Rapid progression of parkinsonism associated with an increase of blood manganese.

In this paper, we report a 72-year-old man whose parkinsonian pictures accelerated rapidly after an ingestion of unknown herb pills. His serum manganese and aluminum level increased 2-fold and 5-fold over physiological level respectively. A reverse of his parkinsonian deterioration was accompanied with a normalization of these metals. Exclusive heavy metals have been widely mentioned in parkinsonism. While industrial source of these metals has extensively been sought, pharmacology is rarely mentioned in this aspect, especially of herb medicine origin. We suggest that an acceleration of parkinsonian pictures should raise the need to re-evaluate the possibility of heavy metal intoxication in parkinsonism. Besides of industrial contamination, we should be alert for the nonindustrial source in our population.

Cavernous sinus syndrome and hepatoma metastasis.

A 46-year-old man presented with left cavernous sinus syndrome and subsequent right leg pain proved clear cell type hepatocellular carcinoma metastasis. An initial liver function test was normal and alpha-fetoprotein was only 15 ng/ml but they increased rapidly and he progressed to hepatic failure 2 weeks later. Therefore, a subclinical hepatoma with metastasis should be differentiated in cavernous sinus syndrome, even in cases of normal hepatic enzymes, because hepatoma is prevalent in Taiwan.

Response of nasopharyngeal carcinoma cells to Epstein-Barr virus infection in vitro.

Many nasopharyngeal carcinoma (NPC) biopsy specimens contain Epstein-Barr virus (EBV). However, the response of NPC cells to EBV infection in vitro and in vivo is not well characterized. In this experiment we infected NPC cells with EBV particles through endocytosis of a complex of EBV immunoglobulin A (IgA) secretory component (SC) protein to observe the response of host cells to the foreign viral infection in vitro. We found that EBV particles were endocytosed and stabilized in NPC nuclei 24 hours after infection; the EBV genomes were then gradually decreased after serial passages within 3 to 4 weeks by the following pathway: the EBV genomes first moved toward the nuclear envelope from the center of the nucleus; after crossing the nuclear envelope, they moved into the cytoplasm and toward the plasma membrane and were discharged by exocytosis. At the 10th day of EBV infection, EBV-latent membrane protein-1 and Epstein-Barr nuclear antigen (EBNA)-1 protein expressions could be detected, but not EBV-viral capsid antigen. Observation of EBNA-1 protein and host growth factor and cytokine gene expressions in the weeks after incubation revealed that the EBNA-1 protein expression was decreased proportionally with decrease of EBV genome. The mRNA expression of epithelial growth factor receptor, transforming growth factor (TGF)-alpha, interleukin (IL)-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor increased within 1 to 2 weeks after infection, and gradually recovered to the original level at 3 to 4 weeks, whereas the mRNAs of TGFbeta1, TGFbeta receptor type I (TGFbetaRI), TGFbetaR type II, IL-8, and tumor necrosis factor-alpha remained unchanged. It is concluded that in vitro EBV infection in NPC cells results in increase of certain growth factor and cytokine gene expressions in host cells. The change in gene expression returns to the original level approximately 3 to 4 weeks after infection because of exocytosis of EBV DNA by the infected cells through an unidentified mechanism.

Downregulation of phospholipase C delta3 by cAMP and calcium.

Four different isoforms of mammalian phospholipase C delta (PLCdelta) have been described. PLCdelta1, the best-understood isoform, is activated by an atypical GTP-binding protein. It has been suggested that it is a calcium signal amplifier. However, very less is known about other subtypes, including PLCdelta3. Therefore, in the present study, we examined the expression of PLCdelta3 in different human tissues. Moreover, the cellular underlying regulation for PLCdelta3 was studied in different cell lines. Our study showed that the mRNA and protein levels differed significantly among human tissues. The human PLCdelta3 gene was composed of 15 exons and 1 putative cAMP response element in the 5'-end promoter region. PLCdelta3 mRNA expression was downregulated by cAMP and calcium in both the human normal embryonic lung tissue diploid WI38 cell line and the glioblastoma/astrocytoma U373 cell line. However, mRNA expression showed no impact by PKC activators or inhibitors. This study shows the human PLCdelta3 expression pattern and is the first report that PLCdelta3 gene expression is downregulation by cAMP and calcium.