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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 523 records · Page 29Linked to original sources
PubMed1991

Expression of the RAG-2 gene in murine central nervous system tumor cell lines.

Two tightly linked recombination activating genes, RAG-1 and RAG-2, are involved in VDJ recombination of the immune system. Although these genes were originally thought to be expressed exclusively in precursor B and T cells, RAG-1 transcripts were recently found in the murine central nervous system (CNS) [Chun et al., Cell 6, 189, (1991)]. We found that the RAG-2 gene was expressed in CNS tumor cell lines, melanoma (B-16) and skin fibroblast (A9). RAG-1 expression was not found in any non-lymphoid cell lines examined including CNS tumor cell lines. Another VDJ recombination-related gene RBP-Jk was expressed in all tumor cell lines examined. It remains to be seen whether expression of RAG-1 and RAG-2 in CNS is abortive or functionally important.

Animals↗
PubMed1991

Effects of transient forebrain ischemia and reperfusion on function of dopaminergic neurons and dopamine reuptake in vivo in rat striatum.

To clarify functional changes of dopaminergic neurons and dopamine (DA) reuptake during and after ischemia, extracellular DA levels in striatum were determined using in vivo brain microdialysis in a 4-vessel occlusion model of male Wistar rats with and without pharmacological interventions. Without interventions, the extracellular DA levels markedly increased during ischemia, but upon reperfusion, rapidly returned to control level. Infusion of tetrodotoxin, a blocker of voltage-dependent Na+ channels, was without effect on the DA surge during ischemia, but decreased the DA levels after reperfusion to the same extent as in control rats. Pretreatment with nomifensine, an inhibitor of DA reuptake, was also without effect on the surge, but reduced the rate of DA decline after reperfusion to one-fifth of the rate without the pretreatment. When nomifensine was administered 40 min after reperfusion, extracellular DA levels increased to the same extent as in control rats. Infusion of high K+ 1 h after reperfusion induced a smaller increase in extracellular DA levels than that in control rats. It took 96 h for this reduced response to high K+ stimulation to recover after reperfusion. These results suggest that the DA surge during ischemia is mainly derived from action potential-independent DA release (means dysfunction of dopaminergic neurons), although activity of DA reuptake is completely inhibited. After reperfusion, the basal function of dopaminergic neurons and activity of DA reuptake rapidly recover, but the neurons are functionally disturbed to release less DA in response to a given stimulus for several days.

Animals↗
PubMed1991

Inhibition of cell growth and tumorigenesis of human glioblastoma cells by a neutralizing antibody against human basic fibroblast growth factor.

We report here that a neutralizing mouse monoclonal antibody against basic FGF inhibited both anchorage-dependent and anchorage-independent growth of U-87MG and T98G human glioblastoma cells and HeLa cells, all of which express both the basic FGF and the FGF receptor genes. In addition, the subcutaneous administration of this antibody significantly suppressed the tumor development of these tumor cells in nude mice. Therefore, basic FGF plays an important role in neoplastic growth of these cells. The neutralization of basic FGF will be effective in controlling the growth of tumors, such as glioblastoma and other cancer cells which bear basic FGF and FGF receptors.

Animals↗
PubMed1991

Fracture healing induces expression of the proto-oncogene c-fos in vivo. Possible involvement of the Fos protein in osteoblastic differentiation.

Here we report marked in vivo expression of the c-fos gene in the external soft callus (ESC) and periosteal hard callus (PHC) at the fracture site of adult rat tibia. Northern-blot analysis showed that the ESC expressed a high level of c-fos mRNA from post-fracture day 10 to day 28, the time when endochondral ossification progressed, and that the ossifying PHC also expressed c-fos mRNA. This c-fos expression was followed by sequential expression of the genes for alkaline phosphatase, osteopontin and osteocalcin, which are osteoblastic markers. Immunohistochemical analysis showed that the c-Fos protein was predominantly located in osteoblasts in the ossifying calluses.

Alkaline Phosphatase↗
PubMed1991

Gene expression of fibroblast growth factor receptors in the tissues of human gliomas and meningiomas.

Northern blot analysis showed transcripts of two types of the fibroblast growth factor (FGF) receptor genes, flg and bek, in almost all the tissues samples of 18 human gliomas and 22 human meningiomas, which produced abundant basic and/or acidic FGF. From immunohistochemistry, FGF receptors were expressed in the tumor cells of a glioma and a meningioma. RNA expression of these FGF receptors was also detectable in normal human brains and normal bovine meninges. The expression level of either FGF receptor gene was not significantly different between tumor tissues and normal tissues.

Blotting, Northern↗
PubMed1991

Enzyme inhibition by analgesic and hypnotic agents on anaerobic dehalogenation of halothane.

Enzyme inhibition on anaerobic dehalogenation of halothane by various analgesic or hypnotic agents was investigated in vitro using rat liver microsomal fraction. The production rate of chloro-difluoro-ethylene (CDE) and chloro-trifluoro-ethane (CTE), anaerobic metabolites of halothane, was measured when various concentrations of analgesic or hypnotic agents (fentanyl, morphine, pentazocine, buprenorphine, ketamine, diazepam, chlorpromazine and hydroxyzine) were supplemented. Inhibitor constant (Ki) of each agent was calculated and compared with each other. The activity of NADPH-cytochrome c reductase (fp(2)) and NADH-ferricyanide reductase (fp(1)) was measured when each agent was added. The values of inhibitor constants (Ki) for CDE and CTE formation were in the following order from large to small values; morphine (656 microM and 2570 microM), chlorpromazine (49.7 microM and 68.1 microM), ketamine (24.9 microM and 64.4 microM), fentanyl (23.9 microM and 34.6 microM), hydroxyzine (19.2 microM and 50.8 microM), diazepam (17.0 microM and 13.9 microM), buprenorphine (11.2 microM and 22.4 microM), and pentazocine (1.96 microM and 6.67 microM) respectively. Pentazocine inhibited the formation of CDE 300 fold greater than morphine. The activity of fp(2) and fp(1) did not change by the addition of these analgesic or hypnotic agents. These results indicate that various analgesic or hypnotic agents, which are commonly used with halothane in clinical anesthesia, suppress the anaerobic dehalogenation of halothane in vitro. They also imply that the suppression of production of halothane metabolites is the result of direct enzyme inhibition on cytochrome P-450, since these agents did not affect the activity of fp(2) and fp(1) which are flavoproteins existing in the microsomal electron transport system.

Journal Article↗
PubMed1991

Immunohistochemical characterisation of extracellular matrix components of salivary gland tumours.

Proteoglycans (PGs) were localised immunohistochemically in 52 salivary gland tumours including pleomorphic adenoma, adenoid cystic carcinoma, acinic cell carcinoma, oncocytoma, mucoepidermoid carcinoma, clear cell tumour and Warthin tumour, using antibodies raised against large PG, small PG, chondroitin 4-sulphate PG, chondroitin 6-sulphate PG, heparan sulphate PG and keratan sulphate PG. Large PGs were mainly observed in mucinous materials of extracellular matrix (ECM) and interstitial fibrous element of tumour tissues, while small PGs were located only in hyaline matrix and surrounding fibrous (capsular) connective tissues. Chondroitin 6-sulphate PG was detected in the ECM of pleomorphic adenomas and clear cell carcinomas and in pseudocystic spaces of adenoid cystic carcinomas, but only in vessel walls in non-neoplastic tissues. Keratan sulphate PG was observed to locate in mucinous material of pleomorphic adenomas, acinic cell carcinomas and clear cell carcinomas, but not in the adenoid cystic carcinomas examined, and it was also unobservable in non-neoplastic salivary gland tissues. Heparan sulphate PG was observed on the inner surfaces of true ductal spaces of adenoid cystic carcinomas and on cell surfaces of oncocytoma cells. By HPLC analysis, individual glycosaminoglycans contained in tumour tissues were compared. Chondroitin 6-sulphate PG was very rich in ECM of pleomorphic adenomas and adenoid cystic carcinomas. Pleomorphic adenomas contained relatively more low-sulphated chondroitin sulphate than adenoid cystic carcinomas and other tumours.

Chondroitin Sulfates↗
PubMed1991

Hamster cytochrome P-450 IA gene family, P-450IA1 and P-450IA2 in lung and liver: cDNA cloning and sequence analysis.

Two cDNA clones, 2C19 and 4C1, were isolated from a lung cDNA library of 3-methylcholanthrene (MC)-treated hamster by using rat P-450c cDNA as a probe. The cDNA determined from 2C19 and 4C1 was 2,916 bp long and contained an entire coding region for 524 amino acids with a molecular weight of 59,408. The deduced amino acid sequence showed a 85% identity with that of rat P-450c indicating 2C19 and 4C1 encode the hamster P-450IA1 protein. Another cDNA clone, designated H28, was isolated from a MC-induced hamster liver cDNA library by using the hamster lung 2C19 or 4C1 cDNA clone as a probe. H28 was 1,876 bp long and encoded a polypeptide of 513 amino acids with a molecular weight of 58,079. The N-terminal 20 residues deduced from nucleotide sequence of H28 were identical to those determined by sequence analysis of purified hamster hepatic P-450MCI. The high similarity of the nucleotide and deduced amino acid sequences between H28 and P-450IA2 of other species indicated that H28 encoded a P-450 protein which belongs to the P-450IA2 family. Northern blot analysis revealed that the mRNAs for hamster P-450IA1 and IA2 were about 2.9 and 1.9 kb long, respectively. Hamster P-450IA1 mRNA was induced to the same level in lungs as in livers by MC treatment, whereas hamster P-450IA2 mRNA was induced and expressed only in hamster liver.

Amino Acid Sequence↗
PubMed1991

Association between restriction fragment length polymorphism of the human cytochrome P450IIE1 gene and susceptibility to lung cancer.

Cytochrome P450IIE1 (P450IIE1) is involved in metabolic activation of carcinogenic nitrosamines, aniline and benzene. We detected a restriction fragment length polymorphism of the human P450IIE1 gene with the restriction endonuclease DraI. The population was thus divided into three genotypes, namely, heterozygotes (CD) and two forms of homozygotes (CC and DD). The distribution of these genotypes among lung cancer patients differed from that among controls with statistical significance of P less than 0.05 (chi 2 = 7.01 with 2 degrees of freedom). This result strongly suggests that host susceptibility to lung cancer is associated with the DraI polymorphism of the P450IIE1 gene.

Adenocarcinoma↗
PubMed1991

Degradation of mitochondrial phospholipids during experimental cerebral ischemia in rats.

Changes in content of brain mitochondrial phospholipids were examined in rats after 30 and 60 min of decapitation ischemia compared with controls, to explore the degradation of the mitochondrial membrane and its relation to dysfunction of mitochondria. Activities of respiratory functions and respiratory enzymes (cytochrome c oxidase; F0F1-ATPase) decreased significantly during ischemia. Considerable decreases in cardiolipin and phosphatidylinositol content were observed after 60 min, and other phospholipids showed similar but nonsignificant decreases in content. The amount of polyunsaturated fatty acids chains, such as arachidonic and docosahexaenoic acids, was reduced in each phospholipid, in some cases significantly, after 30 and 60 min of ischemia in time-dependent manners. Degradation of mitochondrial phospholipids during ischemia associated with the deterioration of mitochondrial respiratory functions suggested the significance of such changes in phospholipid content in disintegration of cellular energy metabolism during cerebral ischemia.

Animals↗
PubMed1991

Effects of hypoxia on the activity of the dopaminergic neuron system in the rat striatum as studied by in vivo brain microdialysis.

The purpose of the present study is to clarify the effects of hypoxia on the activity of the dopaminergic neurons in the brain and its mechanism of action. For this purpose, the effects of hypoxia on the extracellular levels of 3,4-dihydroxyphenylethylamine (dopamine) were examined in the rat striatum using in vivo brain microdialysis in the presence or absence of pretreatment with either tetrodotoxin (a blocker of voltage-dependent sodium channels) or nomifensine (a blocker of dopamine reuptake). Exposure to various degrees of hypoxia (15, 10, and 8% O2 in N2) increased dopamine levels in striatal dialysates to 200, 400, and 1,100%, respectively, of the control value. On reoxygenation, dopamine levels in the dialysates rapidly returned to the control level. Reexposure to hypoxia increased the dopamine levels to the same extent as during the first exposure. After addition of tetrodotoxin (40 microM) to the perfusion fluid or pretreatment with nomifensine (100 mg/kg, i.p.), exposure to hypoxia no longer increased the dopamine levels. These results suggest that although hypoxia induces an increase in the extracellular dopamine levels (hence, an apparent increase in the activity of the dopaminergic neurons), this increase is not the result of an increase in dopamine release itself, but rather the result of inhibition of the dopamine reuptake mechanism.

Animals↗
PubMed1991

[A case of smoldering adult T-cell leukemia complicated by various pulmonary infections].

A 46-year-old man was admitted to Oita Medical College Hospital on October 16, 1987, because of cough and sputum. Chest X-ray and chest CT films showed diffuse reticulonodular shadow. The specimens obtained by transbronchial lung biopsy revealed cysts of pneumocystis carinii. Abnormal lymphocytes with lobulated nuclei were found 2-7% of peripheral leucocytes. The anti HTLV-I antibody was positive. According to these data, we diagnosed the patient as smoldering adult T cell leukemia with pneumocystis carinii pneumonia. The abnormal shadow on chest X-ray disappeared after SMX-TMP and pentamidine treatment. After about 1 year, he was again admitted for high fever. Chest X-ray showed infiltration with cavity in right upper lobe. Streptococcus pneumoniae was isolated from the sputum. The infiltration shadow on chest X-ray disappeared after antibiotics treatment. However, multiple nodular shadow appeared on the chest X-ray and ATL cell infiltration was found in the specimens of transbronchial lung biopsy. ATL cells in peripheral blood also increased and serum LDH and Calcium levels were markedly high. According to these data, we diagnosed the patient as having a ATL crisis. Although chemotherapy for ATL was started, the ATL, cell infiltration shadow on the chest X-ray enlarged, and bilateral diffuse patchy shadows was appeared on the chest X-ray. He died of respiratory failure on April 26, 1989. Cytomegalovirus pneumonia and ATL cell infiltration were revealed by necropsy.

Anemia, Refractory, with Excess of Blasts↗