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Biomedical subjects

T Koji

Publications and source records attributed to T Koji.

At least 163 records · Page 9Linked to original sources
PubMed1985

Mitogenic effects of certain cathepsins and calciferin on the intact liver in vivo.

Calciferin, a new parathyroid hormone stimulating the release of cathepsins D and L (but not B) from isolated lysosomes, or the release of cathepsin D from erythrocytes or ghosts in vitro, elevated free cathepsin D in the blood, and at the same time stimulated DNA synthesis in the intact liver when it was injected into mice. Both calciferin and free cathepsin D in the blood (rats) were elevated concomitantly soon after 70% hepatectomy, reaching a peak around 5 hr. The cathepsin D-elevation was almost proportional to fractional hepatectomies. Cathepsin L (but not B), when injected intraperitoneally into mice, stimulated DNA synthesis and mitosis in the intact liver much like cathepsin D, the effect of which was reported earlier. In contrast to the mitogenic effects of calciferin or cathepsins (D and L) in vivo, only cathepsin L (but not cathepsin D or calciferin) in low concentrations appeared to stimulate DNA synthesis in the cultured liver cells, and also stimulated adenylate cyclase of isolated liver plasma membranes in vitro. Dibutyryl-cyclic AMP in concentrations lower than 10(-5) M also stimulated DNA synthesis in cultured liver cells.

Animals↗
PubMed1984

Arginase as one of the inhibitory principles in the density-dependent as well as plasma membrane-mediated inhibition of liver cell growth in vitro.

Liver cells isolated from the adult rat livers under mild conditions were preincubated for 1 day with Williams medium E (WE) containing serum, dexamethasone and insulin, and then the cells (monolayered) were incubated for 2-3 days with WE (1 ml) containing only insulin to measure DNA synthesis and/or mitosis. DNA synthesis of cultured liver cells was dependent on cell densities within a region from 0.1 X 10(6) to 1.0 X 10(6) nuclei/dish (Falcon, diameter 35 mm). The addition of EGF from the beginning of preincubation stimulated DNA synthesis (or replication) as well as cell proliferation in vitro, but the density-dependent inhibition of DNA synthesis was observed similarly in the presence of EGF. In contrast to the low and high density cultures, DNA synthesis in the intermediary density cultures was enhanced by enlarging the medium volume or by adding ornithine (arginase inhibitor). DNA synthesis in low density cultures was inhibited by liver plasma membranes in a concentration-dependent fashion. The inhibition of DNA synthesis by liver plasma membranes in low concentrations (less than 30 micrograms protein/ml) was reduced by adding either extra arginine or ornithine. DNA synthesis of cultured liver cells (low density) was inhibited by replacing arginine in WE with equimolar ornithine and urea or by adding a commercial arginase (bovine liver). These, together with earlier findings indicating the presence of arginase in liver plasma membranes (outer leaflet), seem to support the idea that arginase may be involved in density-dependent as well as plasma membrane-mediated inhibition of DNA synthesis of cultured liver cells. However, this does not exclude possible involvement of other inhibitory principle(s), such as direct cell-to-cell or cell-to-plasma membrane interactions, especially in higher cell densities or larger plasma membrane concentrations.

Animals↗
PubMed1984

[Significance of anti-HBc IgM in acute hepatitis and hepatitis B associated chronic liver disease].

To determine the diagnostic value of anti-HBc IgM in acute viral hepatitis or chronic liver disease B, Anti-HBc IgM was measured by a RIA and an ELISA in 32 patients with acute hepatitis (4 with type A, 15 with type B and 13 with type non A non B), 18 patients with chronic hepatitis and 19 patients with liver cirrhosis. In acute hepatitis B, anti-HBc IgM (both RIA and ELISA) was positive in 14(93%) of 15 patients and its cut-off index value was very high. However, anti-HBc IgM was always negative in one patient with typical course of type B. In 1 of 4 patients with acute hepatitis A and 2 of 13 with non A non B, anti-HBc IgM (RIA and/or ELISA) was positive. These 3 patients were positive for anti-HBs at the onset of disease, so we could not made the diagnosis of acute hepatitis B. Anti-HBc IgM was positive in 21(51%) of 37 patients with HBsAg-positive chronic liver disease by RIA and in 11 (30%) by ELISA, and its cut-off index value was relatively low. These results suggest that when adequate cut-off index value is established, anti-HBc analysis is useful for differentiating recent and current infections from remote infections.

Acute Disease↗
PubMed1984

Significance of HB virus infection in an area of Japan with high incidence of liver cirrhosis and hepatocellular carcinoma: an analysis of consecutive studies among inhabitants of Tomié-Town, Goto Islands.

In an attempt to clarify the relationship of liver cirrhosis and hepatocellular carcinoma, we have carried out investigations at an area where both these diseases develop frequently. 1) We studied the incidence of HBsAg and its antibody in 3521 inhabitants of Tomié-Town in the Goto Islands; 5.5% proved to be positive for HBsAg and 22.0% positive for anti-HBs. 2) In the HBsAg-positive group, the incidence of hepatomegaly and abnormal liver function were significantly higher than those in other groups. 3) In relation to HBsAg, anti-HBs and histological abnormalities of the liver, positive HBsAg was detected in one subject with hepatocellular carcinoma associated with liver cirrhosis, six of nine with liver cirrhosis, and four of 11 with chronic hepatitis. A positive antibody was found in one subject with liver cirrhosis and four with chronic hepatitis. Thus, HB virus infections was closely associated with latent liver disease in Tomié-Town.

Adolescent↗
PubMed1984

Tumor/serum ratios of alphafetoprotein and radioimmunolocalization of primary liver cancer.

Twenty six patients with primary liver cancer (PLC) were injected with 131I-labeled antibodies to alphafetoprotein (AFP). Each patient was tested by external photoscanning, 24 and 48 hours after injection. Positive imaging in the tumors was obtained in only 50 percent of patients. Serum AFP levels did not correlate with the radioimmunolocalization results. In 15 patients with PLC, concentrations of AFP in the tumors and sera were determined simultaneously. Although tumor AFP concentrations correlated significantly with serum AFP levels, tumor/serum AFP ratios differed greatly among tumors, indicating that there exists a dissociation between the production and the secretion of AFP. In 8 patients in whom the measurement of serum and tumor AFP concentrations and radioimmunolocalization were performed, tumor/serum AFP ratios correlated significantly with the results of radioimmunolocalization. This suggests that a high tumor/serum AFP ratio is important for the detection of PLC by radioimmunolocalization with antibodies to AFP.

Carcinoembryonic Antigen↗
PubMed1983

Radioimmunodetection of cancer using antibodies to alpha-fetoprotein and carcinoembryonic antigen.

This study reports the use of radiolabeled antibody to AFP and CEA for the detection and localization of AFP- or CEA-producing tumors. Thirty-one patients received 131I-labeled anti-AFP or anti-CEA antibodies. Photoscans were taken at 24 and 48 hours after injection of radioantibodies. In three of six patients with CEA-producing tumors, radioimmunodetection with anti-CEA antibody showed positive scans. In AFP-producing tumors, 7 of 15 patients had positive findings on immunoscintigraphy using polyclonal anti-AFP antibody, and two of nine patients had positive findings when monoclonal antibodies were used. Analysis of radioantibody in the blood after injection showed both complex and free antibody with immunoreactivity in the circulation, and smaller complexes were seen to form after administration of monoclonal antibodies.

Abdomen↗
PubMed1983

Presence of immunoglobulin G in human sera binding to alphafetoprotein.

Sera from patients with collagen diseases, chronic liver diseases and hepatocellular carcinoma were analysed for alphafetoprotein (AFP)-binding protein. The method used was a 125I-labeled AFP-binding assay with goat anti-human immunoglobulin G (IgG) as the precipitating antibody. AFP-binding IgG was found in the sera from one of 34 patients with systemic lupus erythematosus (SLE) and one of nine patients with hepatocellular carcinoma. This protein may interfere with the conventional radioimmunoassay of human AFP, and may be of interest because of its usefulness as a carrier of radioactivity or therapeutic agents to AFP-producing tumors.

Carcinoma, Hepatocellular↗
PubMed1983

Localizing properties of antibody to alphafetoprotein (AFP) to AFP-producing tumor cells.

Studies have been undertaken to clarify the localizing properties of radioactively labeled antibody to AFP using ascitic hepatoma cells which produce AFP. In the in vitro studies, radioantibodies to AFP were incorporated into the AFP-producing cells, even though excess antigen existed in the medium and the antibodies remained on the cell surface for a long time. In the in vivo studies, the radioantibodies to AFP bound to the AFP-producing cells, especially those producing high levels of AFP (AH66). Tumor localization by scintigraphy was clearer with the AH66 hepatoma than with the AH41C hepatoma, which produces less AFP. The presence of large amounts of AFP in the circulation did not prevent the tumor radioimmunodetection. It is suggested that radioantibodies to AFP bind to the AFP-producing cells despite the presence of large amounts of AFP in the circulation or in ascitic fluid.

Animals↗
PubMed1983

Serotherapy of AFP-producing tumors with the purified antibody to AFP.

14 patients with hepatocellular carcinoma and one with a hepatoblastoma were given AFP antibodies and changes in serum AFP levels and clinical courses were observed. Anti-human AFP horse IgG was purified by immunoadsorbent column chromatography. 1 mg of the purified antibody was able to bind 100-150 micrograms of AFP. 200-800 mg were given to each patient, according to their AFP levels. Also, conventional anti-cancer agents were administered consecutively. In all cases, the serum AFP levels measured by RIA decreased rapidly to undetectable levels within 24-48 h after the infusion. Then, in seven of 15 cases, the relatively low level was maintained for periods of 10-96 weeks. In the remaining eight cases, the serum AFP level increased again after 1-2 weeks and rose further with clinical deterioration. Since the antibody administered was undetectable in the serum within 2 weeks after its infusion, it is suggested that the AFP antibody had an inhibitory effect on the production or the release of AFP in some patients.

Adult↗
PubMed1983

Accumulation of radioactively labeled antithyroglobulin antibody by thyroid carcinoma.

The present experiments were undertaken to investigate (1) accumulation of radioactively labeled anti-thyroglobulin antibody by thyroid carcinomas and (2) the mechanism by which radioactively labeled antibody reaches to and stays in carcinoma cells. Anti-thyroglobulin antibody was purified by affinity chromatography using serum obtained from a patient with Hashimoto's disease. 125I-labeled anti-thyroglobulin antibody was injected into nude mice bearing transplanted human thyroid carcinomas. Scintigrams were taken 3 and 7 days after injection. Mice were killed thereafter and the radioactivity in each tissue and in serum was analyzed by gel filtration and affinity column chromatography of thyroglobulin, anti-thyroglobulin antibody and anti-human IgG antibody. In a total thyroidectomized patient with a metastatic thyroid carcinoma of the lymph node, 131I-labeled antibody was injected and scintigraphy and blood sampling performed for 7 days after injection. Scintigrams of the mice clearly showed the highest density over the transplanted carcinoma. Most radioactivity in the carcinoma was found to be in the thyroglobulin-antibody immune complex, while in other tissues, including serum samples, the radioactively was in free anti-thyroglobulin antibody. Scintigrams of the patient also showed a hot area over a metastatic carcinoma of the lymph node. It is concluded that (1) radioactively labeled anti-thyroglobulin antibody is accumulated by thyroid carcinoma in spite of the presence of thyroglobulin in blood and stays in cells as thyroglobulin-antibody immune complex, and (2) radioimmunodetection of thyroid carcinomas using labeled anti-thyroglobulin antibody is useful especially for patients with metastases which produces thyroglobulin and do not take up radioiodide.

Animals↗
PubMed1982

Arginase as an inhibitory principle in liver plasma membranes arresting the growth of various mammalian cells in vitro.

Plasma membranes prepared from rat livers inhibited the in vitro growth of various mammalian cells including hepatoma cells in a concentration-dependent manner, showing almost complete arrest of cell growth at 0.1 mg protein/ml. Some of these cells tested, i.e., leukemia (L1210 and P388) and myeloma (P3-NS-1/1-Ag4-1) cells, were labile in the presence of plasma membranes (losing the viability), and CHO (Chinese hamster ovary) cells became round without detaching from the substratum. The culture medium preincubated with liver plasma membranes no longer supported the growth of hepatoma cells (AHI3 and AH66F). However, the 'conditioned' medium supplemented with L-arginine, supported the growth of the cells. Moreover, the addition of L-ornithine to the cultures containing plasma membranes markedly reduced the inhibitory effect of plasma membranes. The plasma membrane preparations were found to possess considerable arginase activity. There results seem to indicate the possible involvement of arginase in the inhibition of cell growth by liver plasma membranes.

Animals↗
PubMed1981

Purification of specific antibody to alpha-foetoprotein and its immunological effect on cancer cells.

Human of rat alpha-foetoprotein (AFP) was highly purified from ascitic fluid or serum of hepatoma bearers. The purification was carried out mainly by means of immunoadsorbent chromatography using Sepharose coupled to specific anti-AFP antibody with BrCN activation, and by Sephadex gel filtration. Horses were immunized with the purified AFP and the specific antibody was isolated from the antiserum by means of an immunoadsorbent coupled to purified AFP. The specific antibody was found to bind specifically with AFP-producing tumour cells. The antibody was applied for radio immunodetection of the tumour. 125I-labelled antibody was administered to patients or rats with hepatoma, and radioactivity localized in the tumours was scintiscanned with a scintillation camera. In this way, the location of the tumour was detected in about 50% of the hepatoma bearers. The cytotoxicity of the antibody was clearly demonstrated both in vitro and in vivo in animal experiments. The antibody was administered to patients with advanced hepatoma. Although no improvement of the disease was demonstrated, serum AFP levels decreased greatly and in some cases low AFP levels were maintained for long periods suggesting that the antibody suppressed AFP-producing hepatoma cells. No significant side effects were observed in patients who had been administered with the horse antibody.

Animals↗