bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental tumourigenesis: NCAM as a putative marker for the malignant renal stem/progenitor cell population
Authors: Pode‐Shakked Naomi , Metsuyanim Sally , Rom‐Gross Eithan , Mor Yoram , Fridman Eduard , Goldstein Itamar , Amariglio Ninette , Rechavi Gideon , Keshet Gilmor , Dekel Benjamin 
Published: December 2008

AbstractDuring development, renal stem cells reside in the nephrogenic blastema. Wilms’ tumour (WT), a common childhood malignancy, is suggested to arise from the nephrogenic blastema that undergoes partial differentiation and as such is an attractive model to study renal stem cells leading to cancer initiation and maintenance. Previously we have made use of blastema‐enriched WT stem‐like xenografts propagated in vivo to define a ‘WT‐stem’ signature set, which includes cell surface markers convenient for cell isolation (frizzled homolog 2 [Drosophila] – FZD2, FZD7, G‐protein coupled receptor 39, activin receptor type 2B, neural cell adhesion molecule – NCAM). We show by fluorescence‐activated cell sorting analysis of sphere‐forming heterogeneous primary WT cultures that most of these markers and other stem cell surface antigens (haematopoietic, CD133, CD34, c‐Kit; mesenchymal, CD105, CD90, CD44; cancer, CD133, MDR1; hESC, CD24 and putative renal, cadherin 11), are expressed in WT cell sub‐populations in varying levels. Of all markers, NCAM, CD133 and FZD7 were constantly detected in low‐to‐moderate portions likely to contain the stem cell fraction. Sorting according to FZD7 resulted in extensive cell death, while sorted NCAM and CD133 cell fractions were subjected to clonogenicity assays and quantitative RT‐PCR analysis, exclusively demonstrating the NCAM+ fraction as highly clonogenic, overexpressing the WT ‘stemness’ genes and topoisomerase2A (TOP2A), a bad prognostic marker for WT. Moreover, treatment of WT cells with the topoisomerase inhibitors, Etoposide and Irinotecan resulted in down‐regulation of TOP2A along with NCAM and WT1. Thus, we suggest NCAM as a marker for the WT progenitor cell population. These findings provide novel insights into the cellular hierarchy of WT, having possible implications for future therapeutic options.
Dexamethasone inhibits lipopolysaccharide‐induced hydrogen sulphide biosynthesis in intact cells and in an animal model of endotoxic shock
Authors: Li Ling , Whiteman Matthew , Moore Philip K. 
Published: December 2008

AbstractDexamethasone (1 mg/kg, i.p.) administered either 1 hr before or 1 hr after E. coli lipopolysaccharide (LPS, 4 mg/kg, i.p.) in conscious rats inhibited the subsequent (4 hrs) rise in plasma cytokine (interleukin [IL]‐1β, tumour necrosis factor [TNF]‐α), nitrate/nitrite (NO×), soluble intercellular adhesion molecule‐1 (sICAM‐1) concentration and lung/liver myeloperoxidase activity indicative of an anti‐inflammatory effect. Dexamethasone also reduced the LPS‐evoked rise in plasma hydrogen sulphide (H2S) concentration, liver H2S synthesizing activity and expression of cystathionine γ lyase (CSE) and inducible nitric oxide synthase (iNOS). Mifepristone (RU‐486) inhibited these effects. Dexamethasone (1–10 μM) reduced the LPS‐evoked release of IL‐1β, TNF‐α and L‐selectin, decreased expression of CSE and iNOS and diminished nuclear factor κB (NF‐κB)‐DNA binding in isolated rat neutrophils. In contrast, NaHS (100 μM) increased L‐selectin release from rat neutrophils. Dexamethasone also reduced LPS‐induced up‐regulation of CSE in foetal liver cells. 6‐amino‐4‐(4‐phenoxyphenylethylamino) quinazoline (QNZ, 10 nM), a selective inhibitor of transcription via the NF‐κB pathway, abolished LPS‐induced up‐regulation of CSE expression. We propose that inhibition of CSE expression and reduction in formation of the pro‐inflammatory component of H2S activity contributes to the anti‐inflammatory effect of dexamethasone in endotoxic shock. Whether H2S plays a part in the anti‐inflammatory effect of this steroid in other forms of inflammation such as arthritis or asthma warrants further study.
Haemopexin affects iron distribution and ferritin expression in mouse brain
Authors: Morello Noemi , Tonoli Elisabetta , Logrand Federica , Fiorito Veronica , Fagoonee Sharmila , Turco Emilia , Silengo Lorenzo , Vercelli Alessandro , Altruda Fiorella , Tolosano Emanuela 
Published: December 2008

AbstractHaemopexin (Hx) is an acute phase plasma glycoprotein, mainly produced by the liver and released into plasma where it binds heme with high affinity and delivers it to the liver. This system provides protection against free heme‐mediated oxidative stress, limits access by pathogens to heme and contributes to iron homeostasis by recycling heme iron. Hx protein has been found in the sciatic nerve, skeletal muscle, retina, brain and cerebrospinal fluid (CSF). Recently, a comparative proteomic analysis has shown an increase of Hx in CSF from patients with Alzheimer’s disease, thus suggesting its involvement in heme detoxification in brain. Here, we report that Hx is synthesised in brain by the ventricular ependymal cells. To verify whether Hx is involved in heme scavenging in brain, and consequently, in the control of iron level, iron deposits and ferritin expression were analysed in cerebral regions known for iron accumulation. We show a twofold increase in the number of iron‐loaded oligodendrocytes in the basal ganglia and thalamus of Hx‐null mice compared to wild‐type controls. Interestingly, there was no increase in H‐ and L‐ferritin expression in these regions. This condition is common to several human neurological disorders such as Alzheimer’s disease and Parkinson’s disease in which iron loading is not associated with an adequate increase in ferritin expression. However, a strong reduction in the number of ferritin‐positive cells was observed in the cerebral cortex of Hx‐null animals. Consistent with increased iron deposits and inadequate ferritin expression, malondialdehyde level and Cu–Zn superoxide dismutase‐1 expression were higher in the brain of Hx‐null mice than in that of wild‐type controls. These data demonstrate that Hx plays an important role in controlling iron distribution within brain, thus suggesting its involvement in iron‐related neurodegenerative diseases.
Measuring and monitoring apoptosis and drug toxicity in HIV patients by ligation‐mediated polymerase chain reaction
Authors: Hooker David J. , Gorry Paul R. , Ellett Anne M. , Wesselingh Steven L. , Cherry Catherine L. 
Published: December 2008

AbstractApoptosis has a critical role in normal physiology while its dysregulation has causal links with certain pathologies. A biochemical hallmark of apoptosis, internucleosomal genomic DNA fragmentation, is detectable by ligation‐mediated polymerase chain reaction (LM‐PCR). Here we converted LM‐PCR into a new apoptosis quantifier by dividing trace quantities of 600 bp apoptotic amplicons into those of a single copy house‐keeping gene, generating the LM‐PCR ‘value’. Dynamic range was ∼17‐fold correlating with a ∼200‐fold difference in degree of apoptotic fragmentation. Inter‐ and intra‐gel reliability were both excellent, supporting LM‐PCR's utility with large sample sets. Validation experiments comprising cell exposure to staurosporine over time revealed LM‐PCR is as sensitive as caspase‐3/ELISA and more sensitive than terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling/flourescence‐activated cell sorting (TUNEL/FACS) for distinguishing low degrees of apoptosis (the spectrum most relevant in vivo). The LM‐PCR profile mirrored that of caspase‐3/ELISA but not TUNEL/FACS. We then applied this molecular tool to clinical investigation. Increased apoptosis is implicated in lipoatrophy (subcutaneous fat wasting), a serious, persistent toxicity of some nucleoside analogue reverse transcriptase inhibitors (NRTIs) used in anti‐HIV highly active antiretroviral therapy (HAART). We demonstrated in 105 peripheral blood mononuclear cell samples that elevated LM‐PCR values are seen during therapy with stavudine (d4T), a particularly toxic NRTI (P< 0.0001 versus no HAART, unpaired t‐test). Elevated values were also independently associated with clinical evidence of lipoatrophy (P= 0.007, multiple logistic regression modelling) but not with patient age, CD4 T‐cell count nor HIV viral load (P> 0.8 for each). Together these data demonstrate that LM‐PCR is a robust and reliable quantifier of apoptosis with potential for basic science and clinical investigation.
Effect of acute postural variation on diabetic macular oedema
Authors: Vinten Martin , La Cour Morten , Lund‐Andersen Henrik , Larsen Michael 
Published: December 2008

Abstract.Purpose:  This study aimed to study the pathophysiology of diabetic macular oedema (DMO) by analysis of concomitant changes in macular volume (MV), mean arterial blood pressure (MABP), intraocular pressure (IOP), and retinal artery and vein diameters in response to acute postural changes in patients with DMO and healthy subjects.Methods:  Thirteen patients with DMO (13 eyes) and five healthy subjects (five eyes) were examined after resting in a chair for 15 mins using optical coherence tomography to measure MV and fundus photography to assess retinal vessel diameters. The patients then lay down for 60 mins, during which they were examined repeatedly before they were reseated and examined again. Intraocular pressure was measured using pulse‐air tonometry, arterial blood pressure by sphygomanometry and fluid columns using rulers and a spirit level.Results:  In healthy subjects, retinal artery (p = 0.02) and vein (p = 0.001) diameters decreased when subjects lay down, whereas MV remained stable. In patients with DMO, no orthostatic variation in retinal vessel diameters could be demonstrated, whereas MV had increased by 2.4 ± 0.6% (mean ± standard error of the mean; p = 0.006) 50 mins after assuming a recumbent position. In both healthy subjects and DMO patients, MABP decreased and IOP increased in a recumbent position, with no significant difference between the groups.Conclusions: The increase in MV that occurs in DMO when changing from a seated to a recumbent position is associated with a failure of retinal artery contraction, a response seen in healthy subjects that appears to counter‐regulate the increase in ocular perfusion pressure caused by assuming a recumbent position.
Conjunctival impression cytology and tear‐film changes in patients with familial Mediterranean fever
Authors: Karalezli Aylin , Borazan Mehmet , Yilmaz Sema , Kiyici Halil , Akova Yonca Aydin 
Published: December 2008

Abstract.Purpose:  To evaluate the ocular surface changes and tear‐film functions in patients with familial Mediterranean fever (FMF).Methods:  This prospective case–control clinical study examined 35 patients with FMF (group 1) and 35 controls (group 2). All patients underwent a full ophthalmological examination. Ocular surface changes were evaluated by determining cell content of surface conjunctival epithelium using conjunctival impression cytology and tear‐film functions using Schirmer‐I, break‐up time (BUT), corneal fluorescein and Rose Bengal tests. Subjective ocular complaints were scored with a four‐point scale. Between‐group results were compared.Results:  In group 1, impression cytology revealed grade 0 changes in 15 eyes, grade 1 changes in 11 eyes and grade 2 changes in nine eyes in group 1; in group 2, it revealed grade 0 changes in 27 eyes, grade 1 changes in five eyes and grade 2 changes in three eyes (p = 0.013). Mean goblet cell density was 765 ± 45 cells/mm2 in group 1 and 1730 ± 100 cells/mm2 in group 2 (P < 0.001). Mean results on the Schirmer‐I test results were 17.36 ± 3.18 mm in group 1 and 19.60 ± 4.17 mm in group 2 (p = 0.364). Mean BUT was 8.20 ± 1.60 seconds in group 1 and 9.93 ± 2.33 seconds in group 2 (p = 0.001). Mean corneal fluorescein and Rose Bengal staining scores were 3.26 ± 1.67 and 0.96 ± 0.71 in group 1 and 1.37 ± 0.34 and 0.40 ± 0.49 in group 2 (p = 0.037, p = 0.005). The presence of subjective ocular complaints was more frequent in group 1 than in group 2.Conclusion:  Despite normal tear production, the ocular surface and tear‐film functions of FMF patients differ from those of healthy individuals. These changes may be related to the chronic inflammatory nature of FMF.
Age-Specific Cluster of Cases of Serotype 1
Streptococcus pneumoniae
Carriage in Remote Indigenous Communities in Australia
Authors: Smith-Vaughan H. , Marsh R. , Mackenzie G. , Fisher J. , Morris P. S. , Hare K. , McCallum G. , Binks M. , Murphy D. , Lum G. , Cook H. , Krause V. , Jacups S. , Leach A. J. 
Published: December 2008

ABSTRACT

Seven-valent pneumococcal conjugate vaccination commenced in 2001 for Australian indigenous infants. Pneumococcal carriage surveillance detected substantial replacement with nonvaccine serotypes and a cluster of serotype 1 carriage. Our aim was to review
Streptococcus pneumoniae
serotype 1 carriage and invasive pneumococcal disease (IPD) data for this population and to analyze serotype 1 isolates. Carriage data were collected between 1992 and 2004 in the Darwin region, one of the five regions in the Northern Territory. Carriage data were also collected in 2003 and 2005 from four regions in the Northern Territory. Twenty-six cases of serotype 1 IPD were reported from 1994 to 2007 in the Northern Territory. Forty-four isolates were analyzed by BOX typing and 11 by multilocus sequence typing. In the Darwin region, 26 children were reported carrying serotype 1 (ST227) in 2002 but not during later surveillance. Scattered cases of serotype 1 carriage were noted in two other regions. Cocolonization of serotype 1 with other pneumococcal serotypes was common (34% serotype 1-positive swabs). In conclusion, pneumococcal carriage studies detected intermittent serotype 1 carriage and an ST227 cluster in children in indigenous communities in the Northern Territory of Australia. There was no apparent increase in serotype 1 IPD during this time. The rate of serotype 1 cocolonization with other pneumococcal serotypes suggests that carriage of this serotype may be underestimated.
Generation of Immune Responses against Hepatitis C Virus by Dendritic Cells Containing NS5 Protein-Coated Microparticles
Authors: Gehring Stephan , Gregory Stephen H. , Wintermeyer Philip , Aloman Costica , Wands Jack R. 
Published: December 2008

ABSTRACTDendritic cells (DCs) internalize and process antigens as well as activate cellular immune responses. The aim of this study was to determine the capacity of DCs that contain antigen-coated magnetic beads to induce immunity against the nonstructural hepatitis C virus (HCV) antigen 5 (NS5). Splenocytes derived from Fms-like tyrosine kinase receptor 3 (Flt3) ligand-pretreated BALB/c mice were incubated with magnetic beads coated with HCV NS5, lipopolysaccharide (LPS), and/or anti-CD40; purified; and used for immunization. Cellular immunity was measured using cytotoxic T-lymphocyte (CTL) and T-cell proliferation assays, intracellular cytokine staining, and a syngeneic tumor challenge using NS5-expressing SP2/0 myeloma cells in vivo. Splenocytes isolated from animals vaccinated with DCs containing beads coated with NS5, LPS, and anti-CD40 secreted elevated levels of interleukin-2 (IL-2) and gamma interferon in the presence of NS5. The numbers of CD4+, IL-2-producing cells were increased >5-fold in the group immunized with DCs containing beads coated with NS5, LPS, and anti-CD40, paralleled by an enhanced splenocyte proliferative response. Immunization promoted antigen-specific CTL activity threefold compared to the level for control mice and significantly reduced the growth of NS5-expressing tumor cells in vivo. Thus, strategies that employ NS5-coated beads induce cellular immune responses in mice, which correlate well with the natural immune responses that occur in individuals who resolve HCV.
Immunogenicity of a Reduced Schedule of Meningococcal Group C Conjugate Vaccine Given Concomitantly with the Prevenar and Pediacel Vaccines in Healthy Infants in the United Kingdom
Authors: Southern Jo , Borrow Ray , Andrews Nick , Morris Rhonwen , Waight Pauline , Hudson Michael , Balmer Paul , Findlow Helen , Findlow Jamie , Miller Elizabeth 
Published: December 2008

ABSTRACT

This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids,
Haemophilus influenzae
type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of ≥8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM
197
). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies.
Cocirculation of Antigenic Variants and the Vaccine-Type Virus during the 2004-2005 Influenza B Virus Epidemics in Japan
Authors: Nakagawa Naoko , Higashi Natsumi , Nakagawa Toshimasa 
Published: December 2008

ABSTRACT
In the 2004-2005 season, there was a large epidemic of the influenza B virus Yamagata group in Kobe, Japan. In hemagglutination inhibition tests, most of the clinical isolates from Kobe showed antigenicities similar to those of previous isolates (the vaccine-type virus). Only a few antigenic variants were isolated around the peak of the epidemic; however, Kobe residents developed antibodies against the variants during the season. The antigenic variants showed a one-point mutation of a nucleotide in the HA1 gene (C440A or G421A), which resulted in the substitution of one amino acid in the 150 loop of the HA molecule (T147N or G141R). The 150 loop is one of four epitopes of the hemagglutinin molecule of the influenza B virus. We established a system to detect one-point differences in the nucleotides of the 150 loop by means of high-resolution melting curve analysis with LCGreen. With this system, the isolates were determined to be the vaccine-type virus, antigenic variants, or a mixture of both. Some isolates were shown to be mixtures although they had been recognized as the vaccine-type virus with the hemagglutination inhibition tests. Thus, the antigenic variants appeared in the early period of the epidemic and were cocirculating with the vaccine-type virus during the epidemic.
Abbott RealTime Hepatitis C Virus (HCV) and Roche Cobas AmpliPrep/Cobas TaqMan HCV Assays for Prediction of Sustained Virological Response to Pegylated Interferon and Ribavirin in Chronic Hepatitis C Patients
Authors: Matsuura Kentaro , Tanaka Yasuhito , Hasegawa Izumi , Ohno Tomoyoshi , Tokuda Hiroshi , Kurbanov Fuat , Sugauchi Fuminaka , Nojiri Shunsuke , Joh Takashi , Mizokami Masashi 
Published: December 2008

ABSTRACT
Two commercial real-time PCR assays are currently available for sensitive hepatitis C virus (HCV) RNA quantification: the Abbott RealTime HCV assay (ART) and Roche Cobas AmpliPrep/Cobas TaqMan HCV assay (CAP/CTM). We assessed whether the two real-time PCR assays were more effective than Roche Cobas Amplicor HCV Monitor test, v.2.0 (CAM) for prediction of the sustained virological response (SVR) to pegylated interferon (PEG-IFN) plus ribavirin (RBV) in chronic hepatitis C. Sixty patients chronically infected with HCV genotype 1b (37 males and 23 females, 53 ± 12 years of age) were treated with PEG-IFNα2b plus RBV for 48 weeks. Stored specimens at nine time points for each patient (at baseline, on treatment, and 24 weeks after treatment) were tested by the two real-time PCR assays and CAM. Twenty-six (43.3%) patients reached SVR. The positive predictive values (PPVs) for SVR of undetectable HCV RNA at week 12 by CAM, ART, and CAP/CTM were 74.3%, 88.0%, and 95.2%, respectively. An undetectable HCV RNA level by CAM, ART, and CAP/CTM correctly predicted SVR at week 4 in 100%, 100%, and 100% of patients, at weeks 5 to 8 in 91.7%, 100%, and 100% of patients, at weeks 9 to 12 in 55.6%, 75%, and 87.5% of patients, and at weeks 13 to 24 in 0%, 26.7%, and 40% of patients, respectively. Of 16 patients who relapsed after treatment, HCV RNA was detectable in 2 patients at the end of treatment by CAP/CTM but undetectable by ART and CAM. HCV RNA tests using ART and CAP/CTM are considered to be more effective at predicting SVR than CAM, and the PPV for SVR was slightly higher in CAP/CTM than in ART.
Proteasomal Turnover of Hepatitis C Virus Core Protein Is Regulated by Two Distinct Mechanisms: a Ubiquitin-Dependent Mechanism and a Ubiquitin-Independent but PA28γ-Dependent Mechanism
Authors: Suzuki Ryosuke , Moriishi Kohji , Fukuda Kouichirou , Shirakura Masayuki , Ishii Koji , Shoji Ikuo , Wakita Takaji , Miyamura Tatsuo , Matsuura Yoshiharu , Suzuki Tetsuro 
Published: December 2008

ABSTRACT
We have previously reported on the ubiquitylation and degradation of hepatitis C virus core protein. Here we demonstrate that proteasomal degradation of the core protein is mediated by two distinct mechanisms. One leads to polyubiquitylation, in which lysine residues in the N-terminal region are preferential ubiquitylation sites. The other is independent of the presence of ubiquitin. Gain- and loss-of-function analyses using lysineless mutants substantiate the hypothesis that the proteasome activator PA28γ, a binding partner of the core, is involved in the ubiquitin-independent degradation of the core protein. Our results suggest that turnover of this multifunctional viral protein can be tightly controlled via dual ubiquitin-dependent and -independent proteasomal pathways.