Biomedical subjects

H Kuramoto

Publications and source records attributed to H Kuramoto.

At least 37 records · Page 2Linked to original sources

PubMed2001

Time course of Fos and Fras expression in the hypothalamic supraoptic neurons during chronic osmotic stimulation.

The Fos family comprises Fos and several subtypes of Fos-related proteins (Fras) such as FosB, Fra-1, Fra-2, DeltaFosB, and chronic Fras. Changes in the expression of Fos family proteins with time are not well elucidated, particularly during chronic stimulation. In the present experiments, we investigated quantitatively the time course changes in Fos, FosB and Fras immunoreactivity in the magnocellular neurons of the supraoptic nucleus (SON) during acute and chronic osmotic stimulation. A small number of Fos- and FosB-positive neurons were observed in the SON of control rats, while many Fras-positive neurons were seen in control animals. Significant increases in the numbers of Fos-, FosB-, and Fras-positive neurons were observed 2 h after acute osmotic stimulation by intraperitoneal (i.p.) injection of 3% NaCl solution. Although the number of Fos-positive neurons returned to the control level 4 h after i.p. injection, a significant number of FosB- and Fras-positive neurons were still observed 8 h after i.p. injection. During chronic osmotic stimulation by giving 2% NaCl solution for 2 and 5 days, a large number of Fos-positive neurons were observed, but the cessation of chronic osmotic stimulation by normal water drinking immediately decreased the number of Fos-positive neurons to the control level within 2 h. The number of FosB-positive neurons was increased with period of chronic osmotic stimulation, and a significant number were observed 2-8 h after the cessation of the stimulation. The number of Fras-positive neurons was also significantly higher during chronic osmotic stimulation, and this number was significantly high 2-8 h after the cessation of the stimulation. RT-PCR analysis demonstrated the persistent expression of c-fos mRNA in the SON during chronic osmotic stimulation. These results suggest that c-fos mRNA and Fos protein are constitutively elevated during chronic osmotic stimulation and the time course changes in Fos are different from those seen in FosB and Fras.

Animals↗

PubMed2001

Growth and gene expression profile analyses of endometrial cancer cells expressing exogenous PTEN.

The PTEN tumor suppressor gene encodes a multifunctional phosphatase that plays an important role in inhibiting the phosphatidylinositol-3-kinase pathway and downstream functions that include activation of Akt/protein kinase B, cell survival, and cell proliferation. Enforced expression of PTEN in various cancer cell lines decreases cell proliferation through arrest of the cell cycle, accompanied in some cases by induction of apoptosis. We used cDNA microarrays containing 4009 cDNAs to examine changes in gene-expression profiles when exogenous PTEN was induced in PTEN-defective cells. The microarrays and subsequent semi-quantitative reverse transcription-PCR analysis revealed transcriptional stimulation of 99 genes and repression of 72 genes. Some of the differentially expressed genes already had been implicated in cell proliferation, differentiation, apoptosis, or cell cycle control, e.g., overexpression of PTEN-induced transactivation of cyclin-dependent inhibitor 1B (p27Kip1) and 2B (p15INK4B), members of the TNF receptor family, tumor necrosis factor-associated genes, and members of the Notch-signaling and Mad families. To our knowledge this is the first report of transactivation of those genes by PTEN. The genes differentially expressed in our experiments also included many whose correlation with cancer development had not been recognized before. Our data should contribute to a greater understanding of the broad spectrum of ways in which PTEN affects intracellular signaling pathways. Analysis of expression profiles with microarrays appears to be a powerful approach for identifying anticancer genes and/or disease-specific targets for cancer therapy.

Adenoviridae↗

PubMed2001

Prognostic factors of stage IV epithelial ovarian cancer: a multicenter retrospective study.

OBJECTIVE: In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic factors of stage IV epithelial ovarian cancer. METHODS: In November 1999, 24 Japanese institutions received questionnaires regarding stage IV epithelial ovarian cancer patients. Eligibility criteria included all patients with stage IV epithelial ovarian cancer who were surgically confirmed and initially treated in each institution between January 1990 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, site of metastasis, preoperative CA125, cytoreductive surgery, residual disease after cytoreductive surgery, and response to primary chemotherapy. Survival analysis and comparisons were performed by univariate and multivariate methods. RESULTS: Two hundred twenty-five patients with stage IV ovarian cancer were identified. The median age of the patients was 54 years. The most common site of extraperitoneal disease was malignant pleural effusion (39.6%). Of the 225 patients who underwent an attempt at surgical debulking, 70 (31.1%) were optimally cytoreduced. Most patients received platinum-based combination chemotherapy for primary chemotherapy. In multivariate analysis, performance status, histology, and residual disease after cytoreductive surgery were independent prognostic predictors of outcome. The overall median survival for optimally debulked patients was 32 months compared to 16 months for suboptimally debulked patients (P < 0.0001, hazard ratio: 0.415). CONCLUSION: Optimal surgical debulking, performance status, and histology appear to be important prognostic factors of survival in patients with stage IV epithelial ovarian cancer.

Adult↗

PubMed2001

Immunohistochemical study on VEGF expression in endometrial carcinoma--comparison with p53 expression, angiogenesis, and tumor histologic grade.

OBJECTIVE: Vascular endothelial growth factor (VEGF)--that activates endothelial cell growth--has been considered to induce angiogenesis, which is indispensable to tumor-genesis and progression. In this study, an immunohistochemical analysis was carried out to clarify the correlation of VEGF expression with angiogenesis, p53 expression--of which the wild-type is considered to suppress VEGF expression--and histologic grade in endometrial carcinoma. STUDY DESIGN: Immunohistochemical staining for detecting VEGF protein, factor VIII-related antigen of endothelial cells, and p53 protein was performed by the labeled streptavidin-biotin method on the formalin-fixed and paraffin-embedded tumor tissue of 104 patients with endometrial (endometrioid) carcinoma, including 69 with well-differentiated, 25 with moderately differentiated, and ten with poorly differentiated adenocarcinoma. RESULTS: The labeling index of p53 expression was 19.9+/-28.8% in the high VEGF group, whereas in the low VEGF group it was 12.2+/-17.0%, showing that VEGF expression was significantly correlated with p53 expression (P<0.05). VEGF expression, however, was not correlated with either the number of microvessels in the tumor area or tumor histologic grade. CONCLUSION: VEGF expression was not a single specific indicator of angiogenesis in endometrial carcinoma, whereas it was significantly correlated with p53 expression.

Adenocarcinoma↗

PubMed2001

Medroxyprogesterone acetate therapy for patients with adenocarcinoma of the endometrium who wish to preserve the uterus-usefulness and limitations.

BACKGROUND: To determine the effectiveness of medroxyprogesterone acetate therapy for women with endometrial adenocarcinoma who wish to preserve their uterus. STUDY DESIGN: Fifteen patients with endometrial carcinoma (12 with grade 1 endometrioid adenocarcinoma. 2 with grade 2 adenocarcinoma and 1 with adenoacanthoma) were treated with high-dose medroxyprogesterone acetate alone as primary therapy and their clinical responses evaluated. RESULTS: Seven of the 12 cases (58%) with grade I adenocarcinoma and one of the two (50%) with grade 2 carcinoma responded initially to medroxyprogesterone acetate. The median length of treatment required for regression was 29 weeks. Three patients who initially responded relapsed. Thirteen patients are alive without evidence of disease as of December 1999 (10 to 146 months, median; 4 years and 11 months) and one is continuing medroxyprogesterone acetate therapy as a final follow-up. One patient was lost to follow-up. Two patients have conceived having three healthy infants. CONCLUSION: Treatment of endometrial carcinoma with high-dose medroxyprogesterone acetate could be an alternative to hysterectomy, although the successful rate is limited.

Adenocarcinoma↗

PubMed2001

Treatment for complex atypical hyperplasia of the endometrium.

OBJECTIVE: To clarify the clinical outcome of women with complex atypical hyperplasia of the endometrium who were treated either by hysterectomy or a non-surgical treatment with medroxyprogesterone acetate (MPA). STUDY DESIGN: Thirty of the 53 patients with complex atypical hyperplasia of the endometrium were treated by undergoing hysterectomy and 20 were treated with MPA alone as the primary therapy. Their clinical features and outcomes were evaluated. RESULTS: The ages of the 53 patients ranged from 28 to 62 years (mean 46.2). Fifteen (75%) of the 20 patients (8 of 12 with low-dose MPA and 6 of 8 with high-dose MPA) responded initially to MPA therapy. Two of the 12 patients who were treated with low-dose MPA progressed to endometrial adenocarcinoma. Three patients treated with high-dose MPA conceived after treatment having three healthy infants. CONCLUSION: Primary treatment with high-dose MPA is a safe and effective therapy for women with complex atypical hyperplasia of the endometrium who wish to preserve their fertility.

Adult↗

PubMed2000

Uterine leiomyoma causing massive ascites and left pleural effusion with elevated CA 125: a case report.

A 51-year-old patient presented with an abdominal mass and ascites as well as a left pleural effusion. Her serum CA125 was 820 U/ml. Surgical exploration revealed a benign leiomyoma of the uterus without malignant cytology in the ascites. Postoperatively, the pleural effusion was resolved dramatically and the CA125 decreased to the normal range after 4 months post-operatively. This is an extremely rare case of pseudo-Meigs' syndrome caused by uterine leiomyoma.

Ascites↗

PubMed2000

Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases.

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.

Adenocarcinoma↗

PubMed2000

Margin clearance and HPV infection do not influence the cure rates of early neoplasia of the uterine cervix by laser conization.

A lesion existing in the endocervical and/or ectocervical conized margin and HPV-DNA existing in a conized specimen are reported to be at risk of persistence or recurrence of early neoplasia of the cervix when treated by conization. The aim of this study was to investigate whether margin clearance and HPV infection influenced the outcome in our series of laser conization. Excisional conization with the KTP/YAG Surgical Laser System or Nd-YAG laser was performed in this study. Eighty patients with cervical neoplasias were included: 47 with dysplasia, 25 with carcinoma in situ (CIS) and eight with microinvasive carcinoma. The endocervical and ectocervical conized margins were examined microscopically. HPV-DNA was analyzed with the primer for types 16, 18, 31, 33, 35, 52b and 58 amplified by the PCR method. The margins of the conized specimens were confirmed histopathologically to be clear in 58 cases (73%), whereas in 22 cases (27%) they were involved by neoplasia. HPV-DNA was positive in 38% of dysplasias, 40% of CISs and 50% of microinvasive carcinomas. The overall rate of the initial cure at 10 weeks after treatment appeared to be 100% in all 80 cases. Primary cure rates were 100% for 47 cases with dysplasia, 96% for 24 cases with CIS and 100% for four cases with microinvasive carcinoma regardless of margin positivity and HPV-DNA status. Involved margins and HPV infection did not influence the cure of early neoplasia of the uterine cervix achieved by our laser conization procedure. The favorable results may be due to the procedure of vaporizing the cut surface forming a dome-shaped tissue defect.

Conization↗

PubMed2000

Comparison of endometrial carcinoma coexisting with and without endometrial hyperplasia.

OBJECTIVE: It has been reported that endometrial carcinoma has two pathogenic types; one with and the other without endometrial hyperplasia. The present study was done to clarify whether this was true in our series of a large number of Japanese patients. METHODS: Three hundred and twenty-eight patients with endometrial carcinoma were classified into two groups, one coexisting endometrial hyperplasia (group 1; 182 cases) and the other having normal endometrium without endometrial hyperplasia (group 2; 107 cases). The clinical and pathological observations of the two groups were compared. RESULTS: The ages of the patients were significantly lower in group 1 (30-83; mean 50.7) than in group 2 (34-81; mean, 57.2). The incidence of the carcinoma with invasion limited to less than 1/3 of the myometrium, with surgical stage I, lower grade endometrioid type and higher levels of progesterone receptor, and without lymph node metastasis were significantly higher in group 1 than in group 2. The cumulative survival rate for stage I was also significantly higher in group 1 patients. CONCLUSION: A significant difference was found between groups 1 and 2 in age distribution, degree of progress and pathological observations. Stage I patients in the former group had a better prognostic than the latter.

Adult↗

PubMed1999

Morphological relationship between serotonergic neurons and nitrergic neurons for electrolytes secretion in the submucous plexus of the guinea pig distal colon.

In the submucous plexus, double immunocytochemistry revealed that nitric oxide synthase (NOS)-immunoreactivity was found in both numerous nerve fibers and some nerve cell bodies, while 5-hydroxytryptamine (5-HT)-immunoreactivity was limited to many nerve fibers, but not any nerve cell bodies. About 30% of the total NOS positive neurons (978) had close or some contact with 5-HT positive nerve fiber, suggesting that NO may participate in the 5-HT-evoked chloride secretion.

Animals↗

PubMed1999

Motor innervation by enteric nerve fibers containing both nitric oxide synthase and galanin immunoreactivities in the striated muscle of the rat esophagus.

The relationship between nitric oxide synthase (NOS)- and galanin-immunoreactive nerve terminals and the origin of NOS-immunoreactive nerve terminals on the motor endplates in the striated muscles of the rat esophagus was investigated. Double immunohistochemical staining revealed a dual innervation of motor endplates by calcitonin gene-related peptide (CGRP)-immunoreactive axons and by axons that were immunoreactive for both NOS and galanin. On average, 91% of NOS terminals were galanin immunoreactive. NOS-immunoreactive fibers were revealed at 67% of endplates, identified by the presence of CGRP terminals. The left vagus and superior laryngeal nerve were cut and 15 days allowed for terminals to degenerate. This caused a significant loss of CGRP fibers, but did not affect the density of innervation of the striated muscle by NOS-immunoreactive fibers. Thus the NOS/galanin fibers are deduced to originate from ganglia in the esophageal wall. This is supported by our observation of numerous NOS-immunoreactive nerve cell bodies in the myenteric ganglia of the esophagus, 74% of which were galanin immunoreactive. There were no CGRP-immunoreactive nerve cell bodies in the wall of the esophagus.

Animals↗

PubMed1999

Androgen-producing ovarian tumors: a clinicopathological study of 3 cases.

The clinical course and pathological findings of 3 rare cases of androgen-producing ovarian tumors are presented. The ages of the 3 patients (Cases 1, 2, and 3, respectively) were 43, 34, and 57 years, respectively. Their preoperative serum testosterone levels were 506, 491, and 231 ng/dl, respectively. The pathological diagnoses of Cases 1, 2, and 3 were a Sertoli-stromal cell tumor of intermediate differentiation, a stromal tumor containing Leydig cells, and a stromal tumor with minor sex cord elements, respectively. Patient 1 experienced a recurrence, of a lesion at the vaginal stump 1 year and 2 months after the initial surgery. The clinical courses of Cases 2 and 3 have been non-contributory.

Adult↗

PubMed1998

Calretinin-immunoreactive laminar nerve endings in the laryngeal mucosa of the rat.

The distribution of laminar nerve endings that contained immunoreactive calretinin was examined in the laryngeal mucosa of the adult rat. In whole-mount preparations, the immunoreactive laminar endings were distributed in the supraglottic region but not in the subglottic region. The laminar endings that arose from thick nerve fibers with or without swellings were identified as corpuscles with many variform terminal arborizations. They appeared to be located at the interface between the epithelium and the subepithelial connective tissue. The terminals were scattered under the basal lamina of the epithelium, and some of them were located within the epithelial layer. Immunoelectron microscopy revealed that both sub- and intraepithelial immunoreactive terminals that were filled with mitochondria were partly or totally ensheathed by Schwann cell processes. The denervation experiments, in which the superior laryngeal nerve was cut unilaterally or bilaterally, suggested that the laminar endings originate from the superior laryngeal nerve with strict ipsilateral innervation. The laminar endings might be associated with detection of changes in pressure in the laryngeal cavity or chemical stimuli.

Animals↗

PubMed1998

5-HT activates nitric oxide-generating neurons to stimulate chloride secretion in guinea pig distal colon.

The participation of nitric oxide (NO) in serotonin (5-hydroxytryptamine; 5-HT)-evoked chloride secretion in guinea pig distal colon was examined. Submucosal/mucosal segments were mounted in Ussing flux chambers, and an increase in short-circuit current (Isc) was used as an index of secretion. Addition of 5-HT to the serosal side produced a concentration-dependent (10(-7)-10(-5) M) increase in Isc caused by chloride secretion. NG-nitro-L-arginine (L-NNA) significantly reduced the 5-HT-evoked early (P-1) and late (P-2) responses to 61.1 and 70.6% of control, respectively. Neurally evoked response was also inhibited by L-NNA. The NO donor sodium nitroprusside (SNP, 10(-4) M) increased basal Isc mainly because of chloride secretion. The SNP-evoked response was significantly reduced by tetrodotoxin but was unchanged by atropine or indomethacin. These results suggest that the 5-HT-evoked increase in Isc is associated with an NO-generating mechanism. Atropine significantly reduced the 5-HT (10(-5) M)-evoked P-1 and P-2 responses to 71.8 and 19.7% of control, respectively. Simultaneous application of atropine and L-NNA further decreased the 5-HT-evoked responses more than either drug alone; application of L-NNA and atropine decreased the 5-HT-evoked P-1 and P-2 responses to 68.5 and 39.2% of atropine-treated tissues, respectively. These results suggest that noncholinergic components of P-1 and P-2 responses are 71.8 and 19.7% of control, respectively, and that NO components of P-1 and P-2 responses are 32 and 61%, respectively, of the noncholinergic component of the 5-HT-evoked responses. The results provide evidence that NO may participate as a noncholinergic mediator of 5-HT-evoked chloride secretion in guinea pig distal colon.

Animals↗

PubMed1998

Role of estrogen and estrogen-related growth factor in the mechanism of hormone dependency of endometrial carcinoma cells.

The role of estrogen and estrogen-related growth factors in the mechanism of hormone dependency of endometrial adenocarcinoma cells was investigated. The proliferation of hormone-responsive human endometrial adenocarcinoma cells (Ishikawa cells), which possess both estrogen and progesterone receptors, was optimally stimulated by 10 nM estradiol. Both transforming growth factor (TGF)-alpha and epidermal growth factor (EGF), added to the culture media, stimulated the proliferation of Ishikawa cells in a dose-dependent manner. Anti-TGF-alpha antibody completely eliminated the stimulatory effects of TGF-alpha. Anti-EGF receptor antibody inhibited the proliferation of these cells. The production of TGF-alpha into culture media was 5-40 pg/10 cells/24 h in 9 human endometrial adenocarcinoma cells. Ten nanomoles of estradiol increased the TGF-alpha production of Ishikawa cells by approximately 2.5-fold of the control level. In contrast, the production of TGF-alpha in hormone-unresponsive HEC-50 cels was not influenced by estradiol. C-erbB-2 oncoprotein expression of human endometrial adenocarcinoma cells, detected by both immunocytochemical staining and Western blot analysis, was associated with the tumor grade of the original tumor tissues. Ten nanomoles of estradiol clearly increased the c-erbB-2 oncoprotein levels at an optimal incubation period of 72 h, whereas estradiol did not affect the expression in HEC-50 cells.

Adenocarcinoma↗

PubMed1997

NGF and BDNF increase the immunoreactivity of vesicular acetylcholine transporter in cultured neurons from the embryonic rat septum.

The expression of vesicular acetylcholine transporter (VAChT), which transports ACh into synaptic vesicles, is coregulated with choline acetyltransferase (ChAT). Therefore, the effects of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) on the levels of VAChT in cultured neurons from the septum of embryonic rats were investigated by immunocytochemistry. NGF and BDNF increased the number of VAChT-immunoreactive neurons by approximately 1.5-fold and enhanced the immunoreactivity in each positive cell. These results suggest that the neurotrophins enhance not only synthesis but also storage of ACh in septal neurons.

Acetylcholine↗

PubMed1997

Occurrence of myelin-associated glycoprotein (MAG)-like immunoreactivity in some nervous, endocrine, and immune-related cells of the rat. An immunohistochemical study.

The occurrence and distribution of myelin-associated glycoprotein (MAG)-like immunoreactivity was investigated in the rat using a polyclonal antibody to MAG purified from rat brain. In the nervous system, MAG immunoreactivity was found in the periaxonal portion of the myelinated fibers and in a small number of oligodendroglia in the cortex, hippocampus, and the spinal cord. The sheath of Schwann cells in unmyelinated fibers and satellite cells in the spinal ganglia were also immunoreactive for MAG. In the endocrine system, the noradrenaline-containing cells in the adrenal medulla and some endocrine cells in the duodenum showed MAG immunoreactivity. In the immune system, numerous reticular cells with slender cytoplasmic processes, which formed a dense network, were immunopositive for MAG within the germinal center in the lymph nodes and spleen. In the thymus, a number of epithelial reticular cells within the medulla showed variation in staining intensity. These findings provide new information on the wide distribution of MAG immunoreactivity in the nervous, endocrine, and immune systems, and may contribute to the further understanding of the biological roles of this protein.

Adrenal Glands↗