気管支喘息患者における白血球ロイコトリエン産生能に対する不飽和脂肪酸食の効果に影響する因子

Dietary supplementation with perilla seed oil, a vegetable oil rich in α -lin- olenic acid, inhibits the generation of leukotrienes(LTs) by leucocytes in patients with bronchial asthma. We examined the factors that affect the suppression of LT generation by leucocytes with perilla seed oil-rich supplementation in patients with asthma, by comparing the clinical features of patients with asthma, whose generation of leukotriene (LT) C4 was suppressed by dietary supplementation with perilla seed oil (n-3 fatty acids) (group A), with those of patients who showed no suppression of LTC4 generation (group B). Group A showed a significant increase in the generation of LTB4 and L TC4 by leucocytes after corn oil-rich supplementation (n-6 fatty acids), and a significant decrease in the generation of LTB4 and LTC4 after perilla seed oil-rich supplementation (n-3 fatty acid). However, this was not observed in group B. The level of serum IgE and peak expiratory flow (PEF) in group A were significantly higher than in group B. Furthermore, the serum levels of LDL-cholesterol, β-lipoprotein and　phospholipid were significantly lower in group A than in group B. These results suggest that the clinical features differ between these two asthmatic populations with respect to suppression of LTB4 and LTC4 generation by n-3 fatty acids in perilla seed oil-rich supplementation.a-リノレン酸の豊富なエゴマ油の食事は気管支喘息患者の白血球ロイコトリエン(LT)産生能を抑制する｡気管支喘息患者の内,エゴマ油食によりLTC4の産生が抑制された群(A群)と抑制されない群(B群)の臨床データを比較することにより,気管支喘息患者の白血球ロイコトリエン産生能に影響する因子を検討した｡A群はコーン油(n-6系脂肪酸)の豊富な食事後,白血LTB4,LTC4の産生能が増加し,エゴマ油(n-3系脂肪酸)の豊富な食事後LTB4,LTC4の産生能が減少した｡これらの変化はB群では認められなかった｡A群のIgE値,ピークフロー(PEF)値はB群に比し,有意に高値であった｡またLDL-コレステロール,β-リポ蛋白,リン脂質はA群ではB群に比し,有意に低値であった｡これらの結果はエゴマ油の豊富な食事のn-3系脂肪酸によるLTB4,LTC4の産生能の抑制に関して2群の気管支喘息患者群間に臨床データの相違があることを示唆している

A new prognostic index for overall survival in malignant pleural mesothelioma: the rPHS (regimen, PS, histology or stage) index.

First published online: April 2, 2015[Objective] Existing prognostic indices for malignant pleural mesothelioma do not incorporate the recent advances in oncology care. The purpose of this study was to provide a prognostic index for overall survival in malignant pleural mesothelioma patients treated with chemotherapy with pemetrexed or best supportive care in the recent clinical setting. [Methods] A retrospective cohort study was performed in two hospitals in Japan (2007–13). The primary outcome was overall survival. The Cox proportional hazards model was used for multivariable analyses to identify prognostic factors. A final model was chosen based on both clinical and statistical significance. [Results] A total of 283 patients (chemotherapy: n = 228, best supportive care: n = 55) were enrolled in the study. On multivariate analysis, regimen including platinum plus pemetrexed, a performance status >0, non-epithelial histological type and Stage IV disease predicted poor overall survival in chemotherapy patients. As hazard ratios of individual risk factors were approximately similar, a prognostic index for overall survival was constructed by counting the risk factors. Median overall survival in chemotherapy patients decreased by each one-point increase in this count: 1030 days for zero; 658 days for one; 373 days for two; 327 days for three; 125 days for four. Internal validation using the bootstrapping technique showed robustness of the model (c-index, 0.677; 95% confidence interval, 0.624–0.729). Further, the discrimination was consistent in best supportive care patients (c-index, 0.799; 95% confidence interval, 0.725–0.874). [Conclusions] This novel index can provide clinicians and malignant pleural mesothelioma patients with a better framework for discussing prognosis at the time of diagnosis

The Macrophage Is a Key Factor in Renal Injuries Caused by Glomerular Hyperfiltration

Glomerular hyperfiltration is a common pathway leading to glomerulosclerosis in various kinds of kidney diseases. The 5/6 renal ablation is an established experimental animal model for glomerular hyperfiltration. On the other hand, low-grade inflammation is also a common mechanism for the progression of kidney diseases including diabetic nephropathy and atherosclerosis. Here we analyzed the gene expression profile in the remnant kidney tissues of 5/6 nephrectomized mice using a DNA microarray system and compared it with that of sham-operated control mice. The 5/6 nephrectomized mice showed glomerular hypertrophy and an increase in the extracellular matrix in the glomeruli. DNA microarray analysis indicated the up-regulated expression of various kinds of genes related to the inflammatory process in remnant kidneys. We confirmed the up-regulated expression of platelet factor-4, and monocyte chemoattractant protein-1, 2, and 5 in remnant kidneys by RT-PCR. The current results suggest that the inflammatory process is involved in the progression of glomerulosclerosis and is a common pathway of the pathogenesis of kidney disease

Functional expression of thiocyanate hydrolase is promoted by its activator protein, P15K

AbstractThiocyanate hydrolase (SCNase) is a cobalt-containing enzyme with a post-translationally modified cysteine ligand, γCys131-SO2H. When the SCNase α, β and γ subunits were expressed in Escherichia coli, the subunits assembled to form a hetero-dodecamer, (αβγ)4, like native SCNase but exhibited no catalytic activity. Metal analysis indicated that SCNase was expressed as an apo-form irrespective of the presence of cobalt in the medium. On the contrary, SCNase co-expressed with P15K, encoded just downstream of SCNase genes, in cobalt-enriched medium under the optimized condition (SCNase(+P15K)) possessed 0.86 Co atom/αβγ trimer and exhibited 78% of the activity of native SCNase. SCNase(+P15K) showed a UV–Vis absorption peak characteristic of the SCNase cobalt center. About 70% of SCNase(+P15K) had the γCys131-SO2H modification. These results indicate that SCNase(+P15K) is the active holo-SCNase. P15K is likely to promote the functional expression of SCNase probably by assisting the incorporation of cobalt ion

n-3系脂肪酸食の気管支喘息に対する臨床効果:n-6系脂肪酸との比較

N-3 fatty acids, such as fish oil, have been reported to have some beneficial effects in patients with bronchial asthma by suppressing leukocyte function, followed by reduction of the need for pharmacologic agents. To examine the effects of dietary supplementation with perilla seed oil rich in α-linolenic acid (ALA), 23 patients with　asthma took corn oil rich in linoleic acid (LA) for the former two weeks, perilla seed oil for the later two weeks. The asthmatic patients were classified into two groups by the changes of the generation of leukotrienes B4 (LTB4), C4 (LTC4), and B5 (LTB5) during the two courses of dietary modification: one was sensitive to dietary modification, and the other was insensitive to dietary supplementation. We compared the two groups in clinical characteristics. Significant differences were observed in peak flow (PEF), forced expiratory volume in one second (FEV1.0), IgE, sex, obesity index (OI), concentration of serum total cholesterol, albumin, low density lipoprotein {LDL)-cholesterol, β-lipoprotein and phospholipids between two groups. This study indicated that these factors influence the generation of LTB4, C4 and B5 of asthmatic patients in dietary supplementation.気道への炎症性白血球の集合が気管支喘息の病態に関わっている。魚油などのn-3系脂肪酸が白血球の機能を抑制することにより気管支喘息患者に良好な効果をもたらし,薬剤の必要性を減じたとの報告がなされている｡α-リレノン酸を豊富に含有するエゴマ油食の効果を調べるため,気管支喘息患者23名に2コースの食事-リノール酸の豊富なコーン油食を2週間摂取後,エゴマ油食を2週間-を摂取してもらった｡喘息患者は2コースの食事間のロイコトリエンB4(LTB4),CA(LTC4),B5(LTB5)の変化から2群-1群は食事に対し感受性のある群,もう1つは感受性の無い群-に分類した｡我々はこの2群を臨床的に検討したところ,ピークフロー(PEF),1秒量(FEV10),IgE,性別,肥満率(OⅠ),血清総コレステロール,アルブミン,低比重リポ蛋白(LDL)-コレステロール,β-リポ蛋白,リン脂質において2群間に有意差が認められた｡今回の研究から,これらの因子が,喘息患者において,LTB4,LTC4,LTB5の産生に対する食事療法の効果に影響を及ぼしていることが示唆された

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1, 995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction