Nackt (nkt), a new hair loss mutation of the mouse with associated CD4 deficiency

 A spontaneous recessive mutation named nackt (symbol: nkt) affecting hair growth and T-cell development was discovered in a moderately inbred stock of mice. Skin lesions were characterized by sparse rough coat, bare patches around the eyes and neck, and a scratching behavior throughout life. Fluorescence-activated cell sorter analysis indicated a deficiency in the CD4⁺ 8^– T-cell subset in the thymus and a marked decrease in CD4⁺ T cells in peripheral lymphoid organs. Linkage analysis using a set of molecular markers and an F₂ intersubspecific cross indicated that the mutation maps to the central region of mouse chromosome 13, in a region homologous to human chromosome 5q22-q35. Received: 15 July 1998 / Revised: 27 October 1998     

Reduced cardiomyocyte Na+ current in the age-dependent murine Pgc-1β−/− model of ventricular arrhythmia

Peroxisome proliferator-activated receptor-γ coactivator-1 deficient (Pgc-1β^−/−) murine hearts model the increased, age-dependent, ventricular arrhythmic risks attributed to clinical conditions associated with mitochondrial energetic dysfunction. These were accompanied by compromised action potential (AP) upstroke rates and impaired conduction velocities potentially producing arrhythmic substrate. We tested a hypothesis implicating compromised Na⁺ current in these electrophysiological phenotypes by applying loose patch-clamp techniques in intact young and aged, wild-type (WT) and Pgc-1β^−/−, ventricular cardiomyocyte preparations for the first time. This allowed conservation of their in vivo extracellular and intracellular conditions. Depolarising steps elicited typical voltage-dependent activating and inactivating inward Na⁺ currents with peak amplitudes increasing or decreasing with their respective activating or preceding inactivating voltage steps. Two-way analysis of variance associated Pgc-1β^−/− genotype with independent reductions in maximum peak ventricular Na⁺ currents from −36.63 ± 2.14 (n = 20) and −35.43 ± 1.96 (n = 18; young and aged WT, respectively), to −29.06 ± 1.65 (n = 23) and −27.93 ± 1.63 (n = 20; young and aged Pgc-1β^−/−, respectively) pA/μm² (p < 0.0001), without independent effects of, or interactions with age. Voltages at half-maximal current V*, and steepness factors k in plots of voltage dependences of both Na⁺ current activation and inactivation, and time constants for its postrepolarisation recovery from inactivation, remained indistinguishable through all experimental groups. So were the activation and rectification properties of delayed outward (K⁺) currents, demonstrated from tail currents reflecting current recoveries from respective varying or constant voltage steps. These current–voltage properties directly implicate decreases specifically in maximum available Na⁺ current with unchanged voltage dependences and unaltered K⁺ current properties, in proarrhythmic reductions in AP conduction velocity in Pgc-1β^−/− ventricles.     

云南HPV-16型E6、E7基因的突变分析

人乳头瘤病毒(Human papillomavirus,HPV)16型(HPV-16)是引起宫颈癌的一种主要高危型病毒,其2个致癌基因E6和E7的核酸序列变异可能会影响其对宿主细胞的致癌性,已有研究表明其序列突变呈现地域差异性。因此,研究不同地域HPV-16这2个基因的变化情况是宫颈癌流行病学调研的主要内容,也可为研究E6和E7的致癌性积累数据。研究以NCBI登录号为NC_001526.2的HPV-16型病毒的序列为参照,采用Neighbor-joining方法对云南地区74例HPV-16样本的E6、E7的DNA序列构建进化树,结果显示:只有亚洲和欧洲变异亚型,而没有发现非洲1、非洲2、亚-美洲和北美洲这4种变异亚型。DNA序列分析显示:E6的碱基突变以T178G(D25E,59.46%)和T350G(L83V,8.11%)为主,E7的碱基突变主要以A647G(N29S,59.46%)和T846C(同义突变,60.81%)为主。发现E6的新突变有A95G(同义突变,1.35%)和A135G(K11R,1.35%);E7的新突变有C625T(L22F,1.35%)、C627T(同义突变,12.16%)、G689A(G43E,1.35%)、T748G(S63A,1.35%)。此外还发现有一个共突变现象:T178G(D25E,59.46%)-A647G(N29S,59.46%)-T843C(同义突变,21.62%)-T846C(同义突变,60.81%)。     

Growth and development in school-age children from Rostov region,Russia: Comparison between urban and rural settings

The purposes of the current study were: (1) to describe growth and physical development and establish norms for schoolchildren from Rostov region in Russia; (2) to compare major characteristics of development between urban and rural children by sex and age.Nearly 200,000 children (198,712) aged between 7 and 17 years from 232 urban and rural schools of Rostov region (Southern Federal District of Russia) participated in the study. School age is a period of intensive growth and physiological and psychological development. Irregularities of personal development are caused by a multitude of factors, such as sex differences, heredity, socio-economic status of a family, standard of living, particular environmental conditions, and lifestyle.It has been established that children from the Southern Federal District of Russia had body mass index values higher than age-appropriate norms for all Russians (Total Russian, Rudnev et al., 2014) and World Health Organization charts. Children from urban settings were taller and heavier than children from rural settings.Sex is one of the most influential factors which play key role in determining specific characteristics of growth and personal development. According to our results, boys and girls both had similar age-related changes in weight and height, but their respective dynamics differed. Girls’ height and weight values accelerated at the age 10 to 12 years and plateaued after the age fourteen, whereas in boys height and weight steadily increased with age, showing slight acceleration at the age 12 to 13 years, and reached a plateau by the age of seventeen.     

腺苷高产菌株Bacillus subtilis DI4-24退化的遗传机制与控制研究

经人工诱变获得的腺苷高产菌株Bacillus subtilis DI4-24很容易发生退化,通过分析回变菌株的遗传性状和考察理化条件对回复突变的影响,研究退化的机制,找到控制的方法。在选择培养基上筛选回变菌株,生长谱法分析其遗传型;于743 nm条件下分光光度法测定回复突变细胞内积累的特有红色物质,研究各理化条件对回复突变的影响。退化原因是由于组氨酸缺陷型发生回复突变所致,突变菌株腺苷产量大幅度下降;降低保藏温度、减少传代次数可以有效地减缓菌种的衰退;种子制备过程中适当降低培养温度2℃~3℃、缩短培养时间(8 h)、降低培养基pH至中性偏酸性(6.5)以及加入胡萝卜素、叶酸等物质都可以有效降低回变率,在此条件下制备的种子生产性能得到提高,其腺苷产量可比对照提高9%。     

B7家族的新成员

T细胞的活化需要共刺激分子和其受体及特异性抗原与T细胞受体的双信号作用。B7家族成员是重要的共刺激分子,除B7－1和B7－2,新近又发现了一些新成员：B7RP－1（又名B7h,GL50或ICOSL）为鼠ICOS（inducible costimulator,CD28家族的第三位成员）的配体,其人的同源物命名为B7－2（也称为GL50或ICOSL）,它对TG细胞生长及细胞因子产生的共刺激作用已明显,B7－H1（也称PD－1L）,B7H3是一类不与ICOS结合的B7家族新成员。现已证实。现已证实,这些分子与其受体之间的作用在T细胞增殖及发挥效应中扮演重要角色,它们在许多疾病中的作用也引起学者的普遍关注。     

脊髓小脑共济失调第7型的临床特征及基因突变研究

对一脊髓小脑性共济失调(Spinocerebellar ataxia, SCA)家系的患者进行临床特征及相关基因突变研究。对该家系进行详细的病史采集, 并对患者行视力、眼底血管造影、眼底拍照、视觉诱发电位、视网膜电图以及头颅MRI等辅助检查; 采用聚合酶链反应分别扩增SCA1、SCA2、SCA3、SCA6、SCA7、SCA17及DRPLA基因的CAG重复序列, 用8%变性聚丙烯酰胺凝胶电泳及直接测序进行突变分析。结果2名患者主要表现为小脑性共济失调、视力下降、眼底视网膜色素变性、小脑和脑干萎缩; 并存在SCA7基因的突变, 而未发现SCA1、SCA2、SCA3、SCA6、SCA17及DRPLA基因突变。说明该家系为SCA7突变家系, SCA7基因中CAG三核苷酸重复拷贝数的异常扩增是其致病原因。     

Bradykinin counteracts the stimulatory effect of angiotensin-(1-7) on the proximal tubule Na+ -ATPase activity through B2 receptor

Recently, we demonstrated that angiotensin-(1–7) (Ang-(1–7)) stimulates the Na⁺-ATPase activity through a losartan-sensitive angiotensin receptor, whereas bradykinin inhibits the enzyme activity through the B₂ receptor [Regul. Pept. 91 (2000) 45; Pharmacol. Rev. 32 (1980) 1]. In the present paper, the effect of bradykinin (BK) on Ang-(1–7)-stimulated Na⁺-ATPase activity was evaluated. Preincubation of Na⁺-ATPase with 10⁻⁹ M Ang-(1–7) increases enzyme activity from 7.9±0.9 to 14.1±1.5 nmol Pi mg⁻¹ min⁻¹, corresponding to an increase of 79% (p<0.05). This effect is reverted by bradykinin in a dose-dependent manner (10⁻¹⁴–10⁻⁸ M), reaching maximal inhibitory effect at 10⁻⁹ M. Des-Arg⁹ bradykinin (DABK), an agonist of B₁ receptor, at the concentrations of 10⁻⁹–10⁻⁷ M, does not mimic the BK inhibitory effect, and des-Arg⁹-[Leu⁸]-BK (DALBK), a B₁ receptor antagonist, at the concentrations of 10⁻¹⁰–10⁻⁷ M, does not prevent the inhibitory effect of BK on Ang-(1–7)-stimulated enzyme. On the other hand, HOE 140, an antagonist of B₂ receptor, abolishes the inhibitory effect of BK on the Ang-(1–7)-stimulated enzyme in a dose-dependent manner, reaching maximal effect at 10⁻⁷ M. Taken together, these data indicate that stimulation of B₂ receptors by BK can counteract the stimulatory effect of Ang-(1–7) on the proximal tubule Na⁺-ATPase activity.     

Paracentric inversions in human chromosome 7 as a graphic example of reverse chromosomal mutation

A famillialy inherited paracentric inversion of human chromosome 7 is described. The breakpoints are localized in the bands q1 1.2 and q2 2.1. The similarity between the inverted chromosome 7 and the chromosome 6 of the gorilla characterizes this inversion as a reverse chromosomal mutation. The parallels between human chromosome pathology and the chromosomal evolution of Pongidae and man are discussed.     

The clinical importance of CD4+CD7− in human diseases

The CD7 antigen is a member of the immunoglobulin superfamily that expresses on the surface of all thymocytes, a majority of mature T cells, and also natural killer cells. Interestingly, under physiological and different pathological conditions, the loss of CD7 antigen occurred in the subset of CD4⁺ memory T cells. Various functions have been proposed for CD7, including its role in the activation and intercellular adhesiveness of T cells. Several studies indicate that the number of CD4⁺CD7⁻ T cells increases in diseases such as chronic inflammation and T-cell malignancies, these being skin inflammatory lesions. Therefore, this can be useful for the diagnosis of cancer cells, especially with reference to blood origin, treatment monitoring, and establishment of new therapies. Therefore, a comprehensive review could be useful to increase our knowledge about the clinical importance of these cells in human disease.