DNA damage modulates interactions between microRNAs and the 26S proteasome

26S proteasomes are known as major non-lysosomal cellular machines for coordinated and specific destruction of ubiquitinylated proteins. The proteolytic activities of proteasomes are controlled by various post-translational modifications in response to environmental cues, including DNA damage. Besides proteolysis, proteasomes also associate with RNA hydrolysis and splicing. Here, we extend the functional diversity of proteasomes by showing that they also dynamically associate with microRNAs (miRNAs) both in the nucleus and cytoplasm of cells. Moreover, DNA damage induced by an anti-cancer drug, doxorubicin, alters the repertoire of proteasome-associated miRNAs, enriching the population of miRNAs that target cell cycle checkpoint regulators and DNA repair proteins. Collectively, these data uncover yet another potential mode of action for proteasomes in the cell via their dynamic association with microRNAs.     

Pathogenetic and pathomorphological problems of viral-bacterial associations in children dying of meningococcal infection

The information on 63 children dying from hypertoxic forms of meningococcal infection is presented. Four groups of brain damage by respiratory viruses (RV) are distinguished on the basis of the results of morphological and virological examination: 1) with a recent RV generalization (26 cases); 2) with dissemination of an etiological agent but without clear-cut structural changes (6 cases); 3) with an isolated affection of the brain (13 cases); 4) without clear-cut brain damage. Experimental influenza-meningococcal infection was reproduced in 260 white rats. Enhancement of the animal death rate, multiplication of virus and the degree of brain damage in cases of combined action of both etiological agents is demonstrated. The ability of influenza virus, when inoculated intranasally together with meningococcus, to penetrate and to multiply in the brain provoking meningitis and choroiditis is shown virologically, histologically and electron microscopically.     

Polymorphism of the thiopurine S-methyltransferase gene in African- Americans

The molecular basis for the genetic polymorphism of thiopurine S - methyltransferase (TPMT) has been estab-lished for Caucasians, but it remains to be elucidated in African populations. In the current study, we determined TPMT genotypes in a population of 248 African-Americans and compared it with allele frequencies in 282 Caucasian Americans. TPMT genotype was determined in all individuals with TPMT activity indicative of a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n = 21 Caucasians) and a control group with TPMT activity indicative of a homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23 African-Americans, n = 21 Caucasians). No mutant alleles were found in the high activity control groups. The overall mutant allele frequencies were similar in African-Americans and Caucasians (4.6 and 3.7% of alleles, respectively). However, while TPMT*3C was the most prevalent mutant allele in African-Americans (52.2% of mutant alleles), it represented only 4.8% of mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant alleles), whereas TPMT*3A was the most prevalent mutant allele in Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing a single nucleotide transition (G644A), leading to an amino acid change at codon 215 (Arg-->His), was found in one African-American with intermediate activity. These data indicate that the same TPMT mutant alleles are found in American black and white populations, but that the predominant mutant alleles differ in these two ethnic groups.      

硝苯吡啶与格列本脲相互作用对正常大鼠和高血糖大鼠血糖水平的影响

目的 :研究硝苯吡啶以及硝苯吡啶与格列本脲合用对空腹大鼠和肾上腺素诱发高血糖大鼠血糖水平的影响。方法 :本实验采用葡萄糖氧化酶法测定血糖含量。结果 :硝苯吡啶 2 .5mg/kgig使空腹大鼠血糖水平显著升高(P <0 .0 1 ) ,并加重肾上腺素诱发的高血糖反应。而硝苯吡啶与降糖药格列本脲 0 .9mg/kg合用时不影响空腹大鼠的血糖水平 ,硝苯吡啶对肾上腺素诱发高血糖大鼠灌胃格列本脲后的降血糖作用亦无明显影响。结论 :尽管硝苯吡啶对空腹大鼠以及肾上腺素诱发高血糖大鼠有显著升高血糖的作用 ,但对格列本脲的降血糖作用无明显不良影响     

HPLC法同时测定注射用甲氧异腈中FSA和MIBI的含量

目的 :采用RP HPLC法同时测定了注射用甲氧异腈中两种主要成份二氧硫脲 (FSA)和四 (甲氧基异丁基异腈 )络铜 (I)氟硼酸盐 (MIBI)的含量。方法 :以甲醇、磷酸二氢铵 ( 80∶2 0 )为流动相 ,检测波长 2 1 5nm ,HPLC法测定含量。结果 :试验表明 ,FSA和MIBI在 2 5～ 1 2 5μg/ml,50～ 2 50 μg/ml范围内呈良好的线性关系 ,回归方程分别为Y =0 .2 3 0 .0 2X(r =0 .994 6) ,Y =-2 .1 9 0 .0 3X(r =0 .9998) ,相对标准偏差分别为 1 .2 5%和 0 .4 2 %。结论 :该方法简便、准确、可靠     

Preparation of spiro[indole-3,5′-isoxazoles] via Grignard conjugate addition/spirocyclization sequence

A highly efficient one-pot procedure combining conjugate addition of Grignard reagents to (2-nitroalkenyl)indoles and sub-sequent Brønsted acid-assisted spirocyclization allowed for preparation of 4′H-spiro[indole-3,5′-isoxazoles] in a diastereomerically selective fashion. Utilization of alkyl Grignard reagents provided an easy access to 4′-alkylsubstituted derivatives hardly available by other means.

One-pot procedure combining conjugate addition of Grignard reagents to (2-nitroalkenyl)indoles and subsequent acid-assisted spirocyclization allowed for diastereoselective preparation of 4′H-spiro[indole-3,5′-isoxazoles].     

动脉功能不全与溃疡的诊断与治疗选择

多种全身疾病可以导致下肢溃疡,其中最常见的原因是诸如周围动脉和静脉的血管疾病。周围动脉疾病是一种进展缓慢的、隐匿的疾病进程,在美国大约800万~1 200万人受累于此病,而且每年的发病率还在不断增长。有20%的65岁以上的美国人患有周围动脉疾病,其中只有25%的人接受治疗。据估计,1 050万该病患者有症状,而另外1 650万的该病患者则无症状。有研究结果报道下肢溃疡的发病率为0·12%~1·8%。由于病人及初级治疗提供者不清楚周围动脉疾病的早期表现,并且几乎没有治疗方面的知识,因此常常不能做出正确诊断。动脉溃疡的病理生理学动脉血供不足…     

The pathogenesis of intrauterine infections

The placenta is a specific organ of extracorporeal immunity. It has a tissue-blood barrier that protects a developing fetus against infectious agents. Owing to this, placental infection is not fatal to a fetus and always falls far short of intrauterine infection. Fetal inflammatory diseases occur in immune defects and placental morphological barrier damages.