Hepatic gene downregulation following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to lead to the development of hepatotoxicity and carcinogenicity in the liver of female rats. In this study, we investigated hepatic gene downregulation in response to acute and subchronic TCDD exposure. We identified 61 probes which exhibited a downregulation of twofold or greater following subchronic (13 weeks) exposure to TCDD. Comparative analysis of the hepatic expression of these 61 probes was conducted with rats subchronically exposed to PeCDF, PCB126, PCB153, and a mixture of PCB126 and PCB153. PCB153 produced little or no alteration in these probes, while the binary mixture mimicked most closely the downregulation observed with TCDD. To discern if the repression of genes within this probe set occur as a primary response to TCDD exposure, we analyzed the early responsiveness of 11 genes at 6, 24, and 72 h following a single exposure to TCDD. We observed early repression of the 11 genes within this early time course, indicating that the repression of this subset of genes occurs as a primary response to TCDD exposure and not as a secondary response to 13 weeks of subchronic treatment. In addition, the gender, species, and AhR dependence of these responses were also investigated. Gender- and species-dependent repression was observed within this subset of genes. Furthermore, utilizing AhR knockout mice, we were able to determine the AhR-dependent downregulation of seven of 11 genes. Together these results assist efforts to understand the multitude of effects imposed by TCDD and AhR ligands on gene expression.     

Subchronic Toxicity of 2,4,4'-Trichlorobiphenyl in the Rat Liver: An Ultrastructural and Biochemical Study

2,4,4'-Trichlorobiphenyl or PCB congener 28 was given to Sprague-Dawley weanling rats and the experimental diets were prepared by mixing the congener in 4% corn oil. The congener was administered to animals placed in four groups, each comprising 10 males or females. The diets contained 0.05, 0.5, 5, or 50 ppm congener. The fifth or control group comprised animals that received diets mixed with corn oil. Thirteen weeks after commencement of dosing, animals were euthanized and liver specimens were harvested from the animals and prepared for electron microscopy and biochemical analyses. The hepatocyte architectural modifications included an augmentation of SER profiles and an elevation of peroxisome numbers in animals regardless of gender, and mitochondrial abnormalities in the females only. Mitochondrial aberrations consisted of abnormal shapes and cristae in atypical orientation. The alterations were revealed in animals of the 5-and 50-ppm groups and were more extensive in the females. Ethoxyresorufin-O-de-ethylase activity was significantly high in the animals of the 50-ppm group. The results suggest that the female rats were more sensitive than the males to congener 28, and the no observable adverse effect level (NOAEL) was believed to be 0.5 ppm for the congener.     

Fetal RhD genotyping: A more efficient use of anti-D immunoglobulin

The most important application of blood group genotyping by molecular genetics is the prediction of fetal RhD phenotype in pregnant women with anti-D, in order to assess the risk of haemolytic disease of the fetus and newborn. This diagnostic test performed on cell-free fetal DNA in the maternal plasma, is now a routine procedure in some countries. High-throughput modifications of this form of fetal D-typing would be valuable for testing fetuses of all D-negative pregnant women to avoid unnecessary antenatal treatment with anti-D immunoglobulin in the 40% of D-negative pregnant women with a D-negative fetus. The results of trials in Bristol and Amsterdam suggest that such routine testing is feasible and accurate.     

碱性成纤维细胞生长因子对卵巢癌CAOV3细胞cyclin D1及GADDl53表达的影响

目的:研究碱性成纤维细胞生长因子(bFGF)对人卵巢癌CAOV3细胞细胞周期调节蛋白cyclinD1及GADD153表达的影响,探讨bFGF促进人卵巢癌CAOV3细胞增殖、抑制凋亡的信号机制。方法:利用无血清饥饿诱导卵巢癌CAOV3细胞凋亡。分为对照组、bFGF组。分别应用MTT、流式细胞术、琼脂糖凝胶电泳观察25、50、75μg/L bFGF对CAOV3细胞增殖率、细胞周期及细胞凋亡的影响。利用Western blotting检测bFGF对CA-OV3细胞cyclin D1、GADD153以及转录因子(c-Fos、c-Jun)表达的影响。结果:与对照组相比,bFGF呈剂量依赖性加速CAOV3细胞细胞周期进程,促进细胞增殖,抑制饥饿诱导的凋亡(P<0.01);呈时间依赖性促进cyclinD1、c-Fos、c-Jun,抑制GADD153蛋白表达(P<0.01)。结论:bFGF可能通过上调cyclin D1、c-Fos、c-Jun,下调GADD153表达促进细胞增殖,抑制饥饿诱导的卵巢癌CAOV3细胞凋亡。     

The biodistribution and Kinetics of the Samarium-153 labeled avidin, streptavidin and biotin

Theextraordinaryhighaffinityofavidin(Av)andstrepavidin(SA)forbiotin(Bt)hasbeenutilizedinpretargetingtechniquefordeliveringradiolabeledbi-otinderivativessuitableforimagingandtherapytotarget-boundstreptavidin-oravidin-conjugatedmono-clonalantibodies(mAb).Preliminaryreportsusingthistechniquehavebeenavailableinbothexperimen-talandclinicaltrials,andmuchsuccesshasbeenachieved[1－3].However,questionsremainpertainingtothepharmacokineticsandbiodistributionofradiola-belledSAandAvinmice,andtherolesoft…     

153Sm-EDTMP和骨膦治疗骨转移癌症疼痛

目的　评价 1 5 3 Sm- EDTMP和 (或 )骨膦治疗骨转移癌症疼痛 6 0例的治疗效果 .方法　对 6 0例确诊为骨转移癌的患者随机分为 3组 ,分别为 1 5 3 Sm - EDTMP治疗组、骨膦治疗组和 1 5 3Sm- EDTMP加骨膦治疗组 ,观察止痛效果、骨病变有效率和毒副反应 .结果　 1 5 3 Sm- EDTMP组 30例、骨膦组 2 0例、联合用药组 10例的骨痛止痛有效率分别为 80 % ,85 %和90 % ;3组分别比较无显著差异 (P>0 .0 5 ) .3组骨病变有效率分别为 2 0 % ,10 %和 5 0 % ;联合用药组与其他两组比较有显著差异 (P<0 .0 5 ) ,3组毒副反应均少 .结论　1 5 3 Sm-EDTMP加骨膦联合治疗疗效显著 ,安全可靠 ,可能是当今治疗骨转移癌疼痛的优选疗法     

Orbital immunocytoma simulating Hodgkin‘s disease by mimicking Hodgkin- and Reed-Sternberg-like cells

Purpose. The present case report describes primaryorbital immunocytoma (IgM-) mimicking Hodgkinsdisease of the diffuse, lymphocyte predominance type byexpressing Hodgkin simulating cells as well asReed-Sternberg simulating cells (both: H-RScells). Patients and methods. The patient (87a; male)was admitted to hospital with increasing left upper eyelidprotrusion. Computed tomography revealed an unspecificaccumulation of soft tissue within the orbit. A biopsy wastaken. Light microscopical sections were stained with PAS, Giemsa andhaematoxylin-eosin. Immunohistochemistry was performedfollowing standard procedures. Results. By means oflight microscopy, Hodgkins disease of the diffuse,lymphocyte predominance type was indicated.This initial diagnosis was mainly based onmorphological criteria, e.g. the presence of H-RS-like cells.Since staging work-up produced no evidence of systemicdisease, immunohistochemistry was performed. It revealedthat the misleading cells were H-RS simulating cells. Finally, the diagnosis made was thatof immunocytoma (IgM-); stage I EA. Conclusion.The diagnosis of Hodkins disease of the diffuse, lymphocytepredominance type is normally based on morphologicalcriteria. However, in very rare cases immunocytomas simulate this variant ofHodgkins disease by expressing misleading H-RS simulatingcells. Thus, immunohistochemical investigations shouldgenerally be included in the criteria for the diagnosis ofHodgkins disease of the diffuse, lymphocyte predominance type. As far as we areaware, primary immunocytoma mimicking this variant ofHodgkins disease within the orbit has never been reported.     

Transfer of 2,4,5,2′,4′,5′-hexachlorobiphenyl and 2,2-bis-(p-chlorophenyl),1,1,1-trichloroethane (p,p′-DDT) from maternal to newborn and suckling rats

Pregnant rats were given a small dose of ¹⁴C-2,4,5,2,4,5-hexachloro-biphenyl (HCB) and ³H-DDT intraperitoneally. The transfer of HCB and DDT through the placenta and milk was then investigated. Transfer through the placenta was 2.7 and 1.5% (respectively) of the initial doses; transfer through milk was 39.2 and 21.5%. HCB is obviously more transferable than DDT through the placenta and milk, the ratio of the amount of HCB transferred through milk to the amount transferred through the placenta agrees with that for DDT.Concentrations of HCB and DDT in the whole suckling rat increases rapidly and is similar to the sigmoidal growth curve and change in lipid concentration. Therefore, the concentrations of the chemicals in the maternal tissue generally decrease in comparison with those of nonpregnant rats.     

Body burden of polychlorinated biphenyls among persons employed in capacitor manufacturing

Summary In an effort to assess exposure among workers engaged in capitor manufacture, PCB concentration was determined in plasma (290) and adipose tissue (61). In general, males had higher concentrations of PCBs than females.The correlation of plasma concentration (1–546 ppb) of the more highly chlorinated PCBs, which had been used in the past, with total duration of employment suggested accumulation over time. The gc-ec pattern of these PCB peaks was, in most cases, characteristic of exposure to a PCB mixture with 54% chlorine.The less highly chlorinated PCBs, di-, tri-, and tetrachlorobiphenyls, were the source of current exposure, and were observed in concentrations of 6–2530 ppb in plasma. Higher exposure occurred among persons with direct contact with PCBs, in jobs such as capacitor filling.Adipose tissue concentrations, for both the more highly chlorinated PCBs (1–165 ppm) and lower chlorinated PCBs (0.6-414 ppm), were proportional to those in plasma.Abbreviations PCB polychlorinated biphenyl - p,p-DDE 2,2-bis-(4-chlorophenyl)-1,1-dich-loroethylene - DDT dichlorodiphenyltrichloroethane Presented in part, at the XIX. International Congress on Occupational Health, Dubrovnik, September, 1978