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Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 91 records · Page 5Linked to original sources

Twin pregnancy consisting of 46, XY heterozygous complete mole coexisting with a live fetus.

Complete hydatidiform mole and coexistent fetus (CMCF) is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic diseases. The aim of this study was to reveal a potential risk factor and to determine optimum management of CMCF cases. Molar tissues are cytogenetically divided into two types, homozygous and heterozygous. The molar tissue of our case showed a 46, XY heterozygous complete mole. Genomic DNA was analyzed by the polymerase chain reaction using sets of unlabelled forward and Cy-5-labelled reverse primers for DNA marker loci. The patient developed persistent trophoblastic disease (PTD) with lung metastasis. Since 1980 there have been 13 reports (including our case) that cytogenetically revealed CMCF and clarified the clinical outcome. Nine of the 16 CMCF cases before 21 weeks of gestation and seven of the 12 CMCF cases after 22 weeks of gestation developed PTD. The incidence of PTD from CMCF was not related to the gestational age at termination or delivery. There were 10 case reports that analyzed the zygosity of a mole, heterozygous or homozygous. Two of six homozygous and three of four heterozygous moles in CMCF cases developed PTD. A heterozygous mole is thought to be a high risk factor for the incidence of PTD. Cytogenetic study is clinically useful for the optimum management of CMCF cases.

Adult↗

Two cases of colonic adenomatous polyps accompanied by a migrated surgical suture.

A 56-year-old man and a 70-year-old woman, with histories of left colectomy and appendectomy respectively, were admitted to our hospital. In both cases, colonoscopy showed a pedunculated colonic polyp in the ascending colon, and a silk suture became visible in the stalk during polypectomy. The histological diagnosis was adenoma. These two cases constitute the first report of colonic adenomatous polyps accompanied by suture migration.

Adenomatous Polyps↗

Preoperative evaluation of submucosal invasive colorectal cancer using a 15-MHz ultrasound miniprobe.

BACKGROUND AND STUDY AIMS: Recently, it was reported that focal submucosal invasive colorectal cancer could be treated by polypectomy or endoscopic mucosal resection (EMR) because of the rarity of lymph-node metastasis. Our objective was to examine the accuracy and efficacy of a 15-MHz ultrasound miniprobe in the preoperative evaluation of the degree of submucosal invasion in colorectal cancer. PATIENTS AND METHODS: A total of 35 patients with submucosal invasive colorectal cancer who underwent ultrasonography with a miniprobe were studied prospectively. The results of this imaging were compared with the histologic findings in resected specimens. RESULTS: Although the accuracy of the miniprobe in categorizing submucosal invasion into three subclasses (SM1, invasion limited to the upper third; SM2, limited to the middle third; SM3, limited to the lower third) was low (37.1%; 13/35), the accuracy in differentiation between < or = SMI (M and SMI) and > or = SM2 (SM2, SM3, MP, and S) was 85.7 % (30/35). CONCLUSIONS: The miniprobe can be useful for therapeutic decision-making in submucosal invasive colorectal cancer.

Adult↗

Intraductal papillary-mucinous tumors of the pancreas: differential diagnosis between benign and malignant tumors by endoscopic ultrasonography.

OBJECTIVES: Recently, intraductal papillary-mucinous tumor (IPMT) of the pancreas has increasingly been recognized. However, differential diagnosis between benign and malignant IPMT is often difficult using conventional imaging modalities. The purpose of this study was to retrospectively investigate the value of endoscopic ultrasonography (EUS) for differentiating malignant from benign IPMT. METHODS: A total of 51 patients with IPMT were preoperatively examined by EUS. The endosonograhic findings were compared with histopathological findings of the resected specimens. RESULTS: In main duct type IPMT, the diameter of the main pancreatic duct (MPD) was > or =10 mm in seven of the eight malignant tumors, compared with two of the seven benign tumors (p < 0.05). In branch duct type IPMT, three of the four large tumors (>40 mm) with irregular thick septa were malignant lesions. In both main duct type IPMT and branch duct IPMT, eight patients had large mural nodules (>10 mm); seven of the eight tumors were malignant and one of the eight tumors was benign. When the tumor was diagnosed as malignant according to above three findings, EUS was able to differentiate between malignant and benign IPMT with an accuracy of 86%. CONCLUSIONS: Main duct type tumors with > or =10 mm dilated MPD, branch duct type tumors (>40 mm) with irregular septa, and large mural nodules (>10 mm) strongly suggest malignancy on EUS. EUS would be a useful modality for differentiating between benign and malignant IPMT.

Adenocarcinoma, Mucinous↗

Inhibition of methanogens increases photo-dependent nitrogenase activities in anoxic paddy soil amended with rice straw.

The interaction between phototrophic dinitrogen fixers and methanogens was examined in soil slurries amended with rice straw using 2-bromoethanesulfonic acid (BES), a specific methanogenic inhibitor. Slurries incubated in light increased phototrophic nitrogenase activity (acetylene reducing activity), and showed growth of phototrophic purple bacteria and reduction of CH(4) emission, indicating outcompetition of purple bacteria with methanogens in photic zones. Adding BES effectively inhibited methane production and markedly increased phototrophic acetylene reducing activity accompanied with acetate accumulation, but did not affect populations of purple bacteria in the slurries. More acetate accumulated in the inhibited slurries incubated in dark. We suggest that increased availability of organic substrates for purple bacteria after stopping methanogenic consumption by BES caused the increased phototrophic acetylene reducing activity. These results indicate that, after purple bacteria grow enough, performance of their N(2) fixation may be limited by substrate availability, which methanogenesis may profoundly influence.

Journal Article↗

Involvement of adenosine in vascular contractile preconditioning.

Measurements of isometric tensions of rat aortic rings revealed the fact that when aortic rings with intact endothelium were precontracted (preconditioned) for 20 min by the alpha1-adrenergic agonist phenylephrine (10 microM), the tonic level of subsequent contraction by the same agonist was depressed and/or declined regardless of the presence or absence of endothelium during the second contraction. The removal of endothelium before preconditioning showed no such phenomenon. With the use of specific blockers, involvements of adenosine or of ATP-sensitive K+ (K(ATP)) channels during preconditioning or second contraction, respectively, were evaluated. Actions of nitric oxide synthase, cyclooxygenase, P(2) ATP purinoceptors, or K(ATP) channels during preconditioning appear not to be involved. Exogenous adenosine (up to 100 microM) without endothelium could mimic the preconditioning; however, contractile preconditioning by phenylephrine, mechanical stretching, or activation of protein kinase C needed to be done. The release of adenosine and adenine nucleotides from aortic rings was augmented by phenylephrine or by mechanical stretching of the rings with intact endothelium. Our results suggest that during vasocontraction, endothelium-derived adenosine acquires an ability to protect vascular tone against subsequent repeated contractions by mediating a delayed, possibly indirect, opening of K(ATP) channels.

Adenine Nucleotides↗

Roles of superoxide dismutase in rat mast cell granules.

BACKGROUND: It has been suggested that in the granules of rat mast cells there is some kind of superoxide dismutase (SOD), but details of this SOD in mast cells remain unclear. In the present study, we studied the mode of existence of SOD in mast cells and its releasing mechanism from the granules. In addition, we discussed the physiological role of SOD in allergic events. METHODS: Purified rat mast cells were disrupted with a sonic disrupter and granules (sample I) were separated from supernatant (sample II) by centrifugation. The granules were treated with 1 mM Ca(2+), and the supernatant (sample III) was separated from the pellet (sample IV). Sample III was applied to a heparin column and the eluate was used as sample V. SOD activity was measured in these samples. RESULTS: SOD existed in mast cell granules as a heparin-binding and an inactive form. However, when granules were released and exposed to high Ca(2+) concentration, SOD was discharged from heparin and shifted to the active form. The expression of macrophage inflammatory protein-1 alpha mRNA was enhanced when hydrogen peroxide (H(2)O(2)) or sample III with the xanthine-xanthine oxidase system were added to the culture media. CONCLUSIONS: These findings suggest that in stimulated rat mast cells, the released SOD may transform the generated superoxide anion into H(2)O(2), and the generated H(2)O(2) may enhance the expression of chemokine mRNA in the mast cells.

Animals↗

Expression and cellular localization of estrogen receptors alpha and beta in the human fetus.

Estrogens exert various biological effects by acting through their native receptors, two of which have been identified to date: estrogen receptors alpha (ERalpha) and beta (ERbeta). In this study we examined the expression and cellular localization of ERalpha and ERbeta in various human fetal tissues by semiquantitative RT-PCR (13 and 20 gestational weeks) and immunohistochemistry (13, 20, and 38 gestational weeks), respectively, to study the possible effects of estrogens on human fetal tissues during development. Relatively high levels of ERbeta expression were detected in various human fetal tissues, whereas those tissues expressing ERbeta had markedly lower levels of ERalpha expression. ERbeta messenger ribonucleic acid expression was especially high in the adrenal gland. ERbeta-immunoreactive protein was localized to the definitive zone, but not in the fetal zone, of the adrenal cortex. Although low levels of ERbeta messenger ribonucleic acid were present in the brain, heart, lung, and kidney, ERbeta immunoreactivity was not detected in these tissues. These results suggest that the effects of estrogens in these tissues are predominantly mediated through ERbeta. ERbeta immunoreactivity was detected in Sertoli cells and spermatogonia in the male reproductive tract and in germ cells in the fetal testis and epididymis. In the female reproductive tract, both ERalpha and ERbeta were immunopositive in epithelium of the oviduct. The results of the present study have demonstrated the possible sites for estrogenic action in the human fetus and suggest that the effects of estrogen via ERbeta may play important roles in human fetal development, especially in the definitive zone of the adrenal cortex, and in the reproductive tissues of the developing fetus.

Estrogen Receptor alpha↗

The analyses of 17beta-hydroxysteroid dehydrogenase isozymes in human endometrial hyperplasia and carcinoma.

Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of human endometrial adenocarcinoma. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone and thereby serve to modulate the tissue levels of bioactive E2. To elucidate the possible involvement of this enzyme in human endometrial carcinoma, we first examined the expression of 17beta-HSD type 1 and type 2 in 20 normal cycling human endometria, 36 endometrial hyperplasia, and 46 endometrial endometrioid adenocarcinoma using immunohistochemistry, and we then studied immunoreactivity of 17beta-HSD type 2 using immunoblotting analyses, the activity of 17beta-HSD type 1 and type 2 using thin-layer chromatography and their expression using RT-PCR in endometrial endometrioid adenocarcinoma. We correlated these findings with various clinicopathological parameters to examine the biological significance of 17beta-HSDs in human endometrial disorders. 17beta-HSD type 2 immunoreactivity in normal endometrium was present in all cases of secretory phase (n = 14), but not in any endometrial mucosa of proliferative phase (n = 6). In addition, 17beta-HSD type 2 immunoreactivity was detected in 27 of 36 (75%) endometrial hyperplasia and 17 of 46 (37%) carcinoma cases. 17beta-HSD type 1 immunoreactivity was not detected in all the cases examined. In both endometrial hyperplasia and carcinoma cases there were significant positive correlations between 17beta-HSD type 2 and progesterone receptor labeling index (LI). In carcinoma cases, a significant inverse correlation was detected between 17beta-HSD type 2 immunoreactivity and age. In addition, 17beta-HSD type 2 immunoreactivity was also correlated with 17beta-HSD type 2 enzymatic activity, and semiquantitative analyses of 17beta-HSD type 2 messenger RNA. No significant correlations were detected between 17beta-HSD type 2 and estrogen receptor LI, Ki67 LI, amount of aromatase messenger RNA or histological grade. These data indicated that the expression of 17beta-HSD type 2 in hyperplastic and/or neoplastic endometrium may represent altered cellular features through hyperplastic and neoplastic transformation. However, 17beta-HSD type 2 may also play some protective and/or suppressive roles toward unopposed estrogenic effects through inactivating E2 in situ, especially in premenopausal patients.

17-Hydroxysteroid Dehydrogenases↗

Inhibitory action of Oren-gedoku-to extract on enzymatic lipid peroxidation in rat liver microsomes.

We examined the inhibitory action of the extract of Oren-gedoku-to, a traditional herbal medicine known to act as an antioxidant, on enzymatic lipid peroxidation in rat liver microsomes. Simultaneous addition of a spray-dried preparation of Oren-gedoku-to extract (Tsumura TJ-15) inhibited enzymatic lipid peroxidation induced by reduced beta-nicotinamide adenine dinucleotide phosphate (NADPH) and ADP/Fe3+ complex in liver microsomes in a dose-dependent manner. When the inhibition by TJ-15 of enzymatic lipid peroxidation in liver microsomes was kinetically analyzed, this medicine showed a competitive inhibition against NADPH or ADP/Fe3+ complex. TJ-15 inhibited the NADPH-driven enzymatic reduction of ADP/Fe3+ complex or cytochrome c in liver microsomes competitively. TJ-15 enhanced NADPH consumption by liver microsomes with ADP/Fe3+ complex. Treatment with TJ-15 after the onset of enzymatic lipid peroxidation in liver microsomes inhibited the progression of lipid peroxidation in a dose-dependent manner. The present results indicate that Oren-gedoku-to extract inhibits enzymatic lipid peroxidation in rat liver microsomes in the initiation and propagation steps in a dose-dependent manner. These results also suggest that Oren-gedoku-to extract inhibits enzymatic lipid peroxidation in rat liver microsomes not only through its antioxidant action but also through reduction of the supply of electrons derived from NADPH to ADP/Fe3+ complex in liver microsomes both in a competitive manner and through stimulation of NADPH oxidation.

Adenosine Diphosphate↗

Rate and equilibrium constants for the epimerization of the endothelin receptor antagonist J-104,132 in aqueous solution.

The degradation of [5S-[5alpha,6beta,7alpha(R*)]]-2-butyl-5-(1,3-benzodioxol-5-yl)-7-[(2-carboxypropyl)-4-methoxyphenyl]-6-dihydro-5H-cyclopenta[b]pyridine-6-carboxylic acid (J-104,132) was studied in aqueous solution as a function of temperature and pH. The degradation reaction does not proceed to completion; rather, a stable equilibrium is attained in which approximately 2% of the degradate is produced. Kinetic data for the formation of the degradate are analyzed using an integrated form of the rate law for a reversible first-order reaction, and the forward and reverse rate constants and overall equilibrium constants are presented. Isolation and spectroscopic structural determination indicate that the degradate is the C7 beta-epimer of the drug. A mechanism for the epimerization reaction involving a novel enamine-like intermediate is proposed and shown to be consistent with the kinetic data. The rate and equilibrium constants are used to predict the room temperature stability of an injectable formulation of J-104,132, and these predictions are compared to actual data from long-term stability studies. It is concluded that the preformulation kinetic studies provide essential data needed for optimum drug product development.

Endothelin Receptor Antagonists↗

Transit endoscopic ultrasound of colorectal cancer using a 12 MHz catheter probe.

The objective of this study was to examine the accuracy of a 12 MHz ultrasound catheter probe in the pre-operative staging of colorectal cancer by assessing the depth of tumour infiltration and involvement of pericolonic lymph nodes. 159 patients with colorectal cancer who underwent ultrasound examination with a 12 MHz catheter probe were studied prospectively. The results of this imaging procedure were compared with the histological findings of the resected specimens. The accuracy of the 12 MHz ultrasound catheter probe for depth of invasion (T category) was 85% (131/154) for all tumours, 87% (46/53) for pT1 tumours, 60% (9/15) for pT2 tumours, 89% (74/83) for pT3 tumours and 67% (2/3) for pT4 tumours. The accuracy for tumours of the rectum and colon was 81% and 89%, respectively. The accuracy of the probe for nodal staging (N category) was 67% (76/114) overall. The sensitivity was 70% (33/47), the specificity 64% (43/67), the positive predictive value 58% (33/57) and the negative predictive value 75% (43/57). Endoscopic ultrasound using a 12 MHz catheter probe accurately assessed tumour stage, although nodal staging remained suboptimal. This method may aid in the selection of treatment for patients with colorectal cancer.

Adult↗

Immunohistochemical localization of steroidogenic enzymes in the corpus luteum and the placenta of the ribbon seal (Phoca fasciata) and steller sea lion (Eumetopias jubatus).

To study the luteal and placental function of pinnipeds, we analyzed the localization of steroidogenic enzymes (P450scc, 3 beta HSD and P450arom) in the corpus luteum and the placenta of ribbon seals (Phoca fasciata) and Steller sea lions (Eumetopias jubatus) immunohistochemically. P450scc and 3 beta HSD were present in all luteal cells of both species. Almost all of the luteal cells were immunostained for P450arom, while P450scc and 3 beta HSD were negatively immunostained in placentae and P450arom was present in the syncytiotrophoblast of placentae. These findings suggest that 1) corpora lutea of both species synthesize pregnenolone, progesterone and estrogen during the entire pregnancy period, and 2) like other terrestrial carnivores in the suborder Caniformia, placentae of both species do not have the capability for synthesizing progesterone in the latter half of active pregnancy period.

3-Hydroxysteroid Dehydrogenases↗

Immunolocalization of steroidogenic enzymes in the corpus luteum and placenta of the Japanese black bear, Ursus thibetanus japonicus, during pregnancy.

The Japanese black bear, Ursus thibetanus japonicus, is a seasonal breeder and shows delayed implantation for several months during pregnancy. The objective of this study was to clarify the steroidogenic capability of the corpus luteum and placenta during pregnancy, including both delayed implantation and fetal development, by immunolocalization of steroidogenic enzymes in these organs of the Japanese black bear. Ovaries and placentae from 15 wild Japanese black bears, which had been killed legally by hunters and were thought to be pregnant, were used in an immunocytochemical study to localize the cholesterol side chain cleavage cytochrome P450 (P450scc), 3beta-hydroxysteroid dehydrogenase (3betaHSD), 17alpha-hydroxylase cytochrome P450 (P450c17) and aromatase cytochrome P450 (P450arom) by the avidin-biotin-peroxidase complex method using polyclonal antisera raised in mammals against P450scc, 3betaHSD, P450c17 and P450arom. P450scc and 3betaHSD were localized in all luteal cells throughout pregnancy. P450c17 was present in a few luteal cells, especially in the outer area of the corpus luteum throughout pregnancy, but the number of positively immunostained cells decreased during the post-implantation period. Cells positively immunostained for P450c17 were significantly smaller than negatively immunostained cells (P < 0.01). P450arom was present sporadically in a few luteal cells throughout pregnancy, but the number of positively immunostained cells decreased during the post-implantation period. The size of cells positively immunostained for P450arom was not significantly different from that of negatively immunostained cells. The whole placenta was negatively immunostained for P450scc, 3betaHSD and P450c17, but P450arom was present in the syncytiotrophoblasts and endothelial cells of maternal blood vessels. These results indicate that, in the Japanese black bear, corpora lutea are a source of progesterone which may play an important role in the maintenance of delayed implantation and fetal development during pregnancy. Corpora lutea have a minimum capability to synthesize androgen in small luteal cells and oestrogen in normal-sized luteal cells during pregnancy, and placentae have the ability to synthesize oestrogen during late pregnancy.

3-Hydroxysteroid Dehydrogenases↗