Loss of Tumor Necrosis Factor Production by Human Monocytes in Falciparum Malaria after Their Maturation in Vitro

In Plasmodium-infected mammals, phagocytosis and production of tumor necrosis factor (TNF) by monocytes and macrophages are prominent features. The present work aimed at clarifying the relationship between the maturation of human monocytes to macrophages and their TNF productivity and phagocytic ability in the presence of Plasmodium falciparum-infected erythrocytes. Fresh monocytes produced a significantly higher quantity of TNF in the presence of schizont-infected erythrocytes than macrophages obtained by in vitro monocyte maturation on autologous serum, whereas phagocytic activity of macrophages was much higher than that of fresh monocytes. This indicated that the TNF-inducing factors from P. falciparum-infected erythrocytes could stimulate fresh monocytes, but not macrophages, to release TNF, regardless of their development of phagocytosis. Activation of macrophages by interferon-{gamma} could not recover their TNF productivity in the presence of P. falciparum-infected erythrocytes, but it enhanced their TNF productivity in the presence of lipopolysaccharide(s). The TNF-inducing factors were contained mainly in erythrocytes infected with mature schizonts but not in erythrocytes infected with the younger stages of the parasites. Fractionation of infected erythrocytes revealed that both soluble and insoluble components almost equally contained those factors

In Vitro Assessment of Factors Affecting the Apparent Diffusion Coefficient of Jurkat Cells Using Bio-phantoms

It is well known that many tumor tissues show lower apparent diffusion coefficient (ADC) values, and that several factors are involved in the reduction of ADC values. The aim of this study was to clarify how much each factor contributes to decreases in ADC values. We investigate the roles of cell density, extracellular space, intracellular factors, apoptosis and necrosis in ADC values using bio-phantoms. The ADC values of bio-phantoms, in which Jurkat cells were encapsulated by gellan gum, were measured by a 1.5-Tesla magnetic resonance imaging device with constant diffusion time of 30sec. Heating at 42℃ was used to induce apoptosis while heating at 48℃ was used to induce necrosis. Cell death after heating was evaluated by flow cytometric analysis and electron microscopy. The ADC values of bio-phantoms including non-heated cells decreased linearly with increases in cell density, and showed a steep decline when the distance between cells became less than 3μm. The analysis of ADC values of cells after destruction of cellular structures by sonication suggested that approximately two-thirds of the ADC values of cells originate from their cellular structures. The ADC values of bio-phantoms including necrotic cells increased while those including apoptotic cells decreased. This study quantitatively clarified the role of the cellular factors and the extracellular space in determining the ADC values produced by tumor cells. The intermediate diffusion time of 30msec might be optimal to distinguish between apoptosis and necrosis

Gene Transfer Using Micellar Nanovectors Inhibits Choroidal Neovascularization In Vivo

PURPOSE: Age-related macular degeneration caused by choroidal neovascularization (CNV) remains difficult to be treated despite the recent advent of several treatment options. In this study, we investigated the in vivo angiogenic control by intravenous injection of polyion complex (PIC) micelle encapsulating plasmid DNA (pDNA) using a mice CNV model. METHODS: The transfection efficiency of the PIC micelle was investigated using the laser-induced CNV in eight-week-old male C57 BJ/6 mice. Firstly, each mouse received intravenous injection of micelle encapsulating pDNA of Yellow Fluorescent Protein (pYFP) on days 1,3 and 5. The expression of YFP was analyzed using fluorescein microscopy and western blotting analysis. In the next experiments, each mouse received intravenous injection of micelle encapsulating pDNA of soluble Fms-like tyrosine kinase-1 (psFlt-1) 1,3 and 5 days after the induction of CNV and the CNV lesion was analyzed by choroidal flatmounts on day 7. RESULTS: Fluorescein microscopy and western blotting analysis revealed that the expression of YFP was confirmed in the CNV area after injection of the PIC micelle, but the expression was not detected neither in mice that received naked pDNA nor those without CNV. Furthermore, the CNV area in the mice that received intravenous injection of the psFlt-1-encapsulated PIC micelle was significantly reduced by 65% compared to that in control mice (p<0.01). CONCLUSIONS: Transfection of sFlt-1 with the PIC micelle by intravenous injection to mice CNV models showed significant inhibition of CNV. The current results revealed the significant potential of nonviral gene therapy for regulation of CNV using the PIC micelle encapsulating pDNA

コウジョウセン クリーゼ 20レイ ノ チリョウ ト ヨゴ : コウジョウセン クリーゼ シンダン キジュン オ モチイタ ケントウ

日本甲状腺学会から甲状腺クリーゼの診断基準が2008 年に発表された.2004 年4 月から2009 年3月に当院で臨床的に甲状腺クリーゼと診断,治療した20 症例を,その診断基準にあてはめ,治療と予後等について解析した.基礎疾患は全例バセドウ病だった.誘因として服用不規則や中断が9 例,感染症6 例,糖尿病性ケトアシドーシス3 例,情動ストレス2 例,脳血管障害1 例,外傷1 例だった.診断基準で確定診断例が15例,疑い例が1 例,除外症例が4 例だった.症状では中枢神経症状が疑い・確定診断例では11 例,脈拍130/分以上は12 例認められたが,除外例では認められなかった.治療としてはチアマゾールが全症例に使用されていた.ヨードは13 例,b ブロッカーは17 例,ステロイドは12 例の症例で使用されており全例救命できた.服用不規則や中断,感染症が誘引となりやすく,症状では中枢神経症状・脈拍が特にクリーゼの診断には重要と考えられた.後遺症を残す重症例は6 例で全て新診断基準によって確定診断された症例であり,新診断基準は予後への有用性も期待できると考えられた.The Japan Thyroid Association established diagnosticcriteria for thyroid crisis in 2008. Using these criteria, weanalyzed 20 cases clinically diagnosed as thyroid crisis andtreated in our hospital from April 2004 to March 2009. Allpatients had Basedow\u27s disease at the basal disease. Thecauses were irregular compliance or interruption of treatment(9 cases), infection (6 cases), diabetic ketoacidosis (3cases), emotional stress( 2 cases), stroke( 1 case), and trauma(1 case). Fifteen cases were confirmed as thyroid crisis,1 case was suspected as thyroid crisis, and 4 cases were rejectedas thyroid crisis according to the diagnostic criteria.Central nervous symptoms were observed in 11 cases, andtachycardia (over 130 beats/min) in 12 cases in the definitiveand suspicious cases, although there were no centralnervous symptoms or tachycardia in the excluded cases.Thiamazole was administered to all patients. In addition, iodine(13 cases), b -blocker (17 cases), and corticosteroids(12 cases) were administered. All patients were recovered.Irregular internal use, stopping treatment, and infectionwere likely to induce thyroid crisis. In paticular, centralnervous symptoms and tachycardia were important factorsfor diagnosis. As 6 serious cases with aftereffect were diagnosedas definitive cases of thyroid crisis according to thenew criteria, these new criteria may be useful to predictthe prognosis