Aggressive angiomyxoma of the vulva associated with severe infection.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
S Fujii
Publications and source records attributed to S Fujii.
Preparation of optically active trifluoromethylated (3'-indolyl) thiacarboxylic acids, novel plant growth regulators, through lipase-catalyzed enantioselective hydrolysis.
Among a variety of lipases tested, that obtained from Candida antarctica (SP 435) induced enantioselective hydrolysis of trifluoroethyl 5,5,5-trifluoro-4-(3'-indolyl)-3-thiapentanoate (1c). The selectivity could be increased by optimizing the reaction conditions. Thus, good selectivity was achieved (E = 37) in a buffer containing 10% dichloroethane. In order to improve the optical yields, a sequential kinetic resolution was utilized for the preparative-scale enantioselective hydrolysis of 1c using SP 435. Hydrolysis of trifluoroethyl 6,6,6-trifluoro-5-(3'-indolyl)-4-thiahexanoate (2c) with the lipase of Pseudomonas aeruginosa (LIP) in a buffer containing 20% tert-amyl alcohol at 25 degrees C gave excellent selectivity (E=357).
Journal Article↗
Long-term blockade of nitric oxide synthesis in rats modulates coronary capillary network remodeling.
Long-term blockade of nitric oxide synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces cardiac perivascular fibrosis in rats. Its relationship to expression of angiogenic growth factors and capillary network remodeling is not understood. This study was designed to determine whether capillary proliferation and angiogenic growth factor regulation occur in response to L-NAME. Three groups of rats were studied: C, control; L1, L-NAME 13 mg/kg/day; L2, 130 mg/kg/day. One and eight weeks later the hearts were removed and subjected to morphometric analysis and analysis of gene expressions of molecules related to angiogenesis. Arterial hypertension was observed within 8 weeks in the L1 and L2 groups compared with control. After 1 week immunohistochemical assays demonstrated basic fibroblast growth factor (bFGF) in the arteriolar media. Northern blot analysis revealed increase in bFGF and transforming growth factor-beta (TGF-beta) mRNA during this period. At 8 weeks arteriolar medial thickening and perivascular fibrosis were seen microscopically in the L1 and L2 groups, which were accompanied by only a modest remodeling of capillary network due to increase in venular or intermediate capillary portions. Concomitantly immunoreactivity for vascular endothelial growth factor (VEGF) and TGF-beta were detected in perivascular area. These results suggest that (1) blockade of NO synthesis induces expression of angiogenic growth factors as well as vessel wall remodeling, and (2) TGF-beta may counteract angiogenic growth factors and limit subsequent alterations in capillary network remodeling.
Journal Article↗
Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus.
We examined bcl-2 expression as well as p53 expression and mutation in human uterine smooth muscle tumours to determine the influence of bcl-2 expression on prognosis in patients with uterine leiomyosarcomas. bcl-2 protein was expressed in nearly all benign smooth muscle tumours but in only 57% of leiomyosarcomas. Benign smooth muscle tumours were usually negative for p53 protein, but 16 out of 21 (76%) leiomyosarcomas were positive. A p53 gene mutation was detected in nine of the 16 leiomyosarcomas that showed p53-positive staining. A significant positive correlation was observed between p53 mutation and p53 expression, between the number of mitoses and the Ki-67 labelling index, and between clinical stage and p53 mutation. A significant negative correlation was observed between bcl-2 expression and p53 mutation, and between bcl-2 expression and p53 overexpression. Univariate survival analysis revealed that bcl-2 expression, p53 mutation and clinical stage (stage 1 vs stages 2-4) all showed a significant correlation with prognosis. In a multivariate stepwise regression analysis, positive bcl-2 expression and stage 1 disease were the independent predictors of a favourable prognosis. Our results suggest that bcl-2 is frequently expressed in human uterine smooth muscle tumours, and that its expression may correlate with a favourable prognosis in patients with uterine leiomyosarcoma.
Adult↗
Induction of haem oxygenase-1 nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth.
Induction of haem oxygenase-1 (HO-1) as well as nitric oxide (NO) biosynthesis during tumour growth was investigated in an experimental solid tumour model (AH136B hepatoma) in rats. An immunohistochemical study showed that the inducible isoform of NO synthase (iNOS) was localized in monocyte-derived macrophages, which infiltrated interstitial spaces of solid tumour, but not in the tumour cells. Excessive production of NO in the tumour tissue was unequivocally verified by electron spin resonance spectroscopy. Tumour growth was moderately suppressed by treatment with either Nomega-nitro-L-arginine methyl ester (L-NAME) or S-methylisothiourea sulphate (SMT). In contrast, HO-1 was found only in tumour cells, not in macrophages, by in situ hybridization for HO-1 mRNA. HO-1 expression in AH136B cells in culture was strongly enhanced by an NO (NO+) donor S-nitroso-N-acetyl penicillamine. HO-1 mRNA expression in the solid tumour in vivo decreased significantly after treatment with low doses of NOS inhibitors such as L-NAME and SMT (6-20 mg kg(-1)). However, the level of HO-1 mRNA in the solid tumour treated with higher doses of NOS inhibitor was similar to that of the solid tumour without NOS inhibitor treatment. Strong induction of HO-1 was also observed in solid tumours after occlusion or embolization of the tumour-feeding artery, indicating that ischaemic stress which may involve oxidative stress triggers HO-1 induction in the solid tumour. Lastly, it is of great importance that an HO inhibitor, zinc protoporphyrin IX injected intra-arterially to the solid tumour suppressed the tumour growth to a great extent. In conclusion, HO-1 expression in the solid tumour may confer resistance of tumour cells to hypoxic stress as well as to NO-mediated cytotoxicity.
Animals↗
Impact of cigarette smoking on the incidence of Type 2 diabetes mellitus in middle-aged Japanese men: the Osaka Health Survey.
AIMS: To assess the impact of cigarette smoking on the incidence of Type 2 diabetes mellitus (DM) in middle-aged Japanese men. METHODS: The study enrolled 6250 men aged 35-60 years and free of diabetes, impaired fasting glucose and hypertension at entry. Type 2 DM was defined by a fasting plasma glucose level > or =7.0 mmol/l or physician-diagnosed Type 2DM. RESULTS: Four hundred and fifty cases of Type 2 DM were confirmed during the 60904 person-years follow-up. After adjustment for multiple covariates, including age, body mass index, alcohol consumption, physical activity, parental history of diabetes and the level of fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol and haematocrit, the relative risk of Type 2 DM among current smokers compared with non-smokers was 1.47 (95% confidence interval (CI) 1.14-1.92). Men who smoked >30 cigarettes/day had a multivariate-relative risk of 1.73 (95% CI 1.20-2.48) compared with non-smokers. The number of cigarettes smoked daily and the pack-year values were positively related to the development of Type 2 DM in a dose-dependent manner (P for trends = 0.0026 and 0.001, respectively). CONCLUSIONS: A cigarette smoking habit is an independent risk factor for Type 2 DM.
Adult↗
Changes of sinusoidal basement membrane collagens in early hepatic fibrosis induced with CCl4 in cynomolgus monkeys.
CCl4 was chronically administrated for 25 months to induce hepatic fibrosis in three cynomolgus monkeys so as to examine the alteration of basement membrane-related collagens during the liver injury. Although type IV collagen was immunohistochemically present along sinusoidal walls before and during the CCl4 administration, basement membrane-associated collagen (BAC), which was recognized with JK-132 monoclonal antibody, appeared around sinusoids at five to ten months of CCl4 administration. We previously developed a sandwich enzyme linked-immunosorbent assay, utilizing two monoclonal antibodies, anti-BAC antibody (JK-132) and anti-type IV collagen antibody (JK-199) [Int Hepatology Commun 1995; 4: 1-8]. The serum level of the collagen complex, which is disulfide-bridged with BAC and type IV collagen, was simultaneously monitored. The serum level of the complex at the initial stage of the examination was 19-34 ng/ml and gradually increased in relation to the intensity of immunofluorescence of BAC and type IV collagen in sinusoids and connective tissues, up to 51-57 ng/ml. The serum collagen complex levels showed a weak correlation with serum hyaluronic acid, a serum marker of hepatic fibrosis. The serum GOT, GPT, ALP and CHE levels did not reflect the alteration of sinusoids or relate to the serum collagen complex level. The increase in BAC around sinusoids and the increase of collagen complex with BAC and type IV collagen in the sera, correlate with early lesional events in hepatic fibrosis.
Alanine Transaminase↗
In vivo distribution and behavior of paramagnetic dinitrosyl dithiolato iron complex in the abdomen of mouse.
It has been shown that a dinitrosyl dithiolato iron complex is formed under physiological conditions and that it functions as an NO transporter. In the present study, a diglutathionyl dinitrosyl iron complex [DNIC-(GS)2] was injected into mice and its abdominal distribution and behavior were examined by using electron paramagnetic resonance (EPR) spectroscopy. The X-band EPR signal intensity of the blood, liver, kidney, and spleen decreased with time but signals from the liver and kidney were readily detectable even 24h after the injection. The time courses of signal intensity were quite similar when the agent was administered via intravenous and subcutaneous injection routes, suggesting that DNIC-(GS)2 can penetrate readily and rapidly through the membranes. Real-time detection of DNIC-(GS)2 in the upper abdomen of the living mice was performed by employing an in vivo EPR spectroscopy. These results suggest that DNIC-(GS)2, an endogenous NO carrier, has an excellent membrane permeability and has a relatively high affinity for the liver and kidney.
Abdomen↗
p53 mutations in tumor and non-tumor tissues of thorotrast recipients: a model for cellular selection during radiation carcinogenesis in the liver.
Concerns over cancer development from exposure to environmental sources of densely ionizing, high linear energy transfer (LET) radiation, such as alpha-particles from radon, is a current public health issue. The study of tumors attributable to high LET irradiation would greatly augment our insights into the biological mechanisms of carcinogenesis. Chronic low-dose-rate internal exposure to alpha-radiation from thorium dioxide deposits following intravascular administration of the radiographic contrast agent Thorotrast is known to markedly increase the risk of cancer development, especially that of hepatic angiosarcomas and cholangiocarcinomas. Although the mechanism is hypothesized to be via cellular damage, DNA being a major target, wrought by the high LET alpha-particles, the specific genes and the actual sequence of events involved in the process of transforming a normal cell into a malignant one are largely unknown. To shed some light on the molecular mechanisms of cancer development during a lifetime exposure to alpha-radiation, we analyzed the most commonly affected tumor suppressor gene in humans, p53, in 20 Thorotrast recipients who developed cancer, mostly of hepatic bile duct and blood vessel origin. Of the 20 cases, 19 were found to harbor p53 point mutations. Moreover, the accompanying non-tumor tissues from these patients also had p53 mutations, albeit at lower frequency. The distribution pattern of the point mutations was significantly different between the non-tumor and tumor tissues, with most mutations in malignant tissues located in the highly conserved domains of the p53 gene. Our results support the idea that p53 mutations are important in the genesis of Thorotrast-induced tumors but that these point mutations are a secondary outcome of genomic instability induced by the irradiation. Additionally, non-tumor cells harboring p53 mutations may gain some survival advantage in situ but mutations in the domains responsible for the formation of structural elements critical in binding DNA may be necessary for a cell to reach full malignancy.
Aged↗
Evaluation of ectopic pregnancy by magnetic resonance imaging.
Patients (n = 37) suspected of ectopic pregnancy were prospectively evaluated with magnetic resonance (MR) imaging to assess the capability of MR imaging in the diagnosis of ectopic pregnancy. Five levels of confidence were defined: diagnostic, suspicious, equivocal, questionable, and negative. Tubal wall enhancement and presence of tubal haematoma or gestational sac-like structure were considered diagnostic findings. There were 21 diagnostic, two suspicious, eight equivocal, and six negative findings. MR findings were compared with the surgical findings in 18 patients. Surgical confirmation was obtained in 12 diagnostic, two suspicious, and four equivocal studies. Using the MR diagnostic criteria for tubal pregnancy, MR had 12 true positive, three true negative, three false negative, and no false positive results for the diagnosis of tubal pregnancy. Retrospective analysis of the signal intensity of haematoma and ascites was performed for these 18 surgically confirmed cases. The predominant signal intensity of tubal haematoma was an intermediate signal on T1-weighted image (WI) and a low signal on T2WI. Ascites showed signal intensity higher than that of urine on T1WI in 100% of 13 cases. In conclusion, MR imaging with use of intravenous contrast material allows a specific diagnosis of tubal pregnancy, recognizing tubal wall enhancement and fresh tubal haematoma.
Adult↗
Co-expression of integrin-associated protein (IAP/CD47) and its ligand thrombospondin-1 on human granulosa and large luteal cells.
In the present study, we have raised a monoclonal antibody (mAb) designated OG-4 against human granulosa cells (GC). By immunohistochemistry, the expression of OG-4 antigen was observed on human GC and large luteal cells, but not on thecal and small luteal cells. A complementary DNA (cDNA) clone encoding OG-4 antigen was screened and isolated by a panning method using OG-4 mAb from a human corpus luteum (CL) cDNA library that was expressed transiently in COS-7 cells. Nucleotide sequencing revealed that OG-4 antigen was identical to integrin-associated protein (IAP)/CD47 antigen. Subsequent reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the isoform 2 mRNA of IAP is predominantly expressed in human GC and CL. The expression of thrombospondin-1 (TSP-1), which is a ligand for IAP, was also observed in human GC by immunocytochemistry and RT-PCR. Co-expression of IAP and TSP-1 on human GC may suggest that TSP-1 has a physiological role in GC function possibly via IAP in an autocrine fashion.
Adult↗
Heparin inhibits proliferation of myometrial and leiomyomal smooth muscle cells through the induction of alpha-smooth muscle actin, calponin h1 and p27.
Mast cells are widely distributed in human tissues, including the human uterus. However, the function of mast cells in uterine smooth muscle has not been clearly established. Mast cells possess secretory granules containing such substances as heparin, serotonin, histamine and many cytokines. To help establish the role of mast cells in the human myometrium, the action of heparin was investigated using smooth muscle cells (SMC) from normal myometrium and from leiomyoma. The proliferation of cultured myometrial and leiomyomal SMC was inhibited by heparin treatment. Flow cytometric analysis showed that the population in the G1 phase of the cell cycle increased under heparin treatment. Western blotting analysis showed that markers of SMC differentiation such as alpha-smooth muscle actin (alpha-SMA), calponin h1 and cyclin-dependent kinase inhibitor p27 were induced by heparin, whereas cell-cycle-related gene products from the G1 phase of the cell cycle, such as cyclin E and cdk2, were not changed. Taken together, these results indicate that heparin inhibits the proliferation of myometrial and leiomyomal SMC through the induction of alpha-SMA, calponin h1 and p27. We suggest that heparin from mast cells may induce differentiation in uterine SMC and may influence tissue remodelling and reconstruction during physiological and pathophysiological events.
Actins↗
Expression of calcium binding protein D-9k messenger RNA in the mouse uterine endometrium during implantation.
To investigate the molecular mechanisms of implantation, we constructed a cDNA library of mouse uteri enriched with pregnancy-induced genes by subtractive hybridization and polymerase chain reaction (PCR). One of the isolated clones was the cDNA for the calcium binding protein D-9k (Cabp9k), which is considered to regulate intracytoplasmic concentration and transport of free calcium ions. Northern blot and in-situ hybridization analyses demonstrated that the Cabp9k mRNA was expressed in the endometrial epithelia, both luminal and glandular, in the uterus at the time of implantation. On pregnancy day 5 it was detected in the luminal, but not in the glandular, epithelia. In the oophorectomized adult mice, progesterone enhanced Cabp9k mRNA expression in the uterus, whereas oestrogen did not. Consistent with this, a nucleotide change was identified in the first intron of mouse Cabp9k gene corresponding to the oestrogen responsive element in the rat Cabp9k gene. Transfer of embryos into the uterine cavity of pseudopregnant mice reduced the expression of Cabp9k mRNA in the glandular epithelium, suggesting that Cabp9k mRNA expression is also regulated by embryonal signal(s). These findings demonstrated that Cabp9k mRNA is expressed in the endometrial epithelia during the implantation period under the control of progesterone and the presence of embryo, and suggest that CaBP9k plays a role in implantation by regulating the local calcium concentrations.
Amino Acid Sequence↗
CD9 is expressed in extravillous trophoblasts in association with integrin alpha3 and integrin alpha5.
The CD9 molecule is a 24-27 kDa cell surface glycoprotein, which may be related to Schwann cell migration and adhesion. In this study, we examined the expression of CD9 in human extravillous trophoblasts, which invade into the endometrium during implantation and placentation. CD9 was detected immunohistochemically on the extravillous trophoblasts in the cell columns of first trimester placentae, but not on villous trophoblasts. In the second and third trimester, CD9 was highly expressed on the extravillous trophoblasts in the basal plate of placentae, and in the chorion laeve in the fetal membrane of term placentae. The molecular mass of CD9 in the chorion laeve was shown to be 27 kDa by Western blotting. The mRNA of CD9 was also detected in the chorion laeve by reverse transcription-polymerase chain reaction (RT-PCR). Proteins were purified from chorion laeve by affinity chromatography with anti-integrin alpha3 and alpha5 monoclonal antibodies and Western blotting, revealed that CD9 was associated with both integrins. These findings indicate that CD9 is a differentiation-related molecule present in the extravillous trophoblasts. Since it is associated with integrin alpha5 which has been proposed to regulate trophoblast invasion, CD9 may be implicated in trophoblast invasion at the feto-maternal interface.
Antigens, CD↗
CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line, BeWo cells.
The CD9 molecule is expressed on human extravillous trophoblasts, which invade the endometrium during implantation and placentation. To elucidate the role of CD9 in trophoblastic function, we investigated the expression of CD9 protein and mRNA in BeWo cells, a human trophoblast-like choriocarcinoma cell line, using immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). When BeWo cells were cultured with anti-CD9 monoclonal antibodies (mAb), their invasion through the extracellular matrices was significantly enhanced in a dose-dependent manner. Cell proliferation and human chorionic gonadotrophin production were unaffected. On the other hand, culture in the presence of mAb against integrins alpha3, alpha5 and beta1, which partially block the interaction with the extracellular matrices, inhibited BeWo cell invasion. Anti-CD9 monoclonal antibody had a stimulatory effect on BeWo cell invasion in the presence of anti-integrin alpha3 antibody. In contrast, it had no effect in the presence of mAb against integrins alpha5 and beta1, which were also highly expressed on BeWo cells. These findings suggest that CD9 has a function connected with the invasive properties of BeWo cells, which is partially mediated by integrin alpha5beta1. This may relate to the involvement of CD9 in trophoblastic invasion.
Antibodies, Monoclonal↗
Inverse relationship between apoptosis and Bcl-2 expression in syncytiotrophoblast and fibrin-type fibrinoid in early gestation.
The purpose of this study was to assess the role of apoptosis and cell cycle arrest in the trophoblast during early gestation by determining the location of apoptotic cells and examining the expression of Bcl-2 and p21. Using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) method on human chorionic villi, a cluster of apoptotic nuclei was demonstrated in perivillous fibrin-type fibrinoid, but no apoptotic changes were identified in the syncytiotrophoblast or in other subtypes of the trophoblast. The syncytiotrophoblast was diffusely positive for Bcl-2, but fibrin-type fibrinoid was negative for Bcl-2. Hence, there was an inverse relationship between apoptosis and Bcl-2 expression in both fibrin-type fibrinoid and syncytiotrophoblast. Expression of p21 was present to some extent in the syncytiotrophoblast, but not in fibrin-type fibrinoid. These results suggest that Bcl-2 may play an important role in preventing apoptosis in the syncytiotrophoblast; this may be necessary to prevent any DNA degradation from being spread to other nuclei in a multinuclear cell like the syncytiotrophoblast.
Apoptosis↗
CD9 is expressed on the cell surface of human granulosa cells and associated with integrin alpha6beta1.
The CD9 molecule is a 24-27 kDa cell surface glycoprotein which is reported to be involved in cell adhesion and migration. Recently, CD9 was shown to be associated with beta1-related integrins. We have previously found that integrin alpha6beta1 is expressed on human granulosa cells (GC) and regulates luteinization of GC in concert with its ligand laminin. In this study, we examined the expression of CD9 in human ovary and the relationship between CD9 and integrin alpha6beta1 in GC. By immunohistochemistry, CD9 was detected on GC in a small antral follicle of <1 mm in diameter. In growing follicles, CD9 was moderately expressed on both GC and theca interna cells (TI). The expression intensity of CD9 on GC increased in preovulatory follicles. In the early luteal phase, CD9 was expressed in both luteinizing GC and TI. The expression intensity on large luteal cells decreased in the mid-luteal phase. In the corpus luteum (CL) of pregnancy, CD9 continued to be expressed on large luteal cells, but not on small luteal cells. By flow cytometry, CD9 was detected on the cell surface in approximately 90% of the isolated GC from patients undergoing in vitro fertilization. The molecular weight of CD9 in the isolated GC was shown to be 26.5 kDa by Western blotting. CD9 mRNA was also detected in the isolated GC and CL by reverse transcription-polymerase chain reaction (RT-PCR). The proteins purified from GC by immunoaffinity chromatography using anti-integrin alpha6 monoclonal antibodies were shown by Western blotting to include CD9 as well as integrin beta1. These findings suggest that CD9 is a differentiation-related molecule of GC and TI and that it is associated with integrin alpha6beta1 on the cell surface of GC, suggesting that CD9 is implicated in the function of human GC in cooperation with integrin alpha6beta1.
Adult↗
Human granulosa cells express integrin alpha2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization.
Previously, it has been shown that integrin alpha6beta1 expressed on human granulosa cells regulates luteinization in co-operation with its ligand, laminin. In this study, integrin alpha2 was immunohistochemically demonstrated to be expressed on granulosa and large luteal cells. It was also detected on luteinizing theca interna cells after ovulation. Immunoreactive collagen type IV, which is one of the ligands for integrin alpha2beta1, was detected around granulosa cells in the pre-ovulatory follicles and its expression was rapidly increased during ovulation. By flow cytometry, collagen type IV was detected on the cell surface of luteinizing granulosa cells isolated from pre-ovulatory follicles, confirming the physiological interaction between granulosa cells and collagen type IV. Collagen type IV in follicular fluid was positively related with progesterone concentration. In 4-day cultures of granulosa cells, collagen type IV in the media was significantly increased by human chorionic gonadotrophin (HCG). The progesterone production was significantly attenuated when granulosa cells were cultured on collagen type IV-coated dishes, suggesting that collagen type IV suppresses granulosa cell luteinization. These findings show that collagen type IV, a ligand for integrin alpha2beta1, is rapidly produced around luteinizing granulosa cells during ovulation, probably under the control of luteinizing hormone (LH) and suggest that collagen type IV is a new parameter and/or regulator of granulosa cell luteinization in the periovulatory phases.
Antigens, CD↗