Modeling of bubble removal from glassmelts at fining temperatures

Α new model based on the quasi-stationary approximation is developed for removal of gas bubbles from glassmelts due to buoyant rise of bubbles. The growth and rising of multicomponent gas bubbles in glassmelts are examined from the view point of interfacial mass transfer. It is shown that the models for rising bubbles in glassmelts available in the literature are based on the quasi-steady approximation which is not very reasonable. The growth of a gas bubble initially consisting of nitrogen only is studied in a glassmelt whose diffusing gases are oxygen, water, carbon dioxide, sulfide and nitrogen. The proposed model based on the unsteady-state mass transfer (the quasi-stationary approximation) is compared with the model based on the steady-state mass transfer (the quasisteady approximation). The former, which provides more rational and better descriptions of bubble behavior in refming processes compared with the latter, predicts rather shorter refming times than the latter

トウキ オンダン ゲンカイ チイキ ニオケル ニホンナシ ノ セイサン ソガイ ヨウイン ノ カイメイ ニヨル アンテイ セイサン ギジュツ ノ カイハツ

博士（農学）東京農工大

Chronic partial unloading restores β-adrenergic responsiveness and reverses receptor downregulation in failing rat hearts

ObjectivesMechanical unloading with a left ventricular assist device promotes “reverse remodeling,” including restoration of β-adrenergic receptor signaling and function. We compared the effects of partial unloading and complete unloading on β-adrenergic responsiveness and gene expressions in failing rat hearts by use of heterotopic heart–lung or heart transplantation models.MethodsFour weeks after ligation of the left anterior descending artery in Lewis rats, rats with heart failure were divided into 3 groups: infarcted hearts and lungs transplanted into the recipient rats (heart failure–partial unloading, n = 8); infarcted hearts transplanted into the recipient rats (heart failure–complete unloading, n = 7); infarcted (heart failure, n = 8) hearts without transplantation. Normal rats (n = 7) were used as controls. Papillary muscle function and gene expressions were studied at 2 or 4 weeks after transplantation.ResultsIn 2-week models, baseline developed tension of papillary muscles significantly increased in heart failure–partial unloading and heart failure–complete unloading compared with heart failure (0.15 ± 0.07 and 0.12 ± 0.05 g/mm2 vs 0.02 ± 0.01 g/mm2, P < .05). However, in 4-week models, they decreased to 0.11 ± 0.03 and 0.10 ± 0.03 g/mm2. In 4-week but not in 2-week models, the increase from baseline in baseline developed tension produced by β-adrenergic stimulation (isoproterenol, 10−8 and 10−7 mol/L) was significantly increased in heart failure–partial unloading compared with heart failure–complete unloading and heart failure (P < .05). The mRNA expressions of brain natriuretic peptide and β1- and β2-adrenergic receptors were normalized in both 2- and 4-week models of heart failure–partial unloading.ConclusionsChronic partial unloading but not complete unloading improved β-adrenergic responsiveness and normalized brain natriuretic peptide and β1- and β2-adrenergic receptor mRNA expressions in the failing rat hearts

NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.

Heat shock protein 47 (Hsp47) acts as a client-specific chaperone for collagen and plays a vital role in collagen maturation and the consequent embryonic development. In addition, this protein can be a potential target for the treatment of fibrosis. Despite its physiological and pathological importance, little is currently known about the collagen-binding mode of Hsp47 from a structural aspect. Here, we describe an NMR study that was conducted to identify the collagen-binding site of Hsp47. We used chicken Hsp47, which has higher solubility than its human counterpart, and applied a selective (15)N-labeling method targeting its tryptophan and histidine residues. Spectral assignments were made based on site-directed mutagenesis of the individual residues. By inspecting the spectral changes that were observed upon interaction with a trimeric collagen peptide and the mutational data, we successfully mapped the collagen-binding site in the B/C β-barrel domain and a nearby loop in a 3D-homology model based upon a serpin fold. This conclusion was confirmed by mutational analysis. Our findings provide a molecular basis for the design of compounds that target the interaction between Hsp47 and procollagen as therapeutics for fibrotic diseases

Diagnosis of Myocardial Viability by Fluorodeoxyglucose Distribution at the Border Zone of a Low Uptake Region

Purpose: In cardiac 2-[F-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) examination, interpretation of myocardial viability in the low uptake region (LUR) has been difficult without additional perfusion imaging. We evaluated distribution patterns of FDG at the border zone of the LUR in the cardiac FDG-PET and established a novel parameter for diagnosing myocardial viability and for discriminating the LUR of normal variants. Materials and Methods: Cardiac FDG-PET was performed in patients with a myocardial ischemic event (n = 22) and in healthy volunteers (n = 22). Whether the myocardium was not a viable myocardium (not-VM) or an ischemic but viable myocardium (isch-VM) was defined by an echocardiogram under a low dose of dobutamine infusion as the gold standard. FDG images were displayed as gray scaled-bull’s eye mappings. FDG-plot profiles for LUR ( = true ischemic region in the patients or normal variant region in healthy subjects) were calculated. Maximal values of FDG change at the LUR border zone (a steepness index; Smax scale/pixel) were compared among not-VM, isch-VM, and normal myocardium. Results: Smax was significantly higher for n-VM compared to those with isch-VM or normal myocardium (ANOVA). A cut-off value of 0.30 in Smax demonstrated 100 % sensitivity and 83 % specificity for diagnosing n-VM and isch-VM. Smax less than 0.23 discriminated LUR in normal myocardium from the LUR in patients with both n-VM and isch-VM with a 94 % sensitivity and a 93 % specificity. Conclusion: Smax of the LUR in cardiac FDG-PET is a simple and useful parameter to diagnose n-VM and isch

年齢に応じた血中活性型ビタミンD濃度, 腎Cyp27b1およびCyp24a1発現に対する食餌性リン反応性の変化には腎α-Klotho遺伝子発現が関連する

In this study, we investigated the relationship between age-related changes in renal α-Klotho gene expression, vitamin D metabolism and the responsiveness of dietary phosphate in 1, 2 and 13 month-old mice fed a high phosphate (phosphate 1.2%) diet or low phosphate (phosphate 0.02%) diet for 5 days. We found that 1,25-dihydroxyvitamin D levels in plasma were significantly lower in the high phosphate group than the low phosphate group for 1 and 2 month-old mice, but not 13 month-old mice. In addition, in the high phosphate group plasma 1,25-dihydroxyvitamin D levels were decreased in 2 month-old mice relative to 1 month-old mice, but 13 month-old mice had higher levels than 2 month-old mice. In fact, plasma 1,25-dihydroxyvitamin D levels showed a significant correlation with vitamin D metabolism gene Cyp27b1 and Cyp24a1 mRNA expression in the high phosphate group. Interestingly, renal α-Klotho mRNA and protein levels were significant change with age. Furthermore, α-Klotho mRNA expression showed a significant negative correlation with plasma 1,25-dihydroxyvitamin D levels in the high phosphate group. Our results suggest that age-related alterations in renal α-Klotho expression could affect the responsiveness of dietary phosphate to vitamin D metabolism

ステロール応答領域結合タンパク質1は腎近位尿細管細胞において25-水酸化ビタミンD3 24-水酸化酵素遺伝子の転写を活性化する

The physiological activity of the steroid derived hormone vitamin D is regulated by several enzymatic steps. Both 25-hydroxy vitamin D3 1a-hydroxylase (CYP27B1) and 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1) modulate blood levels of 1,25-dihydroxyvitamin D3, an activated form of vitamin D. We previously demonstrated that CYP27B1 expression was trans-activated by sterol regulatory element binding protein 1 (SREBP1), although whether SREBP1 also regulates CYP24A1 transcription was unclear. Here we investigated the ability of SREBP1 to affect CYP24A1 transcription. In a luciferase reporter assay, mouse and human CYP24A1 promoter activity was strongly activated by SREBP1 in opossum kidney proximal tubular cells (OK-P). Three putative SREs (pSREs) were found in the mouse Cyp24a1 gene promoter and the SREBP1 protein showed specific binding to the pSRE1 element in EMSAs. Site-directed mutagenesis of the pSRE1 element strongly decreased SREBP1-mediated Cyp24a1 gene transcription. Moreover, siRNA-mediated SREBP1 knock-down repressed CYP24A1 expression in human renal proximal tubular epithelial cells (HKC-8). In animal studies, mice given various doses of thyroid hormone (T3) showed dose-dependent reductions in renal Srebp1c and Cyp24a1 mRNA levels. Taken together, our results suggest that SREBP1 trans-activates CYP24A1 expression through SREBP binding elements present in the promoter

シンリョウジョ シュッサン シタ ジョセイ ノ ニンシン リスクスコアヲ モチイタ リスク ヒョウカ ノ ケントウ

目的 平成16年に開発された妊娠リスクスコア自己評価表(以下,スコア)を用いて診療所で出産した女性の得点を算出し,リスクレベルの傾向とスコアの特徴,分娩帰結との関連を検討する.方法 対象はA診療所で平成20年1月～ 12月に分娩し協力が得られた124名である.診療録よりスコアの評価項目と分娩帰結の情報を収集し,スコアA(初診時評価点)とスコアB(妊娠後半期評価点),合計スコア(スコアAとスコアBの総合得点)を算出した.次に,スコアA,スコアB,合計スコアそれぞれについて早産,分娩時異常出血(1,000ml以上),低出生体重児,吸引分娩,帝王切開分娩の5項目と低リスク群(0-1点)・中リスク群(2-3点)・高リスク群(4点以上)間の関連をみた.結果 平均年齢30.5±3.45歳,初産婦4割,経産婦6割であった.スコア別リスク群別割合は,スコアAで1点が37.9%と最も多く,低リスク群が半数(58.9%)を占めた.スコアBでは0点が80.6%と最も多く,同群が8割以上(83.1%)を占めた.合計スコアをみると中・高リスク群合わせて全体の50.1%を占めた.分娩帰結に異常がなかった事例は全体の78.2%で,うち診療所が単独で扱えない中・高リスク群は37.1%であった.一方早産,分娩時異常出血,低出生体重児,吸引分娩,帝王切開の帰結をとった事例は全体の21.8%あり,うち低リスク群は3.2%(4件)あった.スコアBで加点された事例を概観すると分娩帰結に大きな影響を及ぼす事例であった.χ2独立性の検定の結果,特に,Bスコアで骨盤位,IUGR,低位胎盤,双胎により2点以上の得点が付いた場合と,帝王切開や低出生体重児である傾向に関連があった.結論 1.スコアAは容易に加点されるが分娩帰結に影響を与える項目は少なく,スコアBは容易に加点されないが加点されると分娩帰結に直結する項目が多かった.2.妊産婦らが忠実にスコアの評価基準を守れば,約半数が二次・三次医療施設での健診・分娩が適切であると判断される.3.リスク得点が分娩帰結を反映していない事例が一部存在した.4.妊婦の後半期の評価において2点以上のリスク得点が付く場合には,帝王切開と低出生体重児などの異常帰結を取る傾向があり,スコアBの有用性が示唆された.Aim To use the pregnancy risk score self-assessment form developed in 2004 to examine the relationship between the risk level of women who delivered at a clinic and the birth result.Method The subjects were 124 women who gave birth from January～December 2008 at Clinic A and from whom consent was obtained.Birth results and scored items were collected from medical records to calculate Score A(first medical examination),Score B(latter half of pregnancy),and the Total Score(A and B).Next, with regard to each score,correlations were sought between five items(premature delivery,intrapartum abnormal bleeding(1,000ml or more),low birth weight infant,vacuum extraction and caesarean delivery) and the low(0-1 points),intermediate(2-3 points)and high(4 or more points)risk groups. Results Subjects\u27 mean age was 30.5±3.45 years with 40% primipara and 60% multipara.Inspection showed a correlation tending toward caesarean section(r=0.506)or low birth weight infant(r=0.409),particularly when two or more points were assigned for breech presentation, IUGR,low lying placenta or twin fetus to Score B. Conclusion When two or more points were assigned to the risk score during the latter half of pregnancy, there was a tendency toward caesarean operation,lower birth weight infant or other abnormal results, suggesting the utility of Score B