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Biomedical subjects

M Oka

Publications and source records attributed to M Oka.

At least 91 records · Page 5Linked to original sources
PubMed2001

Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions.

Pulmonary veins show greater sensitivity to endothelin (ET)-1-induced vasoconstriction than pulmonary arteries, and remodeling was observed in pulmonary veins under hypoxic conditions. We examined, using an immunohistochemical method, the expression of Big ET-1, ET-converting enzyme (ECE), and ET(A) and ET(B) receptors in rat pulmonary veins under normoxic and hypoxic conditions. In control rats, Big ET-1 and ECE were coexpressed in the intima and media of the pulmonary veins, with an even distribution along the axial pathway. ET(A) and ET(B) receptors were expressed in the pulmonary veins, with a predominant distribution in the proximal segments. The expression of Big ET-1 was more abundant in the pulmonary veins than in the pulmonary arteries. After exposure to hypoxia for 7 or 14 days, the expression of Big ET-1, ECE, and ET receptors increased in small pulmonary veins. Increases in the medial thickness, wall thickness, and immunoreactivity for alpha-smooth muscle actin were also observed in the small pulmonary veins under hypoxic conditions. The upregulation of ET-1 and ET receptors in the small pulmonary veins is associated with vascular remodeling, which may lead to the development of hypoxic pulmonary hypertension.

Actins↗
PubMed2001

Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery.

Since pulmonary vasculature is complex in terms of regional difference in structure and function, it is important to understand the site of endothelin (ET) synthesis and the distribution of the ET system along the axial pathways of pulmonary artery. The expression of big ET-1, ET converting enzyme (ECE) and ET(A) receptors were examined in rat pulmonary arteries under normal and hypoxic conditions using an immunohistochemical method and Northern blot analysis. In normal conditions, big ET-1 was expressed in the intima and media of pulmonary arteries with a predominant distribution in the distal segments and a preferential localization in the media, while ETA receptors were dominantly expressed in the proximal segments. ECE was constitutively expressed in the intima and media. Following exposure to hypoxia, messenger ribonucleic acid (mRNA) expression of ET-1 and ET(A) receptors were up-regulated by two-fold and immunoreactivities for big ET-1, ECE, and ET(A) receptors significantly increased by two to five-fold in the distal segments. Smooth muscle cells are an important source of endothelin-1 in the pulmonary artery. The distribution of big endothelin-1 and endothelin A receptors in pulmonary arteries was discrepant in normal conditions while their expression concomitantly increased in the distal segments in hypoxic conditions. This heterogeneity may play an important role in the regulation of pulmonary vascular tone.

Animals↗
PubMed2001

Expression of a small heat shock protein 27 (HSP27) in mouse skin tumors induced by UVB-irradiation.

We investigated the expression of heat shock protein 27 (HSP27) at intermediate stages of a cutaneous tumor induced by UVB-irradiation stress (290-380 nm, max. 312 nm) using an immunostaining method. After 15-20 weeks of chronic exposure to UVB irradiation at a dose of 2 kJ/m2, HSP27 was found in the upper cell layers of bowenoid multilayers of epidermis, in areas of the lesions where normal stratification seems to be conserved. After 25 weeks, HSP27 was weakly expressed in squamous cell carcinoma (SCC). The HSP27 distribution patterns during cutaneous tumor progression resemble that of cytokeratin 10, a differentiation marker in keratinocytes. In SCC, a low degree of HSP27 expression was detected in the well-differentiated carcinomatous areas, but not in the poorly differentiated areas. These results indicate that the level of HSP27 decreases significantly as epithelial carcinoma growth progresses upon UVB-exposure. The expression of HSP27 may be associated with the onset of skin keratinocyte differentiation, but not with progression of SCC.

Animals↗
PubMed2001

Synthesis and anti-influenza virus activity of tricyclic compounds with a unique amine moiety.

Several novel tricyclic compounds with a unique amine moiety (1, 2a--i) were designed and prepared based on the structure of triperiden for the development of anti-influenza virus agents. An in vitro antiviral assay showed that 1-(1-azabicyclo[3.3.0]octan-5-yl)-1-(4-fluorophenyl)-1-(2-tricyclo[3.3.1.1(3.7)]decyl)methan-1-ol hydrochloride (2f) has a potent anti-influenza A virus activity. Furthermore, since 2f was well tolerated in mice, 2f is promising as a novel anti-influenza virus agent for humans.

Animals↗
PubMed2001

A solitary bronchial papilloma with malignant changes.

We describe a case of solitary papilloma of the bronchus and provide a review of 38 similar cases reported in Japan. A 70-year-old man complained of cough and sputum. Chest X-rays and CT scans revealed atelectasis of the right middle lobe. On bronchoscopy, a polypoid tumor was found at the orifice of the bronchus of the right middle lobe. The tumor was histologically diagnosed as a squamous papilloma with moderate atypia. Because of elevated tumor markers and the reported high incidence of malignant changes in papillomas, the tumor was endoscopically resected by electrosurgical snare. While this procedure resulted in improvement of atelectasis, the chest CT taken subsequently revealed a mass adjacent to the resected polypoid tumor in the middle lobe bronchus. Percutaneous needle biopsy followed by histopathological examination confirmed the tumor to be a squamous cell carcinoma. Only three cases of malignant changes in papillomas have been previously reported in Japan. Electrosurgical snare, which allows the identification of tissue at the tumor base, should be the treatment of choice rather than YAG laser surgery.

Aged↗
PubMed2001

NADH-dependent dehydroascorbate reductase in the rabbit lens.

The present investigation demonstrates the existence of NADH-dependent dehydroascorbate (DHA) reductase activity in the soluble fraction of the rabbit lens. This DHA reductase was specific for NADH, and its apparent Km values for DHA and NADH were 5.7 mM and 4.0 microM, respectively. In a gel filtration of the lens soluble fraction on a Sephadex G-75 superfine column, the NADH-dependent DHA reductase activity was eluted at the oligomeric betaL1-crystallin fraction, which may also contain lambda-crystallin (a rabbit-specific crystallin). Furthermore, about 80% of protein fractions separated from the betaL1-crystallin fraction by DEAE-cellulose ion-exchange column chromatography exhibited DHA reductase activity. In the SDS-PAGE analysis of the protein fractions with DHA reductase activity, 32-33, 27 and 25 kDa protein subunits were commonly identified. These results suggest that oligomers of beta-crystallin and/or lambda-crystallin subunits may be associated with the DHA reductase activity. The present paper also discusses that the function of the reductase may be to enhance the antiphotoxidation capacity of the lens.

Animals↗
PubMed2001

[Local therapy for stage IV advanced breast cancer with brain metastasis].

A 55-year-old female patient was diagnosed with right breast cancer with brain metastasis of 3 cm in size. Neurological examination revealed paralysis in the left upper and lower extremities. Chemotherapy and hormone therapy were performed. Brachytherapy by Cyberknife was performed for the brain metastatic lesion. As a result, the brain metastatic lesion decreased in size to 1 cm on the CT-scan after 2 months. The paralysis disappeared and the patient's QOL improved. Cyberknife therapy was useful for a brain metastatic lesion that harmed the patient's QOL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Examination of eye position after strabismus surgery in Kawasaki Medical School Hospital].

PURPOSE: To examine the factors which affect changes in the position of the eyes following the strabismus surgery. METHODS: The postoperative position of 240 eyes with concomitant strabismus was examined. The factors which seemed to have an effect on the position of the eyes were enumerated, and a logistic regression analysis of the results was done. RESULTS: In comparison with esotropia, in exotropia the eyes showed a tendency to return gradually to a normal position. There was no remarkable improvement in stereoscopic vision following strabismus surgery. Based on the standards of the Japanese Association of Strabismus and Amblyopia [the cure standard for strabismus], the results of strabismus surgery were as follows: Grade 1(cosmetically satisfactory) was mainly observed for esotropia, and Grade 3(good) for exotropia. The factors which had a significant effect on the postoperative position of the eyes were as follows: esotropia amblyopia, muscle movement, and operative methods; exotropia: retinal correspondence, operative methods, and the necessity of inferior oblique muscle surgery. CONCLUSIONS: There was little correction of the position of the eyes. In individual cases, the factors which affect position of eyes were examined, and it was considered necessary to increase the amount of correction. Age is a factor which has an effect, but the effect on esotropia and exotropia is small.

Adolescent↗
PubMed2000

Determination and bioimaging method for nitric oxide in biological specimens by diaminofluorescein fluorometry.

A simple and sensitive assay and a cellular bioimaging method for nitric oxide (NO) were developed using a novel diaminofluorescein DAF-FM and its diacetate. DAF-FM is converted via an NO-specific mechanism to an intensely fluorescent triazole derivative. For the measurement of NO, the triazole derivative of DAF-FM was determined by reversed-phase high-performance liquid chromatography with fluorescence detection. In the presence of 1 microM DAF-FM, the concentrations of NOR-1, an NO donor, in the range of 2-200 nM were linearly related to the fluorescence intensity. This sensitive NO assay enabled us to detect the spontaneous and substance P-induced NO release from isolated porcine coronary arteries, both of which were dependent entirely on the NO synthase activity in vascular endothelial cells. We also obtained fluorescence images of cultured smooth muscle cells of the rat urinary bladder after loading with DAF-FM diacetate. In the cells pretreated with cytokines, the fluorescence intensity increased with time after DAF-FM loading. This increase in the fluorescence intensity was blocked by prior treatment of the muscle cells with an NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester. Therefore, the present novel diaminofluorescein fluorometry should be useful not only for sensitive NO assay, but also for NO imaging in a variety of biological specimens.

Animals↗
PubMed2000

Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;6).

Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recognition motifs of Translin, a protein that associates with chromosomal translocations of lymphoid neoplasms. We further extended our search for Translin binding motifs in sequences adjacent to breakpoints and investigated whether Translin binds to these sequences in vitro by mobility-shift assay. Computer-assisted search found sequences highly homologous (>70%) with Translin binding motifs adjacent to the breakpoints in 10 out of 11 liposarcomas with the TLS-CHOP fusion genes. All of 13 oligonucleotides corresponding to the putative binding sequences in these cases bind to Hela cell extract and also recombinant Translin protein, although the binding affinity of each motif showed considerable differences. The DNA-protein complex formation was inhibited by non-labeled competitor or anti-Translin antibody, suggesting the specificity of the complex formation. Considering the high incidence and specific binding property, the presence of Translin binding motif may be one of the important determinants for the location of breakpoints in the TLS and CHOP genes in liposarcomas.

Binding Sites↗
PubMed2000

Ascorbate Free Radical Reductase Activity in Vertebrate Lenses of Some Species.

Purpose: To clarify the function of ascorbate free radical (AFR) reductase in the lens antioxidation mechanism, we investigated the difference among species in AFR reductase activity in different vertebrate lenses.Materials and Methods: Soluble and insoluble fractions were prepared from the lenses of frogs, guinea pigs, rats, rabbits, pigs, and calves. AFR reductase and diaphorase activity of each fraction was determined.Results: AFR reductase activity in the lens soluble fraction was the highest in frogs. That of guinea pigs and rabbits was at the next level; there was only a little activity in rats and pigs, and none was detected in calves. Membrane-bound AFR reductase in the lens insoluble fraction was extracted by 0.3% Triton X-100. The membrane-bound enzyme activity was almost at the same level in frogs, rats, rabbits, and calves, and a little higher in guinea pigs and pigs. However, such species-specificity of AFR reductase activity as in the soluble fraction was not observed in 0.3% Triton X-100 extracts. Diaphorase activity was 3 to 9 times as much as AFR reductase activity in the soluble fractions of frogs, guinea pigs, and rabbits, but in 0.3% Triton X-100 extracts of all vertebrate species used, it was very high, 108 to 311 times the AFR reductase activity.Conclusion: These results suggest that the lens soluble and membrane-bound AFR reductases are individual enzyme molecules and have different anti-oxidative functions. The lenses of frogs, guinea pigs, and rabbits contain a near-ultraviolet (UV) light absorbing compound, reduced pyridine nucleotide at a high concentration. Therefore, the soluble AFR reductase activity may be high in the vertebrate lenses with a near-UV light filter, and enhance the antiphotoxidation of ascorbic acid.

Journal Article↗
PubMed2000

Involvement of Na+ and Ca2+ channel activation and resultant nitric oxide synthesis in glutamate-mediated hypoxic injury in rat cerebrocortical slices.

The role of Na+ and Ca2+ channels in glutamate-mediated hypoxic injury was investigated in slices of the rat cerebral cortex. Hypoxic injury was determined by mitochondrial reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyltetrazolium bromide after exposure of brain slices to 30-min of hypoxia/glucose deprivation followed by 3-h of reoxygenation. Endogenous glutamate release was markedly elevated during hypoxia/glucose deprivation, but it returned almost to basal level during reoxygenation. Hypoxic injury was prevented by MK-801 or 6-cyano-7-nitroquinoxaline-2,3-dione. Combined treatment with omega-conotoxin GVIA, omega-agatoxin IVA, and tetrodotoxin reversed the hypoxic injury, although none of these agents alone or nifedipine was effective. Moreover, a novel Na+/Ca2+ channel blocker NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride] significantly inhibited the hypoxic injury. Several inhibitors of nitric oxide synthase also blocked the hypoxic injury. Consistently, nitric oxide synthesis, as estimated from cyclic GMP formation in the extracellular fluids, was enhanced during hypoxia/glucose deprivation. NS-7 and other Na+ and Ca2+ channel blockers suppressed the enhancement of nitric oxide synthesis, although these compounds alone, or in combination, did not reduce hypoxic glutamate release. These findings suggest that hypoxic injury in rat cerebrocortical slices is triggered by glutamate and subsequent enhancement of nitric oxide synthesis through activation of both Na+ and Ca2+ channels. Thus, the simultaneous blockade of both Na+ channel as well as N-type and P/Q-type Ca2+ channels is required to sufficiently reverse the hypoxic injury.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6.

Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.

Administration, Oral↗
PubMed2000

A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2', 5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide (Fidarestat): its absolute configuration and interactions with the aldose reductase by X-ray crystallography.

The absolute configuration of the aldose reductase (AR) inhibitor, (+)-(2S,4S)-6-fluoro-2',5'-dioxospiro¿chroman-4, 4'-imidazolidine-2-carboxamide (fidarestat), was established indirectly by single-crystal X-ray analysis of (+)-(2S, 4S)-8-bromo-6-fluoro-2',5'-dioxospiro¿chroman-4, 4'-imidazolidine-2-carboxylic acid (1). The crystal structure of human AR complexed with fidarestat was determined, and the specific inhibition activity was discussed on the basis of the three-dimensional interactions between them. The structure clarified that fidarestat was located in the active site by hydrophilic and hydrophobic interactions and that the carbamoyl group of fidarestat was a very effective substituent for affinity to AR and for selectivity between AR and aldehyde reductase (AHR). Explanations for the differences between the observed activities of fidarestat and its stereoisomer 2 were suggested by computer modeling.

Aldehyde Reductase↗
PubMed2000

Effects of androgens on telomerase activity in normal and malignant prostate cells in vitro.

BACKGROUND: Recent studies have shown that sex hormones regulate telomerase activity in endometrium and breast tissues. The present study was designed to clarify the effects of androgen on telomerase activity in normal and malignant prostate cells. METHODS: Androgen-sensitive (LNCaP) and -independent (TSU-Pr1 and DU145) prostate cancer cell lines and normal prostate cells including basal cells were cultured in the presence or absence of 5alpha-dihydrotestosterone (DHT). RESULTS: Prostate cancer cell lines exhibited high telomerase activity, and normal prostate cells showed low activity. Short or prolonged androgen-deprivation reduced telomerase activity in LNCaP cells, and DHT induced telomerase activity at the G(1) phase of the cell cycle. DHT did not modulate telomerase activity in TSU-Pr1, DU145, and normal cells. CONCLUSIONS: LNCaP cells had an androgen-dependent pathway to activate telomerase, whereas TSU-Pr1 and DU145 cells as well as normal prostate cells had an androgen-independent pathway. These findings suggest that the regulatory mechanism of telomerase varies during the progression of prostate cancers.

Androgens↗
PubMed2000

Involvement of peroxynitrite and hydroxyradical generated from nitric oxide in hypoxia/reoxygenation injury in rat cerebrocortical slices.

The changes in nitric oxide (NO) formation during hypoxia and reoxygenation were measured in slices of rat cerebral cortex, and the possible involvement of NO and its decomposition products, including peroxynitrite and hydroxyradical, in the hypoxia/reoxygenation injury was subsequently investigated. NO formation estimated from cGMP accumulation in the extracellular fluids was enhanced during hypoxia and to a lesser extent in the reoxygenation period. The mRNA for inducible NO synthase (NOS) was detected 3-5 h after reoxygenation, although neuronal NOS mRNA decreased after reoxygenation. Several NOS inhibitors such as N(G)-monomethyl-L-arginine and N(G)-nitro-L-arginine blocked not only the NO formation but also the hypoxia/reoxygenation injury as determined by lactate dehydrogenase (LDH) leakage. The hypoxia/reoxygenation injury was prevented by peroxynitrite scavengers including deferoxamine and uric acid, or several hydroxyradical scavengers such as dimethylthiourea, 2-mercaptopropionylglycine and D(-) mannitol. In addition, the hypoxia/reoxygenation injury was attenuated by poly(ADP-ribose)synthetase inhibitors such as banzamide, 3-aminobenzamide and 1,5-isoquinolinediol. On the other hand, both N-morpholinosidnonimine, a peroxynitrite generator, and hydroxyradical-liberating solution containing FeCl(3)-ADP and dihydroxyfumarate caused a marked LDH leakage in normoxic slices. These findings suggest that the enhanced formation of NO causes hypoxia/reoxygenation injury after degradation to peroxynitrite and hydroxyradical and the resultant activation of poly(ADP-ribose)synthetase.

Adenosine Triphosphate↗