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Biomedical subjects

M Umemoto

Publications and source records attributed to M Umemoto.

At least 19 recordsLinked to original sources
PubMed2004

Clinical implication of expression of cyclooxygenase-2 and peroxisome proliferator activated-receptor gamma in epithelial ovarian tumours.

Expression of cyclooxygenase (COX)-2 plays a key role in tumorigenesis and development and peroxisome proliferator-activated receptor gamma (PPARgamma) has been implicated in the control of COX-2 expression in some tissues. The aim of this study is to investigate (1) whether expression of COX-2 and PPARgamma is associated with ovarian carcinogenesis and progression of ovarian tumours and (2) whether COX-2 expression is controlled through ligand-mediated activation of PPARgamma in ovarian carcinoma cells. For this purpose, the presence of COX-2 and PPARgamma was immunohistochemically examined in 71 epithelial ovarian carcinomas, 18 borderline tumours and 23 benign tumours and the levels of COX-2 and PPARgamma proteins were determined by enzyme immunoassay in four benign tumours, three borderline tumours and 12 carcinomas. The frequency of COX-2 and PPARgamma detection was significantly increased and decreased as lesions progressed to carcinoma, respectively. The COX-2 protein was not detected in the three borderline tumours, whereas PPARgamma protein was detected in all of them. COX-2 protein was detected in eight of the 12 carcinomas, whereas PPARgamma protein was detected in only two cases. In addition, PPARgamma protein was not detected in all of the eight carcinomas in which COX-2 protein was detected, suggesting that expression of PPARgamma and COX-2 was in a reciprocal relationship. Furthermore, in cultured ovarian carcinoma cells, Western blot revealed that PPARgamma and COX-2 expression was regulated conversely as a result of stimulation by 15-deoxy-Delta(12, 14) PGJ(2) (15-PGJ(2)), a PPARgamma activator. In addition, 15d-PGJ(2) suppressed tumour necrosis factor-alpha-induced-COX-2 expression, confirming the reciprocal correlation between COX-2 and PPARgamma. From these results, it was suggested that PPARgamma activation might suppress COX-2 expression via the nuclear factor-kappaB pathway in the ovarian carcinoma cells and that low expression of PPARgamma and high expression of COX-2 might be involved in carcinogenesis and progression of ovarian tumours.

Adenocarcinoma↗
PubMed2003

Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma.

We assessed the presence of vascular endothelial growth factor (VEGF)-C, VEGF-D and their receptor VEGFR-3 by immunohistochemistry in 59 epithelial ovarian carcinomas, 11 borderline tumours and 20 benign cystadenomas. VEGF-C and VEGF-D were generally expressed in tumour cells and also in endothelia adjacent to tumour nests which showed a strong staining for them. VEGFR-3 was expressed in lymphatic and vascular endothelial cells adjacent to tumour nests. Immunoreactivity was significantly more frequent as lesions progressed from a benign tumour to advanced carcinoma. A strong correlation was found between VEGF-C and VEGF-D detected in carcinoma and VEGFR-3 detected in neighbouring endothelial cells. Increased expression of VEGF-C, VEGF-D and VEGFR-3 was significantly associated with lymph node metastasis and peritoneal metastasis outside the pelvis. There was a significant correlation between the high levels of VEGF-C and VEGF-D proteins, and poor survival. The presence of VEGF-D was an independent prognostic indicator by multivariate analysis. We conclude that VEGF-C, VEGF-D and VEGFR-3 play an important role in lymphatic spread and intraperitoneal tumour development in ovarian carcinoma. Since VEGF-D was found to be an independent predictor of poor outcome, its measurement, together with other prognostic markers may improve prospective identification of patients with a poor prognosis.

Adenocarcinoma, Clear Cell↗
PubMed2003

A case of adenocarcinoma of the endometrial type mixed with a clear cell component that metastasized to the vagina.

We present a patient with adenocarcinoma of the endometrial type mixed with a clear cell component (AMC) that metastasized to the vagina and one of the pelvic lymph nodes. She underwent a radical hysterectomy and pelvic and paraaortic lymphadenectomy, and then received postoperative adjuvant chemotherapy. Histologic features of the endometrial tumor included clear cell adenocarcinoma with an approximate 10% extent to endometrioid adenocarcinoma. On the other hand, histologic examination on the vaginal tumor predominatly showed clear cell adenocarcinoma and also revealed endometrioid adenocarcinoma to a very small extent, suggesting metastasis to the vagina from AMC. On immunohistochemical examination, expression of vascular endothelial growth factor (VEGF)-A, VEGF-C and VEGF-D was apparently stronger in the component of clear cell adenocarcinoma than in that of endometrioid adenocarcinoma. She has been a disease-free survivor for 26 months. Interestingly, locations of endometrial and vaginal lesions were consistent with the sites of an intrauterine device and ring pessary insertion, respectively.

Adenocarcinoma, Clear Cell↗
PubMed2001

Carbonyl reductase as a significant predictor of survival and lymph node metastasis in epithelial ovarian cancer.

We have recently reported a novel function for carbonyl reductase (CR), namely, its ability to modulate the metastatic potential of malignant mouse cells. Because there are currently no data addressing a similar function for CR in human cancers, the aim of this study was to assess a correlation between survival and metastasis, and CR level in epithelial ovarian cancer. Using anti-CR antibody, immunohistochemical staining was performed on 73 epithelial ovarian cancers, 13 borderline malignant tumours, and 25 benign ovarian tumours for a total of 111 specimens. The combined rate for strongly and weakly positive reactions for CR was 32.0% for benign tumours, 38.5% for borderline malignant tumours, and 61.6% for ovarian cancers. The CR-positive rate was 35.7% (weakly positive alone) for ovarian cancers with retroperitoneal lymph node (RLN) metastasis and 67.8% for those without RLN metastasis (P< 0.05). The 5-year survival rate was 62.7% for the patients with CR-negative cancer and 86.1% for those with CR-positive cancer (P< 0.05). The present results indicate that decreased CR expression in epithelial ovarian cancer is associated with RLN metastasis and poor survival.

Adult↗
PubMed2000

Prognostic significance of vascular endothelial growth factor and its receptors in endometrial carcinoma.

OBJECTIVE: The aim of this study has been to evaluate the clinical significance of expression of VEGF and its receptors, Flt-1, KDR, and Flt-4, in endometrial carcinomas. METHODS: Specimens of endometrial carcinomas from 86 patients were investigated immunohistochemically using respective specific antibodies. Additionally, samples from 14 patients with complex atypical endometrial hyperplasia (AEH) and 15 patients with normal endometria were also examined. Immunohistochemical assessment was classified as negative, weakly positive, and strongly positive according to staining intensity and the percentage of positive cells. RESULTS: In positive cases, VEGF and its receptors were usually expressed homogeneously in the cytoplasms of cells in the endometrial carcimona, similar to the staining intensity of endothelial cells of stromal microvessels adjacent to carcinoma nests. The overall positive rates in the 86 carcinoma specimens were 66% for VEGF, 51% for Flt-1, 38% for KDR, and 57% for Flt-4. Their expressions in endometrial carcinoma tissues were high with significance or with borderline significance, compared to those in samples of complex AEH or normal endometria. Survival curves determined by the Kaplan-Meier method and univariate analysis showed VEGF, Flt-1, and Flt-4 overexpression to be related to poor prognosis of patients with endometrial carcinomas. However, multivariate analysis revealed that Flt-4 overexpression correlated independently with poor survival, similar to a value for myometrial invasion at one-half or more and that for retroperitoneal lymph node metastasis, whereas VEGF and Flt-1 overexpression did not. CONCLUSION: Flt-4 overexpression might be a promising prognostic indicator for survival of a patient with endometrial carcinoma.

Adult↗
PubMed2000

Effects of hypergravity on morphology and osteopontin expression in the rat otolith organs.

Recovery from balance disorders after spaceflight is supposed to reflect the process of readaptation to normal gravitational environment (1G) from microgravity. Linear acceleration including gravity is perceived by otolith pathways, therefore, it could be assumed that possible plastic changes in any part of otolithic pathways from the level of the vestibular periphery to the central vestibular system might be responsible for adaptive mechanisms to an altered gravitational environment. In the present study, to elucidate a role of otoconia in adaptation to altered gravity, we examined the effects of hypergravity (2G) on morphology and synthesis of saccular and utricular otoconia in young adult rats. Morphology of otoconia was examined by scanning electron microscopy. Otoconial synthesis was assessed by mRNA expression of osteopontin, a matrix protein of otoconia, in otolithic maculae as a marker of otoconial genesis determined by a real-time quantitative PCR method. The present results showed that neither otoconial morphology nor otoconial synthesis was affected by up to one week exposure to hypergravity. These findings suggest that changes in neurotransmission at the synapses of the peripheral and/or central vestibular system rather than the changes in otoconial morphology and synthesis may be involved in adaptive mechanisms to an altered gravitational environment.

Animals↗
PubMed1999

Anesthesia for insertion of a Dumon stent in a patient with a large tracheo-esophageal fistula.

PURPOSE: To present the anesthetic management for the insertion of a Dumon silicon stent to the trachea of a patient with a large tracheo-esophageal fistula. The aim of the stent insertion was to seal the fistula in order to prevent aspiration of esophageal content and subsequent pneumonitis. CLINICAL FEATURES: A 45-yr-old man with a large tracheo-esophageal fistula was scheduled for the insertion of the Dumon stent. Since placement of the stent necessitates the insertion of a rigid bronchoscope, under general anesthesia, with its tip just proximal to the fistula, controlled ventilation was expected to be difficult to achieve because of the diversion of oxygen through the large fistula to the esophagus. We successfully ventilated the lungs, after the fistula was sealed using a large balloon which was inserted in the esophagus, and the stent insertion was completed uneventfully. CONCLUSION: Anesthesia for procedures involving the central airway is challenging. This report describes a simple and practical method to facilitate ventilation by temporary seal of a tracheo-esophageal fistula using a modified esophageal balloon.

Anesthesia, General↗
PubMed1999

A case of Hashimoto's thyroiditis with markedly elevated serum thyroglobulin and evidence of its influence on the measurement of anti-thyroglobulin antibody by highly sensitive assays.

We present the case of a 66-year-old woman with Hashimoto's thyroiditis, who showed extremely high concentrations of serum thyroglobulin (Tg). Serum Tg levels were markedly elevated following a slight elevation of serum thyrotropin (TSH) (22,000 ng/mL and 11.1 microU/mL, respectively). Although elevated concentrations of serum Tg declined concomitant with decrease of serum TSH one month later, Tg concentrations remained high (> 948 ng/mL) even at normal or suppressed TSH levels. There was no evidence of massive thyroid tissue damage or thyroid tumor. To our knowledge, there have been no case reports of such high concentrations of serum Tg (> 2 x 10(4) ng/mL) in the clinical course of Hashimoto's thyroiditis. Furthermore, we showed evidence that extremely high Tg levels could possibly influence the measurement of anti-Tg autoantibody using highly sensitive radioimmunoassays.

Aged↗
PubMed1998

Thrombopoietin level is inversely related to blast count, not platelet number, in Down syndrome neonates with transient myeloproliferative disorder.

Transient myeloproliferative disorder (TMD) in neonates with Down syndrome is characterized by increased megakaryoblastic cells in the peripheral blood. Despite their spontaneous regression in weeks, prognosis is not always favorable because of fatal hepatic fibrosis. In this study, blood thrombopoietin (TPO) levels were measured by ELISA in six TMD patients and the expression of c-Mpl, a ligand for TPO, was examined on the blast cells from four patients by flow cytometer. At the onset, TPO level was undetectable in one patient and significantly lower in five patients than six neonatal controls (mean 0.52 fmol/ml, range 0.30-0.93 vs. 3.70, 1.38-8.33, P < 0.001), although platelet counts were similar (mean 321 x 10(9)/l, range 42-1,040 vs. 253 x 10(9)/l, 124-381). Two patients died of hepatic failure. TPO levels were measured in five patients after regression of the blast cells. With regression of blast cells, TPO levels were remarkably increased in four survived patients. In one patient with hepatic failure, TPO level was poorly elevated and relatively lower compared to the others. TPO levels were inversely correlated with blast numbers (r = -0.85, P < 0.001), but not with platelet counts (r = 0.426). Blast cells from four patients were all positive for c-Mpl. Our findings suggest that megakaryocyte mass is a major regulator of TPO levels and hepatic failure may affect the TPO level because liver is a major source of TPO production.

Cell Count↗
PubMed1998

CD4+ T-lymphocytopenia in long-term survivors following intensive chemotherapy in childhood cancers.

BACKGROUND: It is generally believed the effects of short intensive courses of therapy are rapidly reversible in childhood cancers, and immunologic function following years of maintenance treatment with chemotherapy usually returns to normal by 6 months or less when treatment is terminated. However, we previously demonstrated that dysregulation of immunoglobulins, especially IgD, was observed in long-term survivors following intensive chemotherapy in cancer patients. With regard to cellular immunity, investigators reported that antineoplastic chemotherapy significantly reduces the number of CD4+ T-lymphocytes, and production of newly developing CD4+ T-lymphocytes was inversely related to the patients' age. However, the incidence of CD4+ lymphocytopenia in long-term survivors of childhood cancers is not known. PROCEDURE: Here, we report the flow cytometric analysis of peripheral blood from long-term survivors who continue complete remission off chemotherapy for more than 5 years. RESULTS: Six out of 74 long-term survivors (8.1%), showed low CD4+ T-lymphocyte count (<300/mm3). Three of six patients showed continued CD4+ T-lymphocytopenia over a year. In spite of the persistent low levels of CD4+ T cells, these three patients were not susceptible to severe infections. COMMENT: Intriguingly, in patients with CD4+ T-lymphocytopenia there has been a tendency toward increased numbers of natural killer cells or gamma delta T cells that may be operating as a thymus-independent compensatory mechanism to defend the hosts.

Adolescent↗
PubMed1998

Suppression of alloreactivity with gamma delta T-cells: relevance to increased gamma delta T-cells following bone marrow transplantation.

Several reports have shown that an increase in T-cell receptor gamma/delta-positive T-cells (gamma delta T-cells) have been observed following bone marrow transplantation. gamma delta T-cells expanded from peripheral blood mononuclear cells from normal volunteers were used to investigate the function of gamma delta T-cells in vitro. Peripheral blood mononuclear cells were cultured with synthetic ligand of gamma delta T-cells, monoethyl phosphates (MEP), for 7 days. MEP specifically expanded gamma delta T-cells. Expanded gamma delta T-cells from subject "B" were added to an A anti-B or A anti-C mixed lymphocyte culture (MLC) containing responder cells from subject "A" and irradiated stimulator cells from subjects "B" or "C". The cultures were harvested on day 6 and tested for cytotoxicity against stimulator-type Con A blasts. gamma delta T-cells from subject "B" specifically inhibit generation of allospecific cytotoxic T lymphocytes (CTL) in A anti-B MLC. The results indicate that gamma delta T-cells exhibit veto-type suppression of alloreaction. If the current experiments are also applicable in vivo, gamma delta T-cells originating from the donor after bone marrow transplantation may inhibit graft rejection by suppressing recipient anti-donor reactivity. gamma delta T-cells may be involved in the suppression of allogeneic reaction in vivo following allogeneic bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1998

Cytokine-enhanced mixed lymphocyte reaction (MLR) in cord blood.

Although in cord blood (CB) transplantation graft-versus-host disease (GVHD) is reported to be less severe, GVHD may occur even in patients with HLA-identical sibling donors. This result shows that HLA typing can not entirely predict GVHD. The standard MLR with CB cells was either normal or slightly reduced compared with adult peripheral blood (PB) cells. We used two manipulations to increase the responses of CB cells to allo-antigens. The first was to treat the stimulator cells with cytokines, and the second to amplify weak proliferative responses by adding exogenous cytokines to MLR cultures (modified MLR). The stimulator cells were treated with both interferon-gamma (IFN-gamma) and IL-4. The responder cells were treated with both IL-2 and tumour necrosis factor-alpha (TNF-alpha). It is still to be determined whether or not this cytokine-enhanced MLR could be a possible predictor of GVHD. However, using these cytokines, 90% of CB could recognize allo-antigens, even if the standard MLR was negative.

Adult↗
PubMed1998

Failure of forskolin to elevate the endocochlear potential in experimental endolymphatic hydrops of the guinea pig.

The effect of forskolin (FSK) on the endocochlear potential (EP) in scala media (SM) was examined in experimental endolymphatic hydrops of the guinea pig. Two weeks after obliteration of the endolymphatic sac the EP of hydroptic ears and that of the contralateral control ears were measured by means of microelectrodes. The perfusion of scala vestibuli (SV) with FSK (200 microM) produced EP elevation in the contralateral control ears but failed to do so in the experimental hydroptic ears. Histological examination of experimental endolymphatic hydrops showed mild hydrops with intact appearance of outer and inner hair cells, and the stria vascularis. The mechanism underlying the failure of FSK to elevate the EP in experimental endolymphatic hydrops is discussed.

Animals↗
PubMed1997

Bordetella bronchiseptica dermonecrotizing toxin, which activates a small GTP-binding protein rho, induces membrane organelle proliferation and caveolae formation.

We recently demonstrated that Bordetella bronchiseptica dermonecrotizing toxin (DNT) modifies a small GTP-binding protein rho and causes assembly of actin stress fibers and focal adhesions in MC3T3-E1 cells, indicating that DNT activates the function of rho protein (Horiguchi et al., 1995, J. Cell Sci. 108, 3243-3251). In this study, we examined by electron microscopy ultrastructural changes in DNT-treated MC3T3-E1 cells under conditions in which DNT elicited the above morphological changes. We found that DNT induced proliferation of cytoplasmic membrane organelles, such as Golgi apparatus, smooth and rough endoplasmic reticulum, and mitochondria, and formation of plasmalemmal caveolae. Therefore we examined also the effect of Clostridium botulinum C3 exoenzyme (C3), which has been known to ADP-ribosylate and inactivate rho protein, and found that C3 exoenzyme inhibited the development of membrane organelles in the MC3T3-E1 cells. These findings show that proliferation of membrane organelles and caveolae formation are controlled by the function of rho, which is the target of DNT action.

3T3 Cells↗
PubMed1997

Results of surgery for bronchogenic carcinoma located in the aortic window.

Because of its critical location, lung cancer located in the aortic window can cause complications affecting the pulmonary artery trunk, aortic arch and esophagus. The results of surgical treatment are poor; however, there are few long-term survivors. In an attempt to define the indications for extended surgery, we evaluated eleven patients with non-small cell lung cancer. The tumors were classified according to their clinical extent of invasion as Type A (invading the anterior mediastinum including the central part of the pulmonary artery), Type B (invading upwardly to the mediastinum through the aortic window) or Type C (invading the posterior mediastinum including the thoracic aorta or esophagus). In the five patients with type A invasion, no metastases to the upper mediastinal lymph nodes other than the subaortic lymph nodes were found. The three patients with type B invasion had many metastases to the upper mediastinal lymph nodes. There were no metastases in the upper mediastinum in any of these patients with type C invasion, but metastases were found in a lower mediastinal lymph node #9, and a carinal lymph node. Each group clearly demonstrated a different site of mediastinal lymph nodes metastasis. The long term result was good in Type A invasion, in contrast to Type B or C invasion. Our classification may be useful for planning one's surgical approach to advanced lung cancer of the aortic window.

Adult↗
PubMed1997

Expression of highly polysialylated NCAM (NCAM-H) in developing and adult chicken auditory organ.

Neural cell adhesion molecule (NCAM) is highly polysialylated (NCAM-H) in developing tissues, and recent findings suggest that NCAM-H is more essential for neural development than poorly sialylated NCAM (NCAM-L). In order to understand the precise role of NCAM-H in developing and adult inner ears, the immunohistochemical localization of NCAM-H in developing and adult chicken inner ears was examined using a monoclonal antibody which is only specific for NCAM-H. Immunoreactivity of NCAM-H was initially observed on acoustic ganglion at stage 24, when peripheral (afferent) fibers begin to emerge from the ganglion cells. At stage 38, when peripheral fibers form synapses with hair cells, NCAM-H was observed on peripheral fibers and the base of hair cells in the auditory epithelium. At stage 42, NCAM-H on nerve fibers disappeared, and only some acoustic ganglion cells were still positive for NCAM-H. This immunostain on ganglion cells was retained after birth. These data are consistent with the hypothesis that NCAM-H specifically regulates the afferent nerve fibers' growth and synaptogenesis with hair cells during inner ear development and may be associated with processing of auditory information and neuronal plasticity.

Animals↗