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Biomedical subjects

H Okuno

Publications and source records attributed to H Okuno.

At least 73 records · Page 4Linked to original sources
PubMed1996

Expression of the transcription factor Zif268 in the temporal cortex of monkeys during visual paired associate learning.

In humans and monkeys, memory consists of various components which were initially revealed through neuropsychological studies of amnesic patients. One memory component, the long-term memory about facts and events (declarative memory), has been shown to require the integrity of the medial temporal lobe and the neocortex. To investigate a map of gene expression during declarative memory formation in the primate, we monitored expression of immediate early genes in the temporal lobe of macaque monkeys. We trained the monkeys to learn visual associative memory tasks, and immunohistochemically analysed the expression of protein products of immediate early genes. We found that Zif268, a transcription factor regulated by neuronal activity, accumulated in patches in the anterior temporal lobe during visual stimulus-stimulus association learning, whereas other transcription factors, c-Fos and JunD, were not. By contrast, the patchy expression of Zif268 was not observed during another type of learning, visual discrimination learning. These results suggest that Zif268 activates a gene cascade related to the formation of long-term memory in the primate.

Animals↗
PubMed1996

[Acoustic trauma and development of endolymphatic hydrops among the personnel in the self defense forces].

An investigation was carried out among the military personnel in the Self Defense Forces to assess acoustic trauma in association with the onset of endolymphatic hydrops (ELH). Four hundred seventy servicemen were offered general physical examinations in an inpatient setting prior to their discharge from the SDF for mandatory age retirement. A questionnaire on the history of intense acoustic exposure and of dizzy spells was given to the same individuals. A routine ENT examination and audiography were performed for each of them. The following results were noteworthy: five men had a history of Ménière's disease, and 32.5 percent of those questioned had experienced dizzy spells. Hearing thresholds in those who reported that they had had dizzy spells were considerably higher than those who had not had such spells. Although a quantitative analysis as well as a well-established control study seems necessary to implicate acoustic trauma as one of the etiological factors of ELH, this study strongly suggests a relationship between acoustic trauma and development of ELH among the SDF personnel examined.

Endolymphatic Hydrops↗
PubMed1996

Quantitative analysis of testicular histology in patients with vas deferens obstruction caused by childhood inguinal herniorrhaphy: comparison to vasectomized men.

PURPOSE: We investigated the effects on spermatogenesis of lifelong vas deferens obstruction caused by childhood inguinal herniorrhaphy. MATERIALS AND METHODS: Testicular histology was analyzed quantitatively in 15 post-herniorrhaphy patients with vasal obstruction for a mean of 28.5 years (group 1). The results were compared to those of 19 vasectomy patients with obstruction for a mean of 8.2 years (group 2). RESULTS: There were significantly fewer total germ cells per tubular cross section in group 1 than in group 2 (p < 0.05). There was a significant negative correlation between the duration of obstruction and total germ cells per tubule (r = -0.389, p < 0.03, 34 patients). The tubular diameter was significantly larger in group 2 than in group 1 (p < 0.01). CONCLUSIONS: Patients with vas deferens obstruction caused by childhood inguinal herniorrhaphy have decreased spermatogenesis compared to post-vasectomy patients, probably due to the longer obstruction period.

Adult↗
PubMed1995

Direct evaluation of stereoselectivity of cancer esterases by polyacrylamide gel electrophoresis coupled with activity staining with chiral naphthyl esters.

Both enantiomers of alpha-naphthyl 2-phenylpropanoate (PhPr(ONap)), N-acetylalaninate (AcAla(ONap)), N-methoxycarbonylalaninate (MocAla(ONap)), N-methoxycarbonylvalinate (MocVal(ONap)), N-acetylprolinate (AcPro(ONap)), and N-(trifluoroacetyl)prolinate (TfaPro(ONap)) were prepared and used with Fast Blue RR salt for activity staining of esterases separated by polyacrylamide gel electrophoresis. Comparison of the band thicknesses stained with each enantiomer indicates stereoselectivity of the major esterase in that band. Several esterases in normal rat liver, rat hepatoma-derived cells, and mouse B16 melanoma showed alteration or inversion of stereoselectivity by the substrate change from MocAla(ONap) to MocVal(ONap) or from AcPro(ONap) to TfaPro(ONap). The stereoselectivity of the major esterases for MocVal(ONap) was reversed between the murine liver and the B16 melanoma enzymes. The present staining with chiral naphthyl esters is very effective for surveying rapidly the stereoselectivity of animal tissue and cancer esterases.

Animals↗
PubMed1995

Difference between cancer cells and the corresponding normal tissue in view of stereoselective hydrolysis of synthetic esters.

This study has aimed at taking information necessary for design of anticancer prodrugs modified with chiral acyl group, especially about the effect of chirality of the acyl group on its enzymic removal in specific cells. Thus, 13 species of chiral esters were synthesized and stereoselectivity in their enzymic hydrolysis was investigated with six cancer cell lines, solid tumors, and the corresponding normal tissues. Cultured cancer cells from rat liver, pancreas, and muscle hydrolyzed the R enantiomer of (+/-)-ethyl 2-methoxy-2-phenylacetate (3c) more preferentially than its antipode, whereas this stereoselectivity was reversed in the reaction by homogenate of the corresponding normal tissue of rat. The difference in stereoselectivity between cancer cells and normal tissue was also found in the hydrolysis of other esters including those of actual anticancer agents, p-hydroxyaniline mustard and 5-fluorouridine. The investigation was expanded to real tumor to show that the degree of stereoselectivity or the hydrolytic activity was significantly different between a human brain tumor and its surrounding normal tissue for such substrates as (+/-)-ethyl 2-phenoxypropanoate and N-trifluoroacetylphenylalaninate. The esterases of rat liver cancer cells (Anr4) and normal rat liver gave different band patterns in active staining after gel electrophoresis. The enzymes were fractionated by ion exchange column chromatography and then tested on their stereoselectivity against (+/-)-3c. Comparison of the results and electrophoretograms of the fractions suggests that esterases with different stereoselectivity are expressed in different ways by normal and cancer cells. These results show that stereoselectivity in enzymic hydrolysis of some synthetic chiral esters is different between cancer and normal cells, leading to the possibility that specific activation of ester-type anticancer prodrugs in cancer cells would be controlled by the chiral structure of the acyl group.

Animals↗
PubMed1995

Stereoselective hydrolysis of xenobiotic esters by different cell lines from rat liver and hepatoma and its application to chiral prodrugs for designated growth suppression of cancer cells.

Stereoselectivity in the hydrolysis of racemic ethyl 2-phenylacetate derivatives by cultured cells of noncancerous cell lines from rat liver (BRL, BRL 3A, Clone 9, and ARLJ301-3), spontaneously or oncogene transformed rat liver cell lines (ARLJ301-3TR1, Anr4, Anr9-1, and Anr13-1), and cancer cell lines from rat hepatoma (H4-II-E, McARH7777, and MH1C1) and sarcoma (XC) was studied. A strong (R)-enantiomer preference was found in the hydrolysis of ethyl 2-hydroxy-(2c) and 2-methoxy-2-phenylacetate (3c) by the noncancerous and oncogene-transformed cells and an (S)-enantiomer preference for ethyl N-acylphenylalaninates with all the present cell lines. These inclinations were, however, not recognized with ethyl 2-methoxy-2-phenylpropanoate and ethyl N-difluoroacetyl- or N-trifluoroacetylphenylalaninate. Moreover, the R preference for 3c was reversed in the reaction by hepatoma cells. Thus, the stereoselectivity is influenced by both structure of acyl group and species of cell lines. The hepatoma cells were considerably different from the noncancerous or oncogene-transformed cells in stereoselectivity. This fact was consistent with the order of colony formation in soft agar cultures (index of malignancy) and the resemblance in actively stained esterase patterns in gel electrophoresis. The stereoselective hydrolysis leads to cell-specific activation of anticancer prodrugs. This has been confirmed for the first time by the stereoselectivity of Anr4 and H4-II-E cells in the hydrolysis of a chiral mustard ester, bis(2-chloroethyl)aminophenyl 2-methoxy-2-phenylacetate (14) and by the difference of IC50 values of (R)- and (S)-14 against the two cell lines.

Agar↗
PubMed1995

Subdivision-specific expression of ZIF268 in the hippocampal formation of the macaque monkey.

The hippocampal formation consists of the dentate gyrus, the hippocampus proper, the subicular complex and the entorhinal cortex. This structure is a major component of the medial temporal lobe, which is essential for memory formation. We investigated the expression of Zif268, a transcription factor regulated by physiological synaptic activity, in the monkey hippocampal formation. Immunoprecipitation with an anti-Zif268 antibody identified monkey Zif268 as an 86,000 molecular weight protein. In the subicular complex, the majority of neurons in the presubiculum were intensely immunopositive for Zif268 when stained with this antibody. A moderate number of Zif268-immunopositive neurons were located in the parasubiculum and the number of these neurons in the subiculum proper was smallest among the three subicular subdivisions. In the entorhinal cortex, layer- and subdivision-specific expression of Zif268 was observed. The rostral part of the entorhinal cortex contained many Zif268-immunopositive neurons in layer II, but immunopositive neurons were only sparsely present in deeper layers. By contrast, the caudal part of the entorhinal cortex contained many Zif268-immunopositive neurons in layer VI and a smaller number of those neurons in layer II. In the dentate gyrus, a few granule cells expressed Zif268. The hippocampus proper contained weakly immunostained neurons in CA1-CA3. No glial cells were immunostained by the anti-Zif268 antibody. Fos and Fos-related antigens were expressed only at very low levels in the examined areas. This study is the first report discussing the expression of immediate early genes in the primate hippocampal formation. Many Zif268-expressing neurons were observed in the presubiculum and layer II of the rostral part of the entorhinal cortex. These subdivision-specific patterns of Zif268 expression may reflect differences in synaptic activities in these regions.

Animals↗
PubMed1995

Protective effect of rifampicin against acute liver injury induced by carbon tetrachloride in mice.

Rifampicin conferred significant protection against carbon tetrachloride (CCl4)-induced liver injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were not markedly altered and only hepatocellular fatty degeneration was found in mice pretreated with rifampicin (200 mg/kg), whereas severe centrilobular necrosis was observed and serum ALT and AST activities were as high as 281 and 271 I.U./l, respectively, in the control group following administration of CCl4 (400 microliters/kg). The contents and activities of microsomal drug-metabolizing enzymes in rifampicin-pretreated animals were also much higher than those of the controls. CCl4-mediated malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CCl4 catalyzed by P-450 2E1 to produce free radicals. However, MDA formation was obviously depressed by rifampicin at varying concentrations from 2 to 32 x 10(-6) M in an in vitro cytochrome P-450 (P-450) enzyme system. On the other hand, NADPH oxidation in the metabolism of CCl4 and aniline hydroxylation were not suppressed in the presence of rifampicin in this systems, suggesting that rifampicin did not influence the biotransformation of CCl4 by P-450 2E1 in vitro. Therefore, the protective effect of rifampicin against CCl4 hepatotoxicity appeared to result from the direct inhibition of lipid peroxidation generated by CCl4-derived free radicals.

Animals↗
PubMed1994

A low prevalence of anti-hepatitis C virus antibody in patients with hepatocellular carcinoma in Guangxi Province, southern China.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in southern China, including Guangxi Province, is among the highest in the world. Investigations of the etiology of HCC in this area have focused on hepatitis B virus (HBV) and aflatoxin. However, hepatitis C virus (HCV) has been shown to be a possible pathogenic agent for HCC in a number of countries. METHODS: Antibodies to HCV (anti-HCV), determined by second-generation enzyme immunoassay, and hepatitis B surface antigen (HBsAg) were assayed in the sera of 186 patients with HCC and 48 healthy control subjects from Guangxi Province in southern China. RESULTS: HBsAg was detected in 131 (70.4%) of 186 patients with HCC, whereas only 10 (5.4%) patients were found to be positive for anti-HCV. The prevalence of anti-HCV in patients with HBsAg-positive HCC was 6.9% (9 of 131) and that in patients with HBsAg-negative HCC was 1.8% (1 of 55); there was no significant difference between these two groups. Anti-HCV was not detected in any of the healthy control subjects, in whom the prevalence of HBsAg was 10.4% (5 of 48). CONCLUSIONS: These findings indicate that HCV does not seem to play an important role in the development of HCC in Guangxi Province; however, HBV infection appears to be a major pathogenic factor for HCC in this area.

Adult↗
PubMed1994

A novel in vitro assay system for transendothelial tumor cell invasion: significance of E-selectin and alpha 3 integrin in the transendothelial invasion by HT1080 fibrosarcoma cells.

The interaction of tumor cells with endothelial cells is a key event in tumor metastasis. We established an in vitro invasion assay system, in which the invasion of tumor cells after interaction with endothelial cells can be examined. Two chamber culture wells separated by porous membrane were used. Human umbilical vein endothelial cells (HUVEC) were placed on porous membranes coated with matrix components. The invasion by HT1080 fibrosarcoma cells was determined in this system by counting the number of cells that moved through the membranes from upper to lower chambers. HUVEC cells did not migrate through the membranes as judged by the staining with UEA-I. Observation by scanning electron microscopy revealed that HT1080 cells bound to HUVEC surfaces and migrated underneath the HUVEC monolayer. Effects of antibodies specific for cell surface adhesion molecules on the migration of HT1080 cells were examined. Invasion of uncoated membranes and membranes coated with HUVEC cells was compared. Antibody against E-selectin significantly suppressed an increase of HT1080 cell invasion of HUVEC monolayers stimulated by IL-1 beta or TNF alpha. Antibody against integrin alpha 3 subunit remarkably inhibited the invasion of HUVEC cell-coated membranes, suggesting that integrins with the alpha 3 subunit may play an important role in the transendothelial invasion by HT1080 cells.

Cell Adhesion Molecules↗
PubMed1994

[Interferon-associated retinopathy].

During interferon (IFN) treatment for chronic hepatitis C, retinopathy develops in about one half of the patients. This "IFN-associated retinopathy" is characterized by cotton-wool spots (ischemic lesions) and superficial hemorrhage around the optic disc. It usually occurs 1 to 3 months after initiation of IFN therapy. Most of the patients with retinopathy have no symptoms, while some complain of impairment of visual acuity or flying specks. IFN-associated retinopathy tends to improve without any ophthalmic treatment and IFN therapy can be continued under careful observation. A complication of diabetes mellitus or a decrease in platelet count during IFN treatment may aggravate IFN-associated retinopathy. We emphasize that careful ophthalmologic follow-up is needed for all patients under IFN therapy.

Adult↗
PubMed1994

[Comparison of treatment results of prostatic cancer between radical prostatectomy and radiation therapy].

Between 1982 and 1990, 55 patients with prostate cancer (clinical stage A2-C) underwent pelvic lymphadenectomy at the Public Toyooka Hospital. The patients were subsequently treated either by radical prostatectomy (36 cases) or external radiation therapy (19 cases). The age of the patients varied from 56 to 85 (Mean 73.1). The outcome of the 46 patients with negative lymph node (prostatectomy 31, radiation 15) were compared. The 10-year disease-specific survival rates were 100% for the patients treated by prostatectomy and 78% for those treated by radiation (P = 0.035). The 5-year progression-free survival rates for the prostatectomy group and radiation group were 97% and 56%, respectively (P = 0.013). Among the radiation groups, patients with well differentiated carcinoma showed a lower progression rate as compared to those with moderately or poorly differentiated carcinoma (5-year progression-free survival, 81 vs 20%, P = 0.094). The outcome of the 9 patients with positive lymph node (prostatectomy 5, radiation 4) was not satisfactory because of the high progression rates in the two groups (5 year progression-free survival, 30% in prostatectomy and 25% in radiation group).

Aged↗
PubMed1994

Hepatitis B virus carrier with low titer of antibody to hepatitis B core antigen.

Of 798 hepatitis B virus (HBV) carriers, 22 had low titers (lower than 80% inhibition in 200- or 400-fold diluted serum) of antibody to hepatitis B core antigen (anti-HBc). Among these 22 patients, there were 12 (1.50%) with viremia who were positive for hepatitis B e antigen and had a high titer of HBV-associated DNA polymerase activity. Among these 12 patients, four showed no significant change in the anti-HBc titer, while four others showed significant increases in the anti-HBc titer during the follow-up periods. The former all remained asymptomatic carriers (ASCs), while the latter all developed chronic hepatitis (CH). The liver histology of four patients (ASC: 2, CH: 2) showed mild inflammation, and the localization of hepatitis B core antigen (HBcAg) in the liver specimens showed a nuclear pattern in the two ASCs, but a nuclear plus cytoplasmic pattern in the two CH cases. In HBV carriers, the increase in anti-HBc titer seems to be closely correlated to the change in HBcAg localization from the nucleus to the cytoplasm in the liver. Therefore, rising titers of anti-HBc were assumed to be associated with increased expression of HBcAg on the hepatocyte, and hence increased immune-mediated hepatic damage and the onset of hepatitis in ASC with low titer of anti-HBc.

Adolescent↗
PubMed1994

[Clinical and statistical studies on prostatic cancer: prognostic value of clinical stage, Gleason score and age].

We assessed the outcome of 200 patients with prostatic cancer treated at the Public Toyooka Hospital from 1980 to 1989. The patient's age varied from 53 to 94 years (mean 76.8). Overall actuarial survival rate at 5 and 10 years were 52% and 25%, respectively. The 5-year survival according to clinical stage was 69% for stage A, 66% for stage B, 43% for stage C and 32% for stage D disease. A significant difference was noted between the survival of patients with stage A or B and those with stage C or D. Patients with Gleason score of less than 7 showed significantly better survival as compared to those with Gleason score of 7 or more (5-year survival, 64% vs 33%). No significant difference was observed between the survival of patients under the age of 75 and those 75 or older.

Age Factors↗