE LOUGHEED, GLENN S. PRANSKY, BRIAN DAY, ROBERT M. CASTELLAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Section:ChooseTop of pageAbstract <<INTRODUCTIONCASE DESCRIPTIONOUTBREAK UPDATESWORKSHOP REVIEW PROCESSRESULTSDISCUSSIONReferencesCITING ARTICLES
Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E–Deficient Mice
Authors: Susanne Bro, Flemming Moeller, Claus B. Andersen, Klaus Olgaard, Lars B. Nielsen
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Chronic renal failure markedly accelerates atherosclerosis in apolipoprotein-E–deficient mice, but the mechanism is unknown. The recruitment of inflammatory cells in the arterial wall by vascular adhesion molecules plays a key role in the formation of classical atherosclerosis. This study examines whether the expression of vascular adhesion molecules is increased in uremic atherosclerosis. Uremia was induced by 5/6 nephrectomy; control mice were sham-operated. After 2 wk of uremia, no lesion formation could be demonstrated in uremic or control mice. After 12 wk, aortas from uremic mice had a 9.8-fold increase of the aortic plaque area fraction compared with control mice (P < 0.0001). The aortic expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in uremic mice was 215 ± 31% (P < 0.05) and 243 ± 55% (P < 0.05) of that in controls after 2 and 12 wk, respectively (n = 9 × 4). In contrast, aortic expression of vascular cell adhesion molecule-1 (VCAM-1) mRNA in uremic mice was unchanged after 2 wk but increased to 237 ± 40% (P < 0.01) of that in control mice after 12 wk. On immunohistochemistry of aortas from uremic mice, ICAM-1 was predominantly present in endothelial cells both in nonlesioned and lesioned aortas, whereas VCAM-1 was predominantly present in the medial smooth muscle cell layer in lesioned aortas. The plasma concentration of soluble ICAM-1 (sICAM-1) (but not of sVCAM-1) was slightly elevated after 2 wk of uremia. In contrast, both sICAM-1 and sVCAM-1 plasma concentrations were markedly higher in uremic than control mice after 12 wk. These results suggest that uremic atherosclerosis is preceded by an upregulation of ICAM-1 expression in arterial endothelium and that formation of early uremic lesions is accompanied by upregulation of VCAM-1 expression in the medial smooth muscle cell layer.
B CELL IMMUNOBIOLOGY IN DISEASE: Evolving Concepts from the Clinic
Authors: Flavius Martin, Andrew C. Chan
Journal: Annual Review of Immunology (2006)

The pathogenic roles of B cells in autoimmune diseases occur through several mechanistic pathways that include autoantibodies, immune complexes, dendritic and T cell activation, cytokine synthesis, chemokine-mediated functions, and ectopic neolymphogenesis. Each of these pathways participate to different degrees in autoimmune diseases. The use of B cell-targeted and B cell subset-targeted therapies in humans is illuminating the mechanisms at work in a variety of human autoimmune diseases. In this review, we highlight some of these recent findings that provide insights into both murine models of autoimmunity and human autoimmune diseases.
Hb South milwaukee [β105 (G7) leu → Phe]: A newly‐identified hemoglobin variant with high oxygen affinity
Authors: George R. Honig, Ajit B. Divgi
Journal: American Journal of Hematology (1990)

Abstract Fifteen individuals among four generations of a family of English ancestry demonstrated elevated hemoglobin levels accompanied by leftward‐shifted whole blood oxygen equilibrium curves. Five of the affected family members have required phlebotomies for relief of symptoms attributable to erythrocytosis. An abnormal hemoglobin or globin chain could not be isolated, but 43% of the β chains of the affected individuals contained a Leu → Phe substitution at position 105 (G7). Oxygen equilibrium curves demonstrated a normal Bohr effect but decreased cooperativity.
Oxalate loading test: a screening test for steatorrhoea.
Authors: D S Rampton, G P Kasidas, G A Rose, M Sarner
Journal: Gut (1979)

To investigate the possibility of measuring urinary oxalate output instead of faecal fat excretion as an outpatient screening test for steatorrhoea, we determined 24 hour urinary oxalate and five day faecal fat excretion before and during an oral load of sodium oxalate 600 mg daily (oxalate 4.44 mmol), in 32 patients with suspected malabsorption on a diet containing oxalate 30 mg (0.33 mmol), fat 50 g (180 mmol), and calcium 1 g (25 mmol). Nineteen patients proved to have steatorrhoea (mean faecal fat 62 mmol/24 h, range 19--186 mmol) of varying aetiologies. On the diet alone, urinary oxalate was raised in only nine of these patients (mean 0.25 mmol/24 h, range 0.08--0.59 mmol) (normal less than 0.20). By contrast, when the diet was supplemented with oral sodium oxalate, all 19 patients with steatorrhoea had hyperoxaluria (mean 0.91 mmol/24 h, range 0.46--1.44 mmol) (normal less than 0.44). There was a significant positive linear relationship between urinary oxalate and faecal fat when the 32 patients were on the high oxalate intake (r = 0.73, P less than 0.001), but not when they were on the low oxalate intake. Mean percentage absorption of orally administered oxalate was 5.8 +/- 0.99% (+/- 1 SD) in normal subjects and 14.7 +/- 6.0% (P less than 0.002) in patients with steatorrhoea. Measurement of urinary oxalate output during oral sodium oxalate loading appears to be a reliable and convenient screening test for steatorrhoea.
Rapid Evolution of the Family of CONSTANS LIKE Genes in Plants
Authors: Ulf Lagercrantz, Tomas Axelsson
Journal: Molecular Biology and Evolution (2000)

A family of CONSTANS LIKE genes (COLs) has recently been identified in Arabidopsis thaliana and other plant species. CONSTANS, the first isolated member, is a putative zinc finger transcription factor that promotes the induction of flowering in A. thaliana in long photoperiods. Phylogenetic analysis of the COL family demonstrated that it is organized into a few distinct groups, some of which evolved before the divergence of gymnosperms and angiosperms. Molecular evolutionary analyses showed that COL genes within the Brassicaceae family evolve rapidly. The number of nonsynonymous substitutions was larger, and the ratio of nonsynonymous to synonymous substitutions was higher. The analysis also indicated that the rate of evolution is heterogeneous between different domains in the COL genes. The results support previous data indicating that plant regulatory genes evolve relatively fast and that the rate of evolution varies significantly between different regions of those genes. The rate of evolution of COL genes seems to have accelerated during later stages of evolution, possibly as an effect of frequent gene duplications.
Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial
Authors: Beverly Winikoff, Rasha Dabash, Jill Durocher, Emad Darwish, Nguyen Thi Nhu Ngoc, Wilfrido León, Sheila Raghavan, Ibrahim Medhat, Huynh Thi Kim Chi, Gustavo Barrera, Jennifer Blum
Journal: The Lancet (2010)
The adaptation of enzymes to temperature: catalytic characterization of glucosephosphate isomerase homologues isolated from Mytilus edulis and Isognomon alatus, bivalve molluscs inhabiting different thermal environments.
Authors: J G Hall
Journal: Molecular Biology and Evolution (1985)

Homologues of glucosephosphate isomerase (GPI, EC 5.3.1.9) were purified to homogeneity and kinetically characterized from Mytilus edulis and Isognomon alatus, two bivalve molluscs experiencing contrasting thermal environments. The enzyme isolated from I. alatus functions at warmer temperatures (25-35 C) than GPI from M. edulis, a species that inhabits colder marine littoral habitats (5-20 C). The former exhibits apparent first-order (with respect to substrate) catalytic rate constants (Vmax/KM) in vitro that become progressively greater than the mussel enzyme as the assay temperature is raised. Apparent zero-order catalytic rate constants (Vmax) are relatively less differentiated. Catalytic efficiency, defined as the rate at which a catalytic event occurs in either reaction direction for reference standard states (substrate concentrations), is greater for the enzyme from the tropical species (I. alatus) at all realistic combinations of temperature and substrate concentration except for the lowest temperatures and highest substrate concentrations, where the GPI from the boreal/temperate M. edulis is more efficient. This pattern of catalytic divergence appears to be due primarily to differentiation in Vmax/KM. These results and other published data are reviewed and shown to be inconsistent with claims that adaptation of enzymes to higher cell temperatures requires a loss in catalytic efficiency.
Inhibition of Vascular Endothelial Growth Factor (VEGF)-A Causes a Paradoxical Increase in Tumor Blood Flow and Up-Regulation of VEGF-D
Authors: Bradford A. Moffat, Mark Chen, Muhammed S.T. Kariaapper, Daniel A. Hamstra, Daniel E. Hall, Jadranka Stojanovska, Timothy D. Johnson, Mila Blaivas, Mahesh Kumar, Thomas L. Chenevert, Alnawaz Rehemtulla, Brian D. Ross
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Vascular endothelial growth factor (VEGF)-A is an important mediator of angiogenesis in almost all solid tumors. The aim of this study was to evaluate the effect of VEGF-A expression on tumor growth, perfusion, and chemotherapeutic efficacy in orthotopic 9L gliosarcomas. Experimental Design: Stable 9L cell lines underexpressing and overexpressing VEGF-A were generated. Anatomic, susceptibility contrast, and continuous arterial spin-labeling magnetic resonance imaging were used to quantify the volume, blood volume, and blood flow of tumors orthotopically grown from these and wild-type 9L cells. Histologic, immunohistochemical, and quantitative reverse transcription-PCR analyses were also done on excised tumors. Finally, the effects of carmustine chemotherapy were also evaluated. Results: Orthotopic tumors underexpressing VEGF-A had slower growth rates (increased median survival), greater blood flow, vessel density, and VEGF-D expression, but no statistical difference in blood volume and chemotherapeutic sensitivity, compared with tumors with wild-type levels of VEGF-A. Tumors overexpressing VEGF-A had faster growth rates, greater blood volume, vessel density, and blood flow but no statistical difference in VEGF-D expression and chemotherapeutic sensitivity compared with wild-type VEGF-A-expressing tumors. Conclusion: Blood volume and blood flow are independent and different biomarkers of tumor perfusion. Therefore, both should be measured when characterizing the efficacy of antiangiogenic therapies. Underexpression of VEGF-A does not result in complete inhibition of angiogenesis. Moreover, these tumors have a different perfusion phenotype, suggesting that angiogenesis is mediated by an alternative pathway. The results indicate that VEGF-D is a plausible alternative mediator of this angiogenesis.