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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 397 records · Page 22Linked to original sources
PubMed1996

Loss of H19 imprinting in esophageal cancer.

Recent articles have reported that loss of imprinting (LOI) of the endogenous gene H19 was frequently found in lung cancer and chorio-carcinoma, common adulthood cancers. Consequently, we examined the status of genomic imprinting of H19 in 29 esophageal and 48 colorectal cancer specimens, and studied its relation to the expression of H19. Of 12 esophageal cancer specimens heterozygous for the RsaI polymorphism, 6 (50%) exhibited LOI of H19, but none of the 18 colorectal cancer specimens heterozygous for the RsaI polymorphism exhibited LOI of H19. The present study suggests that LOI of H19 may play an important role in the pathogenesis of esophageal cancer. Moreover, H19 expression was frequently abundant in both cancers, and all six esophageal cancers carried LOI with overexpressed H19. Therefore, this overexpression of H19 seems to be an important phenomenon for the development of esophageal and colorectal cancer cells.

Base Sequence↗
PubMed1996

Human superoxide dismutase cDNA transfection and its in vitro effect on cold preservation.

In order to elucidate the role of superoxide dismutase (SOD on ischemia-reperfusion injury, bovine and porcine aortic endothelial cells were transfected with retroviral vector LSODRNL containing human Cu,Zn-SOD cDNA and their SOD activities were evaluated by measuring superoxide scavenging capability. Successful augmentation of Cu,Zn-SOD up to 2.7-fold in bovine and 1.9-fold in porcine cells was obtained. After 24 h cold preservation followed by 4 h rewarming, cell viability compared with that of pre-preservation was significantly increased in both types of cells (P < 0.01). Moreover, after exposure to superoxide, viability of the porcine cells with high SOD activity was significantly improved compared to control cells. We consider that transfection of human Cu,Zn-SOD cDNA to arterial endothelial cells is useful for preventing from cold preservation-rewarming or ischemia-reperfusion injury.

Animals↗
PubMed1996

Central antinociceptive effect of L-ornithine, a metabolite of L-arginine, in rats and mice.

L-Arginine produces central antinociception by acting as a precursor of kyotorphin (L-tyrosyl-L-arginine), a [Met5]enkephalin releaser. This study investigated the antinociceptive activity of L-ornithine, a metabolite of L-arginine. L-Ornithine given s.c. at 300-1000 mg/kg suppressed carrageenin-induced hyperalgesia in rats in a naloxone-reversible manner. L-Ornithine and L-arginine, when given i.c.v. at 10-100 mu g/mouse, elicited antinociception even in intact mice, the effects being abolished by naloxone or naltrindole, and potentiated by bestatin, an inhibitor of aminopeptidase and kyotorphinase. The antinociception induced by i.c.v. L-ornithine was also inhibited by i.c.v. L-leucyl-L-arginine, a kyotorphin receptor antagonist, but was resistant to intracisternal anti-kyotorphin serum. L-Tyrosyl-L-ornithine, a synthetic dipeptide, (1-10 mu g/mouse, i.c.v.), exerted kyotorphin-like antinociception in mice. These findings suggest that L-ornithine produces L-arginine-like antinociception via kyotorphin receptors. However, this effect does not appear to be mediated by kyotorphin itself, but most likely by L-tyrosyl-L-ornithine, a putative dipeptide.

Analgesia↗
PubMed1996

Detection of ret homodimers in MEN 2A-associated pheochromocytomas.

Using transfection of NIH 3T3 cells, we have recently demonstrated that multiple endocrine neoplasia (MEN) 2A mutations activate the c-Ret protein by inducing its disulfide-linked homodimerization on the cell surface. To investigate whether the homodimers are present in original tumors, the expression of the c-Ret protein was analyzed in eight sporadic and two MEN 2A-associated pheochromocytomas, the latter two of which contained mutations in cysteine 618 or 634 of Ret. The c-Ret protein was expressed at variable levels in all pheochromocytomas examined. By labeling the c-Ret protein immunoprecipitated from tumor tissues with [gamma-32P]ATP in vitro, its homodimers were detected in pheochromocytomas from MEN 2A patients but not in a sporadic tumor. This result represents the first demonstration of Ret homodimers in original tumors.

Drosophila Proteins↗
PubMed1996

Evidence for coupling of phosphotyrosine phosphatase to gonadotropin-releasing hormone receptor in ovarian carcinoma membrane.

BACKGROUND: Gonadotropin-releasing hormone (Gn-RH) receptor (Gn-RHR) has been demonstrated in epithelial ovarian carcinoma (Imai et al., Cancer 1994; 74:2555-61). To examine whether Gn-RHR mediates direct antiproliferative effects, we attempted to determine stimulatory regulation by Gn-RH of phosphotyrosine phosphatase (PTP) activity in plasma membranes isolated from ovarian carcinoma samples. METHODS: Surgically removed ovarian carcinomas were screened for Gn-RHR expression prior to plasma membrane isolation. The phosphotyrosine level was observed by: (1) immunoblotting of membrane extracts with antiphosphotyrosine antibodies, and (2) dephosphorylation from 32P-labeled membrane protein. Membrane PTP activity was determined using the synthetic substrate p-nitrophenyl in a spectrophotometric assay. RESULTS: A Gn-RH analog alone, or guanosine thiotriphosphate (GTP-gamma-S) alone, caused a remarkable loss of phosphotyrosine from a 35-kD protein of the membranes; incubation with a Gn-RH analog and GTP-gamma-S produced a further dephosphorylation of this endogenous protein. The Gn-RH analog buserelin stimulated the PTP activity of the membranes in a dose-dependent manner (P < 0.01). GTP-gamma-S enhanced the stimulatory action of Gn-RH on PTP; GDP-gamma-S reversed the Gn-RH action. A similar stimulation of PTP was observed (P < 0.01) when carcinoma tissue slices were exposed to Gn-RH analog in vivo prior to assay in vitro. CONCLUSIONS: Activation of PTP by Gn-RH stimulated the loss of phosphotyrosine from endogenous proteins through GTP-binding protein within plasma membrane isolated from Gn-RHR-expressing ovarian carcinoma. The antimitogenic action of the hormone may occur by counteracting tyrosine phosphorylation to promote cell growth.

Cell Membrane↗
PubMed1996

Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat.

Concerning the suppressive effect of inorganic iodine on the growth of 7,12-dimethyl-benz(a)anthracene (DMBA)-induced breast tumor in female Sprague-Dawley (SD) rats, we previously reported that although iodine itself had a suppressive effect on the tumor growth, its effect was not as strong as that of MPA (medroxy-progesterone acetate). However, the combined medication of iodine at a low concentration + MPA showed a stronger effect than MPA alone. The purpose of the present study is to elucidate this mechanism of action by determining the uptake of the administered iodine into breast tumor tissue. Breast tumors were induced with DMBA in female SD rats, and these animals were treated with MPA + inorganic iodine at various concentrations for 4 weeks to determine tumor growth and tumor iodine content. In the comparison of tissue iodine content in growth-suppressive tumors with that in nonsuppressive tumors, the former showed a much higher iodine content. This suggests that direct uptake of inorganic iodine by breast tumors led to the suppression of tumor growth.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Expression of MRP and mdr1 in human gastrointestinal cancer cell lines: a correlation with resistance against doxorubicin.

The mRNA expression of mdr1 and MRP, each of which codes for a transport protein belonging to ATP-binding cassette superfamily and are reported to be responsible for multidrug resistance phenotype, were semi-quantified by RT-PCR in a panel of gastrointestinal cancer cell lines. Although the expression of MRP was predominant in esophageal cancer cell lines, expression of either or both of the genes was detected in all the cell lines tested. Expression of these two genes added together correlated significantly with chemosensitivity against doxorubicin, implicating that expression of both genes should be evaluated in the future analysis of multidrug resistance phenotype. The ID50 values for pirarubicin, although generally lower than the values for doxorubicin, correlated well with the latter, suggesting that the similar phenotype as that for doxorubicin might be responsible for drug resistance against this semisynthetic anthracycline glycoside.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Immunohistochemical analysis of the poorly differentiated stomach adenocarcinoma with medullary growth pattern.

Poorly differentiated gastric adenocarcinoma with medullary features (poor medullary) is distinguished by a propensity for hepatic metastasis. To classify it antigenically, we compared it to poorly differentiated adenocarcinoma with scirrhous growth pattern (poor scirrhous), well and moderately differentiated adenocarcinoma (differentiated adenocarcinoma), and normal gastric mucosa (foveolar and deep epithelium) using immunohistochemistry with antibodies against CEA, AFP, NSE, and Lewis-type antigens. Lewis(a) antigen was significantly associated with differentiated adenocarcinoma and foveolar epithelium, although Lewis(x) antigen was significantly expressed in poor medullary, poor scirrhous, and deep gland epithelium. From the viewpoint of expression of Lewis(a), there was no significant differentiation between poor medullary and differentiated adenocarcinoma, but it was definite between poor scirrhous and differentiated adenocarcinoma. Therefore, we conclude that in antigenic expression, poor medullary carcinoma is allied with differentiated adenocarcinoma rather than poorly differentiated scirrhous carcinoma.

Adenocarcinoma↗
PubMed1996

Prospective adjuvant therapy with mitomycin C and carmofur (HCFU) for colorectal cancer, 10-year follow-up: Tokai HCFU Study Group, the first study for colorectal cancer.

A joint study was performed by the Tokai HCFU study group, which included 41 institutions to study the usefulness of the concomitant therapy with Mitomycin C (MMC) and Carmofur (HCFU) as a postoperative adjuvant chemotherapy in patients with colorectal cancer who had curative resection. Patients were divided into two groups, Group MMC and Group MMC+HCFU, using the "envelope" method. Among the 172 patients who had the envelope opened, 149 evaluable cases were analyzed for evaluation of the drug. The cumulative 10-year survival rates of Group MMC+HCFU had a statistically significant increase in survival rate compared with Group MMC. In particular, the rate was statistically significant in patients with colorectal cancer who had lymph node invasion. There were no severe side effects due to the adjuvant chemotherapy with MMC+HCFU. Thus the adjuvant chemotherapy with MMC+HCFU is suggested to be a useful and safe postoperative adjuvant chemotherapy.

Adult↗
PubMed1996

Oral adjuvant chemotherapy with carmofur (HCFU) for colorectal cancer: five-year follow-up. Tokai HCFU Study Group--third study on colorectal cancer.

BACKGROUND: A joint study was performed by the Tokai HCFU study group, which included seven institutions, to examine the value of oral administration of Carmofur (HCFU), a 5-fluorouracil (5-FU) derivative, for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative resection. METHODS: The patients were divided into two groups, a control group receiving no HCFU and a group administered HCFU for 1 year, using a centralized registration system by telephone. Among 173 patients entered into this study, 159 evaluable cases were analyzed for evaluation of the drug. RESULTS: The cumulative 5-year disease-free rate of patients who received HCFU was significantly increased compared with the control group. In particular, the rate was much higher in patients with colon cancer. No severe side effects arose from adjuvant chemotherapy with HCFU. CONCLUSION: Adjuvant chemotherapy with oral HCFU appears to provide a useful and safe postoperative treatment.

Administration, Oral↗
PubMed1996

The valine catabolic pathway in human liver: effect of cirrhosis on enzyme activities.

The activities of key enzymes in the valine catabolic pathway--branched-chain aminotransferase, branched-chain alpha-keto acid dehydrogenase complex, methacrylyl (MC)-coenzyme A (CoA) hydratase (crotonase), and 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolase--were measured in normal and cirrhotic human livers. Unlike rat liver, which does not contain branched-chain aminotransferase, the aminotransferase activity in the normal liver was measurable and is increased somewhat in cirrhosis of the human liver. The total activity of branched-chain alpha-keto acid dehydrogenase complex in the normal human liver was approximately 1% of that in rat liver, and 20% to 30% of the complex was in the active form in both normal and cirrhotic livers. Only the actual activity of the enzyme was significantly decreased by cirrhosis. These results suggest that human liver is less active than rat liver in the catabolism of branched-chain amino and alpha-keto acids. Activities of MC-CoA hydratase and HIB-CoA hydrolase in human liver were very high compared with that of branched-chain alpha-keto acid dehydrogenase complex, suggesting an important role for these enzymes in catabolism of a potentially toxic compound, MC-CoA, formed as an intermediate in the catabolism of valine and isobutyrate. Cirrhosis resulted in a significant decrease in HIB-CoA hydrolase activity but had no effect on the citrate synthase activity, suggesting that the decrease in HIB-CoA hydrolase activity does not reflect a general decrease in mitochondria but that it may contribute to cellular damage that culminates in liver failure.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1996

Beneficial effect of donor pretreatment with thromboxane A2 synthase inhibitor on the graft survival in pig liver transplantation.

With a known evidence that thromboxane A2 (TxA2) is elevated in the perfusate of the liver transplant (LTx) recipient, TxA2 is likely to play a role in the pathogenesis of preservation reperfusion injury. In this study, effectiveness of donor pretreatment with TxA2 synthase inhibitor, sodium ozagrel (SO), in the prevention of primary nonfunction (PNF) was investigated. LTx was performed for eight pigs which received the grafts treated with SO during harvest surgery (treatment group). Eight other animals were the control group. All of the animals in the treatment group survived longer than 7 days, whereas 37.5% (three of eight) of the control group died from PNF within 3 days postoperative. Significantly lower serum LDH levels were noted in the treatment group than control. Serum thromboxane B2 (TxB2) and 6-keto-PGF1 alpha were both elevated in the control group. However, a significant decrease in TxB2 was noted in the treatment group after reperfusion of the liver graft. Polymorphonuclear leukocyte (PMN) infiltration in the graft after reperfusion was significantly greater in the control group than in the treatment group. Hepatocyte microsteatosis was prominent in the control group after reperfusion. Donor pretreatment with SO was effective in the prevention of PNF after LTx. The beneficial effects of this drug are improvement in microcirculation allowing better perfusion of cold preservative and the blocking effect of platelet-PMN-endothelial interaction which is thought to be a primary etiology in reperfusion injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Doxorubicin-induced disturbance of the energy metabolism after hepatectomy.

This study was designed to clarify effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on doxorubicin-induced changes in liver energy metabolism after hepatectomy. Rats were divided into two major groups dependent on whether hepatectomy had been performed. Rats undergoing hepatectomy were subdivided into three groups: the control group, 70% of the liver was resected; the doxorubicin group, after hepatectomy 2 mg/kg body weight doxorubicin was administered intraperitoneally; and the doxorubicin + gamma-glutamylcysteine group, 30 min before hepatectomy 50 mg/kg body weight of gamma-glutamylcysteine ethyl ester was injected intravenously and other procedures were performed as in the doxorubicin group. In the group not undergoing hepatectomy, 2 mg/kg body weight doxorubicin was administered intraperitoneally after a sham operation. Rats in each group were sacrificed 24, 72, and 120 hr after hepatectomy or sham operation, and the remnant liver was isolated. Liver mitochondrial function, adenine nucleotide concentrations, and glutathione and glutathione peroxidase activities were determined. Doxorubicin did not show any significant effects on parameters measured in rats not undergoing hepatectomy. Liver mitochondrial function was increased significantly 24 hr after hepatectomy, and significant decreases in adenine nucleotide concentrations were observed 24 and 72 hr after hepatectomy. Doxorubicin inhibited the increase in mitochondrial function associated with hepatectomy and delayed recovery of liver adenine nucleotide concentrations. Significant increases in tissue glutathione concentrations were observed 24 and 72 hr after hepatectomy. These significant increases in glutathione concentrations were not observed in rats treated with doxorubicin 72 hr after hepatectomy. Furthermore, doxorubicin decreased glutathione peroxidase activity after hepatectomy. Administration of gamma-glutamylcysteine ethyl ester lessened these doxorubicin-induced changes. These results indicate that changes in the glutathione redox system might be involved in the doxorubicin-induced deterioration of the remnant liver energy metabolism. Clinical application of gamma-glutamylcysteine ethyl ester might be expected.

Adenosine Triphosphate↗
PubMed1996

Mitochondrial glutathione redox and energy producing function during liver ischemia and reperfusion.

The glutathione in mitochondria is thought to play a crucial role in protecting mitochondria against ischemia-reperfusion-induced injury. However, little is known about the mitochondrial redox system. This study was conducted to clarify changes of mitochondrial glutathione redox during liver ischemia and reperfusion and its role on energy producing function. Rats were divided into three groups each of which were treated respectively with saline (Control), buthionine sulfoximine (BSO), which induces a rapid decrease in tissue glutathione concentrations, and gamma-glutamylcysteine ethyl ester (GCE), which conversely induces a rapid increase in tissue glutathione concentrations before induction of ischemia. Liver ischemia was induced for 120 min, and blood reflow was subsequently restored for 60 min. Total and mitochondrial glutathione concentrations, mitochondrial respiratory function, and tissue adenine nucleotide were determined after both the ischemic and the reperfusion periods. In all groups, concentrations of the reduced form of glutathione (GSH) gradually decreased during ischemia and reperfusion. On the other hand, significant increases in mitochondrial GSH were apparent after reperfusion despite significant decreases during ischemia in the control and GCE groups. Total and mitochondrial GSH in the BSO and GCE groups were significantly lower and higher, respectively, compared with the control throughout the experiment. Recovery of the mitochondrial energy producing function and cellular adenine nucleotide after reperfusion were dependent on GSH concentrations. We conclude that mitochondrial GSH concentrations dramatically change in a different manner from cytosolic concentrations after reperfusion, and that recovery of the mitochondrial energy-producing function might be closely associated with mitochondrial GSH concentrations.

Adenosine Triphosphate↗
PubMed1996

Morpholological analyses of galaninergic inputs to the rat spinal parasympathetic nucleus.

We examined the characteristic features of galanin (GAL)-containing nerve afferents in the intermediolateral nucleus (IML) of the rat lumbosacral spinal cord (L6, S1), i.e., spinal parasympathetic nucleus, by immunocytochemistry at both light and electron microscopic levels. Firstly, the types of synapses formed by GAL-immunoreactive (IR) axon terminals and their post- or presynaptic elements were examined in random ultrathin sections. A total of 109 synapses were examined. Axodendritic (71%) and axo-somatic (20%) synapses were always of the asymmetrical type. Axo-axonic synapses (9%) were occasionally found; GAL-IR axon terminals were either postsynaptic (3%) or presynaptic (6%) to non-IR axon terminals. By confocal laser microscopy, many GAL-IR axon terminals were seen close to cell bodies and proximal dendrites of the IML neurons that were retrogradely labeled with Fluoro-Gold injected into the pelvic ganglion. Some GAL-IR axon terminals were identified to be presynaptic to them under the electron microscope, by restaining for GAL immunoreactivity with the immunoperoxidase method. These findings suggest that the GAL afferents are involved in the parasympathetic motor regulation of pelvic organs via their central synaptic influences upon preganglionic neurons. Finally, hemi-transection of the upper lumbar segments (L1-L3) or unilateral dorsal rhizotomy (L5-S2) did not significantly alter the immunoreactivity for GAL in the IML. These results suggest that GAL afferents do not originate from regions rostral to the IML nor from the dorsal root ganglion, but probably from GAL cells located at least within the lower lumbar segments and/or sacral spinal cord.

Animals↗
PubMed1996

Establishment of a human DAF/HRF20 double transgenic mouse line is not sufficient to suppress hyperacute rejection.

To solve the chronic donor organ shortage, the pig is considered to be a possible donor candidate for human transplantation. However, hyperacute rejection occurs due to the activation of the complement cascade. Therefore, the introduction of human complement inhibitors into animal cells has been proposed as a means to prevent such exologous complement activation. To investigate the extent to which complement inhibitors are resistant to human sera in discordant animals, we established transgenic mice lines which expressed either human decay-accelerating factor (DAF) and/or homologous restriction factor 20 (HRF20) using microinjection methods. Human sera were injected into (a) 10 control mice, (b) 10 DAF-transgenic mice, (c) 10 HRF20-transgenic mice, and (d) 10 DAF and HRF20-transgenic mice. The results showed that all the mice in groups a, b, and c died immediately after injection. Three of the mice in group d died, while seven survived but showed hyperpnea and low activity. The pathological findings of groups a, b, and c included severe coagulation; however, the survivors of group d showed less severe symptoms. The above findings thus suggest that both DAF and HRF20 tend to prevent complement activation to some extent; however, its effectiveness is not considered to be sufficient for clinical use in transplantation.

Animals↗
PubMed1996

Malignant lymphoma of the gastric stump developing 25 years after a distal gastrectomy for benign gastric disease: report of a case.

We report herein the case of a 57-year-old man in whom malignant lymphoma originating in the gastric remnant was confirmed 25 years after a subtotal gastrectomy with Billroth II reconstruction had been performed for gastric ptosis. Gastroscopy revealed an ulcerated tumor on the fornix, and histologic examination of the endoscopic biopsy specimens demonstrated malignant lymphoma. Thus, total gastrectomy with splenectomy, pancreatectomy, and resection of the previously anastomosed jejunal stoma were performed. Histologic examination of the stomach remnant confirmed a diagnosis of B-cell lymphoma of the large-cell type. Although we were unable to study the surgical specimen from the initial operation, the possible relationship between pseudolymphoma and malignant lymphoma has been presented in the literature, which is reviewed following this case report.

Anastomosis, Roux-en-Y↗