24 Hours-Energy Expenditure of Usual Activity for Some Normal Women (Part1)

24h-HRR法を用いて測定した生理的な数値によりエネルギー消費量予測値を求め,この予測値と生活時間調査法によるエネルギー消費量予測値との関連について,その基礎的データを得ることを目的として本実験を行った。昭和62年10月から昭和63年1月にかけて,著者ら3名を被験者として検討し,以下の結果を得た。1)VO_2と心拍数との関係は,身体活動時にはほぼ正比例の関係(r=0.996,P<0.001)が得られたが,安静時では測定時の種々な条件によって値が容易に変動することが再確認された。2)24h-HRR法において,基準となる安静時心拍数の設定に難点が指摘されているが,VO_2/HR法によるエネルギー消費量推定値との関係から,設定値として睡眠時心拍数÷0.9という数値の有用性が示唆された。3)生活時間調査法によるエネルギー消費量予測値は,睡眠時心拍数÷0.9という数値を採用した24h-HRR法による予測値およびVO_2/HR法による推定値との間にいずれも正相関(P<0.01)が認められた。生活時間調査法によるエネルギー消費量予測値は,生理的数値から得られたエネルギー消費量予測値よりも約10%程度低値となるが,充分信頼できることが裏付けられた

Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease

Background: Galectin-9 (Gal-9) induces apoptosis in activated T helper 1 (T(H)1) cells as a ligand for T cell immunoglobulin mucin-3 (Tim-3). Gal-9 also inhibits the G1 phase cell cycle arrest and hypertrophy in db/db mice, the hallmark of early diabetic nephropathy, by reversing the high glucose-induced up-regulation of cyclin dependent kinase inhibitors such as p27(Kip1) and p21(Cip1). Methods: We investigated the serum levels of Gal-9 in the patients with type 2 diabetes and various stages of chronic kidney disease (CKD) (n = 182). Results: Serum Gal-9 levels in the patients with type 2 diabetes were 131.9 +/- 105.4 pg/ml and Log(10)Gal-9 levels significantly and positively correlated with age (r = 0.227, p = 0.002), creatinine (r = 0.175, p = 0.018), urea nitrogen (r = 0.162, p = 0.028) and osmotic pressure (r = 0.187, p = 0.014) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.188, p = 0.011). Log(10)Gal-9 levels increased along with the progression of GFR categories of G1 to G4, and they were statistically significant by Jonckheere-Terpstra test (p = 0.012). Log(10)Gal-9 levels remained similar levels in albuminuria stages of A1 to A3. Conclusion: The elevation of serum Gal-9 in the patients with type 2 diabetes is closely linked to GFR and they may be related to the alteration of the immune response and inflammation of the patients with type 2 diabetes and CKD

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment

Relationship of serum fatty acid composition and desaturase activity to C-reactive protein in Japanese men and women (Atherosclerosis)

Background: Although fatty acid composition in serum and desaturase activity, which alters serum fatty acid composition, has been associated with C-reactive protein (CRP) concentration in Western populations, no study has been carried out in non-Western populations. We examined the association of serum fatty acids and estimated desaturase activity with CRP concentrations in Japanese men and women. Methods: Subjects were 489 Japanese municipal employees aged 21–67 yearswhoparticipated in a survey at the time of a periodic health check-up. Serum high-sensitivity CRP concentrations were measured using the latex agglutination nephelometry method. Fatty acid composition was measured in serum cholesteryl esters and desaturase activities by fatty acid product-to-precursor ratios. Relationships were assessed using multiple regression.Results: Serum CRP concentration was positively associated with palmitic acid (P for trend = 0.002) and inversely with alpha-linolenic acid (P for trend = 0.01) in men, and positively with dihomogamma-linolenic acid (P for trend in men or women= 0.01) and inversely with delta-5-desaturase (20:4n-6/20:3n-6) (P for trend in men and women= 0.05 and 0.002, respectively) in men and women.Conclusions: Low-grade inflammation may be associated with a serum fatty acid pattern of high palmitic acid or low alpha-linolenic acid in men, and of high dihomo-gamma-linolenic acid or low delta-5-desaturase in both sexes

Relationship of serum fatty acid composition and desaturase activity to C-reactive protein in Japanese men and women

Background: Although fatty acid composition in serum and desaturase activity, which alters serum fatty acid composition, has been associated with C-reactive protein (CRP) concentration in Western populations, no study has been carried out in non-Western populations. We examined the association of serum fatty acids and estimated desaturase activity with CRP concentrations in Japanese men and women. Methods: Subjects were 489 Japanese municipal employees aged 21–67 yearswhoparticipated in a survey at the time of a periodic health check-up. Serum high-sensitivity CRP concentrations were measured using the latex agglutination nephelometry method. Fatty acid composition was measured in serum cholesteryl esters and desaturase activities by fatty acid product-to-precursor ratios. Relationships were assessed using multiple regression.Results: Serum CRP concentration was positively associated with palmitic acid (P for trend = 0.002) and inversely with alpha-linolenic acid (P for trend = 0.01) in men, and positively with dihomogamma-linolenic acid (P for trend in men or women= 0.01) and inversely with delta-5-desaturase (20:4n-6/20:3n-6) (P for trend in men and women= 0.05 and 0.002, respectively) in men and women.Conclusions: Low-grade inflammation may be associated with a serum fatty acid pattern of high palmitic acid or low alpha-linolenic acid in men, and of high dihomo-gamma-linolenic acid or low delta-5-desaturase in both sexes

Non-Canonical Role of IKKα in the Regulation of STAT1 Phosphorylation in Antiviral Signaling

<div><p>Non-self RNA is recognized by retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), inducing type I interferons (IFNs). Type I IFN promotes the expression of IFN-stimulated genes (ISGs), which requires the activation of signal transducer and activator of transcription-1 (STAT1). We previously reported that dsRNA induced STAT1 phosphorylation via a type I IFN-independent pathway in addition to the well-known type I IFN-dependent pathway. IκB kinase α (IKKα) is involved in antiviral signaling induced by dsRNA; however, its role is incompletely understood. Here, we explored the function of IKKα in RLR-mediated STAT1 phosphorylation. Silencing of IKKα markedly decreased the level of IFN-β and STAT1 phosphorylation inHeH response to dsRNA. However, the inhibition of IKKα did not alter the RLR signaling-mediated dimerization of interferon responsive factor 3 (IRF3) or the nuclear translocation of nuclear factor-κB (NFκB). These results suggest a non-canonical role of IKKα in RLR signaling. Furthermore, phosphorylation of STAT1 was suppressed by IKKα knockdown in cells treated with a specific neutralizing antibody for the type I IFN receptor (IFNAR) and in IFNAR-deficient cells. Collectively, the dual regulation of STAT1 by IKKα in antiviral signaling suggests a role for IKKα in the fine-tuning of antiviral signaling in response to non-self RNA.</p></div