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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 253 records · Page 14Linked to original sources
PubMed1998

[Evaluation of blood flows inside hepatic tumors using color Doppler echography with galactose-based intravenous contrast medium "SH/TA 508" administration].

The purpose of this study is to evaluate hemodynamic characteristics of various hepatic tumors using color Doppler echography administered galactose-based intravenous contrast medium "SH/TA 508 (Levovist)". Subject were 9 cases of hepatocellular carcinomas, 5 cases of metastatic liver tumors and a case of hemangioma. We evaluated the characteristics of blood flows inside various hepatic tumors, and also evaluated the first pass through the hepatic tumors during administration of Levovist. The strongly pulsatile branched blood flows inside tumor and the slow-increased and plateau patterns were observed in the all cases of hepatocellular carcinomas, the weakly pulsatile blood flows surrounding tumor and the rapid-increased and slow-decreased patterns were observed in the cases of metastatic liver tumors, and the continuous blood streams in the margin of tumor and the slow-increased and slow-decreased pattern were observed in the case of hemangioma. These findings were characteristic in various hepatic tumors, and color Doppler echography enhanced by Levovist was very useful to distinguish hepatic tumors.

Carcinoma, Hepatocellular↗
PubMed1998

Roles of brain angiotensin II and C-type natriuretic peptide in deoxycorticosterone acetate-salt hypertension in rats.

OBJECTIVE: To investigate the roles of brain angiotensin II and C-type natriuretic peptide (CNP) in the hypertensive mechanism of deoxycorticosterone acetate (DOCA)-salt hypertension. METHODS: We injected 50 microg/kg CV-11 974, an angiotensin II type-1 receptors antagonist, 30 nmol/kg CNP-22, or the vehicle (artificial cerebrospinal fluid) into the cerebral ventricle or intravenously 5 min before the intracerebroventricular infusion of 1.5 mol/I NaCl solution for 30 min into either male normotensive Wistar rats or DOCA-salt hypertensive rats anesthetized with urethane, and their arterial pressures and heart rates were continuously recorded. Blood (2 ml) was collected at the end of the infusion for the measurement of plasma concentration of arginine vasopressin. We infused 10 or 50 microg/kg per day CV-11 974, 10 or 50 nmol/kg per day CNP-22, or the vehicle (1 microl/h) into the cerebral ventricles of DOCA-salt hypertensive rats for 7 days by using osmotic minipumps, and measured their systolic arterial pressures, pulse rates, and urinary excretions of vasopressin. RESULTS: Intracerebroventricular pre-administrations of CV-11 974 and of CNP-22 inhibited increases in mean arterial pressure, heart rate, and plasma vasopressin concentration induced by intracerebroventricular infusion of 1.5 mol/l NaCl into normotensive rats; increases in hemodynamics and plasma level of vasopressin induced by intracerebroventricular infusion of 1.5 mol/l NaCl were suppressed by intracerebroventricular pre-injections of CV-11 974, but not of CNP-22, into DOCA-salt hypertensive rats. Continuous intracerebroventricular infusions of 50 microg/kg per day CV-11 974 attenuated hypertension in DOCA-salt treated rats, accompanied by a reduction in urinary excretion of vasopressin. Continuous intracerebroventricular infusions of 50 nmol/kg per day CNP-22, however, affected neither hypertension nor urinary excretion of vasopressin in DOCA-salt hypertensive rats. CONCLUSION: Brain angiotensin II could play a role in the pressor mechanism of DOCA-salt hypertension by increasing release of vasopressin via type 1 receptors. That brain CNP has an inhibitory effect on release of vasopressin in acute experiments indicates that the impairment of this inhibitory effect of brain CNP on secretion of vasopressin could be involved in the pathogenesis of DOCA-salt hypertension in rats.

Angiotensin II↗
PubMed1998

[Cancer-associated gene abnormalities and chemosensitivity].

One of the most important clinical issues in cancer chemotherapy is the presence of intrinsic resistance or the appearance of acquired resistance against chemotherapy. As for intrinsic resistance, we had to perform direct chemo-sensitivity testing, or had to rely on the knowledge empirically acquired from randomized clinical trials. However, molecular or genetic markers associated with chemo-sensitivity have been reported recently. For example, inactivation of p53 or GML gene has been reported to be associated with chemo-resistance. Overexpression of topo-isomerase I has been reported to be associated with chemo-sensitivity to Topo I inhibitor. Overexpression of Thymidine Phosphorylase has been found to be associated with chemo-sensitivity to prodrug of 5-FU. By checking the status of such chemo-sensitivity markers prior to chemotherapy, it would be possible to predict the chemotherapeutic effect and even the necessity of the chemotherapy in the near future. In this article, we review the chemo-sensitivity markers reported so far, and methodology contributing to the discovery of new chemo-sensitivity markers. As a clinical study, 11 cases of ovarian cancer with high sensitivity to cisplatin-based chemotherapy and 29 cases of ovarian cancer with chemoresistance were analyzed by Comparative Genomic Hybridization (CGH). Copy number decrease in Xp, and copy number increase in 19q were observed in 13, 12 out of 29 resistant cases (45, 41%) and zero, 1 out of 11 sensitive cases (0, 9%), suggesting that -Xp and +19q were likely to be a genetic event associated with intrinsic drug-resistance (p = 0.006, 0.05, respectively). This effort should contribute to the discovery of new chemo-sensitivity and resistance markers.

Antineoplastic Agents↗
PubMed1998

[Tracheal obstruction caused by bucking during general anesthesia in a patient with a mediastinal tumor].

An eleven-year-old girl underwent an open biopsy of a mediastinal tumor extending from the foreneck to the tracheal carina under general anesthesia. Immediately following the bucking developed at the end of the surgery, she fell into serious ventilatory difficulty. A bronchoscopic examination revealed that the tracheal membrane had protruded into the tracheal lumen by its contraction concurring with the bucking, resulting in the obstruction of the endotracheal tube outlet. Endotracheal anesthesia might accompany tracheal stenosis by bucking, particularly in patients with a tumor surrounding the trachea.

Anesthesia, General↗
PubMed1998

[Effect of clarithromycin treatment of natural killer cell activity in patients with advanced non-small cell lung cancer].

The treatment of a 14-membered ring macrolide, clarithromycin (CAM), prolongs the survival time of patients with unresectable nonsmall cell lung cancer, and improves the host factor. As we previously reported, one of the underlying mechanisms is that the treatment of CAM increases the bioactivity of interleukin-12 (IL-12). In the present study, we administered CAM to murine lung cancer treatment models with Lewis lung carcinoma and to 18 patients with unresectable non-small lung cancer whose anticancer treatment had been terminated. The timing of CAM administration was examined and the time course of NK activity was measured. In the murine lung cancer treatment models, administration of CAM 7 days after anticancer chemotherapy more strongly inhibited the tumor growth and more rapidly and significantly increased NK activity, compared to the concomitant use of CAM with an anticancer chemotherapy. In humans, the NK activity which had decreased after anticancer treatment, tended to be increased after one month of treatment with CAM (p = 0.06). One month of treatment with CAM significantly increased the NK activity (p < 0.05) of the following subjects: patients with stage III in the clinical stages, patients with squamous cell carcinoma, patients who had received radiotherapy alone as pretreatment therapy, and patients whose pretreatment therapy effect was partial response (PR). We conjectured that increasing NK activity was one of the underlying mechanisms of the macrobiotic effect of CAM. CAM was especially effective for patients in the early clinical stages and patients who responded well to pretreatment therapy. Murine lung cancer models showed that non-concomitant use of CAM with anticancer chemotherapy was more effective.

Aged↗
PubMed1997

The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas.

Our study was designed to clarify the significance of silencing the E-cadherin gene, which is located on 16q22.1, due to CpG methylation during hepatocarcinogenesis. The CpG methylation status of primary hepatocellular carcinomas (HCCs) and corresponding liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, were assessed by digesting DNA with methylation-sensitive and non-sensitive restriction enzymes. CpG methylation around the promoter region of the E-cadherin gene was detected in 46% of liver tissues showing chronic hepatitis or cirrhosis and 67% of HCCs examined. Immunohistochemical examination revealed reduced E-cadherin expression in 59% of HCCs examined. CpG methylation around the promoter region correlated significantly with reduced E-cadherin expression in HCCs (p < 0.05). CpG methylation around the promoter region, which increases during the progression from a precancerous condition to HCC, may participate in hepatocarcinogenesis through reduction of E-cadherin expression, resulting in loss of intercellular adhesiveness and destruction of tissue morphology.

Cadherins↗
PubMed1997

Lead perturbs the regulation of spontaneous release of tissue plasminogen activator and plasminogen activator inhibitor-1 from vascular smooth muscle cells and fibroblasts in culture.

To evaluate the toxicity of lead on the blood fibrinolytic system during hemostasis, human aortic smooth muscle cells and human fetal lung fibroblasts were cultured in the presence of lead chloride. Tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) released were determined by enzyme immunoassay. It was found that lead decreased the release of both t-PA:Ag and PAI-1:Ag from vascular smooth muscle cells. On the other hand, in fibroblasts, the release of t-PA:Ag was markedly decreased whereas that of PAI-1:Ag was markedly increased by the metal. Fibrin zymography showed that lead reduced the plasminogen activator activity in the conditioned medium of both cell types. However, lead did not cause a nonspecific cell damage and an alteration of protein synthesis when evaluated by lactate dehydrogenase leakage and [14C]leucine incorporation, respectively. Lead accumulated within either vascular smooth muscle cells or fibroblasts in a dose-dependent manner; intracellular accumulation of calcium could be increased by lead. However, the effects of lead on the release of t-PA:Ag and PAI-1:Ag were different from those of calcium ionophore A23187. It was therefore suggested that regulation of spontaneous release of fibrinolytic proteins from subendothelial cells is disturbed by lead through intracellular calcium-independent pathway.

Aorta↗
PubMed1997

Inhibitory effect of lead on the repair of wounded monolayers of cultured vascular endothelial cells.

We investigated the effect of lead nitrate (0.5-5.0 microM) on the repair of wounded monolayer of cultured bovine aortic endothelial cells. It was morphologically found that lead decreases the appearance of the cells in the wounded area in a concentration-dependent manner without degenerative changes after a 48-h incubation. Although mercury weakly inhibited the repair with nonspecific cell damage, the other cations including bismuth, cobalt, manganese and nickel failed to affect the repair. The inhibition of endothelial repair caused by lead was observed even when stimulated by exogenous either basic or fibroblast growth factor. These results indicated that inhibition of the repair process of damaged endothelial cell layer is a component of lead-induced vascular lesions such as atherosclerosis.

Animals↗
PubMed1997

Reduced p21(WAF1/CIP1) expression and p53 mutation in hepatocellular carcinomas.

p21(WAF1/CIP1) is a universal cyclin-dependent kinase (cdk) inhibitor, the expression of which is regulated by p53-dependent and p53-independent pathways. We examined p21(WAF1/CIP1) expression in and p53 status of 21 primary hepatocellular carcinomas (HCCs) by reverse-transcriptase polymerase chain reaction (RT-PCR) and by PCR single-strand conformation polymorphism (PCR-SSCP) analysis. p21(WAF1/CIP1) messenger RNA expression was reduced markedly in 8 of 21 HCCs (38.1%) and 5 of these 8 HCCs bore p53 mutations. The relative p21(WAF1/CIP1) messenger RNA expression value of HCCs with p53 mutations (.73 +/- .13 U, n = 6) was significantly lower than that of HCCs with wild-type p53 (1.00 +/- 0.21 U, n = 14; P < .01). The p21(WAF1/CIP1) expression levels in cancerous tissues (.73 +/- .13 U) were significantly reduced in comparison with those in noncancerous tissues (.97 +/- .13 U) (P < .01) in the 6 cases with p53 mutations. These data indicate that p21(WAF1/CIP1) expression in HCCs is predominantly regulated by dependence on p53 and that reduced p21(WAF1/CIP1 expression may participate in hepatocarcinogenesis.

Adult↗
PubMed1997

Relaxing effect of interleukin-1 on rat cultured Ito cells.

Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were isolated from the livers of male Wistar rats and cultured for 24 hours. Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and intensity of fluorescence of cGMP were examined using a confocal laser microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta were observed over 12 hours, and the area of the same Ito cell was compared before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L-arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence of iNOS was observed, and fluorescent intensity of cGMP increased after addition of IL-1beta. Intracellular cGMP concentration increased dose-dependently after addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated group compared with the untreated group. Relaxation of Ito cells by IL-1beta treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and relaxes the cells via cGMP.

Animals↗
PubMed1997

A comparison of different methods in predicting static pressure distribution in articulating joints.

Pressure distribution along the contact surface of an articulating joint model was analyzed using different numerical and analytical methods: a discrete rigid element method [rigid-body-spring-model (RBSM)], the finite element method (FEM), a simplified elasticity solution (SES) and the modified Hertzian (MH) theory. The FEM and MH methods modeled joints interposed with elastic layers, while the RBSM and SES methods assumed a simplified joint with a rigid convex indenter on an elastic concave surface. Results for an axisymmetric joint model indicate that all of these methods predict similar pressure distributions on joint surfaces. In non-axisymmetric deformation mode, the RBSM method and FEM calculation showed good agreement in contact pressure prediction. Compared to the other three methods, the RBSM is relatively simple and effective in predicting joint contact pressure under symmetric and non-symmetric loading. The computational efficiency of the RBSM method is particularly attractive for pre-operative planning of reconstructive surgical procedures in orthopaedics in which geometric changes dictate the eventual outcome of the surgery.

Biomechanical Phenomena↗
PubMed1997

Evidence for the involvement of transforming growth factor-alpha in implantation in the rat.

This study was conducted to examine the possibility for participation of transforming growth factor-alpha (TGF-alpha), one of the epidermal growth factor (EGF) family of growth factors, in implantation in the rat. Immunostaining of TGF-alpha in the periimplantation uterus showed distinct staining in the luminal and glandular epithelium and moderate staining in stromal and myometrial cells. After implantation decidual cells and embryos were also positive stained for immunostaining. Immunocytochemistry of EGF receptor showed distinct staining in the luminal and glandular epithelium during the preimplantation period, and after implantation decidua at implantation sites and embryos were stained. Intraluminal injection of anti-TGF-alpha antibodies into uterine horns at 0600 h on day 5 of pregnancy decreased the number of rats showing implantation (blue dye reaction) at 0200 h on day 6 in a dose-dependent manner. Intraluminal injection of 100 pg of TGF-alpha on day 5 of pseudopregnancy elicited a greater decidual response when compared with the vehicle-injected contralateral uterine horn. Intraluminal injection of 20 pg of TGF-alpha into each uterine horn induced implantation in 50% of the ovariectomized progesterone-treated delayed implanting rats. These results suggest that TGF-alpha is involved in the implantation process in the rat.

Animals↗