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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 469 records · Page 26Linked to original sources
PubMed1996

IGF2 but not H19 shows loss of imprinting in human glioma.

Genomic imprinting is a gamete-specific modification resulting in the allele-specific expression of genes in somatic cells. A loss of imprinting (LOI) has been found in many embryonal and adult tumors, suggesting that it plays a role in tumor development. The incidence of LOI, however, does not seem to be ubiquitous among tumors because neuroblastoma and colorectal cancer revealed no LOI. We examined the involvement of LOI of IGF2 and H19 genes in human gliomas. The two genes were imprinted in normal brain subcortex tissues. In glioma, 8 of 14 informative cases (57%) revealed LOI in IGF2. The frequency did not depend on the tumor grade. For H19, in contrast, all 13 informative cases maintained imprinting. These results suggest that LOI of IGF2 but not H19 plays a role in the development of human glioma.

Adult↗
PubMed1996

Contribution of chorda tympani and glossopharyngeal nerves to taste preferences of rat for amino acids and NaCl.

To learn how the gustatory nerves convey information about the nutritionally dependent taste preference, intake of amino acid solutions and saline in rats with bilateral chorda tympani (CTX) and/or glossopharyngeal neurotomy (GPX) was determined during the feeding of a control diet (C) and a L-lysine (Lys) deficient diet (LD). Intact rats preferred L-arginine (Arg) more in C and Lys more in LD. The CTX group did not select nor ingest Lys in LD, and its intake of Arg was also low in C. The GPX group did not substantially alter its preference under both diets, while it did show an increase in total liquid intake. The preference changes in the CTX + GPX group appeared as combined effects of the CTX and the GPX groups. In an additional study, the preference for Lys shifted to higher concentrations and the total consumption of Lys increased in LD. The present data suggest that the chorda tympani nerves possibly function as discriminators of the nutritional information by altering the taste preference, and that the glossopharyngeal nerves may convey other functional taste information, such as aversive tastes, and sensory aspects of osmotic regulation. In addition, it is revealed that the animals have ability to search for a nutrient deficient in their body, and to ingest it to a level that at least nullifies the deficiency.

Amino Acids↗
PubMed1996

Cell kill kinetics of an antineoplastic nucleoside, 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine.

The cytotoxic properties of 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine (DMDC) were compared with those of 1-beta-D-arabinofuranosylcytosine (ara-C), using SK-MEL-28(P-36) human melanoma cells. DMDC and ara-C were most cytotoxic to cells in the S phase of the cell cycle. Cell cycle progression in S phase was blocked by both compounds. Treatment with DMDC (1 microgram/mL) or ara-C (1 and 30 micrograms/mL) did not increase cytotoxicity against asynchronous cells when the exposure time was prolonged from 1 to 6 hr, but did increase cytotoxicity thereafter. These findings suggest that cells in S phase are rapidly killed by the treatment but are temporarily prevented or delayed entry into the drug-sensitive S phase. On the other hand, DMDC treatment at a higher concentration (30 micrograms/mL) increased cytotoxicity in a time-dependent manner. Intracellular DMDC 5'-triphosphate (DMDCTP) increased in proportion to exogenous DMDC concentration, which was not saturated by treatment with a maximum concentration of the compound at 80 micrograms/mL. In contrast, intracellular ara-C 5'-triphosphate reached peak level when the cells were treated with ara-C at 8 micrograms/mL. The cytotoxicity of DMDC treatment for 4 hr increased relative to the intracellular DMDCTP accumulated during the period. These findings suggest that in cells treated with DMDC at a high concentration, an effective DMDCTP level is maintained for an extended period after washing out the compound from the medium. Consequently, the cells would be killed in the same way as in the case of extended exposures over 6 hr to DMDC at low concentration or to ara-C, in addition to acute S-phase-specific cytotoxicity.

Antineoplastic Agents↗
PubMed1996

Emotional and behavioral correlates of mediodorsal thalamic neurons during associative learning in rats.

Neuronal activity was recorded from the mediodorsal thalamic nucleus (MD) of behaving rats that were trained to lick a protruding spout just after a conditioned stimulus to obtain reward or to avoid shock. Conditioned stimuli included both elemental (auditory or visual stimuli) and configural (simultaneous presentation of auditory and visual stimuli predicting reward outcome opposite that predicted by each stimulus presented alone) stimuli. Of 122 MD neurons responding during the task, the activity of 13 increased just before licking only during the task, but not before spontaneous licking during the intertrial interval (conditioned behavior related). These conditioned behavior-related neurons were located mainly in the lateral MD, which has intimate anatomical connections with motor-related areas such as anterior cingulate and striatum. The activity of the other 109 neurons was related to conditioned stimulation (conditioned stimulus related). Most of these neurons responded differentially to both elemental and configural stimuli in terms of reward contingency, and also changed their responses during extinction and relearning trials. Conditioned stimulus-related neurons with latencies < 300 msec were located mainly in the rostromedial MD, which receives afferents from the basolateral nucleus of the amygdala in which sensory information from various sources converge. Furthermore, most differential neurons that were tested responded during the delay period in a reward task in which a delay was imposed between the conditioned stimulus and reward delivery. The present results, along with previous anatomical studies, suggest the existence of two limbic circuits: anterior cingulate-striatum-lateral MD (motor) and amygdala-medial MD-orbital prefrontal cortex (short-term memory/emotion).

Acoustic Stimulation↗
PubMed1996

Potent inhibitors of secretory phospholipase A2: synthesis and inhibitory activities of indolizine and indene derivatives.

Phospholipase A2 is an enzyme which hydrolyzes the sn-2 position of certain cellular phospholipids. The liberated lysophospholipid and arachidonic acid are precursors in the biosynthesis of various biologically active products. As human nonpancreatic sPLA2 is present in high levels in the blood of patients in several pathological conditions, the potent sPLA2 inhibitors have been suggested to be useful drugs. Here we describe the synthesis, structure-activity relationship, and inhibitory activities of indolizine and indene derivatives. 1-(Carbamoylmethyl)indolizine derivatives and 1-oxamoylindolizine derivatives exhibited very potent inhibitory activity. The former was unstable to air oxidation, but the latter exhibited an improvement both in stability and in potency. Some compounds approached the stoichiometric limit of the chromogenic assay.

Alkylation↗
PubMed1996

Occupation of the QB-binding pocket by a photosystem II inhibitor triggers dark cleavage of the D1 protein subjected to brief preillumination.

The D1 protein of the photosystem (PS) II reaction center turns over very rapidly in a light-dependent manner initiated by its selective and specific cleavage. The cleavage of D1 was studied by using a PS II inhibitor, N-octyl-3-nitro-2,4,6-trihydroxybenzamide (PNO8), as a molecular probe. The following results were obtained. (i) D1 was selectively cleaved into 23-kDa N-terminal and 9-kDa C-terminal fragments in complete darkness by PNO8 at a single site in a D-E loop connecting membrane-spanning helices D and E. (ii) The cleavage was markedly enhanced when PS II was illuminated for a brief period before the addition of PNO8 in darkness. (iii) The effect of preillumination was slowly lost during incubation in the dark, with a decay half-time of approximately 1 h at 25 degrees C. (iv) The light intensity of preillumination required for the cleavage was much lower than that required for O2 evolution. (v) The light-triggered cleavage of D1 was observed in thylakoids, PS II membranes, and PS II core particles, but not in purified PS II reaction centers. More than 60% of D1 was cleaved into the two fragments with no other by-products. (vi) The cleavage reaction revealed a marked pH dependence that was considerably different from that for inhibition of PS II activity. The results are interpreted as indicating that the binding of PNO8 to the QB-binding pocket triggers proteolytic cleavage of D1 that has been previously modified during illumination.

Benzamides↗
PubMed1996

Alterations of c-fos gene methylation in the processes of aging and tumorigenesis in human liver.

The state of DNA methylation in the c-fos gene was examined in human livers of different ages, cirrhosis and hepatocellular carcinoma. The degree of methylation in the intron 1 to exon 4 region increased with age, whereas all of the 10 cirrhosis samples revealed a decrease in methylation when compared to normal livers of similar ages. The 11 hepatocellular carcinomas showed varied alterations suggesting that the alteration of the c-fos gene methylation is related to aging as well as to early-step of hepatocarcinogenesis.

Adolescent↗
PubMed1996

Effect of bile on the intestinal bile-acid binding protein (I-BABP) expression. In vitro and in vivo studies.

Enterocytes actively transport bile acids from the ileal lumen to the portal blood. This physiological process greatly contributes to maintaining the bile acid homeostasis. However, little is known about the molecular mechanisms involved in this transport system. The effect of bile on gene expression of the intestinal bile-acid binding protein (I-BABP) expressed in the enterocytes was studied in vivo, using the by-pass method, and in vitro, using organ culture of ileum explants and Caco-2 cell line. The low cytosolic I-BABP concentration and I-BABP mRNA level found in diverted ileum was totally recovered when bile was added in the ileal lumen. Northern blot analysis of the ileal explants revealed a dose-dependent increase in the I-BABP mRNA in the presence of bile. In Caco-2 cells, the I-BABP transcript was dramatically increased in the presence of human bile while it was undetectable in the control cultures. These data offer the first evidence that biliary components regulate the I-BABP gene expressed in the enterocytes.

Animals↗
PubMed1996

Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells.

Regulation of squalene epoxidase (SE) gene expression was studied in comparison with those of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and low density lipoprotein (LDL) receptor. An increased expression of SE mRNA and protein content in mouse L929 cells grown in 10% lipoprotein-deficient fetal bovine serum (LPDS) for 48 h was found by performing immunoblot and Northern blot analyses when compared with the culture in the presence of fetal bovine serum (FBS). The same results in mRNA levels were seen using human cell lines HepG2, HeLa, and Chang liver cells. The increase of SE mRNA in HeLa cells grown in LPDS was preventable in a dose-dependent manner by feeding cells with 25-hydroxycholesterol or cholesterol. When an SE inhibitor, NB-598, was fed to HeLa cells grown in LPDS, it caused further increases in mRNA levels of SE, HMG-CoA reductase, and LDL receptor. In contrast, NB-598 had no effect on the message levels of these genes when fed to HeLa cells grown in FBS. These results suggest that sterol produced endogenously can also regulate SE expression at the level of transcription.

Animals↗
PubMed1996

Mastoparan elicits prostaglandin E2 generation and inhibits inositol phosphate accumulation via different mechanisms in rabbit astrocytes.

The effects of mastoparan on phosphoinositide hydrolysis and prostaglandin E2 (PGE2) generation were investigated in astrocytes cultured from rabbit brain. Mastoparan inhibited the accumulations of [3H]inositol phosphates induced by bradykinin (1 microM) in a time- and concentration-dependent manner. Mastoparan (3-30 microM) also released PGE2 in a time- and concentration-dependent manner. Mastoparan-induced release of PGE2 was inhibited by indomethacin, a cyclooxygenase inhibitor, by dexamethasone, a steroidal anti-inflammatory drug, and by pertussis toxin, an inactivator of some G proteins, such as Gi and Go. Mastoparan also caused [3H]arachidonic acid liberation, which was inhibited by dexamethasone or pertussis toxin. In contrast, indomethacin, dexamethasone and pertussis toxin failed to attenuate mastoparan-induced inhibition of [3H]inositol phosphate accumulation induced by bradykinin. Thus, mastoparan-induced inhibition of phosphoinositide hydrolysis does not involve pertussis toxin-sensitive G protein nor arachidonic acid metabolites. In addition to the inhibition of phospholipase C, mastoparan activates phospholipase A2 through pertussis toxin-sensitive G protein.

Animals↗
PubMed1996

Alteration of c-fos gene methylation in human gliomas.

In an attempt to find a common DNA alteration occurring in human glioma, we examined DNA methylation in 34 gliomas of various pathological grades and compared them with those in normal cerebral subcortex DNA. The total methylated cytosine levels in the genome did not differ appreciably between the tumors and the normal tissues; however, the degree of DNA methylation in several proto-oncogenes and suppressor oncogenes showed some alterations. Among them, the c-fos gene demonstrated deviation from that of normal tissues in all cases examined, suggesting that the alteration of c-fos gene methylation plays a role in the early steps of human glioma development.

Adult↗
PubMed1996

Repeat hepatectomy for recurrent hepatocellular carcinoma.

This study evaluated the results of repeat hepatectomy for recurrent hepatocellular carcinoma (HCC) and delineated the limitations of such a treatment strategy. Of 290 patients who had radical hepatic resection, 167 had intrahepatic tumour recurrence. Fifty patients underwent a second hepatectomy. Third and fourth hepatectomies were carried out on six and two patients respectively. There were 36 men and 14 women. Age ranged from 32 to 77 years (mean 59.1 years). Liver cirrhosis was present in 38 and chronic hepatitis in 12 patients. Operative death occurred in four patients (8 per cent) after a second and in one of six after a third hepatectomy, compared with 4.5 per cent after first hepatectomy. The five postoperative deaths were attributed to either Child grade B or C liver disease, or severe intraoperative bleeding. The 5-year survival rate was better in these 50 patients (41 per cent) than in 117 patients who were treated otherwise (7 per cent). The present study indicates that repeat hepatectomy may be useful for recurrent HCC. It is indicated principally for patients with a solitary tumour and Child grade A liver disease.

Adult↗
PubMed1996

FK506 maintains cellular calcium homeostasis in ischemia-reperfusion injury of the canine liver.

Increased morbidity and mortality following transplantation surgery due to the primary nonfunction and dysfunction of the liver poses a great challenge and has increased the crescendo of research work in this field. In this study, we have tried to address the issue concerning the changes in Ca2+ homeostasis and hepatic microcirculation in 90 min of ischemia followed by reperfusion of the liver after FK506 pretreatment. Twenty dogs divided into two groups; group I (0.15 mg/kg/day FK506 for 3 days, im) and group II (control) were used for the measurement of mitochondrial (mit) and total cellular Ca2+ by atomic absorption spectrophotometer and hepatic microcirculation with laser Doppler flowmeter. Serum AST leakage was significantly (P < 0.05) suppressed in group I at 6 hr after reperfusion. The percentage gain in mit Ca2+ in group I was significantly (P < 0.05) inhibited compared to that in group II at 15 min after reperfusion and also when compared with the preischemic value it was significantly (P < 0.05) elevated at 30 min after reperfusion in group II only. FK pretreatment significantly (P < 0.05) inhibited the overload in total cellular Ca2+ at 15 and 30 min after reperfusion. Moreover, hepatic microcirculation was significantly (P < 0.001) better in group I between 2 and 6 hr after reperfusion. In conclusion, the ameliorating property of FK in ischemia-reperfusion may be explained by prevention of the cellular Ca2+ overload during the perireperfusion period.

Animals↗
PubMed1996

Fulminant hepatitis caused by hepatitis C virus during treatment for multiple sclerosis.

A 55-year-old woman was treated at our hospital for multiple sclerosis. Therapy consisted of glucocorticosteroids and cyclosporin. In the 7th week after these drugs were discontinued the patient developed acute liver failure due to fulminant hepatitis (FH) and died. Post-mortem examination showed massive liver necrosis. Serologic examination was negative for hepatitis B virus-related markers. Antihepatitis C virus (anti-HCV) antibody and serum HCV RNA were negative on admission, but HCV RNA appeared concurrently with the onset of FH. Although HCV infection rarely causes FH, it was considered to be the cause of FH in this patient, since there were no other causes of acute liver injury. We suspect that underlying immunologic abnormalities in conjunction with HCV infection may have precipitated the FH.

Anti-Inflammatory Agents↗
PubMed1996

Alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9-producing gallbladder cancer.

We report a rare case of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9-producing gallbladder cancer with high levels of CA125 and protein induced by vitamin K absence or antagonist II (PIVKA II). A 63-year-old man was diagnosed with gallbladder cancer with metastases to the liver, based on ultrasonography and computed tomography of the abdomen showing multiple tumorous lesions in the liver and a thickened gallbladder wall. Laboratory data showed high levels of tumor markers: 4647.4 ng/ml AFP, 9987.1 ng/ml CEA, 11,704.0 U/ml CA19-9, 847.6 U/ml CA125, and 0.2 AU/ ml PIVKA II. AFP in the present case showed an increase in Concanavalin A-nonbinding fraction and an increase in Lens culinaris lectin-binding fraction by affinity column chromatography. The patient died of hepatic failure. Autopsy revealed gallbladder cancer consisting of papillary adenocarcinoma and moderately differentiated tubular adenocarcinoma. By immunohistochemical staining, AFP was detected in the papillary adenocarcinoma portion of the primary focus and metastatic tumor cells in the liver, but was not detected in noncancerous liver tissue. CEA and CA19-9 were detected mainly in the tubular adenocarcinoma portion.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1996

Expression of cutaneous fatty acid-binding protein and its mRNA in rat skin.

Cutaneous fatty acid-binding protein (C-FABP) has been purified from rat skin. Since there was little information about the role of C-FABP in the skin, we investigated the expression of C-FABP and its mRNA in normal rat skin using an immunohistochemical technique and in situ hybridization. In the epidermis, C-FABP mRNA was found to be expressed in basal cells and highly in prickle cells, while C-FABP itself was strongly expressed in the upper prickle and the granular cell layers. In sebaceous glands, both C-FABP and its mRNA were expressed in both peripheral and differentiating cells, although the expression of C-FABP mRNA gradually reduced during differentiation of sebocytes. Since epidermis and sebaceous glands are active sites of fatty acid synthesis, these results suggest that C-FABP may have important roles in the transport and synthesis of fatty acids.

Animals↗