Biomedical subjects

S Mizutani

Publications and source records attributed to S Mizutani.

At least 55 records · Page 3Linked to original sources

PubMed2001

Diagnostic efficacy of tumor markers, sonography, and intraoperative frozen section for ovarian tumors.

Using sonography, we classified the adnexal masses of 292 patients into 4 patterns. Pattern A was benign cystic tumors; B was benign mixed tumors (cysts with a smooth solid component); C was malignant mixed tumors (cysts with an irregular solid component or thickened septum), and D was solid tumors. We diagnosed tumors showing patterns A and B as benign, while patterns C and D represented tumors with low malignant potential or actual malignancy. The sensitivity and specificity of sonography was 82.2 and 82.1%, respectively, and these values were superior to those for tumor markers (CA125, CA19-9, CA72-4). Both the sensitivity and specificity of intraoperative frozen sections were the highest, showing that this is the most reliable examination. However, 15 of 191 patients undergoing frozen section were upgraded by the final pathological diagnosis. If sonography is performed by an experienced gynecologic oncologist, this examination is more reliable than tumor markers. However, intraoperative frozen section should still be performed during surgery for patients with ovarian tumors.

Adolescent↗

PubMed2001

Imbalance between neutral endopeptidase 24.11 and endothelin-1 expression in human endometrial carcinoma.

OBJECTIVES: Neutral endopeptidase 24.11 (NEP)/CD10 is a cell-surface peptidase that degrades various bioactive peptides including endothelin-1 (ET-1). This enzyme is known to play a role in maintaining ET-1-regulated vascular homeostasis in the normal human endometrium. The purpose of the present study was to investigate the expression and localization of NEP and ET-1 in neoplastic endometria, and also to clarify the correlation of their expression with the tumor grade of endometrial carcinoma. METHODS: Immunohistochemical analysis for NEP and ET-1 expression was performed on paraffin-embedded tissue sections of 7 normal endometria (after menopause), 5 atypical endometrial hyperplasias (AEH), and 32 endometrial endometrioid adenocarcinomas. RESULTS: In normal endometrium and AEH, NEP immunoreactivity was detected in stromal cells, but not in glandular cells. In contrast, ET-1 immunoreactivity was detected in both glandular and stromal cells. In the stromal cells of grade 1 endometrial adenocarcinoma, NEP was detected at high or moderate quantities. However, significantly decreased NEP immunoreactivity was observed in the stromal cells of grade 2 and 3 adenocarcinomas. However, NEP was not immunostained in adenocarcinoma cells except for the lesions of squamous differentiation. ET-1 immunoreactivity was weakly detected in the stromal cells of grade 1 adenocarcinoma, but the intensity of ET-1 staining increased with advancing tumor grade. The ratio of the staining scores of stromal ET-1 to stromal NEP was positively correlated with the tumor grade. CONCLUSIONS: These findings demonstrate that NEP expression in the stromal cells of endometrial adenocarcinoma is downregulated, while stromal ET-1 is upregulated, with increasing tumor grade. The present findings also suggest that NEP may play a role in the regulation of neoplastic transformation, tumor progression, and differentiation in endometrial neoplasms, possibly by degrading certain peptide growth factors such as ET-1.

Adult↗

PubMed2001

Expression of nm23-H1 in hydatidiform mole and its relationship with the development of postmolar disease.

The aim of the present study was to investigate the expression of nm23-H1 in human placenta, hydatidiform mole and choriocarcinoma cells. Nm23-H1 protein was localized in the cytotrophoblast, but not in the syncytiotrophoblast. In the hydatidiform mole cases with subsequent spontaneous remission, nm23-H1 mRNA levels were significantly lower than those in first-trimester placentas. However, its levels were elevated in the hydatidiform mole cases that progressed to persistent gestational trophoblastic disease and were comparable to those of first-trimester placentas, and they were further elevated in choriocarcinoma cells. The present data suggest an association of nm23-H1 for the proliferation activity of trophoblast, and its increased expression may influence the development of persistent trophoblastic disease.

Blotting, Northern↗

PubMed2001

[A case of urothelial tumors which occurred simultaneously in bilateral upper urinary tracts and bladder presenting with anuria].

A 72-year-old male was admitted with a chief complaint of anuria. Clinical examinations showed that he was in uremic state and had bilateral hydronephroses. An endoscopic examination revealed a left ureteral tumor and a bladder tumor. Left nephroureterectomy with partial cystectomy and transurethral resection of the bladder tumor were performed. Pathological examinations showed an invasive left renal pelvic tumor (pT3, G3), an invasive left ureteral tumor (pT4, G3), and a bladder tumor (pTis, G3). Following the operation, roentgenological and urinary cytological findings showed a right ureteral carcinoma. He died of multiple liver and bone metastases and local recurrence at 5 months postoperatively.

Aged↗

PubMed2001

[Transitional cell carcinoma of the bladder in a young patient: a case report].

A 14-year-old male patient was admitted with the chief complaint of macroscopic hematuria. Abdominal ultrasonography demonstrated a tumor of the anterior wall of the bladder. Further, cystoscopic examination confirmed a papillary tumor. Transurethral resection of the bladder tumor was performed. Histopathology of the excised tumor showed transitional cell carcinoma (G1, pTa). Recurrence has not been observed for 9 months postoperatively.

Adolescent↗

PubMed2001

[Undescended testicular tumor found by torsion of the testis: a case report].

A 37-year-old man was admitted with a painful mass in his left inguinal region. He had an undescended testis on the left side. Six months earlier, he had noted that his left inguinal testis was larger, and he had suddenly developed pain in the left inguinal region. The levels of AFP, hCG beta and LDH were normal. We diagnosed a left undescended testicular tumor and torsion of the left testis. Left inguinal high orchiectomy showed a torsion of the left testis and histopathological examination of the specimen revealed seminoma.

Adult↗

PubMed2001

[Renal metastasis originating from pulmonary carcinoma: a case report].

A 61-year-old woman, who had undergone total right pneumonectomy 22 months before due to lung cancer (adenosquamous cell carcinoma) was admitted for macroscopic hematuria. Abdominal CT showed two renal tumors in the right kidney. Right radical nephrectomy was performed, because no imaging study showed any other metastasis. Pathological examination revealed adenosquamous cell carcinoma, which was the same pathology as the lung cancer had been. She died of the left lung metastasis 24 months after right radical nephrectomy. Her prognosis was thought to have been prolonged by the operation of right radical nephrectomy.

Carcinoma, Adenosquamous↗

PubMed2001

[Case report of scimitar syndrome in infancy: intracardiac repair after coil embolization of systemic arterial supply to sequestered lung].

A 10-month-old girl was diagnosed with atrial septal defect and pulmonary sequestration and scimitar syndrome. Cardiac catheterization revealed severe pulmonary hypertension, with systemic pulmonary artery pressure 97 mmHg, pulmonary resistance 10.3 U, and Qp/Qs 0.45. Systemic pulmonary artery pressure was decreased from 108 to 75 mmHg by oxygenation. We performed coil embolization of the systemic artery and repair of the partial anomalous pulmonary venous return, division and reimplantation of the anomalous vein into the right atrium, and a patch was inserted to redirect flow to the left atrium. The severe pulmonary hypertension was improved and echocardiography showed systemic pulmonary artery pressure of 45 mmHg. The postoperative hemodynamic and respiratory condition was satisfactory.

Bronchopulmonary Sequestration↗

PubMed2001

[Late metastases of prostatic adenocarcinoma to urinary bladder after radical prostatectomy: a case report].

We report a case of metastasis of prostatic cancer to urinary bladder. A 67-year-old man was admitted with a complaint of macroscopic hematuria, who had undergone radical prostatectomy and surgical castration for prostatic cancer (pT3N0M0) 53 months before. Computed tomographic (CT) scan revealed an invasive tumor on the right wall of the urinary bladder and swelling of paraaortic and pelvic lymph node metastases. These lesions were diagnosed as bladder tumor with lymph node metastases, and then transurethral biopsy of bladder tumor was performed. Because macroscopic hematuria could not be controlled and severe progressive anemia was found after the biopsy, simple cystectomy and bilateral cutaneoureterostomy were performed on the next day. Histopathological analysis showed that the tumor was adenocarcinoma, which was thought to be a metastatic tumor from the prostatic cancer.

Adenocarcinoma↗

PubMed2001

[Prostatic carcinoma presenting as neck lymph node metastases: report of two cases].

We report two cases of prostatic carcinoma presenting as neck lymph node metastases. Case 1: A 56-year-old man was admitted to our hospital with the chief complaint of left lower abdominal pain. A lymph node was palpable on the left side of the neck swollen. Rectal examinations revealed prostatic stony-hard mass. Computed tomography showed a swollen neck and paraaortic lymph nodes on the left side. PSA level was 380 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma, and neck lymph node biopsy also revealed metastatic adenocarcinoma. We diagnosed him with prostatic carcinoma stage D2 (LYM). He underwent hormonal therapy (TAB) but died 13 months later. Case 2: A 66-year-old man was admitted to our hospital with the chief complaint of a large palpable mass on the left side of the neck. Resection of this mass revealed metastatic adenocarcinoma. Rectal examination revealed no malignant lesions, but the PSA level was high, 1,700 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma. Computed tomography revealed paraaortic and pelvic lymph node metastases and bone scintigram revealed abnormal uptake, bone metastases. We diagnosed him with prostatic carcinoma stage D2 (LYM OSS). We performed bilateral testectomy followed by hormonal therapy (TAB). The lymph node metastases disappeared after 4 months of therapy.

Adenocarcinoma↗

PubMed2001

Squamous cell carcinoma of the vulva and adjacent lesions treated at Nagoya University Hospital from 1965 to 1997.

Japan has a lower incidence of vulvar squamous cell carcinoma (VSCC) than Western nations. To pin-point the reasons for this, we reviewed biopsy samples from all cases treated at Nagoya University Hospital over the past 33 years in order to investigate the background lesions for VSCC. Two of 36 VSCC patients had adjacent or coexisting lichen sclerosus (LS), 5 had squamous cell hyperplasia (SCH), and 16 had vulvar intraepithelial neoplasia (VIN). There were 8 cases in which these lesions were thought to be the origin of the VSCC, 1 in which keratinizing squamous cell carcinoma (KSC) was seen in LS, 1 in which verrucous SCH was the origin, and 6 in which 4 basaloid carcinoma and 2 warty carcinoma developed from basaloid VIN and warty VIN, respectively. Although 8 other cases of keratinizing or non-keratinizing squamous cell carcinomas (NSC) coexisted with VIN NOS (not otherwise specified), differentiated VIN or basaloid VIN, we could not be histologically certain of the origin. Among 22 VSCC patients tested for HPV DNA, only an 84-year-old woman presenting a histological feature of KSC tested positive by in situ hybridization (ISH). It was considered that LS and SCH had little and VIN considerable capacity to cause the malignancy of VSCC. We surmise that in Japan the majority of squamous cell carcinoma is unrelated to HPV. One reason for the low incidence of VSCC is largely due to race; the homogeneous, monoethnic Japanese population, as well as the few cases of HPV-related VSCC.

Adult↗

PubMed2001

Characterization of soluble CD40 ligand released from human activated platelets.

We report here that soluble CD40 ligand (sCD40L) is released from human platelets when activated with collagen or thrombin. The sCD40L was detectable in the culture supernatants of platelets within 30 min after stimulation in vitro, and reached maximal levels in 3 h. The release was blocked by the metalloproteinase inhibitor, KB8301, indicating that the soluble CD40L is made by cleaving the membrane bound CD40L expressed on activated platelets. The sCD40L was undetectable in the supernatant of the activated platelets obtained from patients with X-linked hyper IgM syndrome (XHIM), who have defects in CD40L gene. Since sCD40L has been shown to have biologic function on the activation of vascular endothelial cells and B cells, these findings suggest that platelets play some roles in both inflammation and humoral immune response by releasing soluble CD40L.

Antibody Formation↗

PubMed2000

Total synthesis of (+/-)-culmorin and (+/-)-longiborneol: an efficient construction of Tricyclo[6.3.0.0(3,9)]undecan-10-one by intramolecular double Michael addition.

The treatment of 4-[(5E)-6-methoxycarbonyl-5-hexenyl]-3, 4-dimethyl-2-cyclopenten-1-one (5) with LHMDS, TMSI-HMDS, Bu(2)OTf-HMDS, or TMSCl-NEt(3)-ZnCl(2) caused the intramolecular double Michael addition to afford tricyclo[6.3.0.0(3, 9)]undecan-10-one 12 in high yields with perfect stereoselectivity. The methodology was further elaborated to achieve efficient total syntheses of (+/-)-culmorin (1) and (+/-)-longiborneol (2). The common precursor 13 of them was obtained from 14 in 94% yield as a single isomer by the treatment with LHMDS. After the conversion of 13 into the corresponding acid 24 by hydrolysis, oxidative decarboxylation using S-(1-oxido-2-pyridinyl)-1,1,3, 3-tetramethylthiouronium hexafluorophosphate (HOTT, 27), followed by the Birch reduction, stereoselectively afforded (+/-)-culmorin (1). (+/-)-Longiborneol (2) was synthesized from 24 by the standard transformation. Additionally, the treatment of 24 with Pb(OAc)(4) led to 28 via uncommon migration. Its structure was determined by X-ray analysis after the transformation into the diketone 29.

Computer Graphics↗

PubMed2000

The Ras-mitogen-activated protein kinase pathway is critical for the activation of matrix metalloproteinase secretion and the invasiveness in v-crk-transformed 3Y1.

To search for the intracellular signaling pathway critical for the secretion of matrix metalloproteinases (MMP), we studied the effects of dominant negative Ras (S17N Ras) and dominant negative MEK1 (MEK1AA) expression in v-crk-transformed 3Y1. Expression of either S17N Ras or MEK1AA dramatically suppressed the augmented secretion of MMP-2 and MMP-9 in v-crk-transfected 3Y1. Similarly, a Ras farnesyltransferase inhibitor, manumycin A, and a MEK1 inhibitor, U0126, suppressed MMP secretion in a dose-dependent manner, whereas a PI3 kinase inhibitor, wortmannin, could not. In addition, the suppression of MMP secretion by S17N Ras showed good correlation with the inhibition of in vitro invasiveness of the cells. In contrast, expression of dominant negative C3G did not suppress MMP secretion, although it substantially blocked the c-Jun N-terminal kinase activation. Taken together, the Ras-MEK1 pathway, but not the C3G-JNK pathway, seems to play a key role in the activation of MMP secretion and, hence, the invasiveness of v-crk-transformed cells.

Androstadienes↗

PubMed2000

Placental leucine aminopeptidase/oxytocinase in maternal serum and placenta during normal pregnancy.

Placental leucine aminopeptidase (P-LAP), which is identical with cystine aminopeptidase as oxytocinase, was found to be homologous with rat insulin-regulated membrane aminopeptidase (IRAP) by sequence comparison. In the current study, we determined the P-LAP levels in maternal serum and placenta during healthy pregnancy. P-LAP activities in maternal serum increased with gestation and rose to the peak of 80 IU/ml at 38 weeks of gestation. Northern blot analysis revealed the increase of P-LAP mRNA levels in placenta in the third trimester compared to the first trimester. P-LAP protein and related activities could be detected in the conditioned medium of placental tissue, while they could not be detected in that of human umbilical vein endothelial cells. Immunohistochemically P-LAP was positively stained in the apical membrane of syncytiotrophoblast cells throughout the gestation. These results established the normal range of serum and tissue P-LAP levels during pregnancy and the possible source of serum P-LAP, which will be helpful to elucidate the physiological and clinical roles of P-LAP/oxytocinase/IRAP.

Adult↗

PubMed2000

Quantitative analysis of matrix metalloproteinases-2 and -9, and their tissue inhibitors-1 and -2 in human placenta throughout gestation.

To elucidate the implication of type IV collagenases(MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) for placental development, we quantified their levels in the conditioned media of placental organ culture and primary culture of the trophoblast as well as in the tissue extracts of placentas from different stages of gestation using specific enzyme-linked immunosorbent assays. First trimester villous tissue secreted about 10 times more pro-MMP-2 than pro-MMP-9, and pro-MMP-2 levels dramatically decreased in the second trimester. On the other hand, pro-MMP-9 levels were more than 10 times higher than those of pro-MMP-2 in the primary culture of the first trimester trophoblast, indicating the involvement of stromal cells for prominent pro-MMP-2 secretion from first trimester villous tissue described above. Levels of TIMPs, especially those of TIMP-2, remained constant throughout gestation both in the culture media and tissue extracts. Gelatin zymography revealed abundant secretion of the active form of MMP-2 as well as pro-MMP-2 from first trimester villous tissue. Western immunoblot analysis confirmed the presence of both TIMP-1 and TIMP-2 in placental tissue. These results suggest that active secretion of MMP-2 from villous tissue in the first trimester and constant production of TIMPs throughout gestation are characteristic of placental development.

Blotting, Western↗

PubMed2000

Formation of the Ras dimer is essential for Raf-1 activation.

Although it is well established that Ras requires membrane localization for activation of its target molecule, Raf-1, the reason for this requirement is not fully understood. In this study, we found that modified Ras, which is purified from Sf9 cells, could activate Raf-1 in a cell-free system, when incorporated into liposome. Using a bifunctional cross-linker and a protein-fragmentation complementation assay, we detected dimer formation of Ras in the liposome and in the intact cells, respectively. These results suggest that dimerization of Ras in the lipid membrane is essential for activation of Raf-1. To support this, we found that, when fused to glutathione S-transferase (GST), unprocessed Ras expressed in Escherichia coli could bypass the requirement for liposome. A Ras-dependent Raf-1 activator, which we previously reported (Mizutani, S., Koide, H., and Kaziro, Y. (1998) Oncogene 16, 2781-2786), was still required for Raf-1 activation by GST-Ras. Furthermore, an enforced dimerization of unmodified oncogenic Ras mutant in human embryonic kidney (HEK) 293 cells, using a portion of gyrase B or estrogen receptor, also resulted in activation of Raf-1. From these results, we conclude that membrane localization allows Ras to form a dimer, which is essential, although not sufficient, for Raf-1 activation.

Cell Line↗

PubMed2000

The expression and localization of neutral endopeptidase 24.11/CD10 in human gestational trophoblastic diseases.

Neutral endopeptidase 24.11 (NEP)/CD10 is a cell-surface peptidase that hydrolyzes various bioactive peptides. NEP is distributed in both normal and neoplastic cells and plays a functional role by modulating cellular responses to peptide substrates. Recently, NEP has been shown to be expressed in normal placental trophoblasts, suggesting its physiological role during pregnancy. In the present study, we investigated the expression of NEP in hyperplastic and anaplastic trophoblasts in gestational trophoblastic diseases (GTDs). Flow cytometric analysis demonstrated that NEP was expressed in all choriocarcinoma cell lines examined. The NEP enzyme activity in these cell lines correlated with cell-surface protein levels and was abolished by the NEP inhibitor phosphoramidon. On immunoblot analysis, NEP protein was detected in both hydatidiform mole and choriocarcinoma tissues as a double band of 95 and 100 kDa similar to that of the normal placental tissues. Immunohistochemical analysis revealed that NEP was present on syncytiotrophoblasts, while no or very faint NEP immunoreactivity was observed on cytotrophoblasts in the normal placenta. Similarly, NEP in hydatidiform mole and invasive mole was localized on the membrane of syncytiotrophoblasts, but not on hyperplastic cytotrophoblasts. In contrast, in choriocarcinoma, NEP was highly expressed not only on syncytiotrophoblastic cells but also on invading anaplastic cytotrophoblasts. In addition, NEP was also expressed on intermediate trophoblasts in placental site trophoblastic tumors. In summary, this is the first study demonstrating the expression of NEP/CD10 in GTDs. The differential localization of NEP among various trophoblastic tumors suggests that NEP may play a functional role in the regulation of trophoblast transformation and human chorionic gonadotropin secretion.

Blotting, Western↗