Metabolism of parenterally administered zinc and cadmium in livers of newborn rats

The interaction of injected zinc and cadmium with metallothionein was investigated in newborn rats. Tissues of 5-day-old rats were removed 24 h after a single injection (Sc) of saline or zinc (20 mg/kg, body wt.) or cadmium (1 mg/kg, body wt.) with 2.5 μCi of ⁶⁵Zn or ¹⁰⁹Cd or 5 μCi of [³⁵S]cysteine. Injection of zinc resulted in a 75% increase in the hepatic zinc concentration with a concomitant elevation of metallothionein (P < 0.001), zinc in metallothionein increased by 45% (P < 0.05); [³⁵S]cysteine incorporation indicated the induced synthesis of metallothionein. Injection of cadmium did not alter either metallothionein or zinc levels in liver, but cadmium in cytosol was preferentially bound to metallothionein. Neither treatment altered hepatic copper metabolism and copper in metallothionein, nor renal zinc and metallothionein levels. These data indicate that zinc injection can elevate hepatic zinc levels and induce metallothionein synthesis in newborn rats despite high basal levels; cadmium injection does not induce metallothionein synthesis, though cadmium is avidly sequestered by pre-existing metallothionein. The differences in the induction of metallothionein by these divalent cations can be explained by the differences in their binding affinities for thiol groups in intracellular metallothionein.     

Ultrastructural analysis of the human cerebral ventricular system

Summary The ultrastructural organization of the human fetal choroid plexus was assessed with scanning electron microscopy. The membranous modifications of choroidal ependymal cells differ remarkably between 11 and 20 weeks of intrauterine development and suggest a variable functional capacity at different times of ontogenesis. Based upon existing data coupled with the ultra-architectural organization of cilia, clavate and linear microvilli are seen with scanning electron microscopy, a multiple functional role is hypothesized for choroidal ependymal cells.supported by USPH grant NS 08171.career development awardee K04 GM 70001     

Scanning and transmission electron microscopy of human ejaculate spermatozoa with special reference to their abnormal forms

Summary Spermatozoa from fertile and infertile human ejaculates were observed under the scanning electron microscope. A parallel study of sections was performed by transmission electron microscope.The normal head shows under the scanning electron microscope vesicular elevations in the region of the acrosome and a smooth and rigid appearance corresponding to the postnuclear cap whose occurrence is confirmed under the transmission electron microscope. Immediately anterior to this cap a shallow furrow transverses the head. Duplicated, unusually large or small and deformed heads are found under the scanning electron microscope. Most of these abnormal heads show no surface structure suggesting an acrosome.The neck and middle piece are occasionally, though frequently in abnormal spermatozoa, covered by a cytoplasmic droplet. Otherwise, the mitochondrial sheath is recognized under the scanning electron microscope as a beaded thickening in the middle piece. The lack of mitochondria is manifested by a smooth middle piece thinner than the principal portion. Transmission electron microscopy of sections reveals various types of anomalies in the number of cores, core filaments and mitochondria embedded in the cytoplasmic droplets.Abnormalities in the principal portion of the tail such as duplication, unusual thickness and length are shown under the scanning electron microscope.The investigation indicates that scanning electron microscopy is suited for the clinical as well as cytological examination of human ejaculate spermatozoa.     

微核形成与细胞周期关系的初步研究 Ⅲ.丝裂霉素c诱发人淋巴细胞染色体畸变与不同周期阶段的微核形成

为了研究染色体畸变与微核形成的关系,本实验用不同浓度的丝裂霉素C(MMC,0.025—0.4μg/ml),处理人外周血淋巴细胞,观察中期染色体畸变与不同细胞周期形成的微核间的关系。获得如下主要结果:(1)MMC诱发的染色体畸变细胞率(ACF),未经培养的G_0期淋巴细胞的微核细胞率(NC-MNCF)以及培养的淋巴细胞的微核细胞率(C-MNCF),在一定剂量范围内均呈剂量依赖性增加,并可用幂回归方程描述;(2)微核形成与染色体畸变全然无关的NC-MNCF,和C-MNCF一样,与ACF呈良好的正相关;(3)用胞质分裂阻滞(CB)法,检测MMC诱发的CB-MNCF,较C-MNCF无显著提高,MNCF/ACF的比值较小,并随着MMC剂量增加从0.15左右降到0.03。所有上述结果表明,不能简单理解微核形成与染色体畸变间的关系,在分裂的细胞群体中,中期染色体畸变可能仅是微核形成的一种来源。     

正丁酸钠对人胃腺癌细胞染色体数目和DNA含量的影响

培养的人胃腺癌MGc 80-3细胞经过正丁酸钠处理7天后,生长抑制率达50.7%,约有90%的细胞形态发生分化,其超微结构亦有显著改变。而且,在染色体数目上,超二倍体细胞由对照组的78%增加到实验组的96%,超三倍体和超四倍体细胞则分别从6%和14%下降至2%。同时应用~3H-TdR放射自显影和福尔根细胞光度法测定未标记细胞(G_1期)DNA含量,结果显示实验组比对照组降低了。而且在实验组的同一制片中,未分化细胞DNA含量平均为超六倍体值(DI=3.67和3.56),其中90%的细胞超过6C;分化细胞DNA含量则平均为近四倍体值(DI=2.03和1.99),其中近60%的细胞少于4C。两者差异统计显著,表明形态分化的人胃腺癌细胞的遗传物质含量明显减少,但这些细胞并非就是正常二倍体细胞。     

血液病患者的巨细胞病毒感染

用间接酶联免疫吸附实验(ELISA)对新近诊断的179例血液病患者血清巨细胞病毒(HCMV)IgM和IgA抗体进行了检测。阳性率分别为11,17％11,73％,明显高于对照人群(4,76％和3,97％),提示血液病患者由于免疫功能下降,易于发生HCMV活动性感染。     

Enhanced cadmium cytotoxicity in A549 cells with reduced glutathione levels is due to neither enhanced cadmium accumulation nor reduced metallothionein synthesis

Glutathione (GSH) depletion sensitizes human lung carcinoma (A549-727) cells to the cytotoxic effects of Cd⁺⁺. The effects of GSH depletion on Cd⁺⁺ accumulation and Cd⁺-induced metallothionein (MT) content were investigated to determine the possible role of these Cd⁺⁺ responses in the sensitization process. Cellular GSH was depleted to 20% to 25% of control levels with buthionine sulfoximine (BSO), or diethyl maleate (DEM), respectively. Neither treatment significantly affected Cd⁺⁺-induced accumulation of exogenous³⁵s-cysteine into intracellular MT in a dose-dependent fashion. The results indicate that neither enhanced Cd⁺⁺ accumulation nor reduced MT synthesis plays a primary role in affecting enhanced Cd⁺⁺ cytotoxicity in A549 cells with reduced GSH levels. Although BSO inhibition of GSH synthesis enhanced MT synthesis, it sensitized the cells to Cd⁺⁺, which suggests an additive effect of GSH and MT in cadmium cytoprotection. This observation also raises the possibility that intracellular cysteine levels limit Cd⁺⁺-induced MT accumulation rates.Abbreviations GSH glutathione - MT metallothionein - BSO DL-buthionine-[S,R]-sulfoximine - DMSO dimethyl sulfoximine - DEM diethyl maleate - NP-40 nonidet-P40 - PBS phosphate buffered saline - HBSS Hank's balanced salt solution - DTT dithiothreitol 3. This work was presented in part at the 72nd Annual Meeting of the Federation of American Societies for Experimental Biology, Las Vegas, Nevada, May 1–5, 1988.     

Effect of Long-Lasting Diabetes Mellitus on Rat and Human Brain Monoamines

Experimental alloxan- or streptozotocin-produced diabetes in rats was accompanied by an increase in the levels of norepinephrine, dopamine, and serotonin, whereas the contents of metabolites, i.e., 5-hydroxyindoleacetic acid and homovanillic acid, in the whole brain gradually decreased with the duration of diabetes. Among the striatum, thalamus, and hypothalamus of alloxan diabetic rats, monoamine alterations were observed only in the hypothalamus; after 1 week an increase of norepinephrine content and after 13 weeks an increase of norepinephrine and dopamine contents were found. Tissues of 11 brain regions of 10 diabetic and 12 control patients post mortem were investigated for monoamine concentrations. Patients were all male, of similar age and interval between death and autopsy. Diabetic patients had an increase in the content of serotonin in the medial and lateral hypothalamus. The content of dopamine increased in the medial hypothalamus, putamen, and medial and lateral pallidus. In diabetic patients, the content of norepinephrine increased in the lateral pallidus and decreased in the nucleus accumbens and claustrum. Thus, it seems that diabetes mellitus in rats, as well as in humans is associated with regionally specific changes in brain monoamines.     

DNA microenvironments and the molecular clock

Summary A few years ago we presented a stationary Markov model of gene evolution according to which only homologous genes from not too divergent species obeying the condition of being stationary may behave as reliable molecular clocks. A compartmentalized model of the nuclear genome in which the genes are distributed in compartments, the isochores, defined by their G+C content has been proposed recently. We have found that only homologous gene pairs that are stationary, and belong to the same isochore, can be used consistently for the determination of phylogeny and base substitution rate. In particular, for the rodent-human couple, only about half of the homologous gene pairs are stationary. Stationary genes evolve at the third silent codon position with the same velocity independent of the genes and base composition. By contrast, nonstationary genes display apparent rate values (pseudovelocities) that are significantly higher. Our results cast doubt upon recent claims of a large acceleration in the rate of molecular evolution in rodents.