Akira Wakizaka

Relationship between blood plasma prostaglandin E2 and liver and lung metastases in colorectal cancer

The relationship of prostaglandin E2,of which a large amount is produced in various neoplasms, and hematogenous distant metastases was investigated in a total of 44 colorectal cancer patients because of its varied pathophysiologic potentials. The authors found significantly high levels of PGE2in local venous blood draining the carcinoma and in peripheral blood in cases with liver or lung metastasis, as well as a significantly large amount of PGE2production in the carcinoma tissue. The results suggest that increased local blood PGE2could enhance the metastasis formation, and increased peripheral blood PGE2may be useful in the detection of such metastasis in colorectal cancer.

Increased mucosal ornithine decarboxylase activity in large bowel with multiple tumors, adenocarcinoma, and adenoma.

The polyamine biosynthetase, ornithine decarboxylase (ODC), involved in tumor promotion, was investigated in grossly normal mucosa obtained from surgically resected large bowel; 48 cases with and six cases without large bowel cancer. The mucosal ODC activity was significantly higher in 17 multiple tumor cases bearing adenocarcinoma(s) plus adenoma(s) than in 31 solitary tumor cases bearing one adenocarcinoma alone. It was higher in the mucosa of the two groups of cases than in the mucosa of individuals without large bowel cancer. Furthermore, the enzyme activity in left‐sided cancer cases was significantly higher than that in right‐sided cancer cases. Carcinoma tissue showed a remarkable high level of enzyme activity, compared with the normal mucosa. The results indicate the larger the number of tumors the higher the level of the ODC activity in the normal mucosa, particularly in left‐sided cancer cases. It is concluded that the mucosal ODC may provide a good biological marker to detect individuals at higher risk for large bowel cancer due to exogenous or endogenous factors, and thus contribute to the prevention of mortality from large bowel cancer.

IMMUNOLOGICALLY ACTIVE LESIONS INDUCED ON DOUBLE-STRANDED DNA WITH ULTRAVIOLET

Abstract— Some immunochemical properties of double‐stranded DNA irradiated with UV were studied, using a radioimmunoassay with irradiated [3H]‐DNA and experimentally produced antibodies to DNA. Reactivity of antibodies revealed that irradiated DNA contained an immunologically active structure other than the irradiated DNA specific structure, resembling that of thermally denatured DNA. inhibition assay demonstrated that while DNA‐antibody binding was effectively inhibited by mixed purine and pyrimidine oligonucleotides, thymine dimer containing pyrimidine oligonucleotides derived from the irradiated DNA showed no appreciable inhibition. The antigenic structure specific for irradiated DNA was found to be thermally labile in low salt medium. Cupric and ferrous ions and cysteine added to the DNA solution inhibited antigenicity formation during irradiation, but these substances exhibited no effect on dimer formation in irradiated frozen thymine solution. Calcium ions and histidine were inert for the former reaction but inhibited the latter effectively. This suggests that different mechanisms are involved in the 2 processes. The immunologically active UV‐induced lesions appeared to depend mainly on a conformational structure change of the DNA strands rather than on a single modified base moiety.

Reduction of the non-specific binding of DNA to gamma-globulin in Farr radioimmunoassay by addition of dextran sulfate and calcium chloride.

The effect of non-specific binding caused by the interaction between gamma-globulin and denatured DNA was markedly reduced by addition of dextran sulfate or CaCl2 at alkaline pH. This method was shown to be applicable in the detection of anti-DNA antibodies in sera from cases of human systemic lupus erythematosus.

Isolation and characterization of three distinct 34 kDa EDTA-extractable proteins from bovine lens

EDTA-extractable protein (EEP) is known to be a major lens membrane protein with a molecular mass in the range 32 kDa to 38 kDa, and is also known to bind to the lens membrane and phospholipid-containing liposomes in a calcium-dependent manner. Recent results (Russell, P., Zelenka, P., Martensen, J., and Reid, T.W. (1977) Curr. Eye Res. 6, 533-538) on antibody cross-reactivity have demonstrated that a 34-35 kDa component of EEP is identical to calpactin I (lipocortin II). In this study, we have identified and purified three distinct 34 kDa components of EEP (designated as EEP-34A1, EEP-34A2 and EEP-34B) from bovine lens that inhibit phospholipase A2 activity. These proteins bind to phospholipid-containing liposome and F-actin in a calcium-dependent fashion. Two-dimensional electrophoresis demonstrates that the three proteins were distinct from one another. However, immunochemical studies and one-dimensional peptide mapping indicate that EEP-34A1 and EEP-34B are very similar. Our results also indicate that EEP-34A1 is very similar to calpactin II and that EEP-34A2 corresponds to calpactin I. The bovine lens 34-35 kDa component of EEP is a mixture of proteins rather than a single protein.