Biomedical subjects

M Hamada

Publications and source records attributed to M Hamada.

At least 163 records · Page 9Linked to original sources

PubMed1997

Class Ia antiarrhythmic drug cibenzoline: a new approach to the medical treatment of hypertrophic obstructive cardiomyopathy.

BACKGROUND: The class Ia antiarrhythmic drug disopyramide relieves the outflow tract obstruction of hypertrophic obstructive cardiomyopathy (HOCM). Disopyramide, however, has several adverse effects, such as dysuria and thirst, resulting from its anticholinergic activity. A new class Ia antiarrhythmic drug, cibenzoline, has little anticholinergic activity. The aim of this study is to elucidate whether cibenzoline attenuates left ventricular pressure gradient (LVPG) in patients with HOCM. METHODS AND RESULTS: Ten patients with HOCM (mean age, 59+/-12 years) participated in this study. LVPG and left ventricular functions were measured before and 2 hours after administration of a single oral dose of 150 or 200 mg cibenzoline. LVPG decreased from 123+/-60 to 39+/-33 mm Hg (P=.0026). The E/A ratio in transmitral Doppler flow increased from 1.20+/-0.84 to 2.00+/-1.72 (P=.029). Isovolumic relaxation time increased from 73+/-16 to 101+/-23 ms (P=.0026). Left ventricular diastolic dimension remained unchanged, but left ventricular systolic dimension enlarged significantly, from 21.6+/-2.4 to 26.2+/-3.3 mm (P=.0004). Fractional shortening decreased from 47.6+/-6.1% to 34.6+/-8.8% (P=.0007). Left ventricular ejection time index decreased significantly, and preejection period index increased in all the patients. Decreased LVPG remained maintained even in the long-term treatment with cibenzoline. Conclusions These results indicate that cibenzoline can markedly attenuate LVPG in patients with HOCM. A decrease in myocardial contractility seems to be closely related to a marked decrease in LVPG.

Aged↗

PubMed1997

Effect of prolonged hypothermic ischemia and reperfusion on oxygen consumption and total mechanical energy in rat myocardium: participation of mitochondrial oxidative phosphorylation.

BACKGROUND: To reduce ischemia-reperfusion injury of hearts in open heart surgery and transplantation, it is important to know the critical period of ischemia in which donor hearts can sustain their function satisfactorily. Cardiac function has been deduced from oxygen consumption (VO2) and mechanical parameters such as pressure-volume area (PVA). Inhibited mitochondrial oxidative phosphorylation during ischemia indicates that ATP production is uncoupled from VO2. Therefore, both mitochondrial oxidative phosphorylation and total mechanical energy should be examined to evaluate cardiac function after ischemia and reperfusion. METHODS: Isolated rat hearts were stored in Euro-Collins solution at 4 degrees C for 8, 12, and 24 hr and reperfused in a working mode with a modified Krebs-Henseleit bicarbonate solution. PVA and VO2 were examined in isovolumic contraction, and ventricular contractility and total mechanical energy were assessed, respectively, by the end-systolic elastance (Ees) and PVA. Mitochondrial oxidative phosphorylation in the presence of succinate and mitochondrial lipid peroxide levels were estimated in similarly treated rat hearts. RESULTS: Ees was decreased by ischemia without significant difference. The VO2 to PVA ratio remained linear, although VO2 at null PVA and the VO2 to PVA ratio significantly increased after 12 hr of ischemia. Mitochondrial oxidative phosphorylation was decreased significantly by reperfusion after 12 hr of ischemia. Mitochondrial lipid peroxide levels were increased significantly after 12 hr of ischemia. CONCLUSIONS: In isolated rat hearts, decreased efficiency for energy conversion from consumed oxygen to cardiac performance occurs between 8 and 12 hr of hypothermic ischemia, which was coincident with disturbed mitochondrial oxidative phosphorylation, to which lipid peroxidation may contribute.

Animals↗

PubMed1997

Transient leftward QRS axis shift during treadmill exercise testing or percutaneous transluminal coronary angioplasty is a highly specific marker of proximal left anterior descending coronary artery disease.

The efficacy of transient QRS axis shift to the left as a predictor of proximal left anterior descending coronary artery (LAD) disease was assessed. By using receiver operating characteristic curve analysis, we indicated that the difference in modal QRS axis between before and after exercise was useful in detecting proximal LAD disease.

Aged↗

PubMed1997

Essential lysine residues in the N-terminal and the C-terminal domain of human adenylate kinase interact with adenine nucleotides as found by site-directed random mutagenesis.

To elucidate the minimum requirement of amino acid residues for the active center in human adenylate kinase (hAK1), we carried out random site-directed mutagenesis of key lysine residues (K9, K21, K27, K31, K63, K131, and K194), which were conserved in mammalian AK1 species, with the pMEX8-hAK1 plasmid [Ayabe, T., et al. (1996) Biochem. Mol. Biol. Int. 38, 373-381]. Twenty different mutants were obtained and analyzed by steady-state kinetics, and all mutants showed activity loss by Km and/or k(cat) effects on MgATP2-, AMP2-, or both. The results have led to the following conclusions. (1) Lys9 would appear to interact with both MgATP2- and AMP2- but to a larger extent than with AMP2-. (2) Lys21 is likely to play a role in substrate binding of both MgATP2- and AMP2- but more strongly affects MgATP2-. (3) Lys27 and Lys131 would appear to play a functional role in catalysis by interacting strongly with MgATP2-. (4) Lys31 would appear to interact with MgATP2- and AMP2- at the MgATP2- site. (5) Lys63 would be more likely to interact with MgATP2- than with AMP2-. (6) Lys194 in the flanking C-terminal domain would appear to interact not only with MgATP2- but also with AMP2- at the MgATP2- site by stabilizing substrate binding. The loss of the positively charged epsilon-amino group of lysine affects both the affinity for the substrate and the catalytic efficiency. Hence, hydrophilic lysine residues in hAK1 would appear to be essential for substrate-enzyme interaction with the coordination of some arginine residues, reported previously [Kim, H. J., et al. (1990) Biochemistry 29, 1107-1111].

Adenine Nucleotides↗

PubMed1997

Retinal leukocyte behavior in experimental autoimmune uveoretinitis of rats.

In vivo retinal leukocyte behavior in the experimental autoimmune uveoretinitis (EAU) of rats was investigated using acridine orange digital fluorography. The technique employed high resolution images obtained from a scanning laser ophthalmoscope (SLO) subsequent to staining with the fluorescent nuclear dye, acridine orange. Two weeks after immunization with synthetic peptides of retinal soluble antigen (S-Ag), acridine orange was intravenously injected, and fundus images were generated by SLO. Many rolling leukocytes were observed along the venous walls as slowly moving fluorescent dots; moreover, leukocytes infiltrating into the vitreous cavity were also noted especially over the retinal veins, but not over the retinal arteries. In addition, major retinal vessels were significantly dilated. The diameters of the retinal veins at a distance of 1 disc diameter away from the center of the optic disc were 49.8+/-4.5 micron for the normal rats and 88.2+/-3.6 micron for the EAU rats, respectively (P<0.001). Similarly, the diameters of retinal arteries were 32.6+/-3.7 micron for the normal rats, 53.8+/-1.5 micron for the EAU rats, respectively (P<0.01). The dilation was more prominent in the veins than in the arteries. These results suggest that it is possible to visualize the retinal involvement of EAU in vivo. The results also suggest that leukocyte-endothelial interaction and extravascular infiltration in the retinal venous vasculature may play significant roles in the early stages of posterior segment inflammation in EAU.

Acridine Orange↗

PubMed1997

The 3' ends of tRNA-derived SINEs originated from the 3' ends of LINEs: a new example from the bovine genome.

Our group demonstrated recently that the 3' ends of several families of tRNA-derived SINEs (short interspersed repetitive elements) originated from the 3' ends of LINEs (long interspersed repetitive elements) [Ohshima et al. (1996) Mol. Cell. Biol. 16:3756-3764]. Two fully characterized examples of such organization were provided by the tortoise Pol III/SINE and the salmonid HpaI family of SINEs, and two probable examples were provided by the tobacco TS family of SINEs and the salmon SmaI family of SINEs. This organization of SINEs can explain their potential to retropose in the genome since it appears reasonable that the sites for recognition of LINEs by reverse transcriptase should be located within the 3'-end sequences of LINEs. We now add another example to this category of SINEs. In the bovine genome, there are Bov-tA SINEs, which belong to the superfamily of tRNA-derived families of SINEs, and Bov-B LINEs, which were recently demonstrated to belong to a LINE family. Moreover, Bov-tA and Bov-B share the same 3'-end tail. We propose a possible scenario whereby the composite structure of the bovine Bov-tA family of SINEs might have been generated from the Bov-B family of LINEs during evolution.

Animals↗

PubMed1997

Magnetic resonance chemical shift imaging in bone and soft tissue tumours.

A study was carried out in 14 patients to assess the location and differential diagnosis of bone and soft tissue tumours with a 0.5 Tesla scanner, using water and fat images obtained by the three-point Dixon technique. We compared the magnetic resonance imaging findings obtained with this technique with conventional MRI, T1-T2-weighted images, and gadalinium-diethylenetriamine penta-acetic acid enhanced T1-weighted images. Localisation was better with the three-point Dixon technique than with conventional magnetic resonance imaging. Differentiation between the fat and water component around the tumour was possible. The gadalinium-diethylenetriamine penta-acetic acid enhanced water images were very sensitive to enhancement of the tissue. The three-point Dixon technique is useful when the tumour area is difficult to detect by conventional magnetic resonance imaging and information about its components is needed; these images can be made at the low magnet field.

Adipose Tissue↗

PubMed1997

Characterization of yellowfin tuna (Thunnus albacares, Scombroidei) tryptophan hydroxylase.

Tryptophan hydroxylase (EC 1.14, 16.4) was purified from yellowfin tuna liver and properties of this enzyme were compared with those of tryptophan hydroxylase from some other species (mouse mastocytoma and rat brain-stem). The molecular weight of the yellowfin tuna enzyme was estimated to be about 280,000 Da. This value is similar to that for the enzymes from mouse mastocytoma and rat brain-stem. On SDS-polyacrylamide gel electrophoresis analysis, yellowfin tuna enzyme was estimated to be about 96,000 Da. This value is different from that for the enzymes from mouse mastocytoma (53,000 Da) and rat brain-stem (59,000 Da) and suggests that yellowfin tuna enzyme may be a dimer of identical subunits of Mr 96,000 Da.

Animals↗

PubMed1997

Effect of enprostil on omeprazole-induced hypergastrinemia and inhibition of gastric acid secretion in peptic ulcer patients.

This study was performed to examine the effects of additional enprostil administration on hypergastrinemia and gastric acid suppression induced by omeprazole. Serum gastrin concentrations were measured in 10 peptic ulcer patients (six Helicobacter pylori-positive and four Helicobacter pylori-negative patients) before treatment, after two weeks of omeprazole (20 mg/day), and after two weeks of omeprazole and enprostil (50 micrograms/day). The additional acid inhibitory effect of enprostil was evaluated by 24-hr intragastric pH measurements in five healthy Helicobacter pylori-negative volunteers. After omeprazole treatment, the serum gastrin level of Helicobacter pylori-positive patients (3.5-fold of control) was markedly higher than that of Helicobacter pylori-negative patients (1.7-fold of control). Additional treatment with enprostil suppressed serum gastrin levels to 0.4-fold and 0.7-fold of omeprazole treatment levels in Helicobacter pylori-positive and Helicobacter pylori-negative patients, respectively. In healthy volunteers, median pH recorded during the nonmeal daytime interval increased significantly with additional enprostil. Thus, enprostil reduces undesirable omeprazole-induced hypergastrinemia, especially in Helicobacter pylori-positive patients, and effectively suppresses acid secretion.

Adult↗

PubMed1997

Role of gastrin/CCK-B receptor in the regulation of gastric acid secretion in rat.

The aim of this study was to investigate whether gastrin regulates morphological changes and alpha-subunit gene expression in parietal cells through the gastrin/CCK-B receptor on enterochromaffin-like cells by histamine release. Treatment with 100 mg/kg of YM022, a potent and selective gastrin/CCK-B receptor antagonist, for one week in rats did not alter mRNA levels of histidine decarboxylase or H+, K+-ATPase. However, parietal cell morphology predominantly changed to the resting form, although the serum gastrin concentration was significantly increased. Additional treatment with YM022 and oral omeprazole, 100 mg/kg, for one week markedly suppressed the increases of mRNA levels of histidine decarboxylase and H+, K+-ATPase and completely blocked the morphological transformation of the parietal cells to a stimulated form induced by treatment with omeprazole alone. This indicates that the morphological transformation of parietal cells to an activated form with a subsequent increase in H+, K+-ATPase synthesis caused by hypergastrinemia is mediated by increased histidine decarboxylase gene expression in enterochromaffin-like cells via gastrin/CCK-B receptors.

Actins↗

PubMed1997

Changes in free radical scavengers and lipid peroxide in thyroid glands of various thyroid disorders.

To clarify whether the changes of free radicals and its scavengers are induced by thyroid disorders, we measured levels of free radical scavengers and checked O2 radical generating systems in the human thyroid gland. Thyroid specimens from patients with Graves' disease, follicular adenoma, and papillary and follicular carcinomas contained significantly higher concentrations of xanthine oxidase (XOD) and gluthathione peroxidase (GSH-PX), compared to those in the normal thyroid tissue. Catalase concentration was significantly lower in thyroid specimens from patients with Graves' disease and significantly lower in thyroid specimens from patients with follicular adenoma, compared to those in the normal thyroid tissue. Cu/Zn superoxide dismutase (Cu/Zn SOD) concentration was significantly lower in the specimens from follicular adenoma and papillary carcinoma and Mn SOD concentration was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. The lipid peroxide concentration, expressed as malondialdehyde (MDA) concentration, was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. These findings suggest that the levels of free radicals are increased and are scavenged and catalyzed in the thyroid of Graves' disease, whereas free radicals and lipid peroxide are not completely scavenged in papillary carcinoma tissues, suggesting that these substances affect some role in cell function of thyroid tumors.

Adenocarcinoma, Follicular↗

PubMed1997

Substrate-binding and catalytic roles of Lys194 in the C-terminus in human adenylate kinase by site-directed random mutagenesis.

Site-directed random mutagenesis of Lys194 residue in the C-terminus of human adenylate kinase (AK) was performed, and six mutants were analyzed by steady-state kinetics. K194-mutants variously affected the apparent Michaelis constants (K(m) values) for ATP and AMP, although the kcat values strikingly decreased. The Lys194 residue appears to interact not only with MgATP2- but also with the AMP2- substrates by salt bridge formation with a nucleotide and to play a functional role in stabilizing the phosphate-transfer during catalysis. Lys194 could be essential for substrate-holdings and in catalysis and not replaceable to the other amino acids.

Adenylate Kinase↗

PubMed1997

A newly isolated family of short interspersed repetitive elements (SINEs) in coregonid fishes (whitefish) with sequences that are almost identical to those of the SmaI family of repeats: possible evidence for the horizontal transfer of SINEs.

The SmaI family of repeats is present only in the chum salmon and the pink salmon, and it is not present in five other species in the same genus or in other species in closely related genera. In the present study, we showed that another short interspersed repetitive elements (SINEs) family, which is almost identical to the SmaI family, is present in all fishes in the subfamily Coregoninae, being regarded as the most primitive salmonids. This new family of SINEs was designated the SmaI-cor family (SmaI family of repeats in coregonids). The consensus sequence of the SmaI-cor family was found to be 98.6% homologous to that of the SmaI family. Accordingly, it is difficult to explain the high degree of homology between these two families of SINEs by any mechanism other than the horizontal transfer of SINEs. The estimates of the rate of neutral mutation of nuclear genes, comparing chum salmon and European whitefish, confirmed this possibility. Our results strongly suggest that a member(s) of the SmaI-cor family might have been transferred horizontally from one coregonid species to a common ancestor of chum and pink salmon or to these two species independently, to allow subsequent amplification of the SmaI family in their respective genomes.

Animals↗

PubMed1997

The salmon SmaI family of short interspersed repetitive elements (SINEs): interspecific and intraspecific variation of the insertion of SINEs in the genomes of chum and pink salmon.

The genomes of chum salmon and pink salmon contain a family of short interspersed repetitive elements (SINEs), designated the salmon SmaI family. It is restricted to these two species, a distribution that suggests that this SINE family might have been generated in their common ancestor. When insertions of the SmaI SINEs at 10 orthologous loci of these species were analyzed, however, it was found that there were no shared insertion sites between chum and pink salmon. Furthermore, at six loci where SmaI SINEs have been species-specifically inserted in chum salmon, insertions of SINEs were polymorphic among populations of chum salmon. By contrast, at four loci where SmaI SINEs had been species-specifically inserted in pink salmon, the SINEs were fixed among all populations of pink salmon. The interspecific and intraspecific variation of the SmaI SINEs cannot be explained by the assumption that the SmaI family was amplified in a common ancestor of these two species. To interpret these observations, we propose several possible models, including introgression and the horizontal transfer of SINEs from pink salmon to chum salmon during evolution.

Animals↗

PubMed1997

Alterations in expression of sarcoplasmic reticulum gene in Dahl rats during the transition from compensatory myocardial hypertrophy to heart failure.

OBJECTIVES: To clarify whether the functional changes during the transition from compensatory myocardial hypertrophy to failure are associated with changes in sarcoplasmic reticulum gene expression. METHODS: We examined the gene expression of sarcoplasmic reticulum proteins [sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, calsequestrin and ryanodine receptor] in Dahl salt-sensitive (Dahl-S) rats fed a high-salt (8%) diet from the age of 6 weeks. In-vivo contractile functioning was evaluated using echocardiography, and gene expression of sarcoplasmic reticulum proteins in the left ventricle was analyzed by Northern blotting for each stage of left ventricular hypertrophy. RESULTS: SERCA messenger RNA (mRNA) levels in Dahl-S rats with compensatory hypertrophy did not change significantly, whereas phospholamban mRNA levels were increased by 61% (P < 0.01), and calsequestrin mRNA levels were increased by 130% (P < 0.01) compared with those in Dahl salt-resistant (Dahl-R) rats. SERCA mRNA levels in Dahl-S rats with decompensated dilatation were decreased by 32% (P< 0.05), whereas levels of phospholamban and calsequestrin mRNA remained unchanged. Ryanodine receptor mRNA levels did not change either with compensatory hypertrophy or with decompensated dilatation. CONCLUSIONS: Alterations in expression of sarcoplasmic reticulum gene may be related to changes in systolic and diastolic properties in compensatory hypertrophy and heart failure.

Animals↗

PubMed1997

Effects of locally administered argatroban on restenosis after balloon angioplasty: experimental and clinical study.

1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on restenosis after balloon angioplasty. 2. A hydrogel-coated balloon catheter was immersed three times in argatroban/saline solution (1 mg/mL) for 60 s, inflated to a pressure of 606 kPa and left in the rabbit common carotid artery for 1 min. The same procedure was performed, without drug, as a control. The pharmacokinetics of delivered argatroban in the arterial wall were assessed using [14C]-argatroban. Platelet deposition 2 h after balloon injury was quantified by fluorescence studies using antiplatelet antibody. Vascular smooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining for proliferative cell nuclear antigen (PCNA). In a clinical study, we divided 50 elective patients into two groups: argatroban and control. 3. In the experimental study, the mean quantities of argatroban at 0, 2 and 6 h after deflation were 24.63, 0.49 and 0.11 nmol/g wet weight of artery, respectively. Argatroban was undetected 24 h after deflation. Two hours after deflation, argatroban-treated arteries showed less platelet adhesion than saline-treated controls. The mean number of PCNA-positive cells was 16.9 and 43.8% in the argatroban and control groups, respectively (P < 0.01). In the clinical study, the mean late gain loss was 8.2 and 27.3% in the argatroban and control groups, respectively (P < 0.05). The mean late restenosis rate was 11.1 and 41.4% in the argatroban and control groups, respectively (P < 0.05). 4. These data suggest that blood coagulation plays a significant role in VSMC proliferation after balloon injury and that locally administered argatroban using hydrogel-coated balloon catheter may prevent post-percutaneous transluminal coronary angioplasty restenosis.

Angioplasty, Balloon↗

PubMed1997

Small cell carcinoma of the kidney: case report.

An 83-year-old female diagnosed with small cell carcinoma of the kidney is reported on. The clinical picture was similar to that seen with transitional cell carcinoma of the renal pelvis. A right nephroureterectomy was performed and a histological examination revealed similar morphological features to those of small cell carcinoma of the lung. Neuroendocrine differentiation was proven by a positive immunoreaction to neuron-specific enolase. A review of the literature indicated that in the urinary tract, most of the cases of small cell carcinoma occurred in the urinary bladder, with this case being the eleventh reported case of small cell carcinoma originating in the kidney. As with many of the other cases of small cell carcinoma of the urinary tract, this patient's tumor was associated with both adenomatous and squamous differentiation. The patient died 2 months after surgery, prior to any chemotherapy administration.

Aged↗

PubMed1997

Clinical evaluation of the centrifugal pump in open heart surgery: a comparative study of different pumps.

The centrifugal pump is now widely used in open heart surgery for its clinical benefits related to the blood elements and the coagulation system. The purpose of this study was to compare the clinical performances of and the outcomes offered by 4 types of centrifugal pumps. For each pump, we investigated the effects on the blood elements, coagulation system, complements, and immunoglobulins during open heart surgery. Four types of centrifugal pumps were used: the HPM-15 (Nikkiso Co.), the Capiox (Terumo Co.), the Lifestream (St. Jude Medical Co.), and the BP-80 (Medtronic, BioMedicus Co.). The platelet count, lactate dehydrogenase (LDH), antithrombin III (AT III), thrombin-antithrombin complex (TAT), complements (C3, C4, and CH50), and immunoglobulins (IgG, IgA, and IgM) were measured before and after cardiopulmonary bypass (CPB). The platelet count was decreased more significantly by the HPM-15 than by any of the other pumps. The other parameters showed no difference among the 4 pumps. In clinical use, each of the 4 types of centrifugal pumps was safe.

Aged↗