Intracellular distribution of the Wilson's disease gene product (ATPase7B) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson's disease.

In patients with Wilson's disease, both copper incorporation into ceruloplasmin and excretion of this metal into bile are impaired. These conditions are caused by a genetic defect in the Wilson's disease gene (ATP7B). To investigate the Wilson's disease gene protein (ATPase7B) in hepatocytes, we constructed an expression plasmid carrying full-length complementary DNA for human Wilson's disease gene and attempted to express the gene in hepatocytes of LEC rats, an animal model of Wilson's disease. Transfection of hepatocytes, either in vitro or in vivo, was done using a newly developed cationic liposome containing 1,4-bis(3-(N-hexadecyl) aminopropyl) piperazine. Immunological analyses of human ATPase7B with specific monoclonal antibodies showed human ATPase7B to be a membrane protein with a molecular mass of 155 kd. Analysis of human ATPase7B expressed in hepatocytes from LEC rats suggested that this protein is present in the trans-Golgi network and at the plasma membrane, a distribution pattern similar to that of Menkes' disease protein (ATPase7A). These findings suggest that these two putative copper-transporting P-type ATPases function similarly at the cellular level. Cotransfection and coexpression of the human Wilson's disease gene and ceruloplasmin gene in cultured hepatocytes indicate that the distribution of ceruloplasmin is always accompanied by ATPase7B at the perinuclear region, but that part of ATPase7B localizes irrespective of the distribution of ceruloplasmin. Based on these investigations, we propose that ATPase7B exists in the trans-Golgi network and transports copper into this compartment. This seems to ensure an appropriate delivery of copper to the apoceruloplasmin. On the other hand, part of ATPase7B that is not accompanied by ceruloplasmin in the perinuclear region and at the plasma membrane seems to contribute to efflux of this metal from the hepatocytes. Thus the distribution patterns of ATPase7B in hepatocytes may explain the dual roles of this P-type ATPase in hepatocytes.

Usnic acid and diffractaic acid as analgesic and antipyretic components of Usnea diffracta.

Diffractaic acid and usnic acid were identified as the analgesic and antipyretic components of a lichen, Usnea diffracta. Both compounds showed an analgesic effect by the acetic acid-induced writhing and tail-pressure methods in mice. Regarding the effect on normal body temperature and LPS-induced hyperthermia in mice, diffractaic acid showed a significant effect only on the former and usnic acid only on the latter.

Pharmacologically active components from a Peruvian medicinal plant, huira-huira (Culcitium canescens H. & B.).

The methanol extract of Huira-Huira (Culcitium canescens) showed analgesic effects in acetic acid-induced writhing and tail pressure tests, and it also produced potent prolongation of hypnosis induced by pentobarbital. The latter activity was used as an isolation-guide to determine the active components which were identified as dehydrocacalohastine, cacalohastine and cacalonol.

Ascaridole as a pharmacologically active principle of "Paico," a medicinal Peruvian plant.

"Paico," Chenopodium ambrosioides L., is a traditional Peruvian medicine which is considered to be nervine, antirheumatic, anthelmintic, etc. An attempt was made to isolate the component having sedative and/or analgesic properties from "Paico" and "Aritasou" (the Japanese name for C. ambrosioides). Ascaridole was identified as the active principle in both materials.

[An early cancer of the descending colon, histologically showing a poorly differentiated adenocarcinoma].

Reported is the case of a 71 year-old male with a poorly differentiated adenocarcinoma of the colon that had invaded the submucosal layer. A barium enema had revealed a polyp, 1.5 cm in diameter, in the descending colon, and an endoscopic polypectomy was performed. The resected specimen mainly consisted of an adenoma and a partial, poorly differentiated adenocarcinoma that had massively infiltrated into the submucosal layer. A left hemicolectomy was carried out, and no carcinoma was identified in the resected colon and/or the regional lymph nodes.

Pancreatography with contrast medium containing polyethylene hydrogenated castor oil.

A new contrast medium has been used for endoscopic pancreatography. Good visualization of the pancreas was obtained by this method. No side-effects of this method were observed by clinical and histologic examination, either in clinical or experimental studies. Clinically, the new method provided more detailed information regarding pancreatic changes in chronic pancreatitis. It is suggested that this method may make detection of a small tumor of the pancreas in the parenchyma and permit earlier diagnosis of carcinoma of the pancreas.