Association of dengue virus type-specific IgG on platelets is specific for the acute phase in an imported Japanese patient with secondary dengue 2 virus infection

The mechanism of thrombocytopenia in dengue virus infection remains unknown. We report herein an imported case of a 21-year-old male Japanese with dengue fever caused by secondary dengue 2 virus infection. The thrombocytopenia detected around the day of defervescence was associated with an increased level of plateletassociated IgG (PAIgG). The eluate from the platelets during the acute phase of this case contained an increased activity of anti-dengue virus 2 IgG, while the eluate from platelets during the convalescent phase contained a low level of anti-dengue 2 IgG. These findings suggest the transient formation of PAIgG involving anti-dengue 2 virus IgG during the acute phase of secondary dengue 2 virus infection

Increased IP-10 production by blood–nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy

Objective Dysfunction of the blood–nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN. Methods We determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system. Results The induced protein (IP)10 level in the cells in both the MADSAM and MMN groups was markedly increased in comparison with the typical CIDP, ALS and HC groups. The other cytokines, including granulocyte colony-stimulating factor, vascular endothelial growth factor (VEGF) and interleukin-7, were also significantly upregulated in the MADSAM group. The increase of IP-10 produced by PnMECs was correlated with the presence of conduction block in both the MADSAM and MMN groups. Conclusion The autocrine secretion of IP-10 induced by patient sera in PnMECs was markedly upregulated in both the MADSAM and MMN groups. The overproduction of IP-10 by PnMECs leads to the focal breakdown of the BNB and may help to mediate the transfer of pathogenic T cells across the BNB, thereby resulting in the appearance of conduction block in electrophysiological studies of patients with MADSAM and MMN

The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma

Background & Aims: Recent evidence suggests that hepatocellular carcinoma can be classified into certain molecular subtypes with distinct prognoses based on the stem/maturational status of the tumor. We investigated the transcription program deregulated in hepatocellular carcinomas with stem cell features. Methods: Gene and protein expression profiles were obtained from 238 (analyzed by microarray), 144 (analyzed by immunohistochemistry), and 61 (analyzed by qRT-PCR) hepatocellular carcinoma cases. Activation/suppression of an identified transcription factor was used to evaluate its role in cell lines. The relationship of the transcription factor and prognosis was statistically examined. Results: The transcription factor SALL4, known to regulate stemness in embryonic and hematopoietic stem cells, was found to be activated in a hepatocellular carcinoma subtype with stem cell features. SALL4-positive hepatocellular carcinoma patients were associated with high values of serum alpha fetoprotein, high frequency of hepatitis B virus infection, and poor prognosis after surgery compared with SALL4-negative patients. Activation of SALL4 enhanced spheroid formation and invasion capacities, key characteristics of cancer stem cells, and up-regulated the hepatic stem cell markers KRT19, EPCAM, and CD44 in cell lines. Knockdown of SALL4 resulted in the down-regulation of these stem cell markers, together with attenuation of the invasion capacity. The SALL4 expression status was associated with histone deacetylase activity in cell lines, and the histone deacetylase inhibitor successfully suppressed proliferation of SALL4-positive hepatocellular carcinoma cells. Conclusions: SALL4 is a valuable biomarker and therapeutic target for the diagnosis and treatment of hepatocellular carcinoma with stem cell features. © 2013 European Association for the Study of the Liver

ザッシ ニ ケイサイ サレタ コウコク ナイヨウ カラ ミタ ドッグ フード ノ ヘンセン

人とペットの関係が近年経てきた変遷を裏付けることを目的に,ペットの主役である犬の市販フードに着目し,その変容について調査を行なった。調査は犬の雑誌で出版開始年が1952年の「愛犬の友」(誠文堂新光社)とし,手に入れられた1966年から2009年までの雑誌に掲載されたドッグフード広告に使われた文言の出現割合を集計した。掲載広告の中で使われた商品アピールのための文言をその内容から分類し,その抽出数を商品数で割って出現割合として分析した。その結果,広告数と商品数の増減は景気動向の年変化と一致した。調査期間における広告内容をみると,ドッグフードの創成期には便利で使いやすいことを広告し,創成期を過ぎると安全で健康に良いことを広告する内容に変化したことが示された。項目内で文言の経年変化をみると,安全性を謳う文言は人における健康ブームや食への不安意識を追うように,1990年以降に有意に高い出現割合を示した。以上のことから,ドッグフードの広告内容は人の経済や生活意識に強く影響されることが示唆された。In order to examine how the status of pets within families has changed in Japan, this study focuses on developments in commercial dog food advertisements. Along with the number of advertisements for dog food, trends in the words used in printed dog food advertisements in "Aiken" (Seibundo Shinkosha Publishing Co., Ltd.), a magazine for dog owners first published in 1952, were recorded and classified based on meaning. This survey was performed using issues published between 1966 and 2009. The emergence rate of the word items was calculated based on the recorded frequency of items related to dog food. The results revealed that at the start of dog food production in Japan, wording in advertisements stressed the convenience of using the products. In contrast, after the starting period of dog food production, words emphasizing the health of the food began to appear with higher frequency. The emergence rate of the word item category "safety" was significantly higher after 1990, which corresponds to the health boom as well as the general public\u27s distrust of the food industry. Shifts in the number of paid advertisements and the number of types of dog food-related items were influenced by general economic highs and lows. In conclusion, the word items used in dog food advertisements reflected trends in the economy and society

Lack of Efficacy of High-Dose Intravenous Immunoglobulin Treatment of Severe Thrombocytopenia in Patients with Secondary Dengue Virus Infection

Because most cases of secondary dengue virus infection are associated with an increased level of platelet-associated IgG, a high dose of intravenous immunoglobulin (IVIG) may have an effect on the development of severe thrombocytopenia in this disease. A randomized, controlled study was conducted with two treatment groups consisting of a treatment (IVIG) group (n = 15) and a non-treatment (non-IVIG) group (n = 16) to determine whether a high dose of IVIG is effective in hastening the recovery from thrombocytopenia in patients with secondary dengue virus infection. No significant difference was found in the baseline demographic data between the two groups. No adverse effect of IVIG was observed, but no effect in hastening the recovery of platelet counts was found in patients with secondary dengue infections. The lack of efficacy of IVIG suggests that platelet clearance by macrophages through Fc {gamma} receptors is not a primary mechanism in this disease

Increased phagocytosis of platelets from patients with secondary dengue virus infection by human macrophages.

The relationship between the percent phagocytosis of platelets by differentiated THP-1 cells was examined using flowcytometry and the peripheral platelet counts as well as platelet-associated IgG (PAIgG) in 36 patients with secondary dengue virus (DV) infections. The percent phagocytosis and the levels of PAIgG were significantly increased in these patients during the acute phase compared with the healthy volunteers. The increased percent phagocytosis and PAIgG found during the acute phase significantly decreased during the convalescent phase. An inverse correlation between platelet count and the percent phagocytosis (P = 0.011) and the levels of PAIgG (P = 0.041) was found among these patients during the acute phase. No correlation was found, however, between the percent phagocytosis and the levels of PAIgG. Our present data suggest that accelerated platelet phagocytosis occurs during the acute phase of secondary DV infections, and it is one of the mechanisms of thrombocytopenia in this disease

Transcription and Translation Products of the Cytolysin Gene psm-mec on the Mobile Genetic Element SCCmec Regulate Staphylococcus aureus Virulence

The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus

Forestry Education in Japanese Vocational High Schools:Historical outlook and present status

The continuous fostering of young foresters as the future experts is one of the fundamental key's to realize the sustainable forest management. The forestry education in vocational high school in Japan is facing drastic change reflecting nation's social and economical shift so that new perspective and solution in forest and forestry education is required for accelerating forest sustainability at nation level. We therefore analyzed and discussed on the historical outlook and present status of forestry courses in vocational high school in Japan as the training institution of professional foresters. Since Japanese government had launched on educating forestry at schools in 1882 with following German system in order to train the forester candidates, there were some very apparent milestones. Obviously, forestry education is influenced strongly by social and economical condition. Main agents drove objectives of forestry education were the expanding demand on forest renovation and increasing wood production in postwar recovery, decline of forestry due to both fuel revolution and voluntary tariff reduction of timber after 1960's, respectively, as well as the decline of forestry courses applicants due to desiring for higher educational career and declining birth rate. The historical overview suggested the objective of forestry education shifted from training of technician to giving basic education for the candidate of specialists. Totally 70 high schools which have forestry related courses in 2007 are facing to three major issues i.e. (1) decrease of job opportunity relate with forestry and wood products both in official and private forest sector, (2) decrease of students reflecting the decline of birth rate together with the increase of general courses applicants, (3) difficulty in conserving teacher's specialty due to frequent reshuffling. We categorized those high schools with forestry courses into 5 groups as in the following by their educational target which concerned with occupations of graduates i.e. (a) fostering forest technicians in companies, (b)fostering forest officers, (c)fostering local successors, (d)education directing higher educational chance, (e)encouraging the talent through forestry education. Objectives which are groping for new perspectives have differentiated into three directions i.e. fostering forestry successors, fostering human resources who take leadership in regional society, and humanities molding through forestry subjects as well. It is urged to discuss the direction of either as whole Japan or regional condition in order to find proper future of forestry education

Impact of the TRPV2 Inhibitor on Advanced Heart Failure in Patients with Muscular Dystrophy: Exploratory Study of Biomarkers Related to the Efficacy of Tranilast

Cardiomyopathy is the leading cause of death in patients with muscular dystrophy (MD). Tranilast, a widely used anti-allergic drug, has displayed inhibitory activity against the transient receptor potential cation channel subfamily V member 2 and improved cardiac function in MD patients. To identify urinary biomarkers that assess improved cardiac function after tranilast administration, we performed a urinary metabolomic study focused on oxidative fatty acids. Accompanying the clinical trial of tranilast, urine specimens were collected over 24 weeks from MD patients with advanced heart failure. Urinary levels of tetranor-PGDM (tetranor-prostaglandin D metabolite), a metabolite of prostaglandin D2, significantly decreased 12 weeks after tranilast administration and were correlated with BNP. These results suggest that prostaglandin-mediated inflammation, which increases with the pathological progression of heart failure in MD patients, was attenuated. Urinary prostaglandin E3 (PGE3) levels significantly increased 4 weeks after tranilast administration. There were positive correlations between the urinary levels of PGE3 and 8-hydroxy-2′-deoxyguanosine, an oxidative stress marker. High PGE3 levels may have a protective effect against cardiomyopathy in MD patients with high oxidative stress. Although further validation studies are necessary, urinary tetranor-PGDM and PGE3 levels may help the current understanding of the extent of advanced heart failure in patients with MD after tranilast administration