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Biomedical subjects

M Taniguchi

Publications and source records attributed to M Taniguchi.

At least 649 records · Page 36Linked to original sources

Melanoma antigen expression and metastatic ability of mutant B16 melanoma clones.

The biological functions of murine melanoma-associated antigens recognized by monoclonal antibodies (MAbs) (M562, M622 and M2590) were examined by using mutant clones which differed in their degree of expression of these antigens. Four clones of high expressors of 3 types of antigen (MEA group), 5 clones of low or non-expressors of M562- and M622-recognizing antigens (MEB group) and 4 clones of non-expressor of GM3 recognized by M2590 (MEC group) were used. Attachment of these clones to components of extracellular matrix was different between the groups. Two clones of the MEA group showed the highest ability to adhere to laminin and type-IV collagen, whereas the clones of the MEB and MEC groups significantly lost their ability to attach to laminin and type-IV collagen. In experimental lung metastasis, metastasizing ability of MEA-group cells was higher than that of MEB- and MEC-group cells. Our results suggest that these antigens play some functional role in metastasis mediated by increasing capacity for attachment to laminin and type-IV collagen.

Animals↗

Characterization of a human monoclonal antibody with broad reactivity to malignant tumor cells.

Lymphocytes from mediastinal lymph nodes of 9 patients with primary lung cancer were fused with murine myeloma cells (P3U1). One of the clones (4G12) was stable for secretion (10 micrograms/ml) of human IgM lambda for 24 months. The antigen detected by 4G12 was sensitive to both trypsin and periodic acid-Schiff treatment. It immunoprecipitated a glycoprotein with an Mr of 65,000 upon analysis in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reduced conditions. Immunohistochemical staining demonstrated that 4G12 possessed a high reactivity to squamous cell carcinomas of the lung (29 of 29) and also reacted with other lung carcinomas [adenocarcinomas (14 of 20) and large cell carcinomas (3 of 8)] and with some nonpulmonary malignant tumors (15 of 56). However, it did not react with small cell carcinomas of the lung. No benign tumors (0 of 26) so far tested have been positive. 4G12 did not react with most of the normal tissues; an exception was that it was weakly reactive on the glandular cells of the trachea and bronchi and on the proximal tubular cells of the kidneys. Thus 4G12 showed a broad reactivity to malignant tumors (68% of lung carcinomas, 27% of nonpulmonary carcinomas, and 0% of benign tumors). The reactivity of 4G12 on tissues from squamous cell carcinomas of the lung indicated that the expression of the antigenic determinant was much more in the well-differentiated grade than in the poorly differentiated grade. Thus the antigen detected by 4G12 appears to be related to tumor differentiation. Moreover, fluorescence-activated cell sorter analysis demonstrated that the expression of the antigen epitope depended on the cell cycle (G2-M). These data suggest that the 4G12 monoclonal antibody detects a new tumor-associated antigen that is recognized by the human immune system.

Adenocarcinoma↗

Mouse melanoma antigen recognized by Lyt-2- and L3T4- cytotoxic T-lymphocytes.

A mouse melanoma (B16) antigen was investigated at a cellular level by three blocking experiments using monoclonal antimelanoma antibodies, soluble melanoma antigen, and enzyme-treated B16 melanoma cells as inhibitors. The activity of antimelanoma cytotoxic T-lymphocytes (CTL) was specifically reduced by addition of the mixture of two monoclonal antimelanoma antibodies, one (M2590) recognizing the cross-species melanoma epitope on GM3(NeuAc) and the other (M562) reactive with the mouse melanoma-specific epitope on protein molecules. The CTL activity was also blocked by GM3 liposome as well as by the soluble antigen. However, 3,000 times more GM3 than the soluble melanoma antigen is required to obtain a similar inhibitory effect. When pronase-treated B16 melanoma cells, which have had protein molecules removed but GM3 left intact on the surface, were used as an inhibitor, their blocking activity was greatly reduced but was still partly observed at a high inhibitor/target ratio. These results indicate that the melanoma antigen is not GM3 itself but is composed of the GM3-protein complex. This finding was also supported by using an interleukin 2-dependent CTL clone whose activity was blocked by both M562 and M2590. Antimelanoma CTL were found to belong to a double-negative T-cell population with Thy-1+, Lyt-2-, L3T4- phenotypes. L3T4+ T-cells were also demonstrated to be necessary for induction of double negative antimelanoma CTL.

Animals↗

Escape mechanisms of melanoma from immune system by soluble melanoma antigen.

We demonstrate in the B16 melanoma (C57BL/6 derived) system that the soluble form of tumor Ag preferentially suppresses immune responses 1) by inhibiting CTL activity in the effector phase and 2) by induction of specific Ts that block CTL generation in the induction phase. Soluble melanoma antigen Ag injected i.p. into the tumor-bearing host can effectively augment melanoma growth in vivo. Two T cell types with the L3T4+ or double-negative/I-J+ phenotype are involved in the suppression of anti-melanoma CTL responses and can easily be generated in the in vitro primary 12 h-culture. Anti-melanoma Ts recognizes the GM3(NeuAc) structure and distinguishes GM3 molecular species. This is because liposomes constructed with GM3(NeuAc) but not with GM3(NeuGc) gangliosides alone can effectively induce the melanoma-specific Ts. It is thus likely that tumor cells can escape from the immunologic surveillance system by stimulating the repertoire of Ts for self-Ag, GM3, which has existed even in the unprimed conditions in order to maintain self-tolerance. These would appear to be the major escape mechanisms.

Animals↗

A rapid method for the isolation of functional human T lymphocytes using hydroxyapatite column fractionation.

Passage of peripheral blood lymphocytes through a column of hydroxyapatite resulted in a 7-20-fold depletion of immunoglobulin-bearing cells, a 20-fold depletion of monocytes, and a 1.3-fold enrichment of T cells. The effluent population was virtually devoid of B lymphocyte precursors and monocytes, whereas helper cell and suppressor cell populations remained intact. This method will facilitate the rapid preparation of T-enriched cell populations.

B-Lymphocytes↗

Serum proinsulin levels at fasting and after oral glucose load in patients with type 2 (non-insulin-dependent) diabetes mellitus.

A simple and sensitive human proinsulin radioimmunoassay system was developed using guinea pig anti-proinsulin serum, which cross-reacted neither with human insulin nor C-peptide. The recognition site of the antiserum seems to be located near the junction between the B chain and C-peptide. With this assay system, we studied the serum proinsulin concentration at fasting and after an oral 100 g glucose load in 25 healthy subjects, 21 subjects with impaired glucose tolerance and 40 patients with Type 2 (non-insulin-dependent) diabetes mellitus. At fasting, serum proinsulin was 5.8 +/- 3.3 pmol/l in normal subjects as compared to 9.5 +/- 6.9 pmol/l (p less than 0.05) in subjects with impaired glucose tolerance and 12.6 +/- 7.5 pmol/l (p less than 0.001) in diabetic patients. The molar ratio of proinsulin to insulin was also increased in subjects with impaired glucose tolerance or diabetes compared to control subjects. After a 100 g oral glucose load, serum proinsulin increased more slowly than insulin. The proinsulin response after an oral glucose load was augmented in subjects with impaired glucose tolerance and diabetes, while the insulin response decreased with the elevation of fasting plasma glucose. Diabetic patients with high fasting plasma glucose had a very poor insulin response, but the proinsulin response was similar to control subjects. There was a linear correlation between summed proinsulin values and summed insulin values, but the slope of the regression line was steeper in diabetic patients than in control subjects. There was a relative increase in serum proinsulin both in subjects with impaired glucose tolerance and diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

External beam radiotherapy alone or combined with high-dose-rate intracavitary irradiation in the treatment of cancer of the esophagus: autopsy findings in 35 cases.

Autopsy findings of 35 patients, treated with radiotherapy for an esophageal carcinoma, were reviewed. A residual tumor was seen at autopsy in 7 of 16 patients treated with high-dose-rate intracavitary irradiation following external irradiation, in 13 of 14 patients treated with external irradiation of 50 Gy or more, and in all 5 patients treated with external irradiation of less than 50 Gy. Incidence on lymph node metastasis, at autopsy, did not differ between the combined radiotherapy group and the external irradiation groups. However, it correlated with disease stage. It was observed in 11 of 17 patients with Stage 1 and Stage 2 disease, compared to 17 of 18 patients with Stage 3 and Stage 4 disease. Distant organ metastasis, at autopsy, also did not differ between the combined radiotherapy group and the external irradiation groups, and was also correlated with disease stage. It was found in 8 of 17 patients of the patients with Stage 1 and Stage 2 disease, compared to all 18 patients with Stage 3 and Stage 4 disease. Mean (average) survival was different between the patients treated by high-dose-rate intracavitary irradiation following external irradiation and those treated by external irradiation alone; 11.3 months in the 16 patients treated with combined therapy, as compared to 6.9 months in the 14 patients who received external irradiation of 50 Gy or more, and 3.6 months in the 5 patients who received external irradiation of less than 50 Gy.

Aged↗

Discordant hepatic uptake of Tc-99m HIDA and Tc-99m colloid in a patient with segmental biliary obstruction.

Discordant hepatic uptake between Tc-99m HIDA and Tc-99m colloid occurred in a 63-year-old female with segmental biliary obstruction due to cholangioma. Radiographic CT and a percutaneous transhepatic cholangiogram revealed the obstructed right hepatic duct as well as the dilated intrahepatic duct in the right lobe. At surgery this was confirmed, and a 2 cm mass encasing the right hepatic duct was identified. It should be included in the gamut of discordant hepatic uptake of Tc-99m IDA and Tc-99m colloid.

Adenoma, Bile Duct↗

The analysis of immature lymphoid precursors stored in longterm bone marrow culture.

The long-term bone marrow culture system developed by Dexter (MBMC) is known to store immature lymphoid precursors capable of differentiating into mature B cells in irradiated or immunodeficient mice. It has been suggested that pre-B cells are not generated under such culture conditions, but that opinion was not based on any systematic analyses. In the present study under carefully controlled conditions, we observed that pre-B and pro-B cells were eliminated from the late stage of primary MBMC, and the former were not generated in recharged MBMC. Under appropriate conditions, these immature precursors in recharged MBMC generated in vitro immunoglobulin-positive (Ig+) cells to differentiate into antibody-forming cells upon stimulation with lipopolysaccharide (LPS). LPS-reactive B cells were observed in every 10th of the Ig+ cells, the frequency being essentially the same as that observed in normal B cells in different tissues. The immature B cell precursors generating LPS reactive cells were expressed in recharged MBMC at the frequency of 4.2 x 10(-6). A staining experiment showed that cells bearing AA4.1 were stored at the frequency of 10(-4)-10(-5). This frequency is thought to be similar to that of lymphoid precursors in recharged MBMC committed to differentiate along B lineage cells. Based on these results, we discussed the stage, nature, and mode of differentiation of immature lymphoid precursors stored in MBMC.

Animals↗

Eudistomin derivatives, novel phosphodiesterase inhibitors: synthesis and relative activity.

The preparations of novel phosphodiesterase inhibitors, 8-acetoxy-5-iodo-6-methoxypyrido[3,4-b]indole, 5,7-dibromo-6-hydroxypyrido[3,4-b]indole, 5,7-dichloro-6-hydroxypyrido[3,4-b]-indole and 8-acetoxy-5-bromo-6-methoxypyrido[3,4-b]indole, are described together with concentrations giving 50% inhibition against cyclic AMP phosphodiesterase, i.e. 3 X 10(-6), 3 X 10(-6), 7 X 10(-6) and 1 X 10(-5) M, respectively. The relative potency of these eudistomin derivatives is discussed in terms of the chemical structures compared with those of other inactive eudistomins and derivatives.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effect of gangliosides on murine megakaryocytopoiesis in a liquid culture system.

Bovine brain gangliosides were applied to primary cultures of murine bone marrow cells to examine the role of gangliosides in development of megakaryocytes. Megakaryocytes in the cultures were detected by staining for a cytoplasmic enzyme, acetylcholinesterase, and divided into two types, 1) immature megakaryocytes which were stained less intensely, and 2) mature ones which were stained intensely. A medium containing total ganglioside fraction from bovine brain increased the number of both immature and mature megakaryocytes in the presence of pokeweed mitogen-stimulated murine spleen cell conditioned medium. Between the two cell types, the number of the mature cells was more significantly increased than the immature cells. The ganglioside GD1a could substitute for the total ganglioside mixture. The results suggested that bovine brain gangliosides potentiated both megakaryocytic proliferation and maturation in vitro.

Acetylcholinesterase↗

Acid-base changes in ischemic myocardium and intervention with hypothermia or bicarbonate.

Effects of ischemia and reperfusion on acid-base changes in relation to myocardial contractility, and the effects of correcting H+ were studied by lowering PCO2 or increasing HCO3- levels. The hearts were perfused by working heart mode and whole heart ischemia was induced by use of a one way valve followed by myocardial warming (37 degrees C, normothermia), cooling (18 degrees C, hypothermia) or warming plus 2.1 mM NaHCO3 for 15 min. The hearts were then reperfused for 20 min. Coronary effluent was collected through pulmonary artery cannulation and used for the measurement of acid-base changes. There were close correlations between the decrease in coronary flow and LV pressure, LV dP/dt. Close correlations were also observed between the decline in LV pressure and the rise in PCO2, H+, and the decline in HCO3-. A highly significant correlation was seen between H+ and lactate production. Myocardial contractility decreased to the same extent in 3 groups during ischemia, whereas its recovery rate in both the hypothermia and HCO3- -treated groups were significantly higher than in the normothermia group. The increment of H+ was significantly less in both the hypothermia and HCO3- -treated groups than in normothermia. These results indicate that lactate production is the major H+ producing source and the correction of H+ could minimize the ischemic insult and at the same time contribute to the reperfusion injury.

Acid-Base Imbalance↗

[Large-dose intra-arterial injection of lipiodol in liver cancer].

Effects of lipiodol (LPD) on liver functions were examined in 130 patients with primary and metastatic liver cancer who underwent TAE or intraarterial chemotherapy between May 1984 and March 1988 at our department and were available for follow-up studies. Effects of anticancer agents, particularly Adriamycin (ADM), were also evaluated. Large-dose intraarterial infusion of LPD had little effect on the liver functions of patients without liver cirrhosis but often caused a deterioration in liver functions of those with cirrhosis. A combination of this therapy with TAE using Gelfoam sponge caused only a temporary elevation in the transaminase level. The dose of ADM showed little association with the degree of liver disorders, unlike the case of cardiotoxicity or bone marrow suppression. Although the therapeutic effects of intraarterial infusion of ADM-LPD emulsion for advanced cancer (e.g., H4 and Vp3) such as improvements in the Vp factor are remarkable, the dose must be carefully determined, especially when liver cancer is complicated by liver cirrhosis.

Doxorubicin↗