Dietary restriction increases skeletal muscle mitochondrial respiration but not mitochondrial content in C57BL/6 mice

Dietary restriction (DR) is suggested to induce mitochondrial biogenesis, although recently this has been challenged. Here we determined the impact of 1, 9 and 18 months of 30% DR in male C57BL/6 mice on key mitochondrial factors and on mitochondrial function in skeletal muscle, relative to age-matched ad libitum (AL) controls. We examined proteins and mRNAs associated with mitochondrial biogenesis and measured mitochondrial respiration in permeabilised myofibres using high resolution respirometry. 30% DR, irrespective of duration, had no effect on citrate synthase activity. In contrast, total and nuclear protein levels of PGC-1α, mRNA levels of several mitochondrial associated proteins (Pgc-1α, Nrf1, Core 1, Cox IV, Atps) and cytochrome c oxidase content were increased in skeletal muscle of DR mice. Furthermore, a range of mitochondrial respiration rates were increased significantly by DR, with DR partially attenuating the age-related decline in respiration observed in AL controls. Therefore, DR did not increase mitochondrial content, as determined by citrate synthase, in mouse skeletal muscle. However, it did induce a PGC-1α adaptive response and increased mitochondrial respiration. Thus, we suggest that a functionally ‘efficient’ mitochondrial electron transport chain may be a critical mechanism underlying DR, rather than any net increase in mitochondrial content per se.     

Kinetics of the avian influenza-specific humoral responses in lung are indicative of local antibody production

The role and kinetics of respiratory immunoglobulins in AIV infection has not been investigated. In this study we determined the numbers of both total antibody secreting cells (ASC) and virus-specific ASC in lung, spleen, blood and bone marrow (BM) following low-pathogenic AIV infection. Antiviral humoral immune responses were induced both locally in the lung and systemically in the spleen. Responses in the lung and BM preceded responses in the spleen and in blood, with virus-specific IgY ASC already detected in lung and BM from 1 week post-primary inoculation, indicating that respiratory immune responses are not induced in the spleen, but locally in the lung. ASC present in the blood of the lungs and co-isolated during lymphocyte isolation from the lungs have no major impact on the ASC detected in the lungs based on statistical correlation.     

CD48 controls T-cell and antigen-presenting cell functions in experimental colitis

BACKGROUND & AIMS: The cell-surface receptor CD48 is a lipid-anchored protein expressed on all antigen-presenting cells and T cells. CD2 and 2B4 are known ligands for CD48, which themselves are expressed on the surface of hematopoietic cells. Here we examine the effect of CD48 in the development of chronic experimental colitis and how CD48 affects adaptive and innate immune functions. METHODS: The role of CD48 in experimental colitis was first assessed by transferring CD4(+)CD45RB(hi) cells isolated from either wild-type or CD48(-/-) mice into either Rag-2(-/-) or CD48(-/-) x Rag-2(-/-) mice. Development of chronic colitis in these adoptively transferred mice was assessed by disease activity index, histology, and production of interferon-gamma in mesenteric lymph nodes. Relevant functions of CD48(-/-)CD4(+) T cells and CD48(-/-) macrophages were examined using in vitro assays. In a second set of experiments, the efficacy of anti-CD48 in prevention or treatment of chronic colitis was determined. RESULTS: CD48(-/-)CD4(+) cells induced colitis when transferred into Rag-2(-/-) mice, but not when introduced into CD48(-/-) x Rag-2(-/-) recipients. However, both recipient mouse strains developed colitis upon adoptive transfer of wild-type CD4(+) cells. Consistent with a CD4(+) T-cell defect was the observation that in vitro proliferation of CD48(-/-)CD4(+) T cells was impaired upon stimulation with CD48(-/-) macrophages. In vitro evidence for a modest macrophage functional defect was apparent because CD48(-/-) macrophages produced less tumor necrosis factor alpha and interleukin 12 than wild-type cells upon stimulation with lipopolysaccharide. Peritoneal macrophages also showed a defect in clearance of gram-negative bacteria in vitro. Treatment of the CD4(+)CD45RB(hi)-->Rag-2(-/-) mice or the wild-type BM-->tg26 mice with anti-CD48 (HM48-1) ameliorated development of colitis, even after its induction. CONCLUSIONS: Both CD48-dependent activation of macrophages and CD48-controlled activation of T cells contribute to maintaining the inflammatory response. Consequently, T cell-induced experimental colitis is ameliorated only when CD48 is absent from both T cells and antigen-presenting cells. Because anti-CD48 interferes with these processes, anti-human CD48 antibody treatment may represent a novel therapy for inflammatory bowel disease patients.     

Rician噪声水平场的估计及其在MR图像去噪中的应用

针对MR图像中空间变化Rician噪声的抑制问题,提出了一种噪声水平场的估计方法,同时结合方差稳定变换和BM3D算法实现MR图像的去噪.噪声水平场通过Rician噪声水平的局部估计和稀疏性约束模型进行估计,利用噪声水平场对噪声图像幅值进行空间自适应方差稳定变换,使得噪声与信号幅值和空间位置无关,采用BM3D算法即可实现对噪声的抑制,最后通过方差稳定逆变换得到无偏的去噪图像.仿真实验中,噪声水平场估计的平均相对误差小于0.2％,利用空间自适应方差稳定变换进行去噪,相比方差稳定变换,去噪图像的峰值信噪比可提高2 dB;采用真实乳腺MR图像进行去噪实验,利用自适应方差稳定变换可得到较高的Q度量.结果表明,所提出的方法能有效估计Rician噪声水平场,并用于抑制MR图像中空间变化的噪声.     

A histomorphometric study on the hepatoprotective effects of a green rooibos extract in a diet-induced obese rat model

Obesity, type two diabetes mellitus and insulin resistance are associated with increased oxidative stress and inflammation. Unfermented green rooibos is an aspalathin rich variant of traditional fermented rooibos (Aspalathus linearis) and has a high polyphenol content. The present study aimed to determine the histologically observable effects of a commercially produced, aspalathin-rich green rooibos extract, Afriplex GRT? (GRE) in a diet-induced obese rat model. Male Wistar rats (N = 28) were randomly assigned to four study groups (n = 7): control (C), green rooibos (GRT), high-fat diet (HFD) and experimental (HFD-GRT) group. Body mass was determined prior to euthanasia and liver mass was determined after death. The left lateral lobe of the liver was processed to wax and stained using haematoxylin and eosin (H & E), Masson’s trichrome stain, Gordons and Sweet’s reticulin impregnation and periodic acid-Schiff stain. Frozen liver tissue sections were used for Oil red O staining. Morphometric quantification of steatosis, semiquantitative pathology grading and scoring were performed and verified by a veterinary histopathologist. A significant increase in body and liver mass was observed in the HFD groups while co-treatment with green rooibos significantly reduced both. The volume and area of steatosis were significantly increased in the HFD groups while the area of steatosis significantly reduced with green rooibos co-treatment. The percentage, location and type of steatosis as well as presence of inflammation and hepatocellular injury were reduced in the HFD group co-treated with GRE. These findings suggest that a GRE has potential as an anti-steatotic, anti-inflammatory and weight reducing agent in vivo.     

思密达和米雅BM联用治疗肠易激综合症

目的:对比思密达和米雅BM联用与硝苯地平和肠复康联用二组药物治疗肠易激综合症(IBS)的疗效。方法:将患者随机分成2组,每组各32例,A组:思密达3g,3次/d,米雅BM20mg,各3次/d,于服思密达前1h服用。B组:硝苯地平10mg,3次/d,肠复康2片,3次/d,疗程14d。结果:A组:治疗3d,症状缓解约62.5％(20/32),6d后疗效稳定,症状明显改善约81.1％(25/32);B组:治疗3d,症状缓解约37.5％(12/32),6d后症状才开始明显改善,约81.3％(26/32)。结论:2组药物对改善肠易激综合症的症状效果6d后无显著性差异,但A组起效快,3d有效率为62.5％,无任何副作用,患者更容易接受和顺从。     

The 6/2 (AA3) polyclonal antibody identifying a 37 kD keratinocyte protein reacts also with BM-600/nicein, the basement membrane component bound by the monoclonal antibody GB3

An unexpected finding concerning our previously reported polyclonal antibody raised against an extract from human amnion (pAb 6/2, also termed AA3), and which recognizes an epidermal keratinocyte protein, is presented in this study. Using the immunoblot technique, pAb 6/2 binds to a 37 kD intracellular protein antigen. We have subsequently found that, by radioimmunoprecipitation performed after metabolic labelling with 35S-methionine of cultured keratinocytes, pAb 6/2 recognizes the 600 kD epidermal basement membrane component (termed BM-600/nicein) which was reported to be bound by the monoclonal antibody mAb GB3. Specifically, pAb 6/2 reacts with immunoaffinity chromatography-isolated BM-600/nicein blotted onto nitrocellulose. The data suggest the existence of two immunological reactivities borne by pAb 6/2, each of them being directed against, respectively, the 37 kD (seen in immunoblots) and the 600 kD protein (seen in immunoprecipitations). The data further suggest possible independent expression of these two proteins in cell culture. In comparison with the staining pattern of normal skin, immunofluorescence was previously noted to be impaired (pAb 6/2) or absent (mAb GB3) in lethal junctional epidermolysis bullosa. Thus, we conclude that mAb GB3, rather than pAb 6/2, is a more appropriate probe for the comprehensive biochemical study of this genodermatosis.     

Quantified tracheobronchomalacia disorders and their clinical profiles in children

BACKGROUND: Tracheobronchomalacia (TBM) disorders in children have never been studied using quantified measurements and validated clinical outcome measures. The objectives of the study were to prospectively examine the relationship between malacia lesions and their respiratory illness profiles. METHODS: The site of malacia lesions (eg, tracheomalacia, TBM, and bronchomalacia) were determined, measured, and related to the respective cricoid (ie, airway/cricoid ratio) using the color histogram mode technique. These children and normal control subjects were followed up for 12 months with their respiratory illness profiles determined using the Canadian Acute Respiratory Illness Scale (CARIFS) and cough diary scores. MEASUREMENTS: Outcome measures were respiratory illness frequency (> 12 months), severity score (day-1 CARIFS score), and significant cough interfering with daily activity (score of >or= 3) and illness resolution (time to return to a quarter of CARIFS day 1 score). RESULTS: The group of 116 children were composed of patients with malacia (n = 81) and control subjects (n = 35). The median age of the group was 2.1 years (age range, 0.2 to 17.3 years). The adjusted relative risk of illness frequency was 2.1 (95% confidence interval [CI], 1.3 to 3.4), and of significant cough was 7.2 (95% CI, 1.01 to 27.22) for the malacia group while CARIFS day 1 score was 1.66 (95% CI, 1.1 to 2.56) compared to control subjects. Illness resolution rates at day 14 in the malacia group trended 25% slower than those for control subjects. Malacia type and severity of lesions were not associated with increased rates of illness or worse clinical profiles. CONCLUSION: Children with malacia have an increased likelihood of respiratory illness frequency, severity, significant cough, and tendency for delayed recovery. However, neither the site nor the severity of malacia exhibited any significant dose effect on respiratory illness profiles.