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Biomedical subjects

Shingo Fujii

Publications and source records attributed to Shingo Fujii.

At least 73 records · Page 4Linked to original sources
PubMed2003

Mutations in the STK11 gene characterize minimal deviation adenocarcinoma of the uterine cervix.

Minimal deviation adenocarcinoma (MDA) is a well-differentiated variant of mucinous adenocarcinoma of the uterine cervix and is found relatively infrequently in the general population. However, MDA is strongly associated with Peutz-Jeghers syndrome (PJS), a rare hereditary autosomal disorder characterized by benign hamartomatous polyposis in the gastrointestinal tract and mucocutaneous pigmentation. A serine threonine kinase gene, STK11, has been identified as the tumor suppressor gene responsible for the PJS. In this study we investigated the possible direct role of STK11 in the development of MDA of the uterine cervix. Eleven rare cases of mucinous MDA, not known to be associated with PJS, were screened for the presence of mutations in the STK11 gene by single-strand conformation polymorphism analysis of PCR-amplified DNA fragments. Subsequently our findings were confirmed with cloning and sequencing. As a control, 24 cases of endocervical adenocarcinomas of other histologic subtypes, with no family history of PJS (19 mucinous adenocarcinomas, 4 endometrioid adenocarcinomas, and 1 clear cell adenocarcinoma), 15 cases of squamous cell carcinomas of the uterine cervix, 5 cases of endocervical glands with pyloric gland metaplasia, and 2 deeply situated nabothian cysts were investigated. Somatic mutations of the STK11 gene were confirmed in 6 (55%) of the 11 mucinous MDAs and 1 (5%) of the 19 mucinous adenocarcinomas, but not in the 5 nonmucinous adenocarcinomas, the 15 squamous cell carcinomas, nor the 5 endocervical glands with gastric metaplasia. MDAs with the STK11 mutation had a significantly poorer prognosis than MDAs without the STK11 mutation (p = 0.039). A germline mutation of STK11 was detected in one PJS patient with mucinous adenocarcinoma of the uterine cervix. These results suggest that mutations in the STK11 gene may play an important role in the etiology of MDA of the uterine cervix and may distinguish this rare tumor from other common types of adenocarcinoma of the uterine cervix.

AMP-Activated Protein Kinase Kinases↗
PubMed2003

Expression of cold-inducible RNA-binding protein in the normal endometrium, endometrial hyperplasia, and endometrial carcinoma.

Cold-inducible RNA-binding protein (CIRP), an 18-kD protein in the mouse and human, is induced by lowering the temperature of cultured cells. CIRP is possibly a cell cycle regulator because its overexpression results in prolongation of G1 phase in vitro. We investigated the immunohistochemical expression of CIRP in 39 endometrial carcinomas, 12 endometrial hyperplasias, and 27 normal endometria using polyclonal antibody against CIRP and confirmed by Western blot analysis. CIRP was localized in the nuclei of glandular, stromal, and endothelial cells. The intensity of CIRP expression in glandular cells during the menstrual cycle was inversely proportional to its proliferative (Ki-67) activity, whereas it remained unchanged in stromal and vascular endothelial cells. The intensity of CIRP expression in hyperplastic glands was variable, whereas CIRP expression was absent or markedly reduced in most of the endometrial carcinomas. These results suggest that CIRP may participate in the cell cycle regulation of normal endometrium and the loss of its expression may be involved in endometrial carcinogenesis.

Adult↗
PubMed2003

Expression of replication-licensing factors MCM2 and MCM3 in normal, hyperplastic, and carcinomatous endometrium: correlation with expression of Ki-67 and estrogen and progesterone receptors.

Minichromosome maintenance (MCM) proteins are essential for cell cycling due to their function as replication-licensing factors. The aim of the present study was to investigate the clinicopathologic implications of the MCM2 and MCM3 in endometrial carcinogenesis. The authors investigated the immunohistochemical expression of MCM2 and MCM3, Ki-67, estrogen receptor, and progesterone receptor in 23 normal endometria, 9 endometrial hyperplasias, and 60 endometrial carcinomas. In the normal endometrial glands, the expression of MCM2 and MCM3 was significantly higher in the proliferative phase than in the secretory phase and was strongly correlated with Ki-67 expression. Similar correlation between the expression of MCMs and Ki-67 was also found in endometrial hyperplasia. In endometrial carcinomas, however, the expression of MCM2 and MCM3 was significantly lower than that in the normal proliferative endometrium. There was only a weak correlation between MCM2 and Ki-67, and no significant correlation between MCM3 and Ki-67 expression. These findings suggest that the expression of MCM2 and MCM3 directly reflects cell proliferation in normal and hyperplastic endometria. In endometrial carcinomas, however, there is a discrepancy between the expression of MCMs and cell proliferation, suggesting that the replication-licensing system may be aberrant in endometrial carcinomas.

Adult↗
PubMed2003

Uterine arterial embolization for the treatment of diffuse leiomyomatosis.

Diffuse leiomyomatosis of the uterus is an extremely rare condition and presents as a diffuse involvement of the myometrium by numerous leiomyomata. Despite patients being in only the third or fourth decades of life, all previously reported patients with this condition have undergone hysterectomy because myomectomy is impossible for this condition. Uterine arterial embolization (UAE) successfully reduced the uterine volume of diffuse leiomyomatosis without major complications in the case presented herein, and the symptoms improved remarkably. Enhanced magnetic resonance imaging after intravenous injection of gadolinium demonstrated global infarction of the vast majority of nodules.

Adult↗
PubMed2003

Resistin is expressed in the human placenta.

The mechanism for decreased insulin sensitivity in pregnant women is not fully clarified. Resistin, a novel peptide hormone, is specifically expressed in the adipose tissue and decreases insulin sensitivity in rodents. In the present study, we demonstrate resistin gene expression in the human placental tissue, mainly in trophoblastic cells. The resistin gene expression in term placental tissue was more prominent than was seen in the first trimester chorionic tissue. In contrast resistin gene expression in adipose tissue was rather weak and remained unchanged by pregnancy. Thus, resistin is a newly isolated placental hormone in humans which may modulate insulin sensitivity during pregnancy.

Blotting, Northern↗
PubMed2003

Human blastocysts and endometrial epithelial cells express activated leukocyte cell adhesion molecule (ALCAM/CD166).

Activated leukocyte cell adhesion molecule (ALCAM)/cluster of differentiation (CD166) is a type I transmembrane cell adhesion molecule belonging to the Ig superfamily and a ligand for CD6 that is expressed on T lymphocytes. Recently, homophilic (ALCAM-ALCAM) adhesion was shown to play important roles in tight cell-to-cell interaction and regulation of stem cell differentiation. To investigate the involvement of ALCAM in embryo implantation, the expression of ALCAM was examined in human blastocysts and endometrium. Immunohistochemical study showed that ALCAM was expressed on endometrial luminal and glandular epithelial cells but not on the endometrial stromal cells in either the proliferative or secretory phase. Northern blot analysis of isolated endometrial epithelial cells and stromal cells showed that ALCAM mRNA was expressed in endometrial epithelial cells. Flow cytometry confirmed cell surface expression of ALCAM on endometrial epithelial cells. On the other hand, nested RT-PCR analysis demonstrated that ALCAM mRNA was expressed in human blastocysts but not in the embryos in the 8-cell or morula stages, which were obtained from patients undergoing in vitro fertilization treatment. These findings indicate that ALCAM is expressed on human endometrial epithelial cells and blastocysts. The developing stage-specific expression on the embryo suggests that the ALCAM-ALCAM cell adhesion system is involved in an initial interaction of the embryo with maternal endometrium.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2003

Ephrin B1 is expressed on human luteinizing granulosa cells in corpora lutea of the early luteal phase: the possible involvement of the B class Eph-ephrin system during corpus luteum formation.

Ephrins and their Eph receptors are both membrane-bound proteins that function in various cell-cell recognition processes, such as morphogenesis and angiogenesis. In this study we examined the expression of B class ephrins-Ephs in the human ovary during corpus luteum formation, a process of tissue remodeling accompanied by angiogenesis. RT-PCR analysis detected mRNAs for Eph B1, B2, and B4 and ephrin B1 and B2, but not Eph B3 and B6 or ephrin B3, in human corpora lutea of the early luteal phase. By immunohistochemistry, ephrin B1 was moderately expressed on theca interna cells, but was expressed at a low level on granulosa cells in the preovulatory follicles. After ovulation, a rapid increase in ephrin B1 expression was observed on luteinizing granulosa cells, whereas its expression on luteinizing theca interna cells decreased. The mRNA expression of ephrin B1 in luteinizing granulosa cells was confirmed by Northern blotting. Flow cytometry showed that ephrin B1 was expressed on the surface of isolated luteinizing granulosa cells. Moreover, these cells had the ability to bind to recombinant Eph B2-Fc fusion protein. These findings suggest that ephrin B1-expressing granulosa cells can directly interact with Eph-bearing cells during corpus luteum formation in vivo, suggesting that Eph-ephrin system is involved in this process.

Adult↗
PubMed2003

Trophoblasts acquire a chemokine receptor, CCR1, as they differentiate towards invasive phenotype.

At the human feto-maternal interface, trophoblasts differentiate towards extravillous trophoblasts (EVTs) and form the cell column. EVTs acquire invasive activity in the distal part of the cell column and begin to migrate into the maternal tissue. We previously reported that dipeptidyl peptidase IV (DPPIV) is expressed on EVTs in the proximal part of cell column and is involved in the inhibition of their migration. Because DPPIV has been shown to degrade several chemokines, we examined possible roles of chemokines in EVT migration. Immunohistochemistry demonstrated that C-C chemokine receptor 1 (CCR1) was hardly detected on cytotrophoblasts and syncytiotrophoblast but was expressed on EVTs in the cell column. In vitro, CCR1 protein was also present on the surface of EVTs that grew out from chorionic villous explants cultured under 20% O2. Chemokines that can bind to CCR1 (CCR1 ligands), such as regulated on activation, normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein-1alpha (MIP-1alpha), were confirmed in the decidual tissues by RT-PCR and immunohistochemistry. These CCR1 ligands promoted the migration of the EVTs that were isolated from the explant cultures in vitro. These results indicate that CCR1 is expressed on trophoblasts as they differentiate to EVTs and that CCR1 ligands produced from the decidual tissue induce EVT migration. By contrast, CCR1 was scarcely expressed on EVTs that grew out from villous explants cultured in 1% O2, indicating that a relatively high oxygenic environment is needed to induce CCR1 expression. Moreover, CCR1 expression on the isolated EVTs was significantly reduced in the presence of decidua-conditioned medium. Such regulation of CCR1 by surrounding oxygenic and decidual environments supports a close correlation between EVT invasion and their expression of CCR1. This study demonstrates that trophoblasts acquire CCR1 as they differentiate to an invasive phenotype at the villus-anchoring sites and indicates a novel role for the chemokine-CCR1 system in the initial step of trophoblastic invasion towards the maternal tissue.

Cell Division↗
PubMed2003

Free-to-total leptin ratio in maternal plasma is constant throughout human pregnancy.

To clarify the mechanism of leptin resistance during pregnancy, we measured plasma leptin concentrations, free to total leptin ratio (percent free leptin) and soluble leptin receptor concentrations in pregnant women, and compared the results with those in non-pregnant women. We collected plasma samples from 23 non-pregnant and 31 pregnant women in the third trimester. Plasma samples from 5 pregnant women were collected longitudinally in each trimester. Plasma leptin concentrations in pregnant women in the second trimester (17.4 +/- 3.2 ng/ml) were higher than those in the first trimester of pregnancy (11.0 +/- 2.8 ng/ml, n = 5), as previously reported. However, percent free leptin did not change significantly throughout pregnancy. Percent free leptin correlated with total leptin concentrations (ng/ml) in non-pregnant women (r = 0.727, P < 0.0001), but not in women in the third trimester of pregnancy (r = 0.006). Constant percent free leptin during pregnancy despite increased leptin concentrations indicates increased leptin binding capacity in pregnant women, that might partly contribute to the establishment of leptin resistance. On the other hand, soluble leptin receptor concentrations showed significant negative correlation with BMI and plasma leptin concentrations in pregnant women (r = -0.470, P < 0.01 and r = -0.493, P < 0.01, respectively) but not in non-pregnant women. These data suggest the possibility that soluble leptin receptor is a minor component of leptin binding capacity in the plasma of pregnant women.

Adult↗
PubMed2003

Expression of nitric oxide synthase isoforms in the human placenta is not altered by labor.

Nitric oxide has various biological activities including smooth muscle relaxation, anti-inflammatory activity, anti-coagulatory activity. As the human placenta is known to express nitric oxide synthases, this study investigated the possible effect of labor on the expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in human placental tissues at term. Both eNOS and iNOS mRNA expression in placental tissues in labor were significantly higher than those in the amnion, chorion laeve, decidua vera and myometrium. The eNOS mRNA and protein expressions in placental tissues in labor (n = 12) were 1.6023 +/- 0.1652 (eNOS/GAPDH, mean +/- SEM) and 12.8 +/- 1.3 arbitrary units (AU), respectively, which were similar to those not in labor (n = 10), 1.5806 +/- 0.2042 (eNOS/GAPDH) and 11.4 +/- 1.8 AU. The iNOS mRNA and protein expressions in the placental tissues in labor were 1.2831 +/- 0.2436 (iNOS/GAPDH) and 10.7 +/- 2.1 AU respectively, similar to those not in labor, 1.9254 +/- 0.8004 (iNOS/GAPDH) and 13.3 +/- 1.8 AU. The guanosine 3',5'-cyclic monophosphate (cGMP) concentration in the placental tissues in labor was 23.6 +/- 1.4 fmol/g wet tissue, similar to that not in labor, 26.1 +/- 2.0 fmol/g wet tissue. These findings suggest that nitric oxide production in the human placenta is maintained during labor.

Cyclic GMP↗
PubMed2002

Adnexal masses caused by pelvic inflammatory disease: MR appearance.

PURPOSE: To describe the morphologic and signal intensity characteristics of inflammatory adnexal masses in magnetic resonance (MR) images. MATERIALS AND METHODS: MR images of 15 patients with a total of 20 confirmed inflammatory adnexal masses were analyzed retrospectively. RESULTS: The findings obtained from MR imaging were as follows: lesions have ill-defined borders; ill-defined areas of high intensity signals surround the masses on T(2)-weighted images; a "rim" at the innermost layer of the cyst wall exhibits high signal intensity on T(1)-weighted images and low intensity on T(2)-weighted images; secondary changes in the surrounding fat plane and bowel loops are extensive; and adhesions are dense. These findings reflect the basic characteristics of the inflammatory process, which are edema caused by increased permeability and highly vascularized granulation tissue caused by the strong tendency to repair. CONCLUSION: MR imaging findings well reflect the basic pathological process of inflammation, and inflammatory adnexal masses are associated with relatively specific appearances in MR images. MR imaging can be a problem-solving alternative in the diagnosis of inflammatory adnexal masses.

Adnexal Diseases↗
PubMed2002

Immature teratoma of the ovary: correlation of MR imaging and pathologic findings.

The objectives of this study were to describe MR imaging findings of immature teratoma and to correlate imaging findings with histopathologic findings. The MR findings of ten patients (age range 12-29 years, mean age 19.0 years) with pathologically proven immature teratoma were retrospectively reviewed for tumor size, presence and characteristics of fatty content, presence and characteristics of solid components, and presence of ascites and implants. The MR findings were compared with gross (n=3) and microscopic (n=10) findings. Comparisons between relative amounts of solid components and histologic grades were evaluated by Spearman rank-order correlation. On MR images all lesions appeared to be fat-containing tumors with solid components consisting of numerous cysts of various sizes. Solid tissue exhibited a wide variety of signal intensities on T2-weighted images. Punctate foci of fat were identified in all lesions, whereas fatty fluid was observed only in two. Predominant fluid content exhibited signal intensities similar to simple fluid in nine lesions. Ascites was observed in six lesions, and peritoneal dissemination in three. Pathologic studies confirmed scattered foci of adipose tissue in the solid portions of all cases, and revealed numerous cystic structure formations in these solid components. The correlation coefficient between the amount of solid tissue and the tumor grade was not significant (r(s)=0.266). The MR images of immature teratoma tended to show aqueous fluids and the solid components consisting of numerous cysts with punctate foci of adipose tissue, whereas predominant fluid is sebaceous fluid in the vast majority of mature cystic teratomas.

Adolescent↗
PubMed2002

An unusual presentation of endometrial polyp.

A 33-year-old woman was incidentally found to have a polypoid adenofibroma on MR imaging during the evaluation of carcinoma in situ of the cervix. The position of the polypoid lesion was variable from time to time. Although the lesion was a benign pedunculated one, T2-weighted MR images showed disruption of "junctional zone" in the posterior myometrial wall of the uterus, mimicking myometrial invasion of endometrial carcinoma.

Adenofibroma↗
PubMed2002

Cyclical change of hMSH2 protein expression in normal endometrium during the menstrual cycle and its overexpression in endometrial hyperplasia and sporadic endometrial carcinoma.

BACKGROUND: The role of hMSH2 protein, one of the major DNA repair proteins, until now, had not been elucidated in terms of normal endometrial function during the menstrual cycle. The current study was designed to address this issue and to determine whether the expression of hMSH2 is altered in the course of endometrial carcinogenesis. METHODS: Immunohistochemical reactivity with a monoclonal antibody against the hMSH2 protein was examined in endometrial tissue specimens from 45 patients with normal endometrium, 51 patients with endometrial hyperplasia, and 27 patients with endometrial carcinoma. Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) also was studied in the same samples as a measure of the proliferative activity and was compared with hMSH2 expression in each sample. RESULTS: The functional layer of normal endometrium displayed cyclic changes in hMSH2 protein expression during the menstrual cycle, showing positive expression in the proliferative phase and becoming weak to negative in the secretory phase. This expression pattern was similar to that of PCNA. Sixty-three percent of endometrial carcinomas showed strong positivity for both hMSH2 and PCNA expression, and 7.4% had an intensity of hMSH2 protein expression similar to that found in normal proliferative endometrial glandular cells. There was only 1 sample (3.7%) that was completely negative for hMSH2 expression, and 26% of samples were weakly positive for PCNA and hMSH2 protein. All simple hyperplasias and the majority of complex and atypical hyperplasias showed positive immunoreactivity for hMSH2 and PCNA. CONCLUSIONS: This study demonstrates that hMSH2 protein expression changes during the menstrual cycle in parallel with proliferative activity. In most patients with sporadic endometrial carcinoma, the expression of hMSH2 protein is consistent with PCNA expression. In contrast, loss of hMSH2 expression is observed rarely in patients with sporadic endometrial carcinoma.

Adult↗
PubMed2002

A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis.

NF-kappa B is a transcription factor that can protect from or contribute to apoptosis. Here we report identification of HSCO that binds to NF-kappa B and inhibits apoptosis. HSCO mRNA was overexpressed in 20 of 30 hepatocellular carcinomas analyzed. Overexpression of HSCO inhibited caspase 9 activation and apoptosis induced by DNA damaging agents, while it augmented apoptosis induced by TNFalpha. Like I kappa B alpha, HSCO inhibited NF-kappa B activity and abrogated p53-induced apoptosis. However, the underlying mechanism was different. HSCO is a nuclear-cytoplasmic shuttling protein, bound to RelA NF-kappa B, and HSCO sequestered it in the cytoplasm by accelerating its export from the nucleus. These results suggest that overexpression of HSCO suppresses p53-induced apoptosis by preventing nuclear localization of NF-kappa B during signaling and thus contributes to hepatocarcinogenesis.

Amino Acid Sequence↗
PubMed2002

Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC.

BACKGROUND: The aim of this study was to investigate the role of peripheral blood mononuclear cells (PBMC) in embryo invasion at the implantation site and to estimate the effect on PBMC function of human chorionic gonadotrophin (HCG) that is secreted from the human embryo. METHODS AND RESULTS: The effect of PBMC on the invasiveness of murine embryos was examined using an invasion assay. PBMC obtained from women in early pregnancy (5-9 weeks gestation) significantly enhanced both spreading of murine embryos on Matrigel and invasion beneath the gel. These effects were greater than those of PBMC obtained from non-pregnant women in the secretory phase (cycle day 16-24) and the control (in the absence of PBMC). When PBMC obtained from non-pregnant women were incubated with recombinant HCG (10 IU/ml) for 2 days and were subjected to invasion assay using murine embryos, PBMC treated with HCG significantly promoted both spreading and invasion of murine embryos as compared with the non-treated PBMC. On the other hand, embryo outgrowth was not affected by HCG in the absence of PBMC, showing no direct effect of HCG on embryo invasion. CONCLUSION: This study indicated that PBMC from pregnant women promoted murine embryo invasion in vitro and this effect of PBMC was enhanced by HCG. These findings suggest that PBMC at the implantation site are activated by HCG secreted from the embryo, following which PBMC regulate embryo invasion.

Animals↗