Amphibian pepsinogens: purification and characterization of xenopus pepsinogens, and molecular cloning of Xenopus and bullfrog pepsinogens.

Two pepsinogens (Pg C and Pg A) were isolated from the stomach of adult Xenopus laevis by Q-Sepharose, Sephadex G-75, and Mono-Q column chromatographies. Autolytic conversion and activation of the purified Pgs into the pepsins were examined by acid treatment. We determined the amino acid sequences from the NH2-termini of Pg C, pepsin C, Pg A, and pepsin A. Based on the sequences, the cDNAs for Pg C and Pg A were cloned from adult stomach RNA, and the complete amino acid sequences of the Pg C and Pg A were predicted. In addition, a Pg A cDNA was cloned from the stomach of adult bullfrog Rana catesbeiana, and the primary structure of the Pg A was predicted. Molecular phylogenetic analysis showed that such anuran Pg C and Pg A belong to the Pg C group and the Pg A group in vertebrates, respectively. The molecular properties of Pg C and Pg A, such as size, sequences of the activation peptide and active site, profile of autolytic activation, and pH dependency of proteolytic activity of the activated forms, pepsin C and pepsin A, resemble those of Pgs found in other vertebrates. However, the hemoglobin-hydrolyzing activity of Xenopus pepsin C is completely inhibited in the presence of equimolar pepstatin, an inhibitor of aspartic proteinases. Thus, the Xenopus pepsin C differs significantly from other vertebrate pepsins C in its high susceptibility to pepstatin, and closely resembles A-type pepsins.

Prolongation of the survival period with the biological response modifier PSK in rats bearing N-methyl-N-nitrosourea-induced mammary gland tumors.

The antitumor effects of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of Coriolus versicolor in basidiomycetes on mammary gland tumors produced in Sprague-Dawley rats by the intravenous injection of N-methyl-N-nitrosourea were investigated. PSK prolonged the survival period of tumor-bearing rats significantly, when given at the dose of 250 mg/kg twice a week for 3 weeks after the tumor reached 100 mm2 in size (p = 0.011 by log rank test and p = 0.023 by generalized Wilcoxon test). These findings suggest that PSK is effective in the prolongation of the survival period in the rat autochthonous tumor model, acting at the growth stage of the tumor during carcinogenesis.

Midline cervical cleft. A case report.

A case of incomplete midline cervical cleft of the upper neck is reported. It showed histological resemblance to a mature teratoma with three different germ-cell components, including cartilage, striated muscles, small salivary glands, and nerves.

Meniscectomy operation as a surgical treatment for internal derangement of the temporomandibular joint in our department.

This paper describes the surgical treatment of six patients with internal derangement of the temporomandibular joint (nine joints). Meniscectomy was performed on all the patients, because severely advanced cases in which the articular disk could not be preserved or replaced were chosen. Our surgical technique and the results of short-term follow up are presented. Indications of meniscectomy and the criteria for postoperative evaluation are also described. The postoperative outcomes were assessed as "good" for seven joints in five patients and as "acceptable" for two joints in one patient.

Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin).

The fate of 14C-labelled PSK in the body was investigated. Although only substances with low mol. wt were observed in blood shortly after the administration, with time, substances with high mol. wt appeared, suggesting absorption of PSK in its original form from the digestive tract. 14C-labelled PSK was distributed in bone marrow, salivary gland, brain liver, spleen, pancreas and tumor. Approximately 70% of 14C-labelled PSK was excreted by expiratory air after 24 h and approximately 15-20% in urine after 72 h. Only a small amount of 14C-labelled PSK was transferred into lymph and bile. The present study on the in vivo behavior of PSK provides an important basis for further analysis of its pharmacological actions.

Effect of PSK, a protein-bound polysaccharide from Coriolus versicolor, on drug-metabolizing enzymes in sarcoma-180 bearing and normal mice.

The effects of PSK and Propionibacterium acnes (anaerobic Corynebacterium) on hepatic drug-metabolizing enzymes were studied using sarcoma-180 bearing and non-tumor bearing mice. PSK had no influence on aminopyrine N-demethylase and aniline hydroxylase activities, cytochrome P-450 concentration in hepatic microsomes, and the reductase activity of cytochrome c in normal mice. The content of cytochrome P-450 was not significantly reduced in S-180 bearing mice. On the other hand, P. acnes administration significantly decreased the amount of cytochromes P-450 and b5 and aminopyrine N-demethylase activity. When FT-207 (Tegafur) was administered orally to S-180 bearing mice combined with the immunoadjuvants, only P. acnes significantly reduced the 5-FU levels in the serum and some organs.

[Effects of krestin (PSK) on drug-metabolizing enzymes with special reference to the activation of FT-207].

The effects of PSK on hepatic drug-metabolizing enzymes were investigated using Sarcoma 180-bearing and non-tumor-bearing ICR mice. PSK, an immunomodulator, has been commonly used in combination with tegafur for post-operative adjuvant chemotherapy. Tegafur is a typical masked compound transformed into 5-FU by the hepatic drug-metabolizing enzyme P-450. It has been reported that immunostimulants such as BCG and anaerobic Corynebacterium suppress the drug metabolism. PSK and Propionibacterium acnes were administered to mice inoculated s.c. with Sarcoma 180. It was demonstrated that Propionibacterium acnes had an effect of inhibiting these enzymatic activities, especially the amount of P-450 and cytochrome b5 and aminopyrine demethylation. On the other hand, PSK had no influence on the drug-metabolizing enzymes. Propionibacterium acnes was shown to decrease the 5-FU level in organs and sera of mice given FT-207 orally. By contrast, PSK showed no difference in 5-FU level compared to controls, indicating that PSK had no inhibitory effect on the activation of FT-207 by hepatic drug-metabolizing enzymes.