bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative MRI Studies of Chronic Brain White Matter Hyperintensities in Migraine Patients
Authors: Aradi Mihály , Schwarcz Attila , Perlaki Gábor , Orsi Gergely , Kovács Norbert , Trauninger Anita , Kamson David Olayinka , Erdélyi‐Bótor Szilvia , Nagy Ferenc , Nagy Szilvia Anett , Dóczi Tamás , Komoly Sámuel , Pfund Zoltán 
Published: December 2012

ObjectiveThe aim of this study was to examine chronic brain white matter hyperintensities in migraine and to gain data on the characteristics of the lesions.BackgroundMigraine associates with a higher incidence of magnetic resonance imaging (MRI)‐visible white matter signal abnormalities. Several attack‐related pathomechanisms have been proposed in the lesion development, including the effect of repeated intracerebral hemodynamic changes.MethodsSupratentorial white matter hyperintensities of 17 migraine patients were investigated interictally with quantitative MRI, including quantitative single voxel spectroscopy, diffusion, and perfusion MRI at 3.0‐Tesla. The findings were compared with data measured in the contralateral, normal‐appearing white matter of migraineurs and in the white matter of 17 healthy subjects.ResultsSignificantly higher apparent diffusion coefficient values, prolonged T2 relaxation times, and decreased N‐acetyl‐aspartate and creatine/phosphocreatine concentrations were found in the white matter hyperintensities. The cerebral blood flow and blood volume values were mildly decreased inside the hyperintensities. Differences were not present between the migraine patients' normal‐appearing white matter and the white matter of healthy subjects.ConclusionsThe MRI measurements denote tissue damage with axonal loss, low glial cell density, and an enlarged extracellular space with an increased extracellular water fraction. These radiological features might be the consequences of microvascular ischemic changes during migraine attacks.
Evaluation of Sumatriptan‐Naproxen in the Treatment of Acute Migraine: A Placebo‐Controlled, Double‐Blind, Cross‐Over Study Assessing Cognitive Function
Authors: Edwards Keith R. , Rosenthal Barbara L. , Farmer Kathleen U. , Cady Roger K. , Browning Rebecca 
Published: December 2012

ObjectiveTo assess the cognitive effects of acute migraine and the subsequent impact of acute treatment in a controlled setting.BackgroundCognitive dysfunction may be an associated symptom in patients with migraine with or without aura. The loss of cognitive efficiency in migraine may be disabling and is often under recognized.MethodsThirty migraine patients were prospectively studied for cognitive function before and then at the beginning of a migraine using a computerized cognitive battery (Mental Efficacy Workload Test). Each patient then was treated for 2 headaches in a cross‐over manner with sumatriptan‐naproxen (Treximet®) or placebo in a double‐blind, placebo‐controlled fashion with cognitive testing repeated at 1 and 2 hours post‐dose.ResultsTwenty‐five of the 30 screened migraine subjects completed study‐specific procedures and were included in the data analyses. There were no significant side effects from Treximet or placebo and no serious adverse events. At the onset of headache, there was a statistically significant decline in overall cognitive efficiency compared with the baseline cognitive testing (migraine‐free) for all subjects (P = .001 paired samples t‐test). For subjects taking Treximet compared with taking placebo, there was a statistically significant return to cognitive efficiency by measures of immediate and sustained attention, visual‐spatial awareness, mental flexibility, and reaction time between 1 hour and 2 hours (P = .05). There was no statistical significance between patients taking Treximet or placebo in measures of complex reasoning or fine motor coordination. Subanalysis showed a correlation between headache severity and Performance Index in the Treximet group but not in the placebo group (∼Fig. ).ConclusionsThere is a significant decline in global cognitive efficiency at the onset of an attack of migraine. The use of Treximet allows a significantly faster recovery time in some measures of cognitive efficiency compared with placebo. Decline of cognitive efficiency may be independent of headache severity.
Warming effect on miriplatin–lipiodol suspension for potential use as a chemotherapeutic agent for transarterial chemoembolization of hepatocellular carcinoma: In vitro study
Authors: Kora Shin‐ichi , Urakawa Hiroshi , Mitsufuji Toshimichi , Osame Akinobu , Higashihara Hideyuki , Ohki Toshihiro , Yoshimitsu Kengo 
Published: December 2012

AimTo elucidate whether warming may reduce the viscosity of miriplatin–lipiodol suspension (MPT/LPD) and also the injection pressure through microcatheters, for potential use as a chemotherapeutic agent of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).MethodsViscosity of MPT/LPD prepared at on‐label dose was measured in vitro at 25°C, 30°C, 40°C, 50°C and 60°C using capillary tube method. Reproducibility of viscosity change was also tested. Injection pressure through two different commercially available microcatheters was measured using a rheometer. Data sampling was performed at least twice for each measurement.ResultsViscosity of MPT/LPD was significantly reduced as the temperature was elevated (R2 = 0.9586, P < 0.0001, Pearson's correlation); at 40°C, it was almost half of that at room temperature (25°C). Repeated warming and cooling down of MPT/LPD revealed good reproducibility of viscosity change. Injection pressure through either microcatheter showed significant reduction when MPT/LPD was warmed (P < 0.05, Spearman's rank correlation coefficient).ConclusionThe viscosity and injection pressure through microcatheters of MPT/LPD was confirmed to reduce significantly as the temperature is elevated. MPT/LPD warmed to 40°C has half viscosity as that at room temperature and is considered suitable for clinical use. Warming MPT/LPD may have potential to facilitate the procedure of TACE for HCC.
Detection of highly prevalent hepatitis B virus co‐infection with HIV in Indonesia
Authors: Utsumi Takako , Yano Yoshihiko , Lusida Maria I. , Nasronudin  , Amin Mochamad , Juniastuti  , Soetjipto  , Hotta Hak , Hayashi Yoshitake 
Published: December 2012

AimThe prevalence of hepatitis B virus (HBV) co‐infection with HIV is increasing worldwide because of shared transmission routes. This study aimed to assess the prevalence of HBV and HIV co‐infection in Indonesia, and its molecular and clinical characteristics.MethodsA total of 118 serum samples from HIV‐infected patients (age 33.3 ± 8.9 years, 99 male, 19 female) collected in 2009 were serologically examined. HBV DNA was assessed by polymerase chain reaction (PCR) analysis targeting the S region.ResultsOverall, 15.3% (18/118) of the patients were hepatitis B surface antigen (HBsAg) positive, whereas 27.1% (32/118) were HBsAg negative but HBV DNA positive, and were considered to have occult HBV infection. HBsAg antibodies and/or HBV core antibodies were detected in 45.6% (31/68) of HBV DNA negative patients.ConclusionHBV co‐infection, including occult HBV infection, was common in Indonesian HIV patients. Hepatic damage by the interaction of host immunity and HBV is still a remaining issue in these immunosuppressive patients, and further study will be needed.
Evaluation of the effect of sorafenib using serum NX‐des‐γ‐carboxyprothrombin in patients with hepatocellular carcinoma
Authors: Miyahara Koji , Nouso Kazuhiro , Morimoto Yuki , Tomoda Takeshi , Kobayashi Sayo , Takeuchi Yasuto , Hagihara Hiroaki , Kuwaki Kenji , Ohnishi Hideki , Ikeda Fusao , Miyake Yasuhiro , Nakamura Shinichiro , Shiraha Hidenori , Takaki Akinobu , Yamamoto Kazuhide ,   Okayama Liver Cancer Group
Published: December 2012

AimDes‐γ‐carboxyprothrombin (DCP) is known to be increased by the use of sorafenib for the treatment of hepatocellular carcinoma (HCC), despite its therapeutic efficacy. In addition to the tumor progression, hypoxia that impairs vitamin K uptake is known to induce DCP and this mechanism may explain DCP elevation by sorafenib. In this study, we tried to evaluate the effect of sorafenib treatment using a new marker, NX‐DCP, which is specific to vitamin K absence.MethodsSerum DCP and NX‐DCP were measured in 50 consecutive HCC patients before and 1 week after starting sorafenib, and compared with the treatment effect using the modified Response Evaluation Criteria in Solid Tumors guidelines.ResultsDCP and NX‐DCP increased 1.58‐ (median, range 0.21–28.7) and 1.20‐fold (median, range 0.41–14.2) after the administration of sorafenib, respectively. The increases of both markers were less than twofold in approximately half of the patients (low‐elevation group). However, 12 patients showed over twofold increase of both DCP and NX‐DCP (double‐elevation group), and eight patients showed over twofold increase of DCP alone (DCP‐elevation group). The disease control rate (DCR) of the DCP‐elevation group (12.5%) was significantly lower than those of the double‐elevation group (75.0%, P = 0.020) and the low‐elevation group (60.0%, P = 0.042). Progression‐free survival (PFS) was significantly shorter in the DCP‐elevation group than in the double‐elevation group (P = 0.006) and the low‐elevation group (P = 0.001).ConclusionNX‐DCP in combination with DCP could be a useful biomarker of sorafenib treatment for advanced HCC.
Survey of non‐B, non‐C liver cirrhosis in Japan
Authors: Suzuki Yasuaki , Ohtake Takaaki , Nishiguchi Shuhei , Hashimoto Etsuko , Aoyagi Yutaka , Onji Morikazu , Kohgo Yutaka ,   The Japan Non‐B, Non‐C Liver Cirrhosis Study Group
Published: December 2012

AimThe aim of this survey was to reveal clinical features for each etiology of non‐B, non‐C liver cirrhosis (NBNC LC) in Japan.MethodsIn a nationwide survey of NBNC LC in Japan at the 15th General Meeting of the Japan Society of Hepatology, 6999 NBNC LC patients were registered at 48 medical institutions. Epidemiological and clinical factors were investigated.ResultsThe percentage of NBNC LC among LC patients was 26%. NBNC LC patients were categorized into 11 types according to etiological agents: non‐alcoholic steatohepatitis (NASH), 14.5%; alcoholic liver disease (ALD), 55.1%; fatty liver disease (FLD), except NASH, ALD, and other known etiology, 2.5%; primary biliary cirrhosis, 8.0%; other biliary cirrhosis, 0.8%; autoimmune hepatitis, 6.8%; metabolic disease, 0.6%; congestive disease, 0.8%; parasitic disease, 0.2%; other known etiology, 0.2%; and unknown etiology, 10.5%. Compared with previous surveys, the percentage of ALD remained unchanged, whereas that of NASH increased. The mean age and percentage of females were significantly higher in NASH patients than in ALD and FLD patients. Prevalence of diabetes mellitus was significantly higher in NASH and FLD patients than in ALD ones. Prevalence of hepatocellular carcinoma (HCC) in NBNC LC patients was 35.9%. Among NASH, ALD and FLD patients, 50.9%, 34.3% and 54.5% had HCC, respectively. Positivity of hepatitis B core antibody was significantly higher in HCC patients than in those without HCC (41.1% vs 24.8%).ConclusionThis survey determined the etiology of NBNC LC in Japan. These results should contribute new ideas toward understanding NBNC LC and NBNC HCC.
Comprehensive evaluation of twoHLA‐B17 monoclonal antibodies for flow cytometry‐basedHLA‐B57/B58 screening prior to abacavir prescription
Authors: Stevens R. , Coates E. , Street J. , Cook E. , Darke C. 
Published: December 2012

SummaryHypersensitivity reactions to the drug abacavir, used to treatHIV/AIDSpatients, is associated with possession ofHLA‐B*57:01. We have carefully assessed two commercially availableHLA‐B57/B58 murine monoclonal antibodies [0196HAandBIH0243 (OneLambdaInc.)] in a simple flow cytometry‐based assay. The evaluation involved tests on 228 reference and random samples covering 91% of allWHOrecognizedHLA‐A,BandCspecificities. These involved donors with six differentHLA‐B*57 alleles and included 19 examples ofB*57:01. Both antibodies unambiguously detectedB57, but there were small difference in their reactivity againstB57‐positive non‐B*57:01 samples. Importantly, there was no reactivity againstB57/B58‐negative samples. The possible amino acid motifs involved in the reactivity of these antibodies withB57/B58 were delineated. Thus,HLA‐B57/B58, normally present in <10% of patients, can be easily recognized using these two antibodies and further tested by aDNA‐based typing method to identifyB*57:01.
16th IHIW: Global analysis of registry HLA haplotypes from 20 Million individuals: Report from the IHIW Registry Diversity Group
Authors: Maiers M. , Gragert L. , Madbouly A. , Steiner D. , Marsh S. G. E. , Gourraud P.‐A. , Oudshoorn M. , van der Zanden H. , Schmidt A. H. , Pingel J. , Hofmann J. , Müller C. , Eberhard H.‐P. 
Published: December 2012

SummaryThis project has the goal to validate bioinformatics methods and tools for HLA haplotype frequency analysis specifically addressing unique issues of haematopoietic stem cell registry data sets. In addition to generating new methods and tools for the analysis of registry data sets, the intent is to produce a comprehensive analysis of HLA data from 20 million donors from the Bone Marrow Donors Worldwide (BMDW) database. This report summarizes the activity on this project as of the 16IHIW meeting in Liverpool.
Chemokine programming dendritic cell antigen response: part I – select chemokine programming of antigen uptake even after maturation
Authors: Park Jaehyung , Wu Cindy T. , Bryers James D. 
Published: December 2012

SummaryHere, we report on the successful programming of dendritic cells (DCs) using selectively applied mixtures of chemokines as a novel protocol for engineering vaccine efficiency. Antigen internalization by DCs is a pivotal step in antigen uptake/presentation for bridging innate and adaptive immunity and in exogenous gene delivery used in vaccine strategies. Contrary to most approaches to improve vaccine efficiency, active enhancement of antigen internalization by DCs as a vaccine strategy has been less studied because DCs naturally down‐regulate antigen internalization upon maturation. Whereas chemokines are mainly known as signal proteins that induce leucocyte chemotaxis, very little research has been carried out to identify any additional effects of chemokines on DCs following maturation. Here, immature DCs are pre‐treated with select chemokines before intentional maturation using lipopolysaccharide (LPS). When pre‐treated with a mixture of CCL3 and CCL19 in a 7 : 3 ratio, then matured with LPS, chemokine pre‐treated DCs exhibited 36% higher antigen uptake capacity than immature DCs and 27% higher antigen‐processing capacity than immature DCs treated only with LPS. Further, CCL3 : CCL19 (7 : 3) pre‐treatment of DCs modulated MHC molecule expression and secretion of various cytokines of DCs. Collectively, DC programming was feasible using a specific chemokine combination and these results provide a novel strategy for enhancing DC‐based vaccine efficiency. In Part II, we report on the phenotype changes and antigen presentation capacity of chemokine pre‐treated murine bone marrow‐derived DCs examined in long‐term co‐culture with antigen‐specific CD4+ T cells.
Epigenetic aspects of lymphocyte antigen receptor gene rearrangement or ‘when stochasticity completes randomness’
Authors: Jaeger Sébastien , Fernandez Bastien , Ferrier Pierre 
Published: December 2012

SummaryTo perform their specific functional role, B and T lymphocytes, cells of the adaptive immune system of jawed vertebrates, need to express one (and, preferably, only one) form of antigen receptor, i.e. the immunoglobulin or T‐cell receptor (TCR), respectively. This end goal depends initially on a series of DNA cis‐rearrangement events between randomly chosen units from separate clusters of V, D (at some immunoglobulin and TCR loci) and J gene segments, a biomolecular process collectively referred to as V(D)J recombination. V(D)J recombination takes place in immature T and B cells and relies on the so‐called RAG nuclease, a site‐specific DNA cleavage apparatus that corresponds to the lymphoid‐specific moiety of the VDJ recombinase. At the genome level, this recombinase's mission presents substantial biochemical challenges. These relate to the huge distance between (some of) the gene segments that it eventually rearranges and the need to achieve cell‐lineage‐restricted and developmentally ordered routines with at times, mono‐allelic versus bi‐allelic discrimination. The entire process must be completed without any recombination errors, instigators of chromosome instability, translocation and, potentially, tumorigenesis. As expected, such a precisely choreographed and yet potentially risky process demands sophisticated controls; epigenetics demonstrates what is possible when calling upon its many facets. In this vignette, we will recall the evidence that almost from the start appeared to link the two topics, V(D)J recombination and epigenetics, before reviewing the latest advances in our knowledge of this joint venture.
Roles of repressive epigenetic machinery in lineage decision of T cells
Authors: Naito Taku , Taniuchi Ichiro 
Published: December 2012

SummaryDNA methylation and histone modifications are central to epigenetic gene regulation, which has been shown to play a crucial role in development. Epigenetics has often been discussed in the context of the maintenance of cell identity because of the heritable nature of gene expression status. Indeed, crucial roles of the epigenetic machinery in establishment and maintenance of particular lineages during early development have been well documented. However, unexpected observation of a developmental plasticity retained in mature T lymphocytes, in particular in CD4+ T‐cell subsets, by recent studies is accelerating studies that focus on roles of each epigenetic pathway in cell fate decisions of T lymphocytes. Here, we focus on the repressive epigenetic machinery, i.e. DNA methylation, histone deacetylation, H3K9 methylation and Polycomb repressive complexes, and briefly review the studies examining the role of these mechanisms during T‐lymphocyte differentiation. We also discuss the current challenges faced when analysing the function of the epigenetic machinery and potential directions to overcome the problems.
Chemokine programming dendritic cell antigen response: part II – programming antigen presentation to T lymphocytes by partially maintaining immature dendritic cell phenotype
Authors: Park Jaehyung , Bryers James D. 
Published: December 2012

SummaryIn a companion article to this study,1 the successful programming of a JAWSII dendritic cell (DC) line's antigen uptake and processing was demonstrated based on pre‐treatment of DCs with a specific ‘cocktail’ of select chemokines. Chemokine pre‐treatment modulated cytokine production before and after DC maturation [by lipopolysaccharide (LPS)]. After DC maturation, it induced an antigen uptake and processing capacity at levels 36% and 82% higher than in immature DCs, respectively. Such programming proffers a potential new approach to enhance vaccine efficiency. Unfortunately, simply enhancing antigen uptake does not guarantee the desired activation and proliferation of lymphocytes, e.g. CD4+ T cells. In this study, phenotype changes and antigen presentation capacity of chemokine pre‐treated murine bone marrow‐derived DCs were examined in long‐term co‐culture with antigen‐specific CD4+ T cells to quantify how chemokine pre‐treatment may impact the adaptive immune response. When a model antigen, ovalbumin (OVA), was added after intentional LPS maturation of chemokine‐treated DCs, OVA‐biased CD4+T‐cell proliferation was initiated from ~ 100% more undivided naive T cells as compared to DCs treated only with LPS. Secretion of the cytokines interferon‐γ, interleukin‐1β, interleukin‐2 and interleukin‐10 in the CD4+ T cell : DC co‐culture (with or without chemokine pre‐treatment) were essentially the same. Chemokine programming of DCs with a 7 : 3 ratio of CCL3 : CCL19 followed by LPS treatment maintained partial immature phenotypes of DCs, as indicated by surface marker (CD80 and CD86) expression over time. Results here and in our companion paper suggest that chemokine programming of DCs may provide a novel immunotherapy strategy to obviate the natural endocytosis limit of DC antigen uptake, thus potentially increasing DC‐based vaccine efficiency.
Dendritic cells from human mesenteric lymph nodes in inflammatory and non‐inflammatory bowel diseases: subsets and function of plasmacytoid dendritic cells
Authors: Hostmann Arwed , Kapp Kerstin , Beutner Marianne , Ritz Jörg‐Peter , Loddenkemper Christoph , Ignatius Ralf , Duchmann Rainer , Daum Severin , Gröne Jörn , Hotz Hubert , Buhr Heinz‐Johannes , Zeitz Martin , Ullrich Reiner 
Published: December 2012

SummaryPlasmacytoid dendritic cells (pDC) in mesenteric lymph nodes (MLN) may be important regulators of both inflammatory and non‐inflammatory mucosal immune responses but human studies are rare. Here we compare pDC from human MLN and peripheral blood (PB) by phenotype and function. MLN from patients with or without inflammatory bowel disease (IBD) undergoing colon surgery and PB from patients with IBD and from controls were used to isolate mononuclear cells. The pDC were analysed by flow cytometry for the expression of CD40, CD80, CD83, CD86, CCR6, CCR7, CX3CR1, CD103 and HLA‐DR. Purified pDC from MLN and PB were stimulated with staphylococcus enterotoxin B (SEB), CpG‐A, interleukin‐3 (IL‐3), SEB + IL‐3, CpG‐A + IL‐3 or left unstimulated, and cultured alone or with purified allogeneic CD4+ CD45RA+ HLA‐DR‐ T cells. Subsequently, concentrations of IL‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, IL‐17, interferon‐α (IFN‐α), IFN‐γ and tumour necrosis factor‐α (TNF‐α) in culture supernatants were determined by multiplex bead array. The PB pDC from IBD patients exhibited an activated and matured phenotype whereas MLN pDC and control PB pDC were less activated. CpG‐A and CpG‐A + IL‐3‐stimulated MLN pDC secreted less IL‐6 and TNF‐α compared with PB pDC from controls. Compared with co‐cultures of naive CD4 T cells with PB pDC, co‐cultures with MLN pDC contained more IL‐2, IL‐10 and IFN‐γ when stimulated with SEB and SEB + IL‐3, and less IFN‐α when stimulated with CpG‐A. MLN pDC differ phenotypically from PB pDC and their pattern of cytokine secretion and may contribute to specific outcomes of mucosal immune reactions.