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Biomedical subjects

Y Miyagi

Publications and source records attributed to Y Miyagi.

At least 55 records · Page 3Linked to original sources

Diverse functions of protease receptor tissue factor in inflammation and metastasis.

Accumulating evidence suggests that protease receptors and their cognate protease ligands play important roles in cell-signaling events that regulate cell adhesion and migration in inflammation as well as tumor invasion and metastasis. Tissue factor (TF), the cell surface receptor for the serine protease VIIa and the initiator of the coagulation pathways, supports metastatic implantation by activating extracellular, protease-dependent signaling pathways and by intracellular links to the actin cytoskeleton. The adhesion of TF-expressing tumor cells can be mediated by interactions of the receptor-protease complex with specific matrix-associated inhibitors, suggesting a novel bridging mechanism by which proteases participate in migratory functions of cells.

Humans↗

Magnetic resonance appearance of multiple intracranial epidermoid cysts: intrathecal seeding of the cysts? Case report.

A 44-year-old man presented to the hospital with multiple intracranial epidermoid cysts. The clinical manifestations of his disease included chronic headaches and one seizurelike episode. Findings determined by magnetic resonance (MR) imaging, surgery, and histological analysis indicated intrathecal and intraventricular seeding of the cysts. Spontaneous (nontraumatic) seeding of multiple daughter cysts from intracranial epidermoid cysts is still very rare and their multiple appearances on MR imaging should be distinguished from the simple scattering of oily contents due to cyst rupture.

Adult↗

Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage.

OBJECT: Rho A, a small guanosine triphosphate-binding protein, and rho kinases have been suggested to play an important role in the agonist-induced myofilament Ca++ sensitization and cytoskeletal organization of smooth-muscle cells. To discover their possible roles in the prolonged contraction seen in cerebral vasospasm, the authors investigated the messenger (m)RNA expressions of rho A and rho-associated kinases alpha and beta in the basilar artery (BA) of a rat double cisternal blood-injection model. METHODS: An experimental subarachnoid hemorrhage (SAH) was achieved in rats by twice injecting autologous arterial blood into the cisterna magna of each animal. The mRNAs for rho A and rho-associated kinases alpha and beta of the rat BA were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). The cisternal blood injection induced a marked corrugation of elastic lamina and contraction of smooth-muscle cells observed with the aid of light and transmission electron microscopy in the rat BA on Days 3, 5, and 7. Results of the RT-PCR revealed that mRNAs for rho A and rho kinases alpha and beta were expressed in the rat BA and that they were significantly upregulated and reached their peaks on Day 5. CONCLUSIONS: The mRNA upregulation of these proteins indicates that activation of rho A/rho kinase-related signal transduction pathways is involved in the development of long-lasting contraction of cerebral arteries after SAH.

Animals↗

Alteration of the CDKN2/p16 gene is not required for HPV-positive uterine cervical cancer cell lines.

To determine whether alterations of the CDKN2/p16 might be involved in HPV-positive cervical cancers, we examined for alterations of this gene and function of the protein p16 to interact with CDK4 in 5 cervical cancer cell lines. No alteration of this gene was detected. Proteins for p16 and CDK4 were normally expressed and function of p16 to interact with CDK4 was not abrogated in these cell lines. These cell lines were human papillomavirus (HPV)-positive and carried wild-type p53. These findings suggest that phosphorylation of pRb by CDK4 is not critical in the carcinogenesis or in the establishment of HPV-positive cervical cancer cell lines, since HPV E6 or E7 viral-transforming proteins inactivate p53 and pRb tumor suppressor protein function, resulting in deregulated progression of the cell cycle.

Cyclin-Dependent Kinase 4↗

Detection of c-erbB-2 and FGF-3 (INT-2) gene amplification in epithelial ovarian cancer.

We examined gene amplifications of the c-erbB-2 and FGF-3 gene in 48 epithelial ovarian cancers by differential PCR and addressed their association with clinico-pathological features including clinical outcome. Overall, 25.0 and 20.8% of ovarian cancers displayed amplified c-erbB-2 or FGF-3 gene, respectively. Amplification of the c-erbB-2 gene was significantly associated with particular histological cell types, higher histological grade, and low levels of serous CA125. However, there was no correlation between c-erbB-2 gene amplification and patient outcome. No correlation was observed between FGF-3 gene amplification and any clinico-pathological features including overall survival. These findings suggested that c-erbB-2 or FGF-3 gene amplification might be one of the oncogenic events implicated in the development of ovarian cancers, yet is not a useful prognostic marker.

Adult↗

[A case of advanced hepatocellular carcinoma with lung and bone metastases effectively treated by orally administered UFT].

A 52-year-old male underwent hepatic subsegmentectomy for hepatocellular carcinoma (HCC). Five months later, a recurrent tumor was found in the liver and transcatheter arterial embolization (TAE) was performed. However, recurrent tumors were growing rapidly with multiple lung and bone metastases. The titer of serum AFP was elevated to 896,095 ng/ml and the titer of serum PIVKA-II was elevated to 1294.5 AU/ml. The patient was treated by oral administration of UFT (600 mg/day). Two weeks later, his general condition was improved, and several months later, the liver tumor, multiple lung metastases and multiple bone metastases had almost disappeared. The titers of serum AFP and PIVKA-II were reduced to the normal range. He has maintained a good state of health for about four years now. This case suggests the clinical usefulness of UFT for advanced HCC.

Administration, Oral↗

Initial experience with the radial incision approach for atrial fibrillation.

BACKGROUND: Surgery for atrial fibrillation (AF) is performed with the aim of restoring sinus rhythm and atrial transport function, and preventing thromboembolism. The radial incision approach (RIA), in which the atrial incisions radiate from the sinus node toward the atrioventricular annular margins and parallel the coronary arteries, was developed as an outgrowth of and an alternative to the maze procedure in order to preserve a more physiological activation sequence and the atrial transport function. METHODS: To determine whether the RIA is a promising procedure for AF, 23 patients who had undergone the RIA (n = 10) or the maze procedure (n = 13) for chronic AF associated with valvular heart disease were examined in terms of the postoperative cardiac rhythm and atrial transport function. RESULTS: AF was cured in 90% of RIA patients and 92.3% of maze patients (not significant). One patient in each group required pacemaker implantation for an insufficient sinus rate postoperatively. The RIA was technically easier than the maze procedure, because the incisions were more linear and there was no isolation incision or "T-shape" incision in the left atrium. The left atrial transport function, assessed by transthoracic Doppler echocardiography, was greater after the RIA than after the maze procedure, while the right atrial transport function was equally preserved by both procedures. The peak atrial filling/early filling waves of the flow-velocity spectra across the mitral valve was significantly larger after the RIA than after the maze procedure (0.58+/-0.17 vs. 0.25+/-0.07, p<0.005). The left atrial filling fraction was significantly larger after the RIA than after the maze procedure (28.5%+/-5.0% vs. 15.1%+/-4.0%, p<0.001). CONCLUSIONS: RIA provides a greater atrial transport function, and thus may represent a physiological alternative to the maze procedure as a surgical procedure for AF.

Atrial Fibrillation↗

Serum C-reactive protein as a prognostic factor in patients with epithelial ovarian cancer.

OBJECTIVE: It is well known that the serum level of Interleukin-6 (IL-6) correlates with the level of C-reactive protein (CRP). The purpose of this study is to determine the significance of CRP as a prognostic factor in epithelial ovarian cancer. STUDY DESIGN: The present study is comprised of 120 patients with epithelial ovarian cancer from 1985 to 1992. In this study, CRP levels above 50 mg/l were considered high CRP. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with poor survival. RESULTS: The serum CRP value was significantly associated with the volume of ascites (P = 0.000004). Univariate analysis showed that the FIGO stage, primary tumour diameter, size of residual tumour, histologic grade, volume of ascites and high serum level of CRP were significant prognostic factors. Cox's multivariate proportional hazard model showed that histologic grade was the most important prognostic factor (P = 0.0026). FIGO stage and volume of ascites were also independent factors for 5-year survival (P = 0.0310 and P = 0.0216, respectively). However, the serum CRP value was not an independent prognostic factor. CONCLUSION: CRP is an adverse prognostic factor in univariate analysis, but not in multivariate analysis.

Adenocarcinoma, Clear Cell↗

Vascular endothelial growth factor is implicated in early invasion in cervical cancer.

The association between the expression of vascular endothelial growth factor (VEGF) and clinicopathological factors has scarcely been examined in cervical cancer. This study examines the level of VEGF messenger RNA (mRNA) expression in invasive cervical cancer and its association with clinicopathological features including microvessel density. The level of VEGF mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using beta-actin as an internal control in 66 patients with stages Ia-IVb invasive cervical cancer. In 42 patients who underwent surgery, the microvessel count was also assessed by immunostaining for factor VIII-related antigen in the most neovascularised area of the specimen. The highest level of VEGF mRNA expression was observed in early invasive cervical cancers. Except for stage IVb, the stage of the disease inversely correlated with the level of VEGF mRNA (P < 0.05). There was no significant difference in the level of VEGF mRNA with respect to histological cell types. 38 patients with stages Ib-IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. There was no significant difference in the level of VEGF mRNA with respect to lymph node metastasis, depth of stromal invasion, tumour size, parametrial involvement or vaginal involvement among these patients. A significant relationship was found between the microvessel density and the level of VEGF mRNA (P < 0.01). These findings provide evidence that the expression of VEGF is involved in the promotion of angiogenesis in cervical cancer and plays an important role in early invasion.

Endothelial Growth Factors↗

Expression of trypsin in human cancer cell lines and cancer tissues and its tight binding to soluble form of Alzheimer amyloid precursor protein in culture.

It was recently found that overexpression of the trypsin gene in tumor cells stimulates their growth in culture and in nude mice. In the present study, expression of trypsin in various human cancer cell lines and tissues was studied by gelatin zymography and immunoblotting before and after enterokinase treatment and by immunohistochemistry. The analyses showed that many stomach, colon, and breast cancer cell lines secreted trypsinogens-1 and/or -2, as well as an unidentified serine proteinase of about 70 kDa, into culture medium. Lung cancer cell lines secreted 18- and 19-kDa unidentified trypsin-like proteins. Stomach cancer cell lines frequently secreted active trypsin, suggesting that they produced an endogenous activator of trypsinogen, most likely enterokinase. Active trypsin formed a complex with a soluble form of Alzheimer amyloid precursor protein (sAPP), a Kunitz-type trypsin inhibitor, which was secreted by all cell lines tested. This indicated that sAPP is a primary inhibitor of secreted trypsin. Immunohistochemical analysis showed that trypsin(ogen) was frequently expressed at high levels in stomach and colon cancers, but scarcely in breast cancers. In the stomach cancers, the trypsin immunoreactivity was higher in the malignant, non-cohesive type than in the cohesive type. These results support the hypothesis that tumor-derived trypsin is involved in the malignant growth of tumor cells, especially stomach cancer cells.

Amyloid beta-Protein Precursor↗

Assessment of myometrial invasion at the invasion site of an endometrial carcinoma by ultrasonography along with an intrauterine catheter.

OBJECTIVES: To evaluate by transvaginal ultrasonography (TVU) the thickness of the intact myometrium at the presumed tumor-origin site and to establish criteria for a half myometrial invasion. METHODS: A total of 19 successive patients with endometrial cancer who were treated between January 1, 1997, and January 31, 1998, participated in this study. TVU mode B with and without the use of an intrauterine silicon catheter was performed. RESULTS: Using a catheter, the origin site was correctly detected in 15 cases (79%). The best criterion for half myometrial invasion was a 6-mm thickness of the intact myometrium at the origin site. The sensitivity/specificity/accuracy of TVU with the use of a catheter in cases with the correct estimated origin site, were 1.00/0.67/0.86 for myometrial invasion < 1/2, and 0.67/1.00/0.86 for myometrial invasion > or = 1/2. CONCLUSION: It is of value to use 6-mm as the criterion for the thickness of the intact myometrium at the estimated tumor-origin site in connection with TVU with the use of a catheter for preoperatively assessing half myometrial invasion.

Adult↗

Tremor induced by toluene misuse successfully treated by a Vim thalamotomy.

A 22 year old man developed a vigorous tremor of 5 Hz in his right hand, after a 7 year history of toluene misuse. T2 Weighted MRI depicted marked decreases in the signal intensity of the basal ganglia, red nucleus, and thalamus on both sides. The stereotactic coagulation of the left nucleus ventrointermedius (Vim) of the thalamus abolished the tremors in his right hand. This patient clearly exhibited the pathological involvement of rubral lesions in generation of a toluene induced tremor on MRI. Toluene induced tremor is an irreversible symptom which persists even after stopping toluene misuse, therefore in medically intractable cases, it should be positively treated by a Vim thalamotomy.

Adult↗

Tumor cell adhesion and migration supported by interaction of a receptor-protease complex with its inhibitor.

Tissue factor (TF), the cell-surface receptor for coagulation factor VIIa, supports metastasis. Equally important for this process are (a) interactions of the TF cytoplasmic domain, which binds the mobility-enhancing actin-binding protein 280, and (b) the formation of a proteolytically active TF-VIIa complex on the tumor cell surface. In primary bladder carcinoma cells, we find that this complex localizes to the invasive edge, in proximity to tumor-infiltrating vessels that stain intensely for TF pathway inhibitor (TFPI-1), the major inhibitor of the protease activity of the complex. In culture, binding of VIIa to TF-expressing tumor cells is sufficient to allow cell adhesion, migration, and intracellular signaling on immobilized TFPI-1. Immobilized heparin, a mimic for extracellular matrix-associated proteoglycans, binds physiological concentrations of TFPI-1 in a conformation that supports TF-VIIa-dependent cell adhesion. Consistent with a functional role of TFPI-1 in complex extracellular matrices, we show that TF cooperates with integrin-mediated adhesion and migration on composite matrices that contain ligands for both integrins and the TF-VIIa complex. This study thus provides evidence for a novel mechanism of protease-supported migration that is independent of proteolytic matrix degradation but rather involves protease-dependent bridging of TF's extracellular domain to an ECM-associated inhibitor.

Carcinoma↗

Effect of cisplatin on cell death and DNA crosslinking in rat mammary. Adenocarcinoma in vitro.

The pharmacodynamic effects of cisdiamminedichloroplatinum(II) (CDDP) in vitro have been reported, but the dosage and exposure time in vitro have not been based on clinical observations of the drug's actions in vivo. In this study, the authors attempted to evaluate the pharmacodynamic effects of CDDP in vitro in terms of cell survival and DNA crosslinking by simulating unbound CDDP administration at varying concentrations to a rat mammary adenocarcinoma line (known as line 66). CDDP exposure was conducted by both constant concentration procedures and a simulated in vivo procedure. Colony formation assay for the surviving fraction and alkaline elution assay for DNA crosslink measurement were performed in order to evaluate the pharmacodynamics of CDDP. Cell survival was a function of the area under the drug concentration time curve (AUC) of unbound CDDP (R2 = 0.77, P < 0.002) for all drug exposure procedures as analyzed by the analysis of covariance test. There was a strong correlation between the surviving fraction and the crosslink index of the total amount of DNA crosslinks (R2 = 0.85, P < 0.0005). Both the total amount of DNA-DNA crosslinks and the DNA-protein crosslinks, of which the latter were dominant, were affected not by the exposure procedures, but by the AUC value (P < 0.002). The thresholds of cytocidal effect were 1.59 mg.h/l for the AUC and 0.008 for the crosslink index. The pharmacodynamic effects in vitro by simulated in vivo exposure were identical to those of constant.

Adenocarcinoma↗

Posteroventral pallidotomy for midbrain tremor after a pontine hemorrhage. Case report.

This 49-year-old man gradually developed a disabling action tremor in the proximal right upper extremity 8 months after suffering a pontine tegmental hemorrhage. The intraoperative microrecording in the nucleus ventralis intermedius (VIM) of the left thalamus revealed tremor-synchronous grouped discharges with a vigorous (2.7 Hz) action tremor predominantly in the shoulder and upper arm. High frequency electrical stimulation in the VIM did not affect the tremor. A posteroventral pallidotomy (PVP) was performed and resulted in the successful alleviation of all tremor activity. Posteroventral pallidotomy is known to alleviate parkinsonian tremors, especially those occurring in the contralateral lower extremity, trunk, and proximal segment of the contralateral upper extremity. The authors consider the pallidoreticular pathway to be an important tremor-mediating pathway for the proximal segment of the upper extremities and believe it can be controlled more effectively by PVP than by VIM thalamotomy, as demonstrated by the PVP-induced resolution of the midbrain tremor observed in this case.

Cerebral Hemorrhage↗

Angiogenesis and platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in cervical cancer.

The object of this study was to clarify the association of platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (dThdPase), separately assessed in cancer cells and in stroma cells, with clinicopathological factors including tumor angiogenesis and prognosis in cervical cancer. The expression of PD-ECGF was evaluated by immunohistochemical staining in 92 patients with stage Ib-II cervical cancer. The microvessel count was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area. Microvessel count was significantly higher in tumors with non-squamous cell carcinoma. PD-ECGF expression in cancer cells was significantly higher in tumors with pelvic node metastasis and squamous cell carcinoma. Immunopositivity for PD-ECGF in stroma cells was significantly higher in tumors with large size and deep stromal invasion. The microvessel counts in cases with positive PD-ECGF expression in stroma cells were significantly higher than those in cases with negative PD-ECGF expression in stroma cells (p=0.048). Disease-free survival and overall survival were significantly worse in patients with deep stromal invasion, parametrial involvement, vaginal involvement, lymph-vascular space involvement, pelvic lymph node metastasis and high microvessel count. A multivariate analysis using Cox's proportional hazard model showed that high microvessel count independently predicted disease-free and overall survival. The expression of PD-ECGF in stroma cells may play a crucial role in the promotion of angiogenesis and tumor angiogenesis can be used as a useful prognostic marker for cervical cancer.

Adult↗

Angiogenesis and platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in endometrial cancer.

The object of this study was to clarify the association of angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (dThdPase) with clinicopathological factors including tumor angiogenesis and patient outcome in endometrial cancer. There was no correlation between the expression of PD-ECGF in cancer cells and any of the clinicopathological variables. Immunopositivity for PD-ECGF in stroma cells was significantly higher in poorly differentiated adenocarcinomas. The microvessel counts correlated with PD-ECGF positive stroma cells (p<0.0001). Disease-free survival was significantly worse in patients with marked PD-ECGF expression in stromal cells and high microvessel count. A multivariate analysis using Cox's proportional hazard model showed that high microvessel counts independently predicted disease-free survival as well as stage and myometrial invasion. The expression of PD-ECGF in stroma cells may play a crucial role in the promotion of angiogenesis. Tumor angiogenesis can be used to predict prognosis in patients with endometrial cancer.

Adenocarcinoma↗