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Biomedical subjects

T Takebe

Publications and source records attributed to T Takebe.

At least 19 recordsLinked to original sources
PubMed1998

Induction of hepatocyte growth factor/scatter factor by interferon-gamma in human leukemia cells.

Induction of hepatocyte growth factor/scatter factor (HGF/SF) may be one of the critical steps in organ regeneration, wound healing, and embryogenesis. We previously reported the production of HGF/SF from various human leukemia cell lines and a high level of the growth factor in blood and bone marrow plasma from patients with various types of leukemia. We determined here the effects of hematopoietic cytokines on HGF/SF production in human leukemia cell lines, KG-1, a myeloid cell line, and RPMI-8226, a B cell line. Interferon (IFN)-gamma remarkably stimulated HGF/SF production in both cell lines at concentrations of more than 0.1 or 1 IU/ml. IFN-alpha and IFN-beta were as effective as IFN-gamma in RPMI-8226 cells, but less than IFN-gamma in KG-1 cells. HGF/SF gene expression in KG-1 cells was also up-regulated by IFN-gamma. Granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-5 and IL-6 had no effect on HGF/SF production in the 2 leukemia cell lines. We also determined the effects of HGF/SF inducers known for human fibroblasts on the growth factor production in leukemia cells. Out of phorbol 12-myristate 13-acetate (PMA), cholera toxin, IL-1 beta, and tumor necrosis factor (TNF)-alpha, the former three were as effective as IFN-gamma in KG-1 cells, but only TNF-alpha stimulated HGF/SF production in RPMI-8226 cells, whose effect was less than those of IFN-alpha, IFN-beta, and IFN-gamma. The effect of IFN-gamma in KG-1 cells was synergistic with that of PMA. In contrast with the effect in leukemia cells, HGF/SF induction by IFN-gamma in human skin fibroblasts was much less than that by PMA or cholera toxin. These results indicated that IFN-gamma is a potent inducer of HGF/SF in human leukemia cells. This finding suggests the presence of a homeostatic control mechanism in liver regeneration and repair: hepatic injury, DNA synthesis inhibition, or apoptosis caused by IFN-gamma is subsequently overcome by cytokine-induced HGF/SF, a potent promoter of liver DNA synthesis.

Gene Expression Regulation, Neoplastic↗
PubMed1998

Stimulation of hepatocyte growth factor production by ascorbic acid and its stable 2-glucoside.

Hepatocyte growth factor (HGF), a cytokine which is generally produced by mesenchymal cells, has mitogenic, motogenic and morphogenic activities in epithelial cells and it also has tumor-suppressing activities. Induction of HGF production may be involved in organ regeneration, wound healing and embryogenesis. We examined the effects of ascorbic acid (AsA), which stimulates the proliferation of fibroblasts, and its stable derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), on HGF production by human skin fibroblasts. Basal HGF secretion was significantly stimulated by more than 0.1 mM AsA or AA-2G. Both vitamins synergistically enhanced HGF secretion stimulated by growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), cholera toxin and other inducers. Induction by EGF or bFGF was most markedly potentiated by the vitamins. HGF production by the KG-1 human leukemia cell line was also augmented by AsA or AA-2G. Another stable AsA derivative, ascorbic acid 2-phosphate (AA-2P) effectively promoted basal and EGF-induced HGF secretion by the fibroblasts, but ascorbic acid 2-sulfate (AA-2S) was much less effective. Intracellular AsA levels increased after the addition of AA-2G and AA-2P as well as AsA, but not after AA-2S. The effect of AA-2G was completely abrogated by the simultaneous addition of castanospermine, an alpha-glucosidase inhibitor, suggesting that the active form of AA-2G is AsA. Constitutive and EGF-induced HGF gene expression was also up-regulated after adding AsA or AA-2G to the cells. These results indicated that AsA acts alone or in synergy with several inducers to stimulate the production and gene expression of HGF in human skin fibroblasts and that the stable AsA derivative AA-2G is as effective as AsA in promoting HGF production.

Acetylcysteine↗
PubMed1994

Expression of hepatocyte growth factor is up-regulated through activation of a cAMP-mediated pathway.

Hepatocyte growth factor (HGF) is a multifunctional cytokine with mitogenic, motogenic, morphogenic, and tumor-suppressing activities. Despite the broad spectrum of its biological activities, HGF is most likely the physiological hepatotrophic factor that triggers or modulates liver regeneration. Regulatory mechanisms for HGF production are crucial for understanding the control of liver regeneration. We previously reported that HGF production by human skin fibroblasts is stimulated by a protein kinase C (PKC)-mediated pathway. We determined here whether gene expression and production of HGF in human skin fibroblasts can be induced via activation of a cAMP-mediated pathway. HGF secretion by the cells was markedly stimulated by the cAMP-elevating agents, forskolin, cholera toxin, prostaglandin E2 (PGE2), and 3-isobutyl-1-methylxanthine, as well as by the membrane-permeable cAMP analogues, 8-bromo-cAMP and dibutyryl cAMP. The dose-response curves of induction of HGF secretion by cholera toxin and forskolin were nearly parallel with those of the intracellular cAMP levels. HGF mRNA levels did not significantly increase at 5 and 10 h, but increased considerably 15 h or more after the addition of cholera toxin. Forskolin, 8-bromo-cAMP, and PGE2 also caused appreciable up-regulation of HGF gene expression with a similar time course. Although human skin fibroblasts of various origins secreted variable amounts of HGF, the cAMP-elevating agents and the cAMP analogues caused a very marked increase in HGF production in all of them. The agents also enhanced highly active HGF secretion by MRC-5 human embryonic lung fibroblasts. Dexamethasone and transforming growth factor-beta 1, which inhibit PKC-mediated HGF secretion, down-regulated HGF mRNA expression and HGF production in the cells treated with the cAMP-elevating agents and the cAMP analogues. These results indicate that HGF expression in human skin fibroblasts is stimulated by activation of a cAMP-mediated pathway.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Induction of hepatocyte growth factor in human skin fibroblasts by epidermal growth factor, platelet-derived growth factor and fibroblast growth factor.

Hepatocyte growth factor (HGF) is a potent mitogen for rat and human hepatocytes in primary culture and appears to be the physiological hepatotrophic factor that triggers or modulates liver regeneration. Regulation of HGF gene expression and the protein production in human skin fibroblasts was examined. Addition of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF) and transforming growth factor-alpha (TGF-alpha) to confluent cultures of the cells markedly stimulated HGF secretion from the cells. The stimulating effect of EGF, PDGF and bFGF was further investigated. The effect of all three growth factors was maximal at 3-30 ng/ml and was accompanied by an increase in HGF mRNA levels. The mRNA levels were not elevated at 5 h but were at 10 h or more after addition of EGF. The levels of HGF mRNA in fibroblasts treated with the optimal doses of EGF, PDGF, bFGF, aFGF and TGF-alpha for 24 h were 6, 4, 5, 4 and 5 times that of control cultures incubated in medium only, respectively. The growth factor-induced HGF mRNA expression and HGF secretion was inhibited by addition of TGF-beta 1 or dexamethasone. Pretreatment with a high dose of phorbol 12-myristate 13-acetate (PMA), which causes down-regulation in protein kinase C (PKC) activity and PMA-induced HGF secretion, did not reduce the effects of the growth factors on HGF mRNA expression and HGF secretion, but rather enhanced them.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1988

Characterization of amylase linked immunoglobulin G to distinguish human salivary and pancreatic isoamylases.

An immunoglobulin G of the kappa type linked to salivary amylase was identified in the serum of a patient with colon cancer and persistent hyperamylasemia. The binding site on the immunoglobulin in the complex is located in F(ab')2 portion. The purified IgG recombined only with purified human salivary amylase, and could be used to separate human isoamylases.

Antibody Specificity↗
PubMed1988

Tumor-associated antigen defined by a monoclonal antibody against neuraminidase-treated human cancer cells.

A monoclonal antibody, MH-A6, was produced by immunization with a human gastric cancer cell line, MKN 74, treated with neuraminidase. The antigen defined by the monoclonal antibody was detected on various tumor tissues and a limited number of normal tissues in immunoperoxidase assay, and the expression of MH-A6 antigen was not influenced by neuraminidase treatment except for some cases of tumor tissues. Interestingly, neuraminidase treatment enhanced binding of the antibody on some adenocarcinomas, but diminished binding of the antibody on squamous cell carcinomas. Both treatment of the immunizing tissues with trypsin and periodic acid diminished binding of the antibody. In isolation of MH-A6 antigen from MKN 74 cells by the monoclonal antibody coupled-affinity column, the epitope exists on molecules with molecular weights of 30,000 and 72,000, and with an acidic pH range in two-dimensional electrophoresis. CEA and CA 19-9 activities were not detected in purified MH-A6 antigen by solid-phase radioimmunoassay, and the reactivity of the MH-A6 antibody with CEA and CA 19-9 was not detected in enzyme-linked immunosorbent assay. Hemagglutination observed between erythrocytes (Lewisa, Lewisb, or NE-treated) and anti-Lewisa, anti-Lewisb sera, or anti-T-agglutinin (peanut lectin), respectively, was not inhibited by MH-A6 antigen. The results suggest that MH-A6 antigen is a tumor-associated antigen, probably glycoprotein, and different from CEA, CA 19-9, Lewisa, Lewisb, and Thomsen-Friedreich (T) antigen.

Antibodies, Monoclonal↗
PubMed1988

Effect of long-term ethanol feeding on the restoration process of acute necrotizing pancreatitis induced in rats.

This study was conducted to elucidate the possible influence of long-term peroral administration of alcohol on the repair process of acute necrotizing pancreatitis. Male Wistar rats fed with balanced diet were divided into two groups. The first group had free access to 15% ethanol, and the second group, the control group, has access to water instead. After fifty weeks, acute necrotizing pancreatitis was induced in rats by infusing 0.4% lysolecithin into their pancreatic duct. In the course of pancreatitis, pancreatic enzymes in serum, enzymes and protein in pancreas, and DNA synthesis in pancreas in both groups, changed in the same way. Histologically, interstitial edema, necrosis of parenchyma, infiltration of inflammatory cells, and formation of tubular complex were observed. Most of these histological changes of pancreas in both groups disappeared in twenty days and pancreas was repaired almost completely. These findings suggest that the repair process of acute necrotizing pancreatitis is not affected by preceding long-term intake of alcohol.

Acute Disease↗
PubMed1987

[A report on the epidemiology and the clinical features of the patients with chronic pancreatitis in Hokkaido District].

We carried out through questionnaires the second survey on the epidemiology and the clinical features of chronic pancreatitis in Hokkaido district. Chronic pancreatitis was diagnosed in 258 patients in 19 hospitals during the period April 1977 to December 1984. The ratio of male cases to females was 2.7:1.0 and the average age was 53.9. Alcoholic abuse, observed in 55% of the patients, was a main causative factor. A half of the patients was diagnosed on the basis of pancreatogram and/or image of the pancreas (ultrasonogram and computed tomogram). The incidence of chronic pancreatitis in the second survey was about fourfold over that diagnosed during the period January 1970 to March 1977 in the first survey. Such an increasing number of the patients with chronic pancreatitis in Hokkaido district was considered to be resulted from the difference between two surveys in epidemiological aspects and diagnostic criteria. The proportion of female patients and alcoholic patients was calculated to be increasing. The frequency of the patients diagnosed in a relatively early stage was supposed to be also increasing, because in the second survey a new item (pancreatogram, ultrasonogram and computed tomogram) was added to the diagnostic criteria (histological evidence, pancreatic calcification and definitive disturbance of exocrine pancreatic function) in the first survey. Based on whether alcoholic abuse was causative factor or not, the patients were divided into two groups and the clinical manifestations of both groups were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

The usefulness of serum PABA measurement after BT-PABA administration in the diagnosis of chronic pancreatitis.

We examined the maximal serum PABA concentration within 3 hrs (MS-PABA) and the 6 hr urinary PABA recovery (6 hr U-PABA) after BT-PABA administration, PABA excretion index, and chymotrypsin secretory response to caerulein-secretin stimulation in ten control subjects and fifteen patients with chronic pancreatitis diagnosed on the basis of pancreatograms. The results suggested that MS-PABA can distinguish the patients with definite irregular dilatation of the main pancreatic duct from the controls, but not those with localized irregular dilatations of the side branches from the controls. MS-PABA showed a significant correlation with 6 hr U-PABA, PABA excretion index, chymotrypsin output and bicarbonate output. This modified method was shown to be useful in the diagnosis of chronic pancreatitis with unequivocally abnormal pancreatograms and/or markedly decreased chymotrypsin secretion. This modification will serve to simplify the BT-PABA test by eliminating urinary collection and shortening the procedure time.

4-Aminobenzoic Acid↗
PubMed1985

Insulin and glucagon response of the diabetic Chinese hamster in the Asahikawa colony.

The relationship between pancreatic hormone content and pattern of hormone release has not been completely elucidated because of heterogeneity in diabetes. Accordingly, this study was performed to establish the relationship, using spontaneously diabetic Chinese hamsters in the Asahikawa colony, a newly discovered experimental model resembling insulin-deficient diabetes in humans. As a result of investigations of insulin and glucagon responses to glucose or arginine in vivo and in vitro using isolated islets obtained by the collagenase procedure, a decreased insulin response and paradoxical glucagon response to glucose, and an excessive glucagon response to arginine were found in the diabetic animals. While the yield of isolated islets tended to decrease, a decreased pancreatic insulin content and increased pancreatic glucagon content were found as the diabetic state advanced. It may be suggested, therefore, that the relationship between pancreatic hormone content and pattern of hormone release in diabetic animals in the Asahikawa colony is based on the disruption of islets, disruption or dysfunction of B-cells and hyperplasia or hypertrophy of A-cells by some cause genetically determined.

Animals↗