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Biomedical subjects

M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 37 records · Page 2Linked to original sources
PubMed2003

Caveolin-I overexpression is a favourable prognostic factor for patients with extrahepatic bile duct carcinoma.

Extrahepatic bile duct carcinoma (EBDC) is a malignancy well known for its poor prognosis. Some clinicopathological prognostic markers have been proposed, but genetic factors have not been well investigated. We have examined expression patterns of caveolin-1, which has been shown to function as a tumour suppressor in vitro, in EBDC using immunohistochemistry. Normal tissues adjacent to the tumour cells did not show immunoreactivity for caveolin-1. A total of 22 of the 60-carcinoma tissue samples (36.7%) studied were positive for caveolin-1. Caveolin-1 immunostaining negatively correlated with the patient's age and pathological T factor (pT) in a statistically significant manner. Multivariate analysis using Cox's proportional hazards model identified caveolin-1 expression as an independent positive prognostic factor. Thus, our study suggests that caveolin-1 expression may be a useful prognostic marker for EBDC.

Adult↗
PubMed2003

Percutaneous and laparoscopic approaches of radiofrequency ablation treatment for liver cancer.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) and microwave coagulation therapy (MCT) have been gaining acceptance as a standard method in the management strategy of liver cancer, for reasons of minimally invasive techniques and effective results. We present our experience of RFA and MCT in patients with liver cancer, and analyze retrospectively the advantages and disadvantages of both of the percutaneous and laparoscopic approaches. METHODS: Thirty-two consecutive patients (23 men and 9 women) with 19 hepatocellular carcinomas (HCC), 12 metastatic liver cancers, and recurrent cholangiocellular carcinoma (CCC), were enrolled in this study. Out of these 32 patients, as a prior laparotomy, 19 underwent hepatectomy, colectomy, gastrectomy or cholecystectomy, and 15 were treated with the laparoscopic approach, 17 treated with the percutaneous approach, and 2 treated with the combined approach of those two. All of these procedures were carried out under general anesthesia with ultrasound guidance. Seven and 30 days after these procedures, an assessment helical computed tomography was done. RESULTS: No sign of the residual tissues was noted in all patients except only one case. CONCLUSIONS: The percutaneous approach was thought to be a more practical and less invasive method regardless previous laparotomy. For the laparoscopic approach, tumors located at the hepatic surface or margin were preferable candidates.

Adult↗
PubMed2003

Simultaneous stimulation of EP2 and EP4 is essential to the effect of prostaglandin E2 in chondrocyte differentiation.

OBJECTIVE: Prostaglandin E(2)(PGE(2)) has been reported to stimulate chondrocyte differentiation. However, the precise actions and signal transduction pathways of PGE(2)in cartilage are largely unknown. Our purpose is to identify which of the four PGE(2)receptor subtype(s), EP1-4, mediates the action of PGE(2)on chondrocyte differentiation. DESIGN: We used primary chondrocytes derived from the resting zone of rat rib cartilage. The effects on chondrocyte differentiation were assessed by measuring the Alcian blue-stainable proteoglycan content and the expression levels of type II collagen mRNA by Northern blot analysis. The expression of the four PGE(2)receptor subtypes in rat primary chondrocytes was examined by reverse transcription-polymerase chain reaction. RESULTS: PGE(2)stimulated the accumulation of proteoglycan and up-regulated the expression of type II collagen mRNA in primary chondrocytes. Dibutyryl cAMP, a cell-permeable analog of cAMP, an important intracellular mediator of PGE(2)signaling, also enhanced the expression of type II collagen mRNA and proteoglycan accumulation in chondrocytes. No EP agonist alone induced the expression of type II collagen mRNA. However, simultaneous administration of EP2 and EP4 agonists at high concentrations cooperatively induced the expression of type II collagen mRNA, mimicking the PGE(2)effect. The simultaneous stimulation of EP2 and EP4 also cooperatively enhanced proteoglycan accumulation and intracellular cAMP production. Moreover, an EP4 antagonist partially blocked the stimulatory actions of PGE(2)on the expression of type II collagen mRNA. CONCLUSION: These results suggest that simultaneous stimulation of EP2 and EP4 is necessary and sufficient to elicit the effect of PGE(2)on rat primary chondrocyte differentiation.

Animals↗
PubMed2003

TRA-418, a novel compound having both thromboxane A(2) receptor antagonistic and prostaglandin I(2) receptor agonistic activities: its antiplatelet effects in human and animal platelets.

TRA-418 is a novel compound that has been found in our screening for compounds having both thromboxane A2 (TP) receptor antagonistic and prostaglandin I2 (IP) receptor agonistic activities. In the binding assays, TRA-418 showed a 10-fold higher affinity to TP-receptors than IP-receptors. TRA-418 inhibited platelet aggregation induced by the TP-receptor agonist, U-46619 and by arachidonic acid at concentrations lower than those required for inhibition of ADP-induced aggregations. Furthermore, TRA-418 inhibited not only platelet aggregation induced by ADP alone, but also that induced by ADP in the presence of the TP-receptor antagonist, SQ-29548. When the IC50 values of TRA-418 for platelet aggregation were estimated in platelet preparations from monkeys, dogs, cats, and rats using ADP and arachidonic acid as the platelet stimulating agents, it was found that the values estimated in monkey platelets were quite similar to those estimated in human platelets. In ex vivo platelet aggregation in monkeys, TRA-418 exhibited significant inhibitory effects on arachidonic acid-induced aggregation in platelet preparations from monkeys treated at 3 micro g kg min-1 or higher doses, where neither a significant decrease in blood pressure nor a significant increase in heart rate was observed. These results are consistent with the fact that TRA-418 has a relatively potent TP-receptor antagonistic activity together with a relatively weak IP-receptor agonistic activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2003

A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-alpha.

The T-cell cytokine interleukin (IL)-17 selectively accumulates neutrophils in murine airways in vivo and may thus constitute a link between activation of T-lymphocytes and accumulation of neutrophils. In this study, the authors evaluated the role of granulocyte macrophage-colony stimulating factor (GM-CSF) in accumulation of neutrophils in the airways caused by IL-17 and tumour necrosis factor (TNF)-alpha. In vitro, human (h) IL-17 concentration-dependently stimulated the release of GM-CSF protein (enzyme-linked immunosorbent assay) in human bronchial epithelial cells (16HBE). IL-17 also time-dependently stimulated the release of GM-CSF protein in venous endothelial (human umbilical vein endothelial cells) cells in vitro. Co-stimulation with IL-17 plus the pro-inflammatory cytokine TNF-alpha potentiated the release of GM-CSF protein in 16HBE cells. hIL-17 also enhanced the expression of GM-CSF messenger ribonucleic acid in 16HBE cells (reverse transcriptase polymerase chain reaction), with a similar order of magnitude as TNF-alpha. Conditioned cell medium from bronchial epithelial cells co-stimulated with hIL-17 plus TNF-alpha prolonged survival (trypan blue exclusion) of human neutrophils in vitro and this effect was blocked by an anti-GM-CSF antibody. In vivo, local co-stimulation with mouse IL-17 plus TNF-alpha caused an additive potentiation of the accumulation of neutrophils in bronchoalveolar lavage fluid from mouse airways and this effect was blocked by an anti-GM-CSF antibody given systemically. In conclusion, granulocyte macrophage-colony stimulating factor is involved in the accumulation of neutrophils in the airways caused by interleukin-17 and tumour necrosis factor-alpha, probably via effects on both recruitment and survival of neutrophils.

Animals↗
PubMed2003

Candida septic arthritis of the hip in a young patient without predisposing factors.

We present a case of septic arthritis of the hip caused by Candida albicans in a 24-year-old woman. This is the first report of a Candida infection of the hip in a patient without any predisposing factors. She underwent a two-stage total hip arthroplasty three years after the onset of the infection. An elevated plasma level of beta-D-glucan suggested Candida as the infecting organism and the diagnosis might have been made earlier if this test had been undertaken at presentation.

Adult↗
PubMed2002

Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma.

Caveolin-1 is a major component of caveolae and plays a regulatory role in several signalling pathways. Caveolin-1 was recently identified as a metastasis-related gene in prostate cancer. The clinical effects of caveolin-1 expression in pancreatic carcinoma, however, remain unknown. In this study, we have investigated the relationship between caveolin-1 expression and the clinicopathologic variables and clinical outcome in 79 patients with pancreatic adenocarcinoma undergoing surgical resection. Caveolin-1 expression was determined by immunohistochemistry, using a polyclonal anti-caveolin-1 antibody. Patients were divided into two groups based on the extent of caveolin-1 expression: a negative expression group (immunoreactivity in less than 50% of cells) and a positive expression group. Positive caveolin-1 immunostaining was detected in 32 cases (40.5% of total), while non-neoplastic ductal epithelium showed little or no staining. Positive caveolin-1 expression was correlated with tumour diameter (P=0.0079), histopathologic grade (P=0.0272) and poor prognosis (P=0.0008). Upon multivariate analysis with Cox's proportional hazards model, positive caveolin-1 expression was shown to be an independent negative predictor for survival (P=0.0358). These results suggest that caveolin-1 overexpression is associated with tumour progression, thereby indicating a poor prognosis for certain patients undergoing surgical resection for pancreatic carcinoma.

Adenocarcinoma↗
PubMed2002

Effects of human recombinant calcitonin on a rat osteopenia model induced by TPTX and arotinoid.

Recombinant human calcitonin (rh-CT) has been developed as an agent for patients with excessive bone resorption to replace calcitonins from animal species, which are associated with tolerance problems. In this study, inhibitory effects of rh-CT against bone resorption were examined in thyroparathyroidectomized (TPTX) rats, the animal model of accelerated bone resorption induced by administering a synthetic retinoid (arotinoid). The arotinoid-treated TPTX rats exhibited signs of stimulated bone resorption, such as hypercalcemia, reduced bone mineral density, and inferior bone strength. Significant improvements were seen in all of these changes after a daily treatment with rh-CT (30, 300 U/kg s.c.) for 1 week. A histomorphometrical analysis showed that the treatment with rh-CT markedly suppressed the reduction of trabecular bone volume and that of cortical thickness in the femur of arotinoid-treated TPTX rats. These results suggest that rh-CT may prevent osteopenia caused by accelerated bone resorption.

Animals↗
PubMed2002

Influence of aqueous extract of Agaricus blazei on rat liver toxicity induced by different doses of diethylnitrosamine.

The modifying potential of prior administration of an aqueous extract of the mushroom Agaricus blazei Murrill (Agaricaceae) (Ab) on hepatotoxicity induced by different doses of diethylnitrosamine (DEN) in male Wistar rats was evaluated. During 2 weeks, animals of groups G3 (Ab+DEN(50)), G5 (Ab+DEN(100)), G7 (Ab+DEN(200)), and G8 (Ab-treated) were treated with the A. blazei through drinking water. After this period, groups G2 (DEN(50)), G3 (Ab+DEN(50)), G4 (DEN(100)) G5 (Ab+DEN(100)), G6 (DEN(200)), and G7 (Ab+DEN(200)) were given a single i.p. injection of 50, 100 and 200 mg/kg of DEN, respectively, while groups G1 (non-treated) and G8 (Ab-treated) were treated with 0.9% NaCl only. All animals were killed 48 h after DEN or NaCl treatments. The hepatocyte replication rate was estimated by the index of the proliferating cell nuclear antigen (PCNA) positive hepatocytes and the appearance of putative preneoplastic hepatocytes through expression of the enzyme glutathione S-transferase placental form (GST-P). After DEN-treatment, ALT levels, PCNA labeling index, and the number of GST-P positive hepatocytes were lower in rats that received A. blazei treatment and were exposed to 100 mg/kg of DEN. Our findings suggest that previous treatment with A. blazei exerts a hepatoprotective effect on both liver toxicity and hepatocarcinogenesis process induced by a moderately toxic dose of DEN.

Agaricus↗
PubMed2002

Status of NAT screening for HCV, HIV and HBV: experience in Japan.

The first nationwide nucleic acid amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type 1 (HIV-1) of voluntarily donated blood after serological pre-screening and before release of cellular components and plasma for fractionation was implemented by the Japanese Red Cross Blood Transfusion Services. The NAT screening assay using multiplex reagent is time-saving, cost effective, and labour-saving procedure for all blood and blood products including short-shelf life platelets. During the 50-mini-pool NAT screening of serologically negative donations (February 1, 2001-April 30, 2001), we were able to screen out 112 HBV-positive, 25 HCV-positive, and 4 HIV-1 positive units from blood and blood components.

Blood↗
PubMed2001

RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion (P = 0.0180), lymph node metastasis (P = 0.0033), lymphatic involvement (P = 0.0104), venous involvement (P = 0.0224), perineural involvement (P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification (P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis, possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival (P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216-132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer.

Adult↗
PubMed2001

Effect of poly-L-arginine on the nasal absorption of FITC-dextran of different molecular weights and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats.

The effect of poly-L-arginine (poly-L-Arg) on the in vivo nasal absorption of FITC-dextrans with a mean molecular weight ranging from 4.3 to 167 kDa and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats were studied. When FITC-dextrans were co-administered intranasally with 1.0 w/v% poly-L-Args of different molecular weight (MW, ca. 45.5 and 92 kDa, poly-L-Arg (50) and poly-L-Arg (100)), the bioavailability (F(infinity)) increased markedly compared with that after administration of FITC-dextran alone. However, the F(infinity) decreased exponentially with the increasing molecular weight of FITC-dextrans. There was no significant difference between the enhanced nasal absorption of FITC-dextrans achieved by the co-administration of poly-L-Arg (50) and poly-L-Arg (100). Moreover, the relationship between the F(infinity) and the molecular weight of FITC-dextrans indicated that the molecular weight of protein drugs, which exhibited efficient absorption with poly-L-Arg, was about 20 kDa, when the lower limit of bioavailability for developing a potent transnasal delivery system was assumed to be about 10%. Indeed, the nasal absorption of rhG-CSF, which has a molecular weight of 18.8 kDa, was also increased after co-administration of 1.0 w/v% poly-L-Arg (50) and the F(infinity) was about 11%. It seems likely that poly-L-Arg can be used to provide adequate nasal absorption of various protein drugs which have a molecular weight of about 20 kDa, thereby allowing the successful development of a variety of transnasal drug delivery systems.

Absorption↗
PubMed2001

Molecular cloning and biological activity of a novel lysyl oxidase-related gene expressed in cartilage.

We cloned a cDNA encoding a novel lysyl oxidase-related protein, named LOXC, by suppression subtractive hybridization between differentiated and calcified ATDC5 cells, a clonal mouse chondrogenic EC cell line. The deduced amino acid sequence of mouse LOXC consists of 757 amino acids and shows 50% identity with that of mouse lysyl oxidase. Northern blot analysis showed a distinct hybridization band of 5.4 kilobases, and Western blot analysis showed an immunoreactive band at 82 kilodaltons. Expression of LOXC mRNA was detected in osteoblastic MC3T3-E1 cells and embryonic fibroblast C3H10T1/2 cells, whereas none of NIH3T3 fibroblasts and myoblastic C2C12 cells expressed LOXC mRNA in vitro. Moreover, the LOXC mRNA and protein levels dramatically increased throughout a process of chondrogenic differentiation in ATDC5 cells. In vivo, LOXC gene expression was localized in hypertrophic and calcified chondrocytes of growth plates in adult mice. The conditioned media of COS-7 cells transfected with the full-length LOXC cDNA showed the lysyl oxidase activity in both type I and type II collagens derived from chick embryos, and these activities of LOXC were inhibited by beta-aminopropionitrile, a specific inhibitor of lysyl oxidase. Our data indicate that LOXC is expressed in cartilage in vivo and modulates the formation of a collagenous extracellular matrix.

Amino Acid Oxidoreductases↗
PubMed2001

Estimation of absorption rate of alpha-human atrial natriuretic peptide from the plasma profile and diuretic effect after intranasal administration to rats.

The absorption rate of alpha-human atrial natriuretic peptide (alpha-hANP) after intranasal (i.n.) administration to rats was estimated from the plasma profile and pharmacological effect (diuretic effect) using a pharmacokinetic (PK) model and a PK-pharmacodynamic (PD) model involving data obtained after intravenous (i.v.) bolus injection. The plasma concentrations of alpha-hANP after i.v. administration at different doses were fitted to a two-compartment PK model with zero-order excretion and input of endogenous alpha-rat atrial natriuretic peptide (alpha-rANP) and two elimination processes represented by Michaelis-Menten and first-order kinetics. However, the saturable process was ignored at low doses. The plasma concentrations after low doses via the i.n. route could also be expressed by this model, but with first-order absorption, so that an absorption rate constant was calculated using a deconvolution method. In addition, the diuretic effect plotted against the i.v. dose was represented by the Hill equation and showed an anti-clockwise hysteresis loop versus the plasma concentration. These results suggest that the diuretic effect could be estimated by a PK-PD model having an 'effect' compartment or a homeostatic system. Such a PK-PD model accurately expressed the diuretic effect of alpha-hANP at all doses after i.v. and i.n. administrations. The resulting absorption rate constant calculated using the PK-PD model agreed closely with that obtained by the PK model alone. The absorption rate and simulated diuretic effect suggest that, for i.n. administration of alpha-hANP, a higher absorption rate constant causes a more potent diuretic effect (a dramatic effect over the early period), whereas greater bioavailability is associated with a better hypotensive effect (sustained effect).

Absorption↗
PubMed2001

Sequence analysis of hepatitis C virus isolated from a fulminant hepatitis patient.

Although hepatitis C virus (HCV) is a major cause of non-A non-B hepatitis, its pathogenic role in fulminant hepatitis remains controversial. A 32-year-old man contracted hepatitis. Serum ALT concentration was reached to 6,970 IU/L, the lowest prothrombin time value was 16% and jaundice and stage II encephalopathy were developed. HCV RNA was detected in this patient by reverse transcription polymerase chain reaction in sera at the acute phase, and it was undetectable during the remission phase when anti-HCV was found. The entire genome of infected HCV was recovered, cloned, and sequenced from this patient, and compared with the clones of six other chronic hepatitis patients. Phylogenetic analysis revealed a clustering around genotype 2a and a deviation from the other 2a chronic hepatitis strains. Calculating the genetic distance in each subgenomic region revealed that the 5'untranslated region (5'UTR), core, nonstructural (NS) 3, and NS5A were severely deviated. Of 20 clones of the hypervariable region (HVR), 17 showed an identical sequence with the others showing a difference of only one amino acid. HCV was isolated from a fulminant hepatitis patient and its entire genome was recovered; a clustering around genotype 2a was observed, but the sequence deviated especially in 5'UTR, core, NS3, and NS5A; and monoclonality of the HVR sequence was found not only in the fulminant hepatitis patient but in a certain percentage of chronic hepatitis patients.

Adult↗
PubMed2001

Stress caused by minimally invasive cardiac surgery versus conventional cardiac surgery: incidence of systemic inflammatory response syndrome.

The present study was conducted to evaluate the degree of stress in patients induced by minimally invasive cardiac surgery (MICS) in comparison with that caused by conventional cardiac surgery. We did this by assessing the incidence of systemic inflammatory response syndrome (SIRS). A total of 48 adult patients who underwent surgery for single valve disease were included in this study, 27 of whom underwent conventional surgery and 21 MICS. We evaluated the stress inflicted on the patients in these two groups by analyzing the duration and degree of SIRS and the level of C-reactive protein (CRP). SIRS was assessed by measuring body temperature, heart rate, respiratory rate, and white blood cell counts. There were no significant differences in the operating times, perfusion times, or aorta clamp times between the two groups; and the mean volume of blood transfusion did not differ significantly either. There was no significant difference in the incidence of SIRS or the mean duration of SIRS between the two groups. The CRP levels did not differ significantly between the two groups. Thus although MICS is superior to conventional cardiac surgery in that only a small skin incision is required, the stress experienced by the patient may be the same as that experienced by the patient undergoing conventional cardiac surgery.

Aged↗