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Biomedical subjects

M Hamada

Publications and source records attributed to M Hamada.

At least 127 records · Page 7Linked to original sources

A case of effusive-constructive pericarditis: an efficacy of GD-DTPA enhanced magnetic resonance imaging to detect a pericardial thickening.

A 38-year-old man underwent pericardiectomy because of effusive-constrictive pericarditis. The gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging showed pericardial thickening separate from the effusion, which could not be shown by unenhanced computed tomography. Gd-DTPA enhanced magnetic resonance imaging could be useful for the early detection of effusive-constrictive pericarditis.

Adult↗

Cross-sectional area measurement of the semitendinosus tendon for anterior cruciate ligament reconstruction.

We measured the cross-sectional area (CSA) of the semitendinosus tendon (SMT) in 79 anterior cruciate ligament (ACL)-injured patients using magnetic resonance imaging (MRI) to scrutinize their appropriateness for ACL grafts. Measurements of the CSAs of the SMT with MRI were closely correlated with intraoperative direct measurement (y = 0.697). The mean CSAs of the SMT measured with MRI ranged from 6.3 to 15.0 mm2 with a mean of 10.1+/-2.1 mm2. The CSA of the SMT measured with MRI proved to be a useful indicator to determine preoperatively whether the SMT graft would be of adequate dimensions (7 mm or more in diameter, 60 mm or more in length) for ACL reconstruction. If the CSA of the SMT was more than 11 mm2, a sufficiently thick and long graft could be prepared with a tripled or quadrupled SMT in 89% of cases. We conclude that tissue CSA measurements using MRI could potentially be implemented as a useful tool for determining the most appropriate donor autograft tissue preoperatively, thus minimizing harvest-site morbidity.

Adolescent↗

Increased contraction of myocytes isolated from the young spontaneously hypertensive rat: relationship between systolic and diastolic function.

This study was designed to assess heart performance in young (10-week-old) spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, in terms of whole heart function in vivo and mechanics of isolated ventricular myocytes in vitro. The data suggest that left ventricular pressure (LVP) generation is greater, and the maximal velocities of LVP generation and decline are faster in SHR than in WKY. Two-dimensional morphologic measurements show that SHR myocytes are hypertrophied and that augmented contractile function is also present in isolated cells as determined by the extent of shortening and velocity of shortening. Relaxation is also faster at the myocyte level as determined by velocity of relengthening. However, the slope of the relationship between myocyte peak shortening and velocity of relaxation was similar in both groups. These results suggest that hyperdynamic myocyte relengthening may reflect changes in elastic recoil from increased shortening rather than intrinsic changes in cellular mechanisms, which are independent of shortening.

Animals↗

Left ventricular geometry as an independent predictor for extracardiac target organ damage in essential hypertension.

Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. It has not been established, however, whether left ventricular geometry is an independent predictor of extracardiac target organ damage in essential hypertension. Study groups were classified according to relative wall thickness: 27 patients with concentric LVH and 50 patients with eccentric LVH. Age and left ventricular mass indexes of two groups were matched. As indexes of extracardiac target organ damage, retinal funduscopic grade, and serum creatinine level were measured. The severity of hypertensive retinopathy and the renal involvement were more severe in patients with concentric LVH than in patients with eccentric LVH. Extracardiac target organ damage was consistently higher in patients with concentric LVH than in those with eccentric LVH. Systemic hemodynamics paralleled ventricular geometric patterns, with higher peripheral resistance and lower aortic compliance in patients with concentric LVH, whereas end-diastolic volumes and stroke volumes were higher in patients with eccentric LVH than in patients with concentric LVH. In addition, total peripheral resistance was related to retinal fundoscopic grade (r = 0.41, P < .01), and serum creatinine level (r = 0.28, P < .05). Even in the presence of an identical degree of LVH, echocardiographically determined left ventricular geometry may provide a further independent stratification of extracardiac target organ damage in essential hypertension.

Aged↗

Increased plasma levels of adrenomedullin in patients with hypertrophic cardiomyopathy: its relation to endothelin-I, natriuretic peptides and noradrenaline.

1. The aim of this study was to elucidate the pathophysiological role of adrenomedullin and the relation between adrenomedullin and other hormones in patients with hypertrophic cardiomyopathy. 2. Fourteen patients with hypertrophic obstructive cardiomyopathy (HOCM), 26 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) and 14 normal control subjects participated in this study. Radioimmunoassay for plasma adrenomedullin concentration was performed with adrenomedullin-M antibody. Plasma levels of endothelin-1, atrial and brain natriuretic peptides and noradrenaline were also measured. 3. Plasma levels of adrenomedullin were higher in patients with hypertrophic cardiomyopathy (8.43 +/- 3.73 pmol/l) than in normal controls (5.24 +/- 0.44 pmol/l, P < 0.005). There was no significant difference between HOCM and HNCM patients. There was a weak correlation between plasma levels of adrenomedullin and total 12-lead QRS voltage in patients with hypertrophic cardiomyopathy (r = 0.323, P < 0.05). 4. Plasma levels of endothelin-1, atrial and brain natriuretic peptides were higher in hypertrophic cardiomyopathy than in normal controls. Endothelin-1 showed no significant difference between HOCM and HNCM patients, but atrial and brain natriuretic peptides were higher in HOCM than in HNCM patients. There was a positive correlation between plasma levels of adrenomedullin and endothelin-1 (r = 0.575, P < 0.0001), but no correlation between plasma levels of adrenomedullin and atrial natriuretic peptide, brain natriuretic peptide and noradrenaline. 5. Our results indicate that adrenomedullin may play an important role to maintain haemodynamics in patients with hypertrophic cardiomyopathy, and its action may be related to endothelin-1 but independent of atrial natriuretic peptide, brain natriuretic peptide and noradrenaline.

Adrenomedullin↗

Tachykinins as enhancers of prostaglandin E2-induced intraocular inflammation.

The effects of tachykinins on prostaglandin E2 (PGE2)-induced intraocular inflammation were investigated. PGE2 (0.01% or 0.1%) instillation induced iridal hyperemia and protein leakage into the aqueous humor in rabbits, but caused minimal miosis. Intravitreally injected substance P (SP) or neurokinin A (NKA), on the other hand, did not induce protein leakage into the aqueous humor in normal rabbits, but they (SP 10 micrograms/eye or NKA 50 micrograms/eye) did induce long-lasting miosis. The miotic activity of SP was about fivefold stronger than that of NKA. Intravitreally injected SP (10 micrograms/eye) but not NKA (50 micrograms/eye) increased PGE2 concentration in the aqueous humor in normal rabbits. In addition, SP (10 micrograms/eye) or NKA (50 micrograms/eye) markedly enhanced protein leakage into the aqueous humor induced by PGE2 instillation. Pretreatment with indomethacin partially blocked the enhancing effect of SP on protein leakage, while it did not block that of NKA. These results suggest that SP or NKA may enhance intraocular inflammation in vivo. However, the mechanisms of these effects of SP and NKA may be different. The enhancing effect of SP in eye inflammation may be partially due to an increased turnover of arachidonic acid into PGE2 caused by activation of the enzyme cyclooxygenase.

Animals↗

Site-directed mutagenesis and steady-state kinetic analysis of mutant enzymes of human adenylate kinase.

Site-directed mutagenesis of human adenylate kinase (AK) was carried out on residues His36, Lys55, and the C-terminal segment (Val182, V186, and Leu193). Five mutants [(H36T, K55G, V182G, V186S, and L193Stop (deletion of residues 193-194)] were generated and analyzed by steady-state kinetics. H36T, K55G, and L193Stop mutants showed an increase of K(m) values (19.8-, 19.7-, and 11.3-fold) for AMP2- compared to that for the wild-type enzyme, and these residues appeared to interact with AMP2-. V182G showed an increased K(m) value (7.4-fold) for MgATP2-. Therefore, V182 may be essential for interaction with MgATP2-. V186S increased the K(m) value (7.0- and 7.5-fold) for MgATP2- and AMP2-. V186 may thus interact with both substrates. The C-terminal domain of AK appears to be essential for MgATP2- and AMP2- binding.

Adenylate Kinase↗

Effects of thyroid hormone on catecholamine and its metabolite concentrations in rat cardiac muscle and cerebral cortex.

Clinical and experimental data suggest that thyroid hormone affects the actions of catecholamine (CA). However, the serum or tissue levels of CA during thyroid disorders have not been well defined. Accordingly, we investigated the levels of CA and their metabolites in the cardiac muscle, the cerebral cortex, and the plasma of rats with hyperthyroidism and hypothyroidism versus euthyroid animals. The Neurochem analyzer system (ESA, Inc., Bedford, MA) was used in such determinations. The cardiac muscles of hyperthyroid rats exhibited a 16% decrease in the levels of 1-dopa, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) as compared with those in euthyroid rats. The levels of norepinephrine (NE) in cardiac muscle of these rats increased significantly (5.2-fold) relative to the levels in euthyroid rats. NE was undetectable in the cardiac muscles of the hypothyroid rats. Epinephrine (E) and dopamine (DA) were not detected in the cardiac muscles of the rats with either thyroid disorder. Levels of E and 3,4-dihydroxymandelic acid (DOPEG) were detected only in the cerebral cortex of hyperthyroid rats. The cerebral cortex levels of 3-methyoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), metanephrine (MN), and homovanillic acid (HVA) were all significantly increased in the hyperthyroid versus the euthyroid rats. The cerebral cortex levels of DA, NE, normetanephrine (NMN), and VMA in the hyperthyroid rats all showed a significant decrease. Levels of NE, NMN, and DOPAC in the cerebral cortex increased significantly in the hypothyroid rats. The level of VMA was undetectable in cerebral cortex of such animals. Data from studies on cardiac muscle and cerebral cortex indicate that the changes in CA and CA metabolites are responsible in part for the cardiovascular and the central nervous system symptoms observed in hyperthyroidism and hypothyroidism.

Animals↗

Detection of the ongoing sorting of ancestrally polymorphic SINEs toward fixation or loss in populations of two species of charr during speciation.

The FokI family of short interspersed repetitive elements (SINEs) has been found only in the genomes of charr fishes (genus Salvelinus). In an analysis of the insertion of FokI SINEs using PCR, we characterized six loci at which FokI SINEs have been inserted into the genomes of Salvelinus alpinus (Arctic charr) and/or S. malma (Dolly Varden). An analysis of one locus (Fok-223) suggested that a sister relationship exists between S. alpinus and S. malma and the SINE at this locus might have been inserted in a common ancestor of these two species, being fixed in all extant populations examined. By contrast, SINEs at two other loci (Fok-211 and Fok-206) were present specifically in the genome of S. alpinus, with polymorphism among populations of this species. Moreover, the presence or absence of the SINEs of the other three loci (Fok-214, Fok-217, and Fok-600) varied among populations of these two species. The most plausible interpretation of this result is that SINEs, which were ancestrally polymorphic in the genome of a common ancestor of these two species, are involved in an ongoing process of differential sorting and subsequent fixation in the various populations of each species.

Animals↗

Comparison of in vivo activities of 5'-connected and 3'-connected cis-acting ribozymes: selection of intracellularly active ribozymes using the gene for dihydrofolate reductase (DHFR) as a selective marker in Escherichia coli.

If ribozymes are to be exploited in vivo, it is necessary to select ribozymes that are functional in the intracellular environment. Ribozymes selected in the intracellular environment should retain their function in vivo as well as in vitro. We have devised a novel system for selection of active ribozymes from pools of active and inactive ribozymes using the gene for dihydrofolate reductase (DHFR) as a selective marker. In our first attempt, a sequence encoding either an active or an inactive ribozyme was connected upstream of the gene for DHFR. Each plasmid was designed such that, when the ribozyme was active, the ribozyme would cleave the target site and, as a result, the rate of production of DHFR would be high enough to endow resistance to trimethoprim (TMP). However, a critical defect may be associated with introduction of a ribozyme upstream of the DHFR gene because, during actual screening for active ribozymes on the 5' side from a pool of random sequences, there is the danger of selecting sequences that are not related to the activity of ribozymes. Indeed, some upstream linker sequences affected the level of expression of the DHFR protein and, as a result, the resistance of Escherichia coli to TMP. Therefore, we newly constructed a 3'-connected ribozyme system, and activities in vivo of 5'-connected and 3'-connected ribozymes were compared. We found that the cleavage efficiencies in vivo were nearly identical for the two types of ribozyme, 24% for the 5'-side ribozyme and 23% for the 3'-side ribozyme, indicating that polysomes did not seem to inhibit the action of the 3'-connected ribozyme. In both cases, when cells were transformed with a 1 : 1 mixture of active and inactive ribozyme-coding plasmids, it was mainly the cells that harbored the active ribozyme that survived in the presence of TMP.

Base Sequence↗

Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders.

To clarify the different roles of free radical scavenging systems in various thyroid disorders, we measured the levels of alpha-, beta-, and gamma-tocopherols and coenzyme Q in the thyroid tissues of patients with thyroid tumors and Graves' disease using high-performance liquid chromatography. The levels of alpha-tocopherols and gamma-tocopherols in the thyroid tissue of patients with papillary carcinoma and the level of gamma-tocopherol in the thyroid tissue of patients with malignant lymphoma were elevated compared with those in normal thyroid tissues. The level of coenzyme Q was reduced in the thyroid tissue of patients with Graves' disease and follicular and papillary thyroid carcinomas. These findings imply that vitamin E and coenzyme Q as scavengers play some role in thyroid follicular cell hyperfunction or dysfunction.

Graves Disease↗

Treatment outcome of osteofibrous dysplasia.

The disease course of six tibial lesions in five patients with osteofibrous dysplasia who were followed longer than 10 years (average: 16.8 years) was analyzed retrospectively. Three patients had a lesion of the unilateral tibia; one patient had lesions of the unilateral tibia and fibula; and one patient had lesions of the bilateral tibiae and ulnae. Curettage and autogeneic bone graft were performed on two lesions, which then healed. Of four lesions on which curettage and xenogeneic bone grafts were performed, three lesions healed, and one developed local recurrence. Curettage and xenogeneic bone graft were performed on the recurrent lesion, which finally healed and the deformity stopped. Three lesions healed without surgical treatment. During the long-term follow-up, this disease showed a clear tendency of healing. Surgical treatment should be considered in patients with disease uncontrollable by conservative treatment or those who have a high possibility of impending fracture and progressing deformity.

Adolescent↗

Alterations of neutrophil L-selectin and CD18 expression by tobacco smoke: implications for periodontal diseases.

Alterations in neutrophil functions by both chronic low levels of tobacco and by acute short-term higher levels of tobacco smoke, as encountered during the act of smoking, may play a role in the pathogenesis of periodontal diseases in smokers. Among the early migration events of neutrophil function is the alteration in surface expression of L-selectin and the CD11/18 integrins. In the present study we examined the effect of in vitro smoke exposure and nicotine alone on the expression of these 2 adhesion molecules in neutrophils from smokers and non-smokers. We also determined the physiological relevance of this in vitro system by assessing the levels of nicotine exposure in this in vitro system and comparing these levels to acute and chronic levels of nicotine in saliva and gingival crevicular fluid. Peripheral neutrophils were isolated from the blood of smokers (> 1 pack/d) and non-smokers and incubated in vitro with either cigarette smoke (0-5 min), 10(-7) M F-met-leu-phe, or nicotine alone at 1.62 mg/ml to 162 ng/ml (10(-2) M-10(-6) M). The neutrophils were then incubated with fluoresceine conjugated anti-Leu8 (L-selectin), anti-CD18 (CD18 integrin), or gamma-4 (non-specific control), fixed and analyzed by flow cytometry. With cigarette smoke exposure, there was an approximate 75% shedding of L-selectin in both smokers and non-smokers with no marked difference between groups at 1-5 min of smoke exposure. Cigarette smoke exposure resulted in a 15-20% increase in CD18 expression in both smokers and non-smokers. At all time points, there was slightly greater but statistically insignificant expression of CD18 integrin in non-smokers when compared to smokers. These patterns of CD18 increases and L-selectin shedding were similar in magnitude to incubations with 10(-7) M F-met-leu-phe. Acute smoke exposure resulted in elevation of nicotine in the smoke box to 529 ng/ml at 5 min, in saliva from 109.2 ng/ml before smoking to 1821.4 ng/ml after smoking, and in gingival crevicular fluid to 5961 ng/ml after smoking. No significant alterations in L-selectin or CD18 expression were noted with in vitro nicotine from 1.62 mg/ml to 162 ng/ml.

Adult↗

Beneficial hemodynamic effects of oral prostacyclin (PGI2) analogue, beraprost sodium, on a patient with primary pulmonary hypertension--a case report.

A 65-year-old woman was admitted to our hospital because of exertional dyspnea in 1987. A diagnosis of primary pulmonary hypertension was confirmed by right heart catheterization. She had received conventional therapy in the outpatient clinic. She was readmitted with the deterioration of exertional dyspnea in 1995. Stabilization of pulmonary hemodynamics, while not achieved with conventional therapy, was achieved with additive administration of an oral prostacyclin (PGI2) analogue, beraprost sodium.

Administration, Oral↗

Coronary vasospasm at the site of myocardial bridge--report of two cases.

Two patients with angina pectoris and postmyocardial infarction angina due to coronary vasospasm at the site of myocardial bridge are described. Intracoronary injection of isosorbide dinitrate led to resolution of coronary vasospasm on acetylcholine provocation test, and vasospastic angina pectoris has been well controlled after treatment with calcium channel blockers.

Angina Pectoris↗

Clinical characteristics in Japanese patients with coexistent hypertrophic cardiomyopathy and coronary vasospasm.

There are only a few reports concerning coexistent hypertrophic cardiomyopathy (HCM) and vasospastic angina. Clinical characteristics in patients with both diseases have not been clarified yet. This study was designed to elucidate the relationship between chest pain and coronary vasospasm in HCM patients and to delineate clinical characteristics in patients with both HCM and coronary vasospasm. First, 36 patients with HCM underwent acetylcholine provocation test for coronary vasospasm and were divided into two groups on the basis of presence or absence of coronary vasospasm. Next, the following risk factors for coronary artery disease were compared between the two groups: hypertension, smoking, hyperlipidemia, diabetes mellitus, and hyperuricemia. Coronary vasospasm was induced in 10 (28%) of 36 patients with HCM. There were no significant differences in age and male gender between the two groups. Smoking was more prominent in HCM patients with than without coronary vasospasm (80% vs 35%, p<0.05), but there were no differences in the prevalence of other risk factors between the two groups. In conclusion, coronary vasospasm appears to play a significant role in the etiology of myocardial ischemia in Japanese patients with HCM, and smoking might be a major risk factor for coexistence of HCM and coronary vasospasm.

Adult↗

2-(3-Pyridyl)thiazolidine-4-carboxamide derivatives. II. Structure-activity relationships and active configuration of 2-(3-pyridyl)thiazolidine-4-carboxamides as platelet-activating factor receptor antagonists.

Conversion of the 2-(3-pyridyl)thiazolidine part of 1-(3-phenylpropyl)-4-[2-(3-pyridyl)thiazolidine-4-carbonyl]piperazine (YM461), which is a potent platelet-activating factor (PAF) antagonist, to other rings was performed, and PAF antagonistic activities evaluated. The 2-(3-pyridyl)thiazolidine skeleton, which exists as a mixture of cis and trans diastereomers, played an important role in the potency of PAF antagonism. In this study, new effective skeletons were not uncovered, however, 2-(4-pyridyl)thiazolidine-4-carboxamides (1n and 1z) showed potent PAF antagonistic activities equal to the 3-pyridyl derivatives. From the results obtained for 1a, 1a(S), 1g and 1i, a cis-(2R,4R)-2-(3-pyridyl)thiazolidine-4-carboxamide was assumed to be the active configuration for PAF antagonism.

Animals↗