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Biomedical subjects

H Hamada

Publications and source records attributed to H Hamada.

At least 199 records · Page 11Linked to original sources
PubMed1999

Targeting endogenous platelet-derived growth factor B-chain by adenovirus-mediated gene transfer potently inhibits in vivo smooth muscle proliferation after arterial injury.

Platelet-derived growth factor (PDGF), especially its B chain, has been implicated in the pathogenesis of vascular proliferative disorders such as atherosclerosis and restenosis after angioplasty. We constructed a replication-deficient recombinant adenovirus containing the gene encoding the extracellular region of PDGF beta-receptor (PDGFXR) that binds PDGF-B chain and acts as its antagonist. The administration into balloon-injured rat carotid arteries of an adenovirus containing the Escherichia coli lacZ gene as a marker gene at 5 days after injury markedly facilitated efficacy of gene transfer, as compared with its administration immediately after injury. Adenovirus-mediated gene transfer of PDGFXR into injured arteries performed at 5 days resulted in a more than 50% reduction in the neointimal area of injured arteries at 14 days. In contrast, the administration of control adenoviruses containing lacZ gene or containing no foreign gene was without suppressive effects on neointima formation. The inhibition of neointima formation by the expression of PDGFXR was accompanied by a reduction in bromodeoxyuridine-labeled cells and nearly complete inhibition of tyrosine phosphorylation of both alpha- and beta-receptors for PDGF, but not of epidermal growth factor receptor, in injured arteries. This is the first report to indicate the usefulness of targeting a growth factor by expressing an extracellular binding region of a receptor using an adenovirus for the treatment of vascular proliferative disorders, and provide direct evidence that PDGF-B chain plays an essential role in neointimal formation.

Adenoviridae↗
PubMed1999

Gallstone disease risk in relation to body mass index and waist-to-hip ratio in Japanese men.

OBJECTIVE: To examine the relation of body mass index (BMI) and waist-to-hip ratio (WHR) to gallstones and postcholecystectomy risk in middle-aged Japanese men. DESIGN: Cross-sectional study. SUBJECTS: We used 174 men with prevalent gallstones, 104 with postcholecystectomy and 6909 with normal gallbladder in the consecutive series of 7637 men aged 48-59y receiving a preretirement health examination at four hospitals of the Japan Self-Defense Forces between 1986 and 1994. MEASUREMENTS: Gallbladder status was assessed by abdominal ultrasonography after an overnight fast. BMI was calculated as weight in kilogram divided by height in square meters, and WHR was used as a measure of central obesity. Analysis of the WHR was limited to a subset of data for the period 1991-1994 (gallstones 113, postcholecystectomy 66 and normal gallbladder 4410). RESULTS: After adjustment for hospital, rank in the Self-Defense Forces, cigarette smoking, alcohol use and glucose tolerance, BMI was significantly associated with an increased risk of both prevalent gallstones and postcholecystectomy. WHR also showed a significant positive association with each of the two conditions. When BMI and WHR were mutually adjusted for, both of the obesity indices tended to be associated positively with prevalent gallstones and postcholecystectomy. CONCLUSION: These findings indicate that obesity is associated with increased gallstone risk in men.

Asian People↗
PubMed1999

Therapy of established tumour with a hybrid cellular vaccine generated by using granulocyte-macrophage colony-stimulating factor genetically modified dendritic cells.

Dendritic cells (DCs) are the most powerful of all antigen-presenting cells and play a critical role in the induction of primary immune responses. DC-based vaccination represents a potentially powerful strategy for cancer immunotherapy. In this study, a new approach for a DC-based melanoma vaccine was described. Splenic DCs from C57BL/6 mice were fused with B16 melanoma cells, and the resultant B16/DC hybrid cells expressed major histocompatibility complex (MHC) molecules - B7 as well as the B16 tumour marker M562 - which were enriched by Ia-mediated positive selection with a MiniMACS column. The fusion rates were 12.7-26.8%. To generate hybrid tumour vaccines with potentially greater potent therapeutic efficacy, we genetically engineered DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to cell fusion. Recombinant adenovirus vector was used to mediate gene transfer into DCs with high efficiency and DCs expressed GM-CSF at 96-138 ng/105 cells/ml 24 hr after GM-CSF gene transfer. GM-CSF gene-modified DCs (DC.GM) exhibited higher expression of B7 and co-stimulatory capacity in mixed lymphocyte reaction (MLR). Fusion of DC.GM with B16 cells generated B16/DC.GM hybrid cells secreting GM-CSF at 59-63 ng/105 cells/ml. Immunization of C57BL/6 mice with the B16/DC hybrid vaccine elicited a specific cytotoxic T-lymphocyte (CTL) response and protected the immunized mice from B16 tumour challenge, reduced pulmonary metastases and extended the survival of B16 tumour-bearing mice. The B16/DC.GM hybrid vaccine was able to induce a CTL response and protective immunity more potently and tended to be therapeutically more efficacious than the B16/DC vaccine. In vivo depletion of T-cell subsets demonstrated that both CD8+ and CD4+ T cells were essential for the therapeutic effects of B16/DC and B16/DC.GM hybrid vaccines. Additionally, other non-specific effector cells may also contribute to tumour rejection induced by the B16/DC.GM hybrid vaccine. These data indicate that a DC-based hybrid tumour vaccine may be an attractive strategy for cancer immunotherapy, and that GM-CSF gene-modified DCs may lead to the generation of hybrid vaccines with potentially increased therapeutic efficacy.

Animals↗
PubMed1999

An experimental model for side-to-side microvascular anastomosis.

Side-to-side microvascular anastomosis may be required in certain clinical situations, although the technique is difficult and the incidence of usage remains low. A new experimental model using rat femoral vessels for side-to-side microvascular anastomosis is presented, in which 100 percent patency was accomplished immediately and was maintained for 7 days after anastomosis. This model can provide a training tool for acquisition of advanced microsurgical technique for side-to-side anastomosis of small vessels.

Anastomosis, Surgical↗
PubMed1999

Role of preoperative midsagittal magnetic resonance imaging in endoscopic third ventriculostomy.

We measured the distance between the infundibular recess and the tip of the basilar artery (BA) on midsagittal magnetic resonance (MR) images in 217 subjects (mean age, 54.7 years) without intracranial disorders and 8 patients with hydrocephalus treated neuroendoscopically. The mean distance measured in the 217 subjects without intracranial disorders was 10.5 +/- 2.3 mm. There were no significant differences in this distance among age groups. In 28 of these 217 subjects (12.9%), the tip of the BA had shifted anterior to the mamillary bodies on MR images. Twenty-six of these 28 subjects (93%) were 60 years of age or older. The mean distance between the infundibular recess and the tip of the BA was 12 +/- 3.7 mm in 8 patients with hydrocephalus. There was no significant difference between the subjects without intracranial disorders and the patients with hydrocephalus in this distance. In an elderly patient with aqueductal stenosis for whom the distance between the infundibular recess and the tip of the BA was 6 mm, the tip of the BA had shifted anterior to the mamillary bodies and indented the floor of the third ventricle on preoperative midsagittal MR images, and perforation of the floor of the third ventricle therefore had to be carefully performed in order to avoid injury of the BA. Preoperative midsagittal MR images can clearly reveal neurovascular structures beneath the floor of the third ventricle and increase the safety of endoscopic third ventriculostomy.

Adolescent↗
PubMed1999

A case of renal juxtaglomerular cell tumor: usefulness of segmental sampling to prove autonomic secretion of the tumor.

A 27-year-old female patient had been treated for hypertension with conventional therapy for years, because renal vein renin levels failed to show lateralization in renal venous samplings and a renal juxtaglomerular cell tumor (RJGCT) had gone undiagnosed. Abdominal computed tomography revealed a mass at the middle of the right kidney. The right renal venogram demonstrated distinct segmental veins from the upper pole and from the middle and lower poles in the right kidney. On segmental renin sampling from each renal vein, the plasma renin concentration (PRC) of the segmental veins from the middle and lower poles was higher than that from other sites. We diagnosed RJGCT of the right kidney and performed right-sided nephrectomy. After the resection, the PRC rapidly decreased. Immunohistochemical studies using antihuman renin antibodies revealed positive staining of the tumor cells. It is an important strategy to make a segmental sampling at the site as close as possible to the RJGCT.

Adenocarcinoma↗
PubMed1999

Myocardial distribution and biotransformation in vitro and in vivo of nicorandil in rats, with special reference to mitochondria.

This study reports subcellular localization of nicorandil in the myocardium and metabolism in mitochondria after oral dosing of 3 mg/kg nicorandil to rats. In the in vitro experiments, nicorandil, which was incubated with tissue homogenates (liver, kidney, heart, and small intestine), was metabolized to its denitrated compound, SG-86, and unknown substances. In the absence of a NADPH-generating system in the heart, the metabolic activity existed only in the mitochondrial fraction, but not in cytosolic and microsomal fractions. In the presence of the system, the activity in the mitochondrial fraction became much higher. To examine subcellular distribution of nicorandil in the myocardium, [14C]nicorandil was orally given to rats. Fifteen minutes after oral dosing of 3 mg/kg [14C]nicorandil, of which myocardial concentration reached a peak, nicorandil and SG-86 were found in mitochondrial fractions as well as in cytosolic and microsomal ones of the heart. Electron-microscopic autoradiograms, 15 min after oral dosing of 3 mg/kg [3H]nicorandil to rats, also showed the existence of the silver grains (showing radioactivity) in mitochondria of the heart. We conclude that nicorandil given orally is distributed in mitochondria of the heart, being partly transformed into SG-86, and that the myocardial mitochondria may be a potential site of action of nicorandil, an opener of KATP channels, which have been demonstrated to be present in this subcellular particle.

Animals↗
PubMed1999

Circumvention of 5-fluorouracil resistance in human stomach cancer cells by uracil phosphoribosyltransferase gene transduction.

A human stomach cancer cell line with acquired resistance to 5-fluorouracil (5-FU), NUGC-3/5FU/ L, has been found to possess reduced ability to convert 5-FU into active metabolites. We attempted in vitro gene therapy for this 5-FU-resistant cell line. NUGC-3 and NUGC-3/5FU/L cells were infected with recombinant adenovirus (Ad) containing Escherichia coli uracil phosphoribosyltransferase (UPRT) gene driven by CAG promoter (CA), AdCA-UPRT, and changes in their 5-FU metabolism and sensitivity were investigated. Activities of orotate phosphoribosyltransferase increased from 10.2 and 1.56 (nmol/mg protein/30 min) in the uninfected cells of NUGC-3 and NUGC-3/5FU/L to 216 and 237, respectively, after the transfection of UPRT gene. The 5-FU nucleotide level in the acid-insoluble fraction increased from 7.32 to 15.9 (pmol/mg protein) in NUGC-3 cells on infection with AdCA-UPRT, and in NUGC-3/5FU/L cells it increased from 1.91 to 21.4. The 50% growth-inhibition concentration (IC50) was 12.7 micromol/liter for NUGC-3 and much higher than 100 micromol/liter for NUGC-3/5FU/L, indicating over 8-fold resistance. NUGC-3/ SFU/L transfected with the UPRT gene showed very high sensitivity to 5-FU with an IC50 of 3.2 micromol/liter. The high resistance in this metabolic activation-deficient cell line was thus completely reversed by transduction of an exogenous gene coding for a 5-FU-anabolizing enzyme.

Adenoviridae↗
PubMed1999

Obesity, weight gain and risk of colon adenomas in Japanese men.

Obesity has been related to increased risk of colon cancer or adenomas, but the epidemiologic findings are not entirely consistent. We examined the relation of not only body mass index (BMI) but also waist-to-hip ratio (WHR) and weight gain to colon adenoma risk in men who received a preretirement health examination at the Japan Self Defense Forces (SDF) Fukuoka and Kumamoto Hospitals during the period from 1995 to 1996. In the series of 803 men at age 47-55 years, 189 cases of colon adenomas and 226 controls with normal total colonoscopy were identified. Weight at 10 years before was ascertained by referring to the recorded data. After allowance for hospital, rank in the SDF, smoking and alcohol use, weight gain over the past 10 years was significantly associated with increased risk of colon adenomas (odds ratio for > or = 6 kg versus < or =-2 kg = 2.2; 95% confidence interval 1.0-4.8). High BMI and high WHR were each associated with increased risk, but only WHR was related to the risk independently of weight gain. In particular, weight gain accompanied with a high WHR was associated with a significant increase in the risk. Men with high physical activity tended to have lower risk. Associations with obesity-related variables and physical activity were not materially differential as regards the location and size of adenoma. The findings indicate that weight gain in middle age leading to abdominal obesity increases the risk of colon adenomas, and consequently of colon cancer.

Adenoma↗
PubMed1999

Brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) levels in normal pregnancy and preeclampsia.

OBJECTIVE: Our purpose was to evaluate plasma levels of brain natriuretic peptide (pBNP) and cyclic guanosine monophosphate (pcGMP) in preeclamptic patients and controls. STUDY DESIGN: Blood samples were obtained from 35 patients with preeclampsia and from the same women during the subsequent puerperal period. The control group consisted of normotensive pregnant women, matched with the patients for age, gestational age, and parity. The concentrations of pBNP and pcGMP were determined by the RIA method. Statistical analysis was performed using the Mann-Whitney's U test. RESULTS: The pBNP level in the preeclampsia group was significantly increased, to 7-fold that of the control group. The pcGMP level was 50% higher in the preeclampsia group than in the control group, but this was not significant. Both the pBNP level and the pcGMP level in the puerperal period did not significantly differ between the patients and the controls. CONCLUSION: The pBNP concentrations increased in the preeclamptic women, and then these compensations were normalized in the puerperal period.

Adult↗
PubMed1999

Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo.

BACKGROUND/AIMS: Gastric cancer is one of the most prevalent forms of cancer in East Asia. Point mutation of the p53 gene has been reported in more than 60% of cases of gastric cancer and can lead to genetic instability and uncontrolled cell proliferation. The purpose of this investigation was to evaluate the potential of p53 gene therapy for gastric cancer. METHODS: The responses of human gastric cancer cell lines, MKN1, MKN7, MKN28, MKN45, and TMK-1, to recombinant adenoviruses encoding wild type p53 (AdCAp53) were analysed in vitro. The efficacy of the AdCAp53 treatment for MKN1 and MKN45 subcutaneous tumours in nude mice was assessed in vivo. RESULTS: p53-specific growth inhibition was observed in vitro in two of four gastric cancer cell lines with mutated p53, but not in the wild type p53 cell line. The mechanism of the killing of gastric cancer cells by AdCAp53 was found, by flow cytometric analysis and detection of DNA fragmentation, to be apoptosis. In vivo studies showed that the growth of subcutaneous tumours of p53 mutant MKN1 cells was significantly inhibited by direct injection of AdCAp53, but no significant growth inhibition was detected in the growth of p53 wild type MKN45 tumours. CONCLUSIONS: Adenovirus mediated reintroduction of wild type p53 is a potential clinical utility in gene therapy for gastric cancers.

Adenoviridae↗
PubMed1999

Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease.

The molecular mechanism involved in pulmonary vascular disease (PVD) associated with congenital heart disease (CHD) remains uncertain. Evidence suggesting that angiotensin converting enzyme plays an important role in pulmonary vascular pathology led us to hypothesize that mast cell chymase, another angiotensin I converting enzyme, also had the potential to contribute to the development of PVD in CHD. Twenty-three patients 3 mo to 45 yr of age with atrial or ventricular or both septal defects with increased pulmonary arterial blood flow and pressure, with pulmonary vascular resistance ranging from 1.3 to 8.1 units/m(2), were studied. Mast cells and mast cell chymase were immunohistochemically identified in the lung biopsy tissues obtained during corrective surgery. There was a significant difference in numbers of total mast cells between patients (n = 23) and control subjects (n = 10) with normal pulmonary circulation (p < 0.01). Moreover, chymase-containing mast cells in the lung tissues of patients with CHD showed striking differences from those of control subjects. In the patients, 72% of lung mast cells contained chymase, compared with only 15% in control subjects (p < 0.0001). Chymase-containing mast cells predominantly appeared in the media and adventitia of vessel walls. Importantly, angiotensin II was immunohistochemically detected in perivascular lesions where chymase was present, but not in the lesions where chymase was sparsely seen. Furthermore, the number of chymase-containing mast cells was correlated with pulmonary vascular resistance (r = 0.64). These findings suggest a possible role of mast cell chymase in the development of early-stage PVD in patients with CHD.

Adult↗
PubMed1999

Further characterization of earthworm serine proteases: cleavage specificity against peptide substrates and on autolysis.

Cleavage specificity of two fibrinolytic enzymes from Lumbricus rubellus [Nakajima, N., et al., Biosci. Biotechnol. Biochem., 57, 1726-1730 (1993) and 60, 293-300 (1996)] was investigated using beta-amyloid 1-40 and oxidized insulin B-chain as peptide substrates. The serine protease, F-III-2, cleaved the former substrate at six sites, and the latter at five sites. F-II digested them at six and ten, respectively. The cleavage specificity of F-III-2 resembled those of both trypsin and chymotrypsin. F-II had a broader specificity than F-III-2 and preferred also the bonds consisting neutral or hydrophobic amino acids. Furthermore, F-III-2 itself was digested initially on the site of Arg(144)-Tyr(145) to produce two peptide fragments, when it was autolyzed regularly by heating.

Amino Acid Sequence↗
PubMed1999

Multi-enzymatic glucosylation using Eucalyptus UDP-glucosyltransferase coupled UDPglucose-fermentation by bakers' yeast.

The enzymatic synthesis of glucoside compounds using a membrane-associated UDP-glucosyltransferase fraction from Eucalyptus perriniana cultured cells as a water-insoluble catalyst (N. Nakajima, et. al., J. Ferment. Bioeng., 84 (5), pp. 455-460, 1997) has been effectively done by coupling UDPglucose-fermentation by bakers' yeast. For example, beta-thujaplicin (hinokitiol) and p-aminobenzoic acid were converted respectively to their corresponding beta-D-monoglucosides with the conversion rate of around 24-26% by the multi-enzymatic system with UDPglucose as a glucose donor, which is produced by yeast cells from glucose and 5'-UMP. Addition of either cellobiose, a substrate of beta-glucosidase, or DL-1,2-anhydro-myo-inositol, an inhibitor for the enzyme in the reaction mixture, could increased the yield of these beta-D-monoglucosides. This new enzymatic system could also be used for the synthesis of flavonoid glucosides such as isoquercitrin (quercetin 3-O-beta-D-glucoside).

Eucalyptus↗
PubMed1999

Endoscopic aqueductal plasty via the fourth ventricle through the cerebellar hemisphere under navigating system guidance--technical note.

A 1-year 8-month-old boy presented with isolated fourth ventricle after ventriculoperitoneal shunting for hydrocephalus associated with ventricular and subarachnoid hemorrhage. The therapeutic endoscope was inserted through the thin left cerebellar hemisphere. Endoscopic aqueductal plasty was performed via the enlarged fourth ventricle under guidance from a navigating system. Endoscopic aqueductal plasty via the fourth ventricle under navigating system guidance is a useful procedure enabling less invasive surgery for isolated fourth ventricle associated with slit-like ventricle after shunt placement.

Cerebellum↗
PubMed1999

Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer.

PTEN, a gene encoding a dual specificity phosphatase, is frequently altered in endometrial carcinoma. Moreover, these alterations are observed even in atypical hyperplasia of the endometrium. This evidence suggests that mutation of PTEN is an early genetic alteration involved in endometrial carcinogenesis. Adenovirus-mediated gene transfer was carried out using Ishikawa 3 H 12 and RL95-2, the endometrial cancer cell lines with completely inactivated PTEN, together with endometrial cancer cell lines HEC1-A and KLE expressing wild-type PTEN as the control. The PTEN transgene significantly suppressed cell growth in vitro through induction of apoptosis in cells lacking wild-type PTEN. Furthermore, the ex vivo tumor formation by Ishikawa 3 H 12 cells was completely inhibited by the introduction of wild-type PTEN. However, neither regression nor progression was observed in inoculated tumors of either cell line by in vivo introduction of the PTEN gene. These results suggest that PTEN may be a good candidate for gene therapy in patients with endometrial carcinoma.

Adenoviridae↗
PubMed1999

Adriamycin activates E-cadherin-mediated cell-cell adhesion in human breast cancer cells.

E-cadherin-mediated cell-cell adhesion plays a crucial role in intercellular communication, which is related to the regulation of cell proliferation, differentiation, and apoptosis. Our previous study showed that decreased expression of MUC1 can induce E-cadherin-mediated cell-cell adhesion in human breast cancer cell lines proliferating in suspension without aggregation. Using such a cell line (YMB-S), we observed the effects of an anticancer agent, adriamycin, on cell-cell adhesion and expression of E-cadherin-catenin complex and MUC1. The cells showed E-cadherin-mediated cell-cell adhesion after 48 h exposure to 0.4 micromol/l adriamycin. And in these cells, expression of E-cadherin and beta-catenin mRNA obviously began to increase, while expression of MUC1 mRNA decreased, as demonstrated by Northern blot analysis. Such change in mRNA levels were followed by increases in E-cadherin and beta-catenin protein levels and a decrease in MUC1 protein level. Though expression of alpha-catenin mRNA began to increase on day 2, its protein level did not change. In immunohistochemical analysis, beta-catenin protein in untreated cells showed diffuse cytoplasmic localization, whereas beta-catenin in treated cells was present in cytoplasm with a clear submembranous localization, indicating that increased beta-catenin mainly bound with E-cadherin, participating in cell-cell adhesion. These findings show for the first time that adriamycin can induce E-cadherin-mediated cell-cell adhesion by increasing expression of E-cadherin and beta-catenin and decreasing expression of MUC1 during breast cancer cell apoptosis induced by this drug.

Antineoplastic Agents↗