Biomedical subjects

H Hanada

Publications and source records attributed to H Hanada.

At least 19 recordsLinked to original sources

PubMed2004

Dieulafoy's lesion of the esophagus correctly diagnosed and successfully treated by the endoscopic injection of N-butyl-2-cyanoacrylate.

Dieulafoy's lesion is an arterial malformation in the subumucosal layer of the gastrointestinal tract that can cause massive bleeding. The esophagus is not a common location for this lesion. We present here a first report of Dieulafoy's lesion of the esophagus correctly diagnosed and successfully treated by the endoscopic injection of N-butyl-2-cyanoacrylate.

Aged↗

PubMed2003

First results from KamLAND: evidence for reactor antineutrino disappearance.

KamLAND has measured the flux of nu;(e)'s from distant nuclear reactors. We find fewer nu;(e) events than expected from standard assumptions about nu;(e) propagation at the 99.95% C.L. In a 162 ton.yr exposure the ratio of the observed inverse beta-decay events to the expected number without nu;(e) disappearance is 0.611+/-0.085(stat)+/-0.041(syst) for nu;(e) energies >3.4 MeV. In the context of two-flavor neutrino oscillations with CPT invariance, all solutions to the solar neutrino problem except for the "large mixing angle" region are excluded.

Journal Article↗

PubMed2002

Interferon retreatment reduces or delays the incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

Inhibition of hepatocarcinogenesis is a crucial issue in treating chronic hepatitis C patients, especially those who do not respond completely to interferon therapy. Interferon has been reported to reduce the incidence of hepatocellular carcinoma (HCC) not only in sustained virological responders but also in transient biochemical responders. However, the incidence of HCC increases in 5 years or more after interferon therapy in transient biochemical responders. The aim of this study is to assess whether interferon retreatment reduces the incidence of HCC in chronic hepatitis C patients in whom hepatitis C virus was not eradicated during initial interferon therapy. We enrolled 309 patients who were not sustained virological responders after initial interferon treatment consisting of a total dose of more than 250 megaunits of interferon and were followed for more than 2 years after treatment. Ninety-nine patients received interferon retreatment and 210 did not. Two courses of interferon therapy were administered in 84, three courses in 14 and five courses in one. The incidence of HCC was compared between patients with retreatment and those without. In the clinical characteristics, retreated patients were younger and followed up for a longer time period. The cumulative incidence of HCC was significantly lower in retreated patients. In multivariate analysis, patients' age (P=0.018) and the number of courses of interferon therapy (P=0.022) were independently associated with HCC incidence. These results suggest that interferon retreatment reduces or delays the incidence of HCC in chronic hepatitis C patients who did not completely respond to initial therapy.

Adult↗

PubMed2002

Relationships of the systolic blood pressure response during exercise with insulin resistance, obesity, and endurance fitness in men with type 2 diabetes mellitus.

The purpose of the present study was to investigate the relationships among the resting systolic (SBP) and diastolic blood pressure (DBP) or SBP response during exercise with insulin resistance evaluated by a homeostasis model (HOMA-IR), abdominal fat accumulation (visceral fat area [VFA], subcutaneous fat area [SFA]) by computed tomography (CT), and an estimation of the maximal oxygen uptake (V*O2max) in 63 Japanese middle-aged male patients with type 2 diabetes mellitus (type 2 DM). Body mass index (BMI) and waist-to-hip ratio (WHR) in type 2 DM subjects were significantly higher than in age-matched healthy male control subjects (n = 135) with normal glucose tolerance. Resting SBP (127.7 +/- 16.2 mm Hg v 119.4 +/- 13.0 mm Hg) and DBP (82.2 +/- 11.9mmHg v 76.8 +/- 9.4 mm Hg) levels, and the percentage of hypertension (20.6% v 1.5%) in type 2 DM subjects were significantly higher than in the control subjects (P <.05). According to a multiple regression analysis for resting blood pressure in type 2 DM, VFA was found to be an independent predictor of SBP, while V*O2max and HOMA-IR were independent predictors of DBP. In the controls, however, HOMA-IR was not found to be a significantly independent predictor for either resting SBP or resting DBP. Measurement of the SBP response during graded exercise using a ramp test was performed by an electrical braked cycle ergometer in 54 patients with type 2 DM only. The SBP was measured at 15-second intervals during exercise. The exercise intensity at the double product breaking point (DPBP), which strongly correlated with the exercise intensity at the lactate threshold, was used as an index for the SBP response to standardized exercise intensity. The SBP corresponding to exercise intensity at DPBP (SBP@DPBP) was evaluated as an index of the SBP response to standardized exercise intensity. The change in SBP (deltaSBP = SBP@DPBP - resting SBP) was significantly and positively associated with log area under the curve for glucose (log AUCPG) during a 75-g oral glucose tolerance test (OGTT). In addition, deltaSBP significantly and negatively correlated with the log area under the curve for insulin (log AUCIRI) and log AUCIRI/log AUCPG. Based on these results, insulin resistance was suggested to be independently associated with the resting DBP and SBP response to standardized exercise intensity in type 2 DM patients.

Anthropometry↗

PubMed2001

Stretch-induced cell damage in sarcoglycan-deficient myotubes.

Sarcoglycans (SGs) are components of the dystrophin-glycoprotein complex, genetic defects in which cause skeletal muscle dystrophy and cardiomyopathy in humans and animals. To obtain insight into the roles of SGs, we characterized properties of myotubes prepared from cells of the rat L6 line or primary myoblast cultures of rat gastrocnemius muscle that were made SG-deficient by treatment with antisense oligodeoxynucleotides (AS-ODNs). Immunoblot and immunoprecipitation analyses revealed that dystrophin and its remaining associated proteins were tightly associated in these cells despite SG deficiency. 45Ca2+ influx into SG AS-ODN-treated L6 myotubes under resting conditions was significantly higher (1.7-fold at 6 min) than in controls, suggesting that Ca2+ influx is activated in these SG-deficient myotubes. When these cells were subjected to cyclic elongation of up to 20% for 1 h, a marked increase in creatine phosphokinase (CK) release into the medium was observed. Nifedipine, tranilast, FK506 and E64 or intracellular loading with 1,2-bis(2-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid, tetrakis(acetoxymethyl)ester (BAPTA/AM) reduced the stretch-induced CK release; a raised extracellular [Ca2+] increased CK release. The stretch-induced damage to SG-deficient myotubes thus appears to be caused by alterations in cell Ca2+ homeostasis. A similar abnormality in Ca2+ handling has been reported for myoctes from mdx mice or dystrophin-deficient patients, in whom SGs are also greatly reduced or absent. Thus it is possible that SG deficiency may play a critical role in the pathology of dystrophin-deficient muscle.

Animals↗

PubMed2001

Chicken microsatellite primers are not efficient markers for Japanese quail.

Domestic fowl or chicken (Gallus gallus) and Japanese quail (Coturnix japonica) belong to the family Phasianidae. The exchange of marker information between chicken and quail is an important step towards the construction of a high-resolution comparative genetic map in Phasianidae, which includes several poultry species of agricultural importance. We tested chicken microsatellite markers to see if they would be suitable as genetic linkage markers in Japanese quail. Twenty-six per cent (31/120) of chicken primers amplified individual loci in Japanese quail and 65% (20/31) of the amplified loci were found to be polymorphic. Eleven of the polymorphic loci were excluded as uninformative because of the lack of amplification in some individuals or high frequency of nonspecific amplification. The sequence information of the remaining nine loci revealed six of them to contain microsatellites that were nearly identical with those of the orthologous regions in chicken. For these six loci, allele frequencies were estimated in 50 unrelated quails. Although the very few chicken markers that do work well in quail could be used as anchor points for a comparative mapping, most chicken markers are not useful for studies in quail. Therefore, more effort should be committed to developing quail-specific markers rather than attempting to adapt chicken markers for work in quail.

Animals↗

PubMed2001

Plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are increased in the coronary circulation in patients with acute coronary syndrome.

BACKGROUND: Previous studies on atherectomy specimens from patients with acute coronary syndrome (ACS) implicated the role of proteolytic enzymes. We examined whether the plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were increased in the coronary circulation in ACS. METHODS AND RESULTS: The plasma levels (nanograms per milliliter) of MMP-9 and TIMP-1 in the aorta (Ao) and great cardiac vein (GCV) were measured in 29 patients with ACS (20 with acute myocardial infarction [group 1] and 9 with unstable angina [group 2]), 17 with stable effort angina (group 3), and 20 control subjects (group 4). Group 1 patients had occlusion in the left anterior descending artery (LAD), and groups 2 and 3 patients had culprit lesion in the LAD. In group 1 blood samples were obtained at the time of direct coronary angioplasty done within 12 hours after the onset. The Ao level of either MMP-9 or TIMP-1 did not differ among the 4 groups. The GCV-Ao differences in MMP-9 and TIMP-1 were both significantly increased in groups 1 and 2 compared with those in group 4. Neither of them was different between groups 3 and 4. Neither the GCV-Ao difference in MMP-9 or TIMP-1 level was correlated with the maximal creatine kinase level in group 1. CONCLUSIONS: Increased plasma levels of MMP-9 and TIMP-1 were detected in the coronary circulation in ACS patients, suggesting a process of active plaque rupture in ACS.

Acute Disease↗

PubMed2001

Stretch-activated cation channels in skeletal muscle myotubes from sarcoglycan-deficient hamsters.

Deficiency of delta-sarcoglycan (delta-SG), a component of the dystrophin-glycoprotein complex, causes cardiomyopathy and skeletal muscle dystrophy in Bio14.6 hamsters. Using cultured myotubes prepared from skeletal muscle of normal and Bio14.6 hamsters (J2N-k strain), we investigated the possibility that the delta-SG deficiency may lead to alterations in ionic conductances, which may ultimately lead to myocyte damage. In cell-attached patches (with Ba(2+) as the charge carrier), an approximately 20-pS channel was observed in both control and Bio14.6 myotubes. This channel is also permeable to K(+) and Na(+) but not to Cl(-). Channel activity was increased by pressure-induced stretch and was reduced by GdCl(3) (>5 microM). The basal open probability of this channel was fourfold higher in Bio14.6 myotubes, with longer open and shorter closed times. This was mimicked by depolymerization of the actin cytoskeleton. In intact Bio14.6 myotubes, the unidirectional basal Ca(2+) influx was enhanced compared with control. This Ca(2+) influx was sensitive to GdCl(3), signifying that stretch-activated cation channels may have been responsible for Ca(2+) influx in Bio14.6 hamster myotubes. These results suggest a possible mechanism by which cell damage might occur in this animal model of muscular dystrophy.

Actins↗

PubMed2001

Intramyocardial delivery of basic fibroblast growth factor-impregnated gelatin hydrogel microspheres enhances collateral circulation to infarcted canine myocardium.

The present study examined whether basic fibroblast growth factor (bFGF)-impregnated acidic gelatin hydrogel microspheres (AGHM) would enhance collateral development to the infarct area in dogs with coronary occlusion. Studies were conducted in 28 dogs with a 2-week occlusion of the proximal left anterior descending coronary artery (LAD). The dogs were divided into 3 groups according to treatment: Group A treated with bFGF-impregnated AGHM in the infarct area; Group B with free-form bFGF; Group C with AGHM alone. Coronary angiography (n=15; Group A, 7 dogs; Group B, 5 dogs; Group C, 3 dogs) and a regional myocardial blood flow study (n=13; Group A, 6 dogs; Group B, 4 dogs; Group C, 3 dogs) were repeated at a 2-week interval. Coronary angiography revealed that in Group A, antegrade flow in the LAD distal to the occlusion, which was assessed by Thrombolysis in Myocardial Infarction (TIMI) grade, was significantly increased after treatment. In contrast, in Groups B and C, the treatment did not change the flow grade in the LAD. In Group A, the regional myocardial blood flow in the collateral dependent area was significantly increased after treatment, and the regional myocardial blood flow reserve after adenosine injection was also significantly increased. These measurements remained after treatment in Groups B and C. The immunohistochemical study with factor VIII-related antigen revealed an increase of vascular density in the ischemic region in Group A. Intramyocardial delivery of bFGF-impregnated AGHM, but not free-form bFGF, improves the collateral circulation to the infarct area of a coronary occlusion in dogs.

Animals↗

PubMed2001

[Evaluation of coronary heart disease risk model by carotid ultrasonography in the occupational setting--intima-media thickness and coronary heart disease risk].

Recently, because of an increase in aged workers with high risk health conditions in Japan, it is becoming necessary to have a preventive control system for work-related diseases, such as coronary heart disease. We have already built a system by applying the prediction model of Framingham's risk equation for management after an annual check-up since 1999. At that time, we considered the relationship between CHD risk and intimamedia thickness (IMT) as an index of actual atherosclerosis. Correlation coefficients among max IMT, CHD risk and the several health factors in the corporate annual health check-up were obtained by Spearman's method. Significant associations with max IMT were only for CHD risk and systolic blood pressure. Correlation coefficients were 0.30 and 0.21 for CHD risk and systolic blood pressure, respectively. Furthermore, when we divided findings into those for the atherosclerotic and non-atherosclerotic groups defined by a max IMT over 1.1 mm or less, the difference between the two groups in CHD risks was investigated by t-test. The CHD risk for the atherosclerotic group was revealed to be significantly higher than that for the non-atherosclerotic group, with the means +/- SD in the two groups being 21.4 +/- 9.4% and 17.0 +/- 7.7%, respectively. CHD risk was therefore concluded to be important for the objective index of atherosclerosis from the viewpoint of high-risk-strategy in the worksite.

Adult↗

PubMed2000

Enhanced phospholipase C activity in the cultured skin fibroblast obtained from patients with coronary spastic angina: possible role for enhanced vasoconstrictor response.

OBJECTIVES: We measured phospholipase C (PLC) activity in the cultured skin fibroblasts obtained from patients with and without coronary spasm and examined its correlation with coronary artery vasomotility. BACKGROUND: Coronary artery vasomotility is enhanced in coronary spastic angina (CSA), but no information is available for the intracellular signaling. In spontaneously hypertensive rats, PLC activity in the skin fibroblasts has been shown to be enhanced. METHODS: Skin fibroblasts obtained from 24 patients with CSA-14 with organic coronary artery disease (CAD) and 12 control subjects--were cultured by the explant method. Activity of PLC was determined by incubating the membrane fraction with 3H-phosphatidyl inositol bisphosphate and by quantifying 3H-inositol trisphosphate. In patients with CSA and control subjects, the relations between PLC activity and coronary artery basal tone and constrictor response to intracoronary acetylcholine (ACh) were examined. RESULTS: Activity of PLC (pmol/protein [mg] per min) was 1.74+/-0.19 in patients with CSA; 0.90+/-0.12 in patients with CAD; and 0.65+/-0.07 in control subjects (p<0.001, patients with CSA vs. patients with CAD and control subjects; p = NS, patients with CAD vs. control subjects). According to the Lineweaver-Burk plot, Michaelis constant (micromol/liter) of PLC was 28+/-4 in patients with CSA; 49+/-14 in patients with CAD; and 56+/-10 in control subjects (p<0.05, patients with CSA vs. control subjects), whereas the maximal velocity was not different between the three groups. There were significant positive correlations between PLC activity and both basal tone (p = 0.0108) and response to ACh (p = 0.0053). Western blot analysis using membrane fraction demonstrated that 89% of PLC isoenzymes detected was of the delta1 isoform. CONCLUSIONS: Because the PLC activity measured was genetically defined and was positively correlated with coronary artery vasomotility, enhanced PLC activity may be involved in the pathogenesis of coronary spasm.

Angina Pectoris, Variant↗

PubMed2000

Pig cloning by microinjection of fetal fibroblast nuclei.

Pig cloning will have a marked impact on the optimization of meat production and xenotransplantation. To clone pigs from differentiated cells, we microinjected the nuclei of porcine (Sus scrofa) fetal fibroblasts into enucleated oocytes, and development was induced by electroactivation. The transfer of 110 cloned embryos to four surrogate mothers produced an apparently normal female piglet. The clonal provenance of the piglet was indicated by her coat color and confirmed by DNA microsatellite analysis.

Animals↗

PubMed2000

Alteration of the sex determining system resulting from structural change of the sex chromosomes in the frog Rana rugosa.

Rana rugosa in Japan is divided into four geographical races on the basis of the karyotype of the sex chromosomes: one in which heteromorphic sex chromosomes occur in the female sex (ZW/ZZ-system), another in which they are present in males (XX/XY-system), and the remaining two in which no heteromorphism is seen in either sex. The last two inherit the XX/XY sex determining system. Y and Z chromosomes in the former two are of the same karyotype as the no. 7 chromosomes seen in one of the latter two, whereas X and W are caused by two inversions that occurred in the original Xs (no. 7). In this study, we first attempted to detect the structural difference between the resulting X and W by examining their chiasma formation. The chiasma distribution between X and W was closely similar to that between two Xs, suggesting that the W and X are identical in structure. Regarding the change from XX/XY- to ZW/ZZ-system, the simplest explanation is that the putative female-determining gene(s) on the W grew functionally stronger by inversions. Next, we examined the sex of triploids having two Xs and one Z. The data showed that the triploids with two original Xs and a Z were all male, whereas most of those with two resulting Xs and a Z developed into females as expected. We speculated that the female-determining gene(s) on the resulting X grew mildly stronger functionally by position effect, whereas those on the W grew much stronger for some other reason (e.g., duplication). J. Exp. Zool. 286:313-319, 2000.

Animals↗

PubMed2000

Replicative advantage and tissue-specific segregation of RR mitochondrial DNA between C57BL/6 and RR heteroplasmic mice.

To investigate the interactions between mtDNA and nuclear genomes, we produced heteroplasmic maternal lineages by transferring the cytoplasts between the embryos of two mouse strains, C57BL/6 (B6) and RR. A total of 43 different nucleotides exist in the displacement-loop (D-loop) region of mtDNA between B6 and RR. Heteroplasmic embryos were reconstructed by electrofusion using a blastomere from a two-cell stage embryo of one strain and an enucleated blastomere from a two-cell stage embryo of the other strain. Equivalent volumes of both types of mtDNAs were detected in blastocyst stage embryos. However, the mtDNA from the RR strain became biased in the progeny, regardless of the source of the nuclear genome. The RR mtDNA population was very high in most of the tissues examined but was relatively low in the brain and the heart. An age-related increase of RR mtDNA was also observed in the blood. The RR mtDNAs in the reconstructed embryos and in the embryos collected from heteroplasmic mice showed a different segregation pattern during early embryonic development. These results suggest that the RR mtDNA has a replicative advantage over B6 mtDNA during embryonic development and differentiation, regardless of the type of nuclear genome.

Animals↗

PubMed2000

Successful treatment of severe orthostatic hypotension with cardiac tachypacing in dual chamber pacemakers.

Orthostatic hypotension is an evolving and disabling disease usually observed in elderly patients with dramatic consequences on morbidity, mortality, and impairing the quality of life. We studied the effects of the pacing rate and AV interval on the blood pressure drop in the upright position in two patients with previously implanted pacemakers for sinus node dysfunction. Although the AV interval did not affect the blood pressure drop in the upright position, tachypacing at 100 paces/min improved it dramatically and prevented syncope. Cardiac tachypacing is a useful therapeutic option in severe refractory orthostatic hypotensive patients, especially those with chronotropic incompetence.

Aged↗

PubMed1999

Thyroxine enhancement and the role of reactive oxygen species in tadpole tail apoptosis.

Our objective is to clarify the role of reactive oxygen species (ROS) in the atrophying tail of anuran tadpoles (tail apoptosis). Changes in catalase, superoxide dismutase (SOD) and caspase activity, genomic DNA, and nitric oxide (NO) generation were investigated biochemically using Rana japonica tadpole tails undergoing regression during thyroid hormone enhancement. DNA fragmentation and ladder formation with concomitant shortening of tadpole tail were induced by DL-thyroxine (T4) in culture medium. Catalase activity was also decreased by T4 treatment. T4 was also found to increase NO synthase (NOS) activity in cultured tadpole tail with concomitant increase in the concentration of NO2- plus NO3- (NOx) in the culture medium. Additional treatment with N-monomethyl-L-arginine (NMMA), a potent inhibitor of NOS, suppressed the enhancing effects of T4 on tail shortening and catalase activity reduction. It was also found that treatment with isosorbide dinitrate (ISDN), a NO generating drug, alone also had an enhancing effect on tail shortening and catalase activity reduction similar to that seen with T4. Both NO and an NO donor (ISDN) strongly suppressed catalase activity. Kinetic analysis revealed that catalase activity decreased and caspase-3-like activity increased during normal tadpole tail atrophy (apoptosis). These results suggested that T4 enhances NO generation, thereby strongly inhibiting catalase activity, resulting in an increase in hydrogen peroxide, and that the oxidative stress elicited by excess hydrogen peroxide might activate cysteine-dependent aspartate-directed protease-3 (caspase-3-like protease), which is thought to cause DNA fragmentation, leading to apoptosis.

Animals↗

PubMed1999

Evidence for heteromorphic sex chromosomes in males of Rana tagoi and Rana sakuraii in Nishitama district of Tokyo (Anura: Ranidae).

Karyotypes of the Tago brown frog Rana tagoi and stream Tago brown frog Rana sakuraii from a mountain region in the Nishitama district in Tokyo were examined by conventional Giemsa staining, C-banding and late replication (LR)-banding. Chromosome number was 2n = 26 in all cases. The 26 chromosomes consisted of five (1-5) pairs of large chromosomes and eight (6-13) pairs of small chromosomes. Chromosome 10 had a secondary constriction on the long arm. In all frogs, on chromosome pair 8, the XX/XY type sex chromosome was present. C-banding analysis indicated that, in R. sakuraii, neither the X nor Y chromosome possessed interstitial C-bands but each had centromere staining, while in R. tagoi, an interstitial C-band was present on the long arm of the X chromosome. The Y chromosome had no interstitial C-band. LR-banding analysis demonstrated the X and Y chromosomes to have a LR-band on the short arm and two LR-bands, each on the long arm, and the bands on both species to be essentially the same. Heteromorphic sex chromosomes in males of R. sakuraii and R. tagoi were identified for the first time in this study.

Animals↗

PubMed1999

A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility.

The purpose of the present study was to clarify how endogenous nitric oxide (NO) affects cardiac contractility and myocardial oxygen consumption (MVO2) in vivo. alpha-Chloralose-anesthetized dogs (n = 18) were instrumented to perform continuous and simultaneous measurements of coronary blood flow (CBF), anterior interventricular vein oxygen saturation (with the use of a fiberoptic catheter), aortic pressure, left ventricular pressure, and left ventricular volume. CBF, myocardial oxygen extraction (O2-extract), MVO2, the relationship between CBF and O2-extract during direct vasodilation induced by intracoronary papaverine (0.1, 0.2, 0.4 mg/kg), and cardiac contractility (Emax) were examined at control, after intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA, 2 mg/kg) and after antagonization of NO by L-arginine (20 mg/kg). L-NMMA decreased CBF from 62.0 +/- 1.7 to 59.7 +/- 2.4 (mL/min/100 g, P < 0.05) and increased O2-extract from 68.2 +/- 1.7 to 79.0 +/- 1.7% (P < 0.05). Emax was increased after L-NMMA from 3.2 +/- 0.2 to 3.7 +/- 0.1 (mmHg/mL/100 g, P < 0.05). These effects of L-NMMA were antagonized by L-arginine (P < 0.05 vs. after L-NMMA, P = NS vs. before L-NMMA). L-NMMA shifted CBF and O2-extract relationship determined by papaverine injection upward and L-arginine antagonized it to its baseline level. Endogenous NO reduces cardiac contractility and decreases MVO2, while increasing CBF.

Animals↗