放射性碘致大鼠甲状腺损伤超微结构的形态计量学研究

本文应用透射电镜观察了在较低剂量１３１Ｉ作用大鼠甲状腺滤泡上皮细胞超微结构的变化特点，分析了线粒体的变异发生率，并应四川大学研制的ＭＩＡＳ－３００图像分析系统和用形态计量学方法，测定了胞质内粗面内质网的二维和三维形态计量学参数。结果表明：所测的各项参数都有随剂量增高而增大的趋势，并呈现较好的效应剂量依赖关系。由此计算的Ｄ２５值和Ｄ５０值，以粗面内质网体积密度的变化最为明显。提示，低剂量１３１Ｉ作用于滤泡上皮细胞，其早期应重视内质网的损伤效应，以及由此导致合成类固醇激素和外源性蛋白质的障碍     

Mutagenicity of recombinant antihemophilic factor (GC-gamma AHF)

This study was carried out to evaluate the mutagenic potential of recombinant antihemophilic factor VIII (GC-gamma AHF). Salmonella typhimurium (S. typhimurium) reversion assay with/without histidine moiety, chromosomal aberration assay on Chinese hamster lung (CHL) fibroblast cells and in vivo micronucleus assay using mouse bone marrow cells and supravital micronucleus assay using peripheral blood were performed. GC-gamma AHF containing histidine did show inconsistent and irregular mutagenic effects on S. typhimurium TA98, TA100, TA1535 and TA1537 both in the absence and presence of the metabolic activation system, however, GC-gamma AHF without histidine showed no mutagenic effects regardless of the metabolic activation system, thus suggesting that the histidine moiety in GC-gamma AHF might cause inconsistent mutagenic effect. Also GC-gamma AHF did not increase the number of cells having structural or numerical chromosome aberration in the cytogenetic test. In classical and supravital micronucleus assay, no significant increases were observed in the occurrence of micronucleated polychromatic erythrocytes and micronucleated peripheral lymphocytes in male ICR mice. These results strongly indicate that GC-gamma AHF has no genetic toxicity under these experimental conditions.     

Antibodies to Nipah-like virus in bats (Pteropus lylei), Cambodia

Serum specimens from fruit bats were obtained at restaurants in Cambodia. We detected antibodies cross-reactive to Nipah virus by enzyme immunoassay in 11 (11.5%) of 96 Lyle's flying foxes (Pteropus lylei). Our study suggests that viruses closely related to Nipah or Hendra viruses are more widespread in Southeast Asia than previously documented.     

Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations

To estimate the genotoxic risk of occupational exposure to antineoplastic drugs, chromosomal aberration (CAs) frequencies in peripheral lymphocytes were determined for 20 nurses handling antineoplastics and 18 referents matched for age and sex. Urinary cyclophosphamide (CP) excretion rates, which are used as a marker for drug handling, were also measured on these nurses. We have observed significant frequencies of CAs (about 2.5-fold increase) including chromatid breaks, gaps, and acentric fragments for nurses handling antineoplastics as compared to control subjects (p < 0.05, p < 0.01, excluding and including gaps, respectively). The mean value of CP excretion rate for 12 nurses was 1.63 microg/24 h, suggesting that when the nurses handled CP (and other antineoplastic drugs) this particular compound was absorbed. Our study has shown that increased genetic damage was evident in nurses, at population level, due to occupational exposure to antineoplastics. Until the effects of handling antineoplastics from low-level exposure are known, it will be important to keep the exposure to a minimum.     

Inhibition of TNF-alpha,IL-1beta,and IL-6 productions and NF-kappa B activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide,an iridoid glycoside isolated from Catalpa ovata G. Don (Bignoniaceae)

Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniaceae), was found to inhibit the productions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and the activation of nuclear factor kappaB (NF-kappaB) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Catalposide also inhibited the expressions of TNF-alpha, IL-1beta, and IL-6 genes and the nuclear translocation of p65 subunit of NF-kappaB in LPS-activated RAW 264.7 cells. Flow cytometric analysis revealed that catalposide suppressed the binding of FITC-conjugated LPS to CD14 on the surface of cells, probably resulting in the inhibitory effects on TNF-alpha, IL-1beta, and IL-6 productions and NF-kappaB activation. These findings suggest that catalposide could be an attractive candidate for adjunctive therapy in gram-negative bacterial infections.     

非融合重组人碱性成纤维细胞生长因子在大肠杆菌中的克隆及高效表达

目的:获得大肠杆菌中高效表达的非融合重组人碱性成纤维细胞生长因子(rhbFGF).方法:采用RT-PCR技术,以人胎儿脑组织的总RNA克隆出hbFGF基因,再以此为模板,设计引物,对hbFGF的TIR(翻译起始区)部分碱基进行改造和降低G C含量,最后将该新基因克隆于质粒载体pET-3C,转化于大肠杆菌中表达.结果:非融合rhbFGF在大肠杆菌中高效表达,占总蛋白量的30％以上.采用离子交换和亲和层析方法纯化后,生物活性与标准蛋白一致.结论:非融合rhbFGF及调整TIR区域的碱基序列能有效提高重组蛋白的表达效率.     

Mature parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum binds to the 30-kDa domain of protein 4.1 in malaria-infected red blood cells

The Plasmodium falciparum mature parasite-infected erythrocyte surface antigen (MESA) is exported from the parasite to the infected red blood cell (IRBC) membrane skeleton, where it binds to protein 4.1 (4.1R) via a 19-residue MESA sequence. Using purified RBC 4.1R and recombinant 4.1R fragments, we show MESA binds the 30-kDa region of RBC 4.1R, specifically to a 51-residue region encoded by exon 10 of the 4.1R gene. The 3D structure of this region reveals that the MESA binding site overlaps the region of 4.1R involved in the p55, glycophorin C, and 4.1R ternary complex. Further binding studies using p55, 4.1R, and MESA showed competition between p55 and MESA for 4.1R, implying that MESA bound at the IRBC membrane skeleton may modulate normal 4.1R and p55 interactions in vivo. Definition of minimal binding domains involved in critical protein interactions in IRBCs may aid the development of novel therapies for falciparum malaria.     

Elevation of Na+-K+ ATPase immunoreactivity in GABAergic neurons in gerbil CA1 region following transient forebrain ischemia

In a previous study, we suggested that GABAergic neurons might be resistant to ischemic insult, because of the maintenance of the GABA shunt, which is one of the ATP synthetic pathways in neurons. In the present study, we identified Na(+)-K(+) ATPase immunoreactivity in the gerbil hippocampus in order to determine whether changes in Na(+)-K(+) ATPase immunoreactivity correlate with GABA shunt following ischemic insult. At 12 h after ischemia-reperfusion, Na(+)-K(+) ATPase immunoreactivity accumulated in some neurons in the CA1 region. However, the protein content of Na(+)-K(+) ATPase was not altered. Interestingly, the density of Na(+)-K(+) ATPase immunoreactivity in neurons and the protein content in the CA1 region was intensified in the 24 h post-ischemic group. As a result of double immunofluorescence study, Na(+)-K(+) ATPase immunoreactive neurons were identified with GABAergic neurons. Therefore, our findings suggest that the increase of Na(+)-K(+) ATPase in GABAergic neurons may be able to explain the resistance of these cells to ischemic insult, and support our previous hypothesis that GABA may play an important role as a metabolite in the survival of GABAergic neurons after ischemic insult.     

Infantile spasms in a patient with williams syndrome and craniosynostosis

A patient with Williams syndrome, craniosynostosis, and infantile spasms is described. At age 6 months, the infant demonstrated infantile spasms and craniosynostosis and was operated on for craniosynostosis and treated with adrenocorticotropic hormone (ACTH) for the infantile spasms. ACTH completely controlled the seizures, but was halted because of the progression of ventricular hypertrophy. The seizure returned, and he was found to have elfin face, failure-to-thrive, developmental delay, and dental malformation in addition to congenital heart defects. High-resolution chromosome analysis revealed interstitial deletion of 7q11.22-q11.23. Therefore his clinical and cytogenetic diagnosis was Williams syndrome. Thyrotropin-releasing hormone (TRH) therapy reduced his seizures and improved the findings of EEG without cardiac side effects. In addition, his psychomotor development was slightly improved.