Analysis of differential effects of Pb2+ on protein kinase C isozymes

Protein kinase C has been implicated as a cellular target for Pb2+ toxicity. We have previously proposed that Pb2+ modulates PKC activity by interacting with multiple sites within the enzyme. In order to further characterize the Pb-PKC interactions we compared the effects of Pb2+ on the CA-dependent and -independent protein kinase C isozymes using recombinant human PKC-alpha, PKC-epsilon, and PKC-zeta as well as the catalytic fragment of bovine brain protein kinase C, the PKC-M. The results demonstrate that, whereas at pM concentrations Pb2+ activates PKC-alpha half maximally (KAct approximately 2 pM), it has no effect on PKC-epsilon, PKC-zeta, or PKC-M activities. The activation of PKC-alpha by Pb2+ is additive with Ca2+ in a manner indicating interaction with half of the calcium activation sites. In the micromolar range of concentrations, Pb2+ inhibits all PKCs with estimated K0.5 of 1.0, 2.3, 28, and 93 microM for PKC-M, PKC-alpha, PKC-epsilon, and PKC-zeta, respectively. Examination of Pb2+ effects on PKC-M kinetics indicates a mixed type inhibition with respect to ATP and noncompetitive inhibition with respect to histone. Taken together with the results of our previous study (Tomsig and Suszkiw, J. Neurochem. 64, 2667-2673, 1995) and the evidence for the existence of two Ca2+ coordination sites Ca1 and Ca2 within the C2 domain (Shao et al., Science [Washington, D.C.] 273, 248-251, 1996), the results of the current study provide further support for a multisite Pb-PKC interaction scheme wherein lead (1) partially activates the enzyme through pM-affinity interactions with the Ca1 site and inhibits the divalent cation-dependent activity through nM-affinity interactions with Ca2 site in the C2 domain and (2) inhibits the constitutive kinase activity through microM-affinity interactions with the catalytic domain. The concentration dependence of the differential effects of Pb2+ on the calcium-dependent and -independent PKCs underscores the importance of the C2 motif as a high affinity molecular target for Pb2+.     

Mucinous pancreatic ductal ectasia of latent malignancy: an emerging clinicopathologic entity.

The natural history of classic mucinous cystic neoplasms of the pancreas has been previously defined. In this report, an unusual variant of a pancreatic mucinous cystic neoplasm, termed "mucinous pancreatic duct ectasia of latent malignancy," is described. The lesion is characterized by massive dilatation of the main pancreatic duct and its tributaries. Histologically, the ducts are lined by epithelium, which is indistinguishable from the classic mucinous cystic neoplasms. Until the natural history of classic mucinous cystic neoplasm is better documented, resection appears to be the treatment of choice.     

血清CA125检测在子宫内膜癌中的价值

目的探讨血清CA125在子宫内膜癌中的价值.方法选取1992年3月～2002年3月在北京大学第一附属医院、北京大学人民医院住院经手术治疗的子宫内膜癌患者141例,术前及随访中用放射免疫法测定血清CA125水平,CA125≥35 U/ml 为阳性结果.对其中14例行子宫内膜癌组织CA125免疫组化方法检测.收集患者的临床病理资料,分析CA125与这些资料的关系以及复发患者复发前后CA125变化.结果 CA125免疫组化检测14例均呈阳性,阳性细胞着色率与血清CA125之间无明显相关.141例患者术前血清CA125阳性32例(22.7%), Ⅰ、Ⅱ、Ⅲ和Ⅳ期患者血清CA125阳性(阳性率)分别为11例(12.1%)、6例(31.6%)、12例(46.2%)和3例(60.0%). 血清CA125阳性率随子宫内膜癌期别的增加而升高.深肌层浸润、宫颈受累、附件转移、腹腔洗液细胞学阳性、盆腔淋巴结转移及宫内肿瘤病灶≥2 cm者,血清CA125阳性率增加.随访中13例复发,其中9例术前血清CA125＞35 U/ml者复发时均伴血清CA125水平升高,而另4例术前血清CA125正常者,复发后血清CA125水平仍正常.结论子宫内膜癌患者术前血清CA125的测量有助于了解肿瘤的侵犯范围.术前血清CA125水平异常的子宫内膜癌患者,术后定期复查血清CA125水平,将有助于子宫内膜癌病情的监测.     

喉癌组织恶性度与颈淋巴结转移关系

采用五因素评点法对４０例喉鳞癌进行组织学和临床方面的研究。结果表明，组织恶性度与Ｔ分期无相关性，浸润方式弥散及恶性度高（评分≥１１）的肿瘤发生颈淋巴结转移率显著高于有完整肿瘤边界者及恶性度低（评分≤１０）者。提示喉癌组织恶性度在预测颈淋巴结转移上有实用价值，可临导临床治疗方案的选择。     

妊娠期糖尿病患者高密度脂蛋白糖基化与妊高征发病的关系

目的：了解妊娠期糖尿病孕妇体内高密度脂蛋白（ＨＤＬ）糖化程度及受体代谢途径情况，探讨其与妊高征发病的关系。方法：用荧光法测定妊娠期糖尿病患者糖化血红蛋白，≤８．０％为组Ⅰ，共３２例、＞８．０％为组Ⅱ，共３４例，并测定正常妊娠组３６例及正常非妊娠组３２例ＨＤＬ糖化值。用酶联免疫受体法观察ＨＤＬ与培养的人胚肺成纤维细胞表面受体特异结合情况。结果：妊娠期糖尿病患者组Ⅰ、组ⅡＨＤＬ糖化值明显高于正常妊娠组和正常非妊娠组（Ｐ＜０．０１）。其细胞结合、摄入和降解糖化ＨＤＬ均较正常妊娠组和正常非妊娠组升高，使细胞内总胆固醇含量升高（Ｐ＜０．０１）。结论：妊娠期糖尿病患者ＨＤＬ糖化值含量的变化及脂质沉积，可能是妊高征小动脉痉挛的原因之一。     

GLOMUS TUMORS──A REVIEW OF 8 CASES WITH INTRODUCTION OF A MODIFIED COMBINED INTRA-AND EXTRACRANIAL APPROACH

Eight cases of glomus tumors hospitalized in our department from 1982 through 1995 were reviewed. It comprised of five glomus tympanic tumors and three glomus jugular tumors. Discussion was centered on it’s contemporary diagnosis, classification and surgical treatment with introduction of a modified combined intra-and extracranial surgical approach to resect the extensive glomus tumors.     

乳腺癌肿瘤血管生成的临床病理学意义

肿瘤血管生成（ＴｕｍｏｒＡｎｇｉｏｇｅｎｅｓｉｓ，ＴＡ）是目前肿瘤研究的重要课题，其研究目的在于探讨ＴＡ的预后价值以及预测肿瘤对抗血管生成药物的反应。本文应用第八因子相关抗原多克隆抗体对６５例乳腺浸润性导管癌（以下简称乳腺癌）进行了微血管的定量研究。结果显示：腋下淋巴结阳性病例组织的微血管密度（ＭｉｃｒｏｖｅｓｓｅｌＤｅｎｓｉｔｙ，ＭＶＤ）（１２９．７±４４．９）明显高于腋下淋巴结阴性（ＮｏｄｅＮｅｇａｔｉｖｅＢｒｅａｓｔＣａｎｃｅｒ，ＮＮＢＣ）病例组的ＭＶＤ（７９．６±３３．６），差异呈极显著性（Ｐ＜０．００１）；发生术后复发及远处转移的病例的ＭＶＤ均值高达１４５．３；以上结果提示乳腺癌ＭＶＤ与肿瘤转移、复发均密切相关。我们认为乳腺癌ＭＶＤ可反映其血供状态，ＭＶＤ高的病例微血管丰富，肿瘤组织生长快，癌细胞易于进入微循环而发生转移     

健脾通络法治疗中晚期肝癌22例观察

 应用中医药健脾通络法组成相对固定方药治疗22例中晚期肝癌(Ⅱ期1例、Ⅲ期3例、Ⅳ期18例),结果显示对改善主要症状肝痛(14/18,77.8%),腹胀(13/17,76.5%),精神差(11/15,73.3%),乏力(9/14,64.3%),厌油(6/8,75%)及增加食量(7/15,46.7%)效果较好,对稳定肿瘤病灶(12/18,66.7%)、减轻腹水及维护肝功能也有较好效果.     

YAG激光与药物结合治疗文唇后接触性唇炎130例临床观察

目的探讨YAG激光与药物联合治疗文唇后接触性唇炎的疗效。方法随机选取130例文唇后接触性唇炎患者，应用美国Coherent公司生产的多功能多波长皮肤美容激光器（Nd：YAG激光）进行治疗，联合应用抗组胺药物等内服以及皮质类固醇激素外用。结果130例患者，完全治愈112例（占86．2％），显效16例（占12．3％），有效2例（占1．5％），无效为0，总有效率100％。结论YAG激光与药物结合治疗文唇后接触性唇炎获得满意疗效，具有创伤小，疗效高，副作用少，不留疤痕等特点。     

Blood-brain barrier disruption and complement activation in the brain following rapid correction of chronic hyponatremia

In previous studies we developed a rat model in which demyelination is reproducibly produced following rapid correction of chronic hyponatremia and demonstrated that the development of demyelination in this model is strongly associated with NMR indices of blood-brain barrier (BBB) disruption. Because complement is toxic to oligodendrocytes, we evaluated the hypothesis that BBB disruption precipitated by correction of hypoosmolality is followed by an influx of complement into the brain, which then contributes to the demyelination that occurs under these conditions. We studied four groups of rats with immunocytochemical analysis using primary antibodies to IgG and the C3d split-fragment of activated complement: (1) normal rats; (2) rats in which hyponatremia was maintained for 7 days; (3) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 20 h prior to perfusion; and (4) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 5 days prior to perfusion. In normonatremic and uncorrected hyponatremic rats only background staining was observed in areas lacking a BBB and in blood vessel walls, whereas marked increases in IgG and C3d staining were seen in the brains of rats both 20 h and 5 days after rapid correction of hyponatremia. The staining intensity was significantly correlated with the degree of neurological impairment. These results provide evidence for functional BBB disruption following rapid correction of hyponatremia and support the hypothesis that complement activation may be involved in the pathogenesis of osmotic demyelination.