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Background

Deficiency of complex II (succinate dehydrogenase, SDH) represents a rare cause of mitochondrial disease and is associated with a wide range of clinical symptoms. Recently, mutations of SDHAF1, the gene encoding for the SDH assembly factor 1, were reported in SDH-defective infantile leukoencephalopathy. Our goal was to identify SDHAF1 mutations in further patients and to delineate the clinical phenotype.

Methods

In a retrospective data collection study we identified nine children with biochemically proven complex II deficiency among our cohorts of patients with mitochondrial disorders. The cohort comprised five patients from three families affected by SDH-defective infantile leukoencephalopathy with accumulation of succinate in disordered cerebral white matter, as detected by in vivo proton MR spectroscopy. One of these patients had neuropathological features of Leigh syndrome. Four further unrelated patients of the cohort showed diverse clinical phenotypes without leukoencephalopathy. SDHAF1 was sequenced in all nine patients.

Results

Homozygous mutations of SDHAF1 were detected in all five patients affected by leukoencephalopathy with accumulated succinate, but not in any of the four patients with other, diverse clinical phenotypes. Two sisters had a mutation reported previously, in three patients two novel mutations were found.

Conclusion

Leukoencephalopathy with accumulated succinate is a key symptom of defective complex II assembly due to SDHAF1 mutations.     

Hepatic endopolyploidy as a cellular consequence of age-specific selection for rate of development in mice

Endopolyploidy is the generation of polyploid cells by DNA replication without subsequent cell division and is correlated with hypertrophic growth or growth via cell size. Thus, selection that alters growth may also change onset and frequency of endopolyploidy as a correlated response. We search for endopolyploidy in the liver in response to age-specific restricted index selection for the rate of development. Polyploidy changes over ontogeny are described in five mouse lines: two selected for divergence in early growth (0-10 days of age), two selected for divergence in late growth (28-56 days of age), and one randombred control. Polyploid cell frequency within each line increased as ontogeny continued, as expected from previous research. However, selection for altered growth clearly plays a role in the frequency and onset of polyploid cells. Lines selected for divergence in early growth have polyploidy differences after weaning that are not seen in adult mice. However, lines selected for divergence in late growth are divergent in frequency of polyploid cells, starting near sexual maturity and continuing into adulthood.     

大鼠放射性肺损伤模型的建立与动态观察

目的：建立并鉴定大鼠放射性肺损伤模型,摸索大鼠放射性肺损伤的病理变化规律,阐明氧化应激在其发生发展过程中的作用。方法：采用60Co源22Gy单次照射SD大鼠全肺。分别于照射前、照后1天,7天,15天,21天,30天,60天,120天活杀大鼠,计算肺系数,右肺行HE染色、Masson染色及天狼猩红染色,观察肺组织病理变化并对大鼠肺泡炎及纤维化程度进行评分,免疫组化法检测肺组织廿SMA表达情况;左肺进行羟脯氨酸含量测定;血清测定MDA含量、总SOD活力和TGF-β1含量。结果：（1）大鼠肺脏于照后15天开始出现明显大体改变,病理学表现为间质性渗出性炎症并随时间延长逐渐加重,照后60天至120天肺脏塌陷,表面可见纤维化病灶,病理改变以肺间隔内细胞增生和胶原纤维沉积为主;（2）血清T-SOD活力照后1天至7天短暂增加后其活力持续降低;血清MDA含量和TGF-β1含量随时间时间延长逐渐增高;（3）照后60天肺组织a-SMA表达明显增加,至照后120天最为显著。结论：成功建立了大鼠放射性肺损伤模型并阐述了其病理变化规律;氧化应激参与了放射性肺损伤的病理过程。为其防治提供了实验基础和理论依据。     

BTKbase, mutation database for X-linked agammaglobulinemia (XLA)

X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK). A database (BTKbase) of BTK mutations has been compiled and the recent update lists 368 entries from 318 unrelated families showing 228 unique molecular events. In addition to mutations the database lists also some polymorphisms and site-directed mutations. Each patient is given a unique patient identity number (PIN). Information is provided regarding the phenotype including symptoms. Mutations in all the five domains of BTK have been noticed to cause the disease, the most common event being missense mutations. The mutations appear almost uniformly throughout the molecule and frequently affect CpG sites forming arginine residues. These hot spots have generally pyrimidines 5'and purines 3'to the mutated cytosine. A decreased frequency of missense mutations was found in the TH, SH3 and the upper lobe of the kinase domain. The putative structural implications of all the missense mutations are given in the database showing 228 unique molecular events, including a novel missense mutation causing an R28C substitution as previously seen in the Xid mouse.     

Spin Trapping Study in the Lungs and Liver of F344 Rats after Exposure to Ozone

Fischer 344 rats were injected with the spin traps C-phenyl N-tert-butyl nitrone (PBN, 150 mg/kg bw, ip) or 4-pyridine-N-oxide N-tert -butyl nitrone (POBN, 775 mg/kg bw, ip), and exposed to clean air or 2 ppm ozone for two hours. The presence of spin adducts was determined by electron paramagnetic resonance (EPR) spectroscopy of chloroform extracts of lung and liver homogenates. No significant levels of adducts were detected in the lungs of air control animals. Benzoyl N-tert-butyl aminoxyl, attributed to direct reaction of ozone with PBN, and tert-butyl hydroaminoxyl, the scission product of the hydroxyl adduct of PBN, were detected in the lungs of ozone exposed rats. EPR signals for carbon-centred alkoxyl and alkyl adducts were also detected with PBN in the lungs and liver of animals exposed to ozone. With POBN, only carbon-centred alkyl radicals were detected. Senescent, 24 months old rats were found to retain about twice more ¹⁴C-PBN in blood, heart and lungs by comparison to juvenile, 2 months old animals. Accordingly, the EPR signals were generally stronger in the lungs of the senescent rats by comparison to juvenile rats. Together, the observations were consistent with the previously proposed notion that a significant flux of hydrogen peroxide produced from the reaction of ozone with lipids of the extracellular lining, or from activated macrophages in the lungs could be a source of biologically relevant amounts of hydroxyl radical.     

Measles Virus-Specific IgG in Cerebrospinal Fluid in Multiple Sclerosis

The prevalence of measles virus-specific IgG in cerebrospinal fluid (C.S.F.) of patients with multiple sclerosis (M.S.) has been compared with that in fluids from patients with other neurological diseases and from normal control subjects. The prevalence in the three groups was 58·1%, 24·1%, and 0% respectively. Fivefold concentration of the specimens increased the prevalence in the first two groups to 80·6% and 34·5% respectively, while measles IgG was not detected in any fluids of the normal control group, even after concentration.     

Regulation of Arabidopsis thaliana Physiological Responses Through Exogenous Electrical Field Exposures with Common Lab Equipment

Journal of Plant Growth Regulation - Plants have many of the same electrochemical regulatory components as animals, such as sensory receptors, neurotransmitters, and voltage regulated ion channels....     

Mitogen activation induces the enhanced synthesis of two heat-shock proteins in human lymphocytes

We have used mitogenic lectin (PHA) and a monoclonal antibody (OKT3) to stimulate human peripheral blood (G0) lymphocytes, in the presence of monocytes, and have found two major preferentially synthesized proteins, 73 and 95 kD, which are induced by the mitogens. The elevated synthesis of both proteins begins approximately 4-6 h after mitogen addition (early to mid G0/G1) before entry into first S phase. Maximum synthesis of both proteins is reached by 12 h after mitogen addition when P95 synthesis represents approximately 4%, and P73 approximately 2%, of the total protein synthesis, compared with less than 0.5% for each protein in cells cultured without mitogen. Thus, the proteins appear to be major components of activated cells. We find that both P73 and P95 are induced by heat stress as well as mitogenic stimulation. The induction of the proteins is not affected by either deleting glucose from the culture media or, alternatively, by supplementing it. Using polyclonal antibodies prepared to each of the proteins isolated from mitogen activated cells and monoclonal antibodies that were raised to heat shock proteins, we are able to show that P95 is electrophoretically and immunologically identical to the HSP 90 induced by heat stress. P73 is one of the 70 kD HSPs, (termed HSC 70; Pelham, H. R. B. 1986. Cell. 46: 959-961), but is different from the most strongly heat inducible form of HSP 70 (72 kD). The distribution of both proteins in subcellular fractions of mitogen activated lymphocytes is similar to the reported localization of the respective HSP's in other cell types. The results suggest that HSP 90 and HSC 70 may have functional roles in stress response and growth processes of human lymphocytes.