Spontaneous mutation of the lacI transgene in rodents: absence of species, strain, and insertion-site influence

Comparison of spontaneous mutation spectra derived from different transgenic constructs can provide valuable insights for interpreting the mechanisms of spontaneous mutation. In this study, spontaneous mutation frequencies and spectra of the lacI transgene are compared in the liver of C57BL/6, B6C3F1, and BC-1 mice and F344 rats. Before correction for clonal expansion, the mutant frequency varied from 2.6 +/- 0.45 to 5.0 +/- 2.4 x 10(-5). Correction for potential clonal expansion reduced the range in mutation frequency to between 2.3 +/- 0.45 and 3.5 +/- 2.0 x 10(-5). There is thus no statistical difference in spontaneous mutation frequency between the different strains and species. G:C --> A:T transitions and to a lesser extent, G:C --> T:A transversions dominate the mutational spectra in all of these animals. In three strains of mice, G:C --> A:T transitions account for 50.7-53.3% of mutation, 81.7-83.8% of which involve CpG sites, whereas G:C --> T:A transversions account for 17.8-32.9% of mutations with 43.2-50.0% found at CpG sites. In rats, G:C --> A:T transitions account for 38.0% of the spectra, 70.0% of which involve CpG sites, whereas G:C --> T:A transversions account for 23.0% of the spectra, 70.0% of which involve CpG sites. The distribution of other classes of mutations is also very similar. We conclude that, despite reports about species and strain differences in induced mutation, spontaneous mutations in the lacI transgene appear to be similar, regardless of genomic location, rodent strain, or species. In addition to insights into spontaneous mutation, this study also provides essential data for comparison with and interpretation of induced mutations.     

Variations of relative anteversion of the femoral neck during walking

Summary Based on the geometric model developed by Netter [11], we determined the different positions of the femoral neck during monopodal support in walking in relation to a fixed frontal plane of reference (relative anteversion). This relative anteversion ranges on average from 24° of retroversion at the beginning of support to 15° of anterversion at the end if loading. We then studied the relations possibly existing between relative anteversion and acetabular orientation on the one hand, and the orientation of the resultant of the articular stresses on the other (both being variables during monopodal support in walking). The results showed that relative anteversion is well correlated with variations of position of the acetabulum since, at most, the deviation between the respective axes did not exceed the anatomic deviation due to absolute anteversion of the femoral neck and acetabulum. Lastly, analysis of the relations obtained with the orientation of the resultant of the articular stresses allowed a better comprehension of the functional distribution of forces.

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Variations de l'antéversion relative du col fémoral au cours de la marche

Résumé Nous inspirant de la modélisation géométrique développée par R. Netter dans sa thèse, nous avons déterminé les différentes positions du col fémoral au cours de l'appui monopodal de la marche par rapport à un plan frontal fixe de référence (antéversion relative). Cette «antéversion relative» s'échelonne en moyenne de 24° de rétroversion en début d'appui à 15° d'antéversion en fin d'appui. Nous avons alors étudié les relations pouvant exister entre l'antéversion relative et l'orientation de l'acétabulum, d'une part, et, d'autre part, l'orientation de la résultante des sollicitations articulaires (toutes deux variables au cours de l'appui monopodal de la marche). Les résultats nous ont montré que l'antéversion relative est bien corrélée aux variations de position de l'acétabulum puisque, au maximum, l'écart entre leurs axes respectifs ne dépasse pas l'écart anatomique du à l'antéversion absolue du col et de l'acétabulum. Enfin, l'analyse des rapports existant avec l'orientation de la résultante des sollicitations articulaires nous permet de mieux entrevoir la répartition fonctionnelle des contraintes.

     

Allergenicity of α-caseins from cow, sheep, and goat

The allergic potential of α-caseins from bovine, ovine, and goat's milk sharing more than 85% identical amino acids was compared. Caseins were purified by anion-exchange chromatography and used for a specific IgE and IgG ELISA with diluted human sera. Sera were from 17 children with immediate-type allergy to cow's milk, from 59 children with atopy but without food allergy, and from 27 healthy children without atopic disease. The sera of cow's milk-allergic children showed a significantly higher IgE and IgG binding to α-caseins from all three species than the sera of the other groups. All groups showed an increased antibody binding to bovine a-casein compared to the sheep and goat proteins, but the differences were significant only in the groups of atopic children and of healthy controls. Furthermore, inhibition of the IgE binding to bovine α-casein with α-casein from cow, goat, and sheep revealed that the a-caseins from these species are highly cross-reactive, on the basis of the small differences in their primary structure. In conclusion, the milk of goat and sheep harbor an allergic potential and is not suitable for the nutrition of milk-allergic patients.     

Radiation protects adriamycin-induced apoptosis

Combined radiotherapy and chemotherapy have represented major advance in the therapeutic management of cancer therapy. Anthracycline antineoplastic agents are limited by a high incidence of severe and usually irreversible cardiac toxicity, the cause of which remains controversial. When the primary cardiomyocytes isolated from neonatal rats were preirradiated by γ-ray, the cells were highly resistant to adriamycin-induced apoptosis. This study shows that irradiation inhibited apoptosis by enhancing Bcl-2, attenuating Bax induction, and preventing collapse of mitochondrial membrane potential (ΔΨ), cytochrome c release into cytoplasm and caspase-3, -6 and -9 activations.

In addition, the preirradiation stimulated the activity of manganese-superoxide dismutase (Mn-SOD) and the expression of Mn-SOD mRNA and protein. Adriamycin decreased Mn-SOD activity but did not change the activity of copper/zinc (Cu/Zn)-SOD under either pre- or nonirradiated condition. Phosphothioate-linked antisense against Mn-SOD, which specifically knocked down the activity of Mn-SOD but not that of Cu/Zn-SOD, reversed irradiation-induced protective effect in adriamycin-exposed cardiomyocytes. These data suggest that the irradiation-induced expression of Mn-SOD plays an important role in irradiation-mediated protection in adriamycin-exposed rat ventricular cardiomyocytes.     

Clonally restricted insulin autoantibodies in a cohort of 2200 healthy blood donors

Summary Serum samples of 2200 blood donors were screened for anti-insulin IgG by enzyme-linked immunosorbent assay. Specificity of detected antibodies was verified by competition with an excess of insulin and observation that saturated anti-insulin IgG were no longer measurable. The upper limit of measured signal in the population was defined as the mean plus three SD. In the direct assay, 32 sera were positive. Among these, 22 (1%) contained saturable insulin antibodies (true positive) and 10 were non-saturable and considered as non-insulin-specific. The positive blood donors were requested to answer a questionnaire and according to their answers, none had ever received insulin, was a first degree relative of a Type 1 (insulin-dependent) diabetic patient or had experienced a hypoglycaemic episode. None of the 22 true positive sera detected by enzyme-immunosorbent assay bound ¹²⁵-I-insulin to any significant extent. The nine sera yielding the highest signal were further characterized with regard to heavy and light chains as well as species specificity of ligand. Anti-insulin IgG from healthy blood donors contained only one heavy (1 2/9; 3 7/9) and one light ( 8/9; 1/9) chain. Three sera were human insulin specific; two were non-species-specific; the other four bound insulin in the order human = porcine > bovine. These results indicate that low affinity clonally restricted antibodies against insulin are present in unselected blood donors with a prevalence of 1%.     

NADPH氧化酶家族在心血管疾病中作用的研究进展

烟酰胺腺嘌呤二核苷酸磷酸氧化酶是心血管系统中活性氧(reactive oxygen species,ROS)的主要来源,它包 括7种亚型并分别表达在不同的心血管细胞及其细胞器中,参与调节细胞增殖、迁移、分化、凋亡、衰老和炎症反应 等多种活动,其衍生的ROS参与高血压、动脉粥样硬化、糖尿病血管病变、心肌梗死后心室重构等多种心血管疾病 的病理过程。     

当药水提物对大鼠中性白细胞活性氧生成和兔血小板聚集的影响

目的 研究当药水提物对大鼠中性白细胞性细胞内内Ca^2 浓度增加、活性氧生成及兔血小板聚集的影响。方法 用酵母多糖、FMLP和A23 187活化大鼠中性白细胞,用化学发光法测定活性氧,用荧光光度法测细胞内Ca^2 浓度,用比浊法测血小板聚集。结果 当药水提物浓度依赖性地抑制酵母多精、FMLP和A23 187诱导的大鼠中性白细胞内Ca^2 浓度增加及活性氧生成;也抑制花生四稀酸、胶原及ADP诱导的兔血小板聚集。和吲哚美辛比较,当药水提物抑制活性氧生成的作用较强而抑制血小板聚集的作用较弱,其作用远强于swertiamarin。结论 当药水提物是极强的中性白细胞活性氧生成抑制剂,其作用强于swertiamarin。     

Infective endocarditis in paediatrics

Infective endocarditis is a result of infection of the endocardium, particularly of the heart valves (native or prosthetic valves). The most common causative organisms in the paediatric population are: Streptococci, Staphylococci and Enterococci. The classical signs of infective endocarditis like Roth spots, Janeway lesions, splinter haemorrhages and Osler's nodes are relatively rare in children. A high index of suspicion in a febrile child with a new murmur, detailed history, meticulous examination, repeated blood cultures, and echocardiography are essential in establishing the diagnosis. Management of infective endocarditis involves a prolonged course of antibiotics, at least for 4–6 weeks depending upon the causative organism and underlying heart condition. Complications of infective endocarditis include congestive heart failure resulting from valvular damage/regurgitation, infective emboli leading to abscesses in other organs and abnormal host immunological responses. Prophylactic antibiotics for dental and other medical procedures like genitourinary tract procedures are no longer recommended in the UK. The emphasis should be on educating children and their parents in early recognition of infective endocarditis. Children at high risk of developing endocarditis should be assessed urgently after clinical suspicion.     

Periventricular- intraventricular hemorrhage in the premature infant- A historical perspective

The objective of this chapter is to trace the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow changes in the genesis of hemorrhage, clinical factors that increase the bleeding risk, and potential preventative strategies. In 1976, neuropathological studies demonstrated capillary rupture within the germinal matrix as the precursor of hemorrhage. In 1980, introduction of cranial ultrasound facilitated diagnosis of intraventricular hemorrhage. In 1979, loss of cerebral autoregulation in sick newborn infants was demonstrated. In the 1980’s, studies demonstrated the importance of intravascular factors in provoking hemorrhage. In 1983, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. In 1994, antenatal steroids use to accelerate lung development was recommended. This was associated with an unanticipated reduction in hemorrhage. In the mid 1990’s early indomethacin administration was associated with a reduction of severe hemorrhage.     

进行期银屑病患者活性氧代谢变化探讨

目的：探讨进行期银屑病患者活性氧代谢变化。方法：采用细胞化学发光分析技术测定患者及健康对照组外周血淋巴细胞化学发光强度（ Ｌｙｃｌ）及多形核白细胞化学发光强度（ Ｐ Ｍ Ｎｃｌ）,同时测定血浆超氧化物歧化酶（ Ｓ Ｏ Ｄ）、全血谷胱甘肽过氧化物酶（ Ｇ Ｓ Ｈ Ｐｘ）以及血浆丙二醛（ Ｍ Ｄ Ａ）含量。结果：银屑病患者 Ｌｙｃｌ及 Ｐ Ｍ Ｎｃｌ较对照组显著增强（ Ｐ＜ ０．０５）,血浆 Ｓ Ｏ Ｄ活力明显增强（ Ｐ＜ ０．０５）, Ｍ Ｄ Ａ 浓度较对照组明显增高（ Ｐ＜ ００５）。全血 Ｇ Ｓ Ｈ Ｐｘ 活力较对照组显著下降（ Ｐ＜ ０．０５）。结论：进行期银屑病患者细胞功能改变,机体活性氧代谢增强,抗氧化功能下降,组织细胞损伤加快。活性氧损伤可能是该病患者皮损炎症的重要原因。