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Biomedical subjects

T Kaiho

Publications and source records attributed to T Kaiho.

At least 37 records · Page 2Linked to original sources
PubMed1993

[Type IV collagenase activities in human colorectal cancers and its role in cancer invasion and metastasis].

In 36 patients with colorectal cancers, type IV collagenase activities were measured in cancer and non-cancer tissues for evaluating its role in the process of cancer invasion and metastasis. The colorectal cancer tissues revealed remarkably higher activities than the distant normal and tumor-neighboring mucosa (p < 0.001). The activities in the colorectal cancer tissues with high-grade histological venous invasion were higher than those with low-grade histological venous invasion (p < 0.005). But no differences of the activities were found between patients with and without hepatic metastasis. These results suggest that the type IV collagenase plays an important role in the cancer invasion to the blood vessels around the primary site in colorectal cancers.

Adult↗
PubMed1992

Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinediones, novel class III antiarrhythmic agents.

A series of 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)- pyrimidinedione derivatives were synthesized and studied for their class III electrophysiological activity and class II (beta-blocking) effects in in vitro and in vivo models. Structure-activity relationships are discussed for a series of compounds. Several members of this series prolonged the action potential duration at 75% repolarization of isolated canine Purkinje fibers and were 10-30-fold more potent than d-sotalol. 1,3-Dimethyl-6-[[2-[N-[3-(4-nitrophenyl)propyl]-N- (hydroxyethyl)amino]ethyl]amino]-2,4-(1H,3H)-pyrimidinedione (40), is one of the most potent compounds in this series.

Animals↗
PubMed1992

[Hepatic protein synthesis and cytokines in obstructive jaundice].

UNLABELLED: To clarify the mechanism of the increase of hepatic protein synthesis observed in the obstructive jaundiced rats, hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were estimated in the rats with obstructive jaundice and the contents of the following in the peripheral blood were determined in 21 patients with obstructive jaundice before and two weeks after percutaneous transhepatic biliary drainage (PTBD): interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), endotoxin (Et), acute-phase protein (APP) and negative acute-phase protein (NAPP). THE RESULTS: (1) HPS and SPS were markedly increased by obstructive jaundice; (2) IL-1 beta and IL-6 were significantly high and were reduced after PTBD; (3) neither TNF alpha nor Et was detected; (4) APP were significantly high and failed to decline after PTBD; (5) NAPP were significantly low and the contents were restored to the normal levels after PTBD. These results suggest that increased hepatic protein synthesis observed in the rats with obstructive jaundice correspond to the increased hepatic production of APP in patients with obstructive jaundice.

Acute-Phase Proteins↗
PubMed1991

[Inhibition of hepatic DNA synthesis after partial hepatectomy in the rats with obstructive jaundice with special reference to the enhancement of hepatic protein synthesis].

We studied the liver regeneration after partial (68%) hepatectomy in rats with obstructive jaundice followed by the relief of obstruction. Rats received bile duct ligation, then 5 or 14 days later choledocho-duodenostomy was performed. Partial hepatectomy was done at various intervals after the relief of obstruction. DNA synthesis of the regenerating liver, hepatic protein synthesis and mitochondrial swelling induced by exogenous phospholipase A2 (PLA2) were determined. Hepatic DNA synthesis was significantly inhibited in obstructive jaundiced rats compared to controls. While the inhibition disappeared 5 days after the relief of obstruction in 5-day-obstructed group, it was still detectable as late as 21 days after the drainage in 14-day-obstructed group. Hepatic protein synthesis was markedly increased by obstructive jaundice, and this increase continued until 10 days after drainage in 14-day-obstructed group. Partial hepatectomy also increased the hepatic protein synthesis significantly in normal rats, but failed to show any significant changes in obstructive jaundiced rats. Any difference could not be found in PLA2-induced hepatic mitochondrial swelling between obstructive jaundiced rats and normal rats. We concluded the preceding energy-requiring responses in obstructive jaundiced liver resulted in the reduction of hepatic DNA synthesis and in the lack of additional increase of hepatic protein synthesis as the responses to a further insult of partial hepatectomy.

Animals↗
PubMed1991

[Hepatic functional evaluation using the galactose tolerance test in patients with obstructive jaundice].

Hepatic functional mass was evaluated in patients with obstructive jaundice using the galactose tolerance test (GaTT), which reflected cytosolic function of hepatocyte. The T-1/2 values as an index on the GaTT were significantly prolonged in patients with obstructive jaundice in comparison with control subjects whether before or after percutaneous transhepatic biliary drainage (PTBD). But in each cases, some showed nearly normal GaTT-T/2 value and others showed severely prolonged value. Patients with obstructive jaundice could be divided into two groups according to the GaTT-T/2 value before PTBD. The decreasing rate of serum bilirubin level "b" after PTBD was significantly fair in the group A patients (good GaTT-T/2 value before PTBD) than the group B (poor GaTT-T/2 value before PTBD) (P less than 0.05). It was that GaTT-T/2 before PTBD which represented hepatic cytosolic functional mass could predict the effect of PTBD in patients with obstructive jaundice.

Aged↗
PubMed1989

Cardiotonic agents. 1-Methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3 (2H)-isoquinolinones and related compounds. Synthesis and activity.

A series of 1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds were synthesized and evaluated for positive inotropic activity. Most members of this series exerted a dose-dependent increase in myocardial contractility in the dog acute heart failure model, whereas they caused only slight changes in heart rate and blood pressure. Several derivatives, especially those with cyano, acetyl, and ethyl substituents at the 4-position, were more potent than milrinone, which was used as a reference. 4-Acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone (MS-857) is one of the most potent positive inotropic agents in this series.

Animals↗
PubMed1989

[Influence of hepatic ischemia on liver regeneration following hepatectomy, with special reference to the therapeutic choice for ruptured hepatoma].

The influence of partial hepatic ischemia (32%) prior to partial hepatectomy (68%) has been studied in the rat. 3H-thymidine incorporation into the hepatic DNA was significantly suppressed in both 20 min and 30 min ischemia depressed the survival following partial hepatectomy (p less than 0.001). Three cases of ruptured hepatocellular carcinomas were treated: one case by emergency hepatectomy, and two cases by hepatectomy following TAE. Hepatic insufficiency and post-operative death occurred to only the case given an emergency hepatectomy. Thus, it is felt that a ruptured hepatoma should first be treated by TAE and then surgically resected.

Adult↗
PubMed1988

Cardiovascular properties of MS-857, a new and potent cardiotonic agent, on normal and failing hearts.

The cardiovascular properties of MS-857 [4-acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone ], a novel cardiotonic agent, were investigated in anesthetized and conscious dogs. MS-857 (1-100 micrograms/kg i.v.) produced a significant and dose-dependent increase in cardiac contractility with relatively small changes in heart rate and blood pressure. This indicates a sizable separation between positive inotropic and other effects of MS-857. Oral administration of MS-857 to conscious dogs (0.1-1 mg/kg) also produced a sustained increase in cardiac contractility in a dose-dependent manner. The total duration of action was longer than 7 h at a dose of 1 mg/kg p.o. There occurred no arrhythmias and no changes in animal behavior. After chronic oral administration, MS-857 completely retained its activities, indicating the lack of tachyphylaxis. In the acute heart failure models induced by either propranolol or pentobarbital, MS-857 reversed the cardiac depressant effects of these drugs. Moreover, MS-857 also significantly improved the pentobarbital-induced heart failure in the heart-lung preparation. MS-857 did not inhibit the Na+, K+-ATPase, but inhibited the phosphodiesterase (PDE) III selectively, both of which were prepared from the dog ventricular muscle. Thus, MS-857 can be characterized as a potent nonsympathomimetic, nonglycoside cardiotonic drug with a selective inhibitory activity on PDE III. The cardiovascular properties revealed by this study strongly suggest that MS-857 will exert a beneficial effect in the treatment of congestive heart failure.

Anesthesia↗
PubMed1988

[The effect of naproxen on fever following transcatheter arterial embolization of hepatic tumors].

In the cases of trans-catheter arterial embolization (TAE) for hepatic malignancies, naproxen has been evaluated for its antipyretic effect. Each patient not given naproxen manifested a remarkable and prolonged fever despite treatment by antibiotics. In those who received an administration of naproxen, however, a significant suppression of fever was achieved (P 0.01-0.001). No remarkable influence was found on the white blood cell counts, the serum GOT and LDH levels by the naproxen. Similarly, no untoward effect due to naproxen was found on the ulcerogenicity in the gastro-duodenum. Thus, for hepatic malignancies, naproxen could be useful in the symptomatic treatment of a fever following a TAE.

Adult↗
PubMed1985

Development of methotrexate-resistant human choriocarcinoma cells in culture.

A human choriocarcinoma cell line, HCCM-5, was fed with medium containing increasing concentrations of methotrexate (MTX). The initial MTX concentration, 10(-9) M which reduced the [3H] thymidine incorporation into DNA, was raised from 2- to 2.5-fold successively. After about 36 weeks of feeding, the cells became resistant to 5 X 10(-7) M which produced complete inhibition of the parent HCCM-5 cell growth. The parent line and its MTX-resistant subline (HCCM-5MTXr) had almost the same population doubling time. There were no apparent differences in morphology and human chorionic gonadotropin secretion between the two cell lines. The development of resistance was accompanied by a 10-fold decrease in the 3H-MTX uptake and a 5-fold elevation of the intracellular dihydrofolate reductase (DHFR) activity. The impairment of MTX transport in HCCM-5MTXr cells continued after transferring the HCCM-5MTXr cells into MTX-free medium, whereas the DHFR activity returned to the level found in the HCCM-5 cells. These results indicate that the MTX resistance acquired in choriocarcinoma cells chiefly involves the impaired transport of MTX and continues after the deprivation of the drug.

Biological Transport↗
PubMed1985

[Fundamental study on the mechanisms of "cellular effect" in choriocarcinoma].

The relationship between the growth potential and hCG secretion in 2 kinds of human choriocarcinoma cell lines was studied by using 5 kinds of anticancer drugs in strict in vitro conditions. The results are as follows. The hCG secretion per cell was enhanced when the DNA synthesis and growth of the cells were suppressed, irrespective of the human choriocarcinoma cell lines or anticancer drugs used. The hCG secretion per cell was suppressed when the rate of cell death increased. These results indicate that the transient rise in blood or urinary hCG values during chemotherapy ("cellular effect") is due to the suppression of DNA synthesis and growth of the cells and is not due to the result of the cell death.

Bleomycin↗
PubMed1984

Effect of cytochalasin B on growth, Multinucleation and human chorionic gonadotropin secretion in a human choriocarcinoma cell line.

Treatment of human choriocarcinoma cells with cytochalasin B at the doses of inhibiting cell division but not inhibiting nuclear division led to in vitro formation of the multinucleated syncytiotrophoblast-like ( STL ) cells. A concomitant increase in human chorionic gonadotropin (hCG) secretion per cell was noted. Immunocytochemical staining demonstrated the predominant localization of hCG in the STL cells. These results indicate that multinucleation stimulates hCG synthesis and secretion in the choriocarcinoma cells.

Cell Division↗
PubMed1984

[Effects of various agents on the proliferation and hCG secretion of choriocarcinoma cells in vitro].

Effects of sex steroids, LH-RH, cyclic AMP and differentiation promoters on the proliferation and hCG secretion of two choriocarcinoma cell lines (BeWo and HCCM-5) were examined in vitro. The results were as follows. 1) Physiological concentrations of estradiol or progesterone revealed no effect on proliferation or hCG secretion, but pharmacological ones (more than 10 micrograms/ml) inhibited both the cell proliferation and its hCG secretion. 2) LH-RH and cyclic AMP slightly inhibited the proliferation of cells, and hCG secretion per cell was concomitantly enhanced. Cyclic AMP enhanced hCG secretion more markedly than LH-RH. 3) Retinoic acid had no effect on either cell proliferation or hCG secretion, whereas sodium butyrate inhibited both cell proliferation and hCG secretion. These results suggest that modifiers of hCG secretion may be grouped as follows; agents that inhibited cell proliferation slightly and enhanced hCG secretion markedly (LH-RH, cyclic AMP), agents that inhibited cell proliferation markedly and enhanced hCG secretion slightly (anticancer drugs) and agents that inhibited both cell proliferation and hCG secretion (estradiol, progesterone and sodium butyrate).

Cell Division↗
PubMed1984

[Isolation and properties of methotrexate-resistant choriocarcinoma cells in vitro].

The sensitivity to methotrexate (MTX) of ten kinds of human choriocarcinoma cell lines was studied in vitro. The cell line most sensitive to MTX was HCCM-5 and it was fed with a medium containing increasing concentrations of MTX. A resistant subline (HCCM-5R) which could proliferate in the medium containing 5 X 10(-7)M MTX was obtained after about 80 weeks of feeding. The properties of HCCM-5R cells were compared with those of the parent HCCM-5 cells. i) There were no apparent differences in morphology between the HCCM-5 and HCCM-5R lines. The population doubling time was almost the same for both cell lines. ii) The hCG level in the culture fluid of the HCCM-5R cells was about twice as high as that of the HCCM-5 cells. iii) The concentration of MTX which inhibited 50% of DNA synthesis in HCCM-5R cells was 10,000 times higher than that for HCCM-5 cells. iv) Each X and Y chromosome was identified in 90% of the HCCM-5 cells, while no Y chromosome was detected in the HCCM-5R cells. v) The DNA distribution pattern for HCCM-5R cells consisted of a large fraction of each cell with DNA G1 phase content and distributed in the tetraploid range, whereas that of HCCM-5 showed no particular cell cycle pattern. vi) The incorporation of 3H-MTX in the HCCM-5R cells was one tenth of that in the HCCM-5. vii) The intracellular DHFR activity of the HCCM-5R cells was about 5 times higher than that of HCCM-5. These results suggest that MTX-resistant cells among the HCCM-5 cells were selected in long-term contact with MTX, and sensitivity to MTX was concerned with both the MTX transport and intracellular DHFR levels.

Cell Division↗
PubMed1983

Effect of methotrexate on the growth and human chorionic gonadotropin secretion of human choriocarcinoma cell lines in vitro.

The effect of methotrexate (MTX) on the growth and human chorionic gonadotropin (hCG) secretion of five gestational and two nongestational human choriocarcinoma cell lines was studied in vitro. A striking heterogeneity in hCG secretion was noted among the cell lines. The growth of cells which secreted large quantities of hCG, such as HCCM-5, BeWo, and IMa, was inhibited by continuous exposure to 2 X 10(-8)M MTX. In contrast, cells which secreted little hCG, such as SCH, ENAMI-1, and GCH-1, showed no response to the growth inhibitory action of 2 X 10(-8)M MTX and the 3H-thymidine uptake was not reduced by treatment with MTX at doses of up to 10(-4)M for 48 hours. The common morphologic alterations observed in the cells which responded to MTX were an increase in the number of multinucleated giant cells, the appearance of vacuoles and granules in the cytoplasm, and enlargement of the nuclei. Increased hCG secretion was observed in accordance with the appearance of such morphologically altered cells. Part of the mechanisms of resistance to MTX appeared to involve both impairment of MTX uptake by the cells and an increase in the level of intracellular dihydrofolate reductase.

Cell Line↗