Biomedical subjects

Satoshi Suzuki

Publications and source records attributed to Satoshi Suzuki.

At least 55 records · Page 3Linked to original sources

PubMed2005

[Effects of peroxisome proliferator-activated receptor gamma ligands on monocrotaline-induced pulmonary hypertension in rats].

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily, which regulates transcription of target genes in a ligand-dependent manner. Ligands for PPARgamma have been shown to attenuate proliferation of vascular smooth muscle cells, and to induce apoptosis in several cell lines in vitro. Since monocrotaline (MCT)-induced pulmonary hypertension in rats is characterized by proliferation of pulmonary vascular smooth muscle cells, we hypothesized that PPARgamma ligands may reduce MCT-induced pulmonary hypertension. To test this hypothesis, we treated MCT-injected rats with pioglitazone and troglitazone, synthetic ligands for PPARgamma, for three weeks and measured pulmonary artery pressure and pulmonary vessel wall thickness. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and immunostaining for proliferating cell nuclear antigen (PCNA) were utilized to assess apoptosis and cell proliferation in the pulmonary arterial walls of pioglitazone-treated rats. MCT with pioglitazone or troglitazone treatment significantly reduced pulmonary hypertension and wall thickening of the pulmonary arteries. TUNEL-positive apoptotic cells were not seen in the pulmonary arterial walls of either MCT-injected or control rats with or without pioglitazone. PCNA-positive cells were only seen in the thickened pulmonary arterial walls of MCT rats, but not in the pulmonary arterial walls of controls and of pioglitazone-treated MCT rats. We conclude that PPARgamma ligands reduce MCT-induced pulmonary hypertension and pulmonary vascular wall thickening in rats. Inhibition of MCT-induced cell proliferation in the pulmonary arterial walls may account for this effect

Animals↗

PubMed2005

[Problems of case accumulation in a clinical trial of hepatic arterial infusion after resection of hepatic metastases: A summary of the study design and questionnaire survey of the participating centers in study no. 29-0003 of the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC)].

A randomized controlled trial of intermittent hepatic arterial infusion of weekly high-dose 5-FU (WHF) after resection of hepatic metastases from colorectal cancer was conducted to study the survival benefit of two regimens. Patients were randomly assigned to receive one of two arms after resection of hepatic metastases: the WHF arm (study group), 1000 mg/m2 of 5-FU administered over the course of 5 hr once a week by hepatic arterial infusion; or the CVI arm (control group), 300 mg/m2 of 5-FU administered as a continuous intravenous infusion daily for 5 days followed 2 days' rest. This study is the first randomized trial of hepatic arterial infusion chemotherapy with percutaneous hepatic catheter placement and assessment of liver drug distribution by CT angiography after resection of hepatic metastases from colorectal cancer in the world. Fifty-two centers participated, and 91 patients were enrolled. Although the target number of patients was not enrolled, problems of this study and future prospects for trials of hepatic arterial infusion after resection of hepatic metastases were assessed by questionnaire surveys of the participating centers.

Adult↗

PubMed2005

[Advances of clinical studies of acupuncture and moxibustion for treatment of rheumatoid arthritis].

OBJECTIVE: To summarize recent development of studies on acupuncture and moxibustion for prevention and treatment of rheumatoid arthritis, so as to provide a basis and thinking for clinical scientific studies. METHODS: More than 60 papers about clinical and experimental studies were reviewed, choosing clinically commonly-used acupoints and introducing mainly different therapeutic methods. RESULTS: Acupuncture and moxibustion can prevent and cure rheumatoid arthritis with outstanding results. CONCLUSION: Acupuncture and moxibustion have vast vistas for treatment of rheumatoid arthritis.

Acupuncture↗

PubMed2005

[Two case reports on intra-tumor injection therapy of dendritic cells].

DC (dendritic cells) vaccine therapy against cancer has attracted attention in recent years. However, the existence of the immunosuppressive state in cancer individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and DC migration to the target organ. It has been reported that injected intra-tumor DC is expected to work phagocytosis of the tumor as a localized effect, the consequent CTL induction in the tumor and the regional lymphnodes, resulting in a systemic effect. Two cases reported in this article were performed with intra-tumor DC injection therapy by means of EUS (endoscopic ultrasonography) which indicated interesting immunoreaction.

Aged↗

PubMed2004

Impact of warm ischemic time on microsomal P450 isoforms in a porcine model of therapeutic liver resection.

Human microsomes and hepatocytes obtained from non-transplantable livers of brain-dead donors are very useful in predicting the in vivo metabolism of xenobiotics in humans. Fresh liver specimens obtained from therapeutic liver resection are also useful for research in cases where non-transplantable livers are not readily available. In the present study, the effect of warm ischemic duration, in the course of hepatic surgery, on the activities of liver cytochrome P450 (CYP) CYP1A, CYP2C, CYP2D, CYP2E1 and CYP3A were evaluated in a porcine model. Partial occlusion (portal vein and hepatic artery occlusion) decreased the activities of CYP2C, CYP2E and CYP3A, but not those of CYP1A and CYP2D. CYP3A, known to account for an average 30% of total P450 content in the human liver was the most susceptible to the warm ischemia. These results demonstrate that the activities of CYP isoforms, particularly those of CYP3A, are markedly affected by warm ischemia; it is, therefore, essential that care should be exercised when using microsomes prepared from surgically removed livers.

Animals↗

PubMed2004

Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs: therapeutic effect by stem cell transplantation.

OBJECTIVE: Although some patients with limb ischemia have recently undergone therapeutic angiogenesis by cell transplantation, their angiogenic potential has not been well characterized. It is also important to evaluate endothelial progenitor cell (EPC) contents in different stem cell sources to choose the best material for therapeutic angiogenesis. METHODS AND RESULTS: We quantitated the mRNA expression of EPC-specific molecules (eg, Flk-1, Flt-1, CD133, VE-cadherin, etc) in bone marrow-derived or peripheral blood-derived mononuclear cells obtained from patients with ischemic limbs, using real-time reverse-transcription polymerase chain reaction technique. The mRNA expression level of EPC markers was significantly lower in the patients than in healthy controls, which was consistent with results of flow cytometric analysis. However, the implantation of autologous bone marrow mononuclear cells increased the circulating EPCs in the peripheral blood of patients. We furthermore revealed the different expression pattern of EPC markers in possible sources for stem cell transplantation, including normal bone marrow, peripheral blood obtained from recombinant granulocyte colony-stimulating factor-treated donor, and umbilical cord blood. CONCLUSIONS: Patients with peripheral obstructive arterial diseases may have lower angiogenic potential because of decreased expression of EPC specific molecules in their marrow and blood. Therapeutic angiogenesis by transplantation of autologous marrow mononuclear cells increased circulating EPCs in the patients and improved ischemic symptoms.

AC133 Antigen↗

PubMed2004

Paclitaxel prevents loss of pulmonary endothelial barrier integrity during cold preservation.

BACKGROUND: Cold preservation is the most practical method to maintain the viability of isolated lungs. However, rapid cooling may affect pulmonary endothelial function. We examined the effects of microtubule stabilization with paclitaxel on pulmonary endothelial barrier integrity under cold temperature. METHODS: Human pulmonary arterial endothelial cells were incubated at 4 degrees C for 2 hr in the presence or absence of paclitaxel (2.5 micromol/L). Microtubules was visualized using immunocytochemical techniques. Ultrasonic attenuation was measured with scanning acoustic microscopy. Endothelial barrier integrity was measured as transendothelial electric resistance. In addition, we examined graft function in a rat lung transplantation model, in which the donor lung had been preserved in the presence of paclitaxel (2.5 micromol/L) at 4 degrees C for 12 hr. RESULTS: Low temperature caused a reversible microtubule disassembly, but the structure of microtubules was preserved by paclitaxel. Paclitaxel prevented the cooling-induced decrease in ultrasonic attenuation and transendothelial electric resistance. In a rat transplantation model, we found that preservation with paclitaxel successfully improved the oxygenation performance of the donor lung, which demonstrated only mild congestion and less significant interstitial edema without fluid accumulation in the alveolar spaces. CONCLUSIONS: Our results indicate that microtubule stabilization with paclitaxel may be beneficial to prevent the loss of the endothelial barrier during cold preservation. We conclude that the use of paclitaxel in organ preservation solutions is useful in protecting pulmonary endothelial barrier integrity during cold preservation, thereby reducing the occurrence of early graft failure.

Animals↗

PubMed2004

The Tei index permits evaluation of cardiopulmonary function during inhaled nitric oxide therapy in the hypoxic newborn piglet.

The purpose of this study was to test the effectiveness of a new Doppler index combining systolic and diastolic time intervals (the Tei index) in the prospective assessment of ventricular function and pulmonary circulation in a newborn piglet model with hypoxic pulmonary hypertension during inhaled nitric oxide (NO). Piglets were prepared for the experiments under normal air, hypoxia, and hypoxia-with-inhaled-NO conditions. Complete two-dimensional Doppler echocardiographic examinations were performed in each condition. The right-ventricle (RV) Tei index increased with hypoxia and decreased following the inhalation of NO. Furthermore, there was a direct correlation between the individual changes in the RV Tei index and individual changes in mean pulmonary arterial pressure in each condition. We conclude that the Tei index is useful for assessing cardiac function and pulmonary circulation in hypoxic pulmonary hypertension during inhaled NO. These results suggest that the Tei index provides an objective assessment of persistent pulmonary hypertension of the newborn.

Animals↗

PubMed2004

Effect of PSK on the maturation of dendritic cells derived from human peripheral blood monocytes.

Dendritic cells (DCs) are powerful antigen-presenting cells (APCs) that have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of a strongly immunosuppressed state in cancer-bearing individuals inhibits DC maturation, which is one of the problems facing anti-cancer DC vaccine therapy. Protein-bound polysaccharide K (PSK), which is extracted from the cultured mycelium of Coriolus versicolor (Fr.) Quél, is used as an anti-cancer agent in Japan. PSK is reported to improve the immunosuppressed state and might be associated with DC maturation directly. We examined the effect of PSK on the maturation of DC derived from CD14-positive cells obtained from human peripheral blood monocytes using a negative selection method. CD14-positive cells cultured in the presence of PSK significantly increased the expression of HLA class II antigen and CD40; significantly increased the number and expression of CD80-, CD86- and CD83-positive cells; decreased Fluorescein isothiocyanate (FITC)-dextran uptake, augmented IL-12 production; augmented the allogeneic mixed lymphocyte reaction; and induced antigen-specific cytotoxicity. These results indicate that PSK promotes both the phenotypic and functional maturation of DC derived from human CD14-positive mononuclear cells. The clinical significance of the combined use of PSK in DC vaccine therapy remains for study.

Animals↗

PubMed2004

Improvement of serum bilirubin levels after venesection in a patient with Dubin-Johnson syndrome and HCV-positive chronic liver disease.

Direct-type hyperbilirubinemia in Dubin-Johnson syndrome is due to the genetic dysfunction of multidrug resistance protein 2. However, serum bilirubin levels may fluctuate as a result of acquired conditions. Iron-reduction therapy by venesection, an alternative to interferon, was performed in a 55-year-old male patient with Dubin-Johnson syndrome complicated by hepatitis C virus-positive chronic liver disease and hepatic iron overload. His pretreatment serum total bilirubin was 10.2 mg/dl, with a dominant direct fraction. The treatment induced a significant reduction in serum total bilirubin, although it remained as high as 7.9 mg/dl. A negative correlation between serum total bilirubin and cumulative bled volume suggested that venesection could suppress bilirubin production from aged erythrocytes. The hepatic iron overload was distributed in hepatocyte lysosomes with Dubin-Johnson granules; thus, it seems that iron removal from the lysosomal granules may also help to reduce serum bilirubin. In conclusion, deep jaundice in a patient with Dubin-Johnson syndrome complicated by hepatitis C virus-positive chronic liver disease and iron overload was partially improved by iron-reduction therapy.

Bilirubin↗

PubMed2004

Applicability of steroid therapy in 275 adult patients with IgA nephropathy determined using a histological scoring system and degree of proteinuria.

BACKGROUND: The purpose of this study was to propose clinical and pathologic criteria for the indication for steroid therapy (ST) in adult IgA nephropathy (IgAN). METHODS: We analyzed 275 adult IgAN patients retrospectively, using a histological scoring system. The histological score was expressed by evaluating, semiquantitatively, the extent of glomerular and tubulointerstitial lesions in terms of the activity index (AI) and chronicity index (CI). To determine the applicability of ST, three groups were categorized by evaluating the statistical significance of the correlation between the AI and CI, together with the daily amount of urinary protein (UP) and the outcome. RESULTS: In group A, which had a CI > or = 5 alone, 33 out of 43 patients showed a decline in renal function. There was no statistically significant difference between the subgroup with ST and that without ST. In group B, which had CI < 5, AI < 5, and UP < 1.0 g/day, 169 out of 174 patients had normal renal function irrespective of whether or not they received ST. Thus, ST had no beneficial effects in group A and B patients. In group C, which had CI < 5 and AI > or = 5 or UP > or = 1.0 g/day, patients with ST had a significantly higher incidence of an outcome with normal renal function (22 out of 24 patients) than that in patients without ST (19 out of 34 patients) (P < 0.01). Thus, ST had beneficial effects in group C patients. CONCLUSIONS: . We propose that a histological criterion be used in combination with the degree of proteinuria as an indication for ST in adult IgAN patients.

Acute Disease↗

PubMed2004

Mutation analysis of the multidrug resistance protein 2 (MRP2) gene in a Japanese patient with Dubin-Johnson syndrome.

Dubin-Johnson syndrome (DJS) is a recessive inherited disorder with conjugated hyperbilirubinemia caused by a dysfunction of multidrug resistance protein 2 (MRP2) on the canalicular membrane of hepatocytes. A mutational analysis of the MRP2 gene was carried out in a Japanese female with DJS. In this patient, we found a homozygous 2125T > C mutation in exon 17. This mutation affects the conversion of tryptophan(709) to arginine(709) (W709R) in the first ATP-binding cassette in the MRP2 protein. It was concluded that this homozygous mutation of the MRP2 gene contributed to the induction of hyperbilirubinemia in this case.

Journal Article↗

PubMed2004

Clinical significance of heparanase activity in primary resected non-small cell lung cancer.

Clinicopathological significances of heparanase activity in non-small cell lung cancer (NSCLC) were investigated by analyzing 76 resected specimens of NSCLC. Heparanase activities in NSCLC were significantly higher than non-cancerous lung tissues (P < 0.0001). The heparanase activities of NSCLC were significantly higher in larger diameter tumors (P = 0.0141) or with metastasis to ipsilateral mediastinal lymph nodes (P = 0.0004). The activities of heparanase in primary tumors were increased significantly according to the pathological stage of the progression of the disease (P =0.0009). Among the clinicopathological parameters, histological cell type and evidence of ipsilateral lymph node metastasis showed a significant association with elevated heparanase activities, whereas age, degree of differentiation and tumor diameter did not. Kaplan-Meier curves for overall and disease-free survival demonstrated a significant difference between patients with elevated and non-elevated heparanase activity by log-rank test (P = 0.0145 and 0.0002, respectively). Multivariate analysis showed heparanase activity was an independent factor to influence disease-free survival in our study. These results suggest that heparanase activity could be used as a prognostic indicator for postoperative patients with NSCLC and heparanase might be a promising molecular target for treatment of NSCLC.

Aged↗

PubMed2004

Development and characterization of a novel porcine model of neonatal sepsis.

Sepsis and its sequela remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care. Many models of neonatal sepsis have been developed for investigating the pathophysiology of this disease and application of therapy, and a model with an infectious focus is closer to clinical reality. To establish an animal model that mimics the clinical characteristics of neonatal sepsis, the cecal devascularization and perforation procedure was implemented on 15 mixed-strain newborn piglets, which produced an infectious focus that acted as a continuous source of microorganisms to the peritoneal cavity. The mean survival time in animals with sepsis was 10.4 h (range 5.5-17.9 h), whereas all of the sham-operated control animals survived more than 24 h. Animals with sepsis showed a gradual significant decrease in the mean systemic blood pressure (mSBP; 71 +/- 3 mmHg in sepsis vs. 64 +/- 3 mmHg in control at 3 h, 38 +/- 7 mmHg in sepsis vs. 59 +/- 4 mmHg in control at 6 h, mean +/- SEM). They also showed an increase of serum levels of endotoxin (5.6 x 10 +/- 4.5 x 10 pg/mL in sepsis vs. 6.0 x 10 +/- 3.8 x 10 pg/mL in control at 6 h). Serum levels of TNF-alpha in the animals with sepsis became significantly higher than the control animals at 0 h (96 +/- 31 pg/mL in sepsis vs. 12 +/- 1 pg/mL in control) and remained significantly higher than all through the experiment. Serum levels of IL-6 in animals with sepsis showed a gradual increase (484 +/- 231 pg/mL in sepsis in its peak at 6 h vs. 24 +/- 5 pg/mL in control), however, there were no significant differences in serum IL-10 levels between the groups. Microorganisms detected in the blood of animals with sepsis were gram-negative enteric and anaerobic organisms. These results suggested that this model mimics the clinical state of neonatal sepsis and hence may have significant implications for the treatment of sepsis, including its use as a model in further investigations.

Animals↗

PubMed2004

Effects of carbenoxolone on alveolar fluid clearance and lung inflammation in the rat.

OBJECTIVES: 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which requires oxidized nicotinamide adenine dinucleotide as a cofactor, metabolizes endogenous glucocorticoids. Since 11beta-HSD2 has been detected in lung epithelial cells, we examined whether carbenoxolone, a potent inhibitor of 11beta-HSD, would enhance endogenous glucocorticoid action on lung fluid balance and inflammation. DESIGN: Controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Adult Sprague-Dawley rats (n = 66). INTERVENTIONS: Rats were intraperitoneally injected with carbenoxolone (2 x 10 mg.kg(-1).day(-1) for 3 days) and allowed free access to water and food. Rats were further challenged with endotoxin instillation (1 mg/kg). MEASUREMENTS AND MAIN RESULTS: We discovered that carbenoxolone significantly increased messenger RNA expression of all three epithelial sodium channel subunits in distal lung tissues (two-fold increase of alpha-subunit, four-fold increase of beta-subunit, and two-fold increase of gamma-subunit) as well as in trachea. Carbenoxolone increased the amiloride-sensitive alveolar fluid clearance significantly. When rats were further challenged by endotoxin instillation (1 mg/kg), pretreatment with carbenoxolone significantly inhibited endotoxin-induced increase in lung neutrophils as well as tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant-1 concentrations in serum and bronchoalveolar lavage fluid. CONCLUSIONS: These beneficial effects of carbenoxolone on lung fluid balance and inflammation are very similar to those expected when glucocorticoids are introduced exogenously. We conclude that carbenoxolone increased the actions of endogenous bioactive glucocorticoids on lung cells by reducing local steroid breakdown.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2004

Bulge- and basal layer-specific expression of fibroblast growth factor-13 (FHF-2) in mouse skin.

A variety of polypeptide growth factors are involved in the dynamic maintenance of the skin and hair. Here, we demonstrate the presence of high levels of fibroblast growth factor (FGF)-13 in the bulge region of hair follicles. Using real-time PCR, we found that expression of FGF-13 mRNA is comparable to, or higher than, that of other FGF known to regulate hair growth and wound healing. To gain additional insight into the function of FGF-13, we evaluated its distribution using in situ hybridization and immunohistochemical staining. Unlike other FGF, the distribution of FGF-13 mRNA and protein in adult mice was mainly restricted to cells in the bulge region of hair follicles, although lower levels were detected with less frequency in keratinocytes in the basal layer of the epidermis. FGF-13 protein was detectable in the bulge region throughout the hair growth cycle, but its distribution was especially wide during telogen and early anagen. During hair follicle morphogenesis in newborn mice, FGF-13 protein was first detected in the bulge region and basal layer keratinocytes 3 d after birth. These findings suggest that FGF-13 may play a role in regulating the function of cells in the bulge region and basal layer of the epidermis.

Age Factors↗

PubMed2004

Treatment efficiency of a suicide gene therapy using prostate-specific membrane antigen promoter/enhancer in a castrated mouse model of prostate cancer.

Suicide gene therapy has potential for the treatment of prostate cancer under conditions of androgen deprivation. We show here that the combination of promoter/enhancer of prostate-specific membrane antigen (PEPM) and the Cre-loxP system is a good method to express a suicide gene, namely herpes virus thymidine kinase (TK), in prostate cancer cells. We have examined this system in a castration model in vivo, in comparison with a prostate-specific antigen promoter/enhancer system (PP). In the castrated mice, the tumor luciferase activity with the combination of the PEPM plus the Cre-loxP system was about 50 times greater than that with the control GL3 plasmid. A similar increase was observed in non-castrated mice. In contrast, the luciferase activity of the plasmid PP was decreased significantly in tumors from castrated mice as compared with tumors from non-castrated control mice. Regarding the therapeutic effect, the combination plasmid PEPM-Cre plus CMV-loxP-TK exhibited a strong inhibitory effect on tumor growth in the castrated mice, as in the non-castrated mice. In contrast, PP-TK plasmid did not show any significant growth inhibition in the castrated mice. These findings indicate that the combination of PEPM and Cre-loxP system may have a good treatment effect under androgen ablation conditions in vivo, and our system may therefore be applicable to patients who have previously received androgen deprivation therapy.

Adenocarcinoma↗

PubMed2004

Biophoton detection as a novel technique for cancer imaging.

Biophoton emission is defined as extremely weak light that is radiated from any living system due to its metabolic activities, without excitation or enhancement. We measured biophoton images of tumors transplanted in mice with a highly sensitive and ultra-low noise CCD camera system. Cell lines employed for this study were AH109A, TE4 and TE9. Biophoton images of each tumor were measured 1 week after carcinoma cell transplantation to estimate the tumor size at week 1 and the biophoton intensity. Some were also measured at 2 and 3 weeks to compare the biophoton distribution with histological findings. We achieved sequential biophoton imaging during tumor growth for the first time. Comparison of microscopic findings and biophoton intensity suggested that the intensity of biophoton emission reflects the viability of the tumor tissue. The size at week 1 differed between cell lines, and the biophoton intensity of the tumor was correlated with the tumor size at week 1 (correlation coefficient 0.73). This non-invasive and simple technique has the potential to be used as an optical biopsy to detect tumor viability.

Animals↗