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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 433 records · Page 24Linked to original sources

Surgical assessment of tricuspid valve replacement for severe tricuspid regurgitation without stenosis.

Eight patients undergoing tricuspid valve replacement (TVR) for severe tricuspid regurgitation (TR) without stenosis were subjected to the study. Four patients had primary TR due to trauma, infective endocarditis, or Ebstein's anomaly, and the other 4 had secondary TR associated with mitral valve lesions. The right heart pressure as well as clinical manifestations due to right heart failure showed deteriorated values in both the primary and secondary TR groups, though pulmonary arterial pressure was higher in the latter group. In 2 patients, initial annuloplasty procedures could not reduce TR sufficiently and were instantly abandoned for TVR. These 2 patients, one with congenital and one with secondary TR, died of intractable right heart failure early postoperatively, while the remaining 6 patients are alive to date, in the New York Heart Association (NYHA) functional class I, during the follow-up period of 6-192 (mean, 104) months. The 2 patients who died had shown a longer morbid duration and a lower preoperative right ventricular systolic function indicated by stroke work to pulmonary artery resistance. This paper might suggest that an earlier surgical intervention in severe TR is recommended before the right ventricular function deteriorates.

Adolescent↗

Availability of omental flap on prevention against muscular atrophy of a latissimus dorsi cardiomyoplasty.

Dynamic cardiomyoplasty (DCMP) has been performed in more than seven hundreds cases world wide. However, despite symptomatic improvement in the majority of patients surviving the procedure, objective hemodynamic effects have not been consistently demonstrated. Previous studies reported that left ventricular function deteriorated and returned to preoperative level in the chronic phase. We previously reported that atrophy of the latissimus dorsi muscular flap (LDMF) was responsible for the effect of DCMP on improvement of cardiac function in the chronic phase. Ischemia of the muscle flap was proved to induce peripheral muscular atrophy of the flap, and thus preservation of the blood flow is important in preventing muscular atrophy. In the present study, we applied omental flap to LDMF, and postulated that the omentum would improve vascularity and perfusion of latissimus dorsi and prevent peripheral muscle atrophy. In dogs, the right and left latissimus dorsi muscles were dissected free from all attachment except for its thoracodorsal pedicles, and omental flap was wrapped around peripheral part of the left LDMF. Tissue blood flow, maximal muscle isotonic strength, morphologic features, and tissue vascular endothelial growth factor (VEGF) were examined in left LDMF with omental flap (OM group) and in the right LDMF served as the control (Control group). In the distal part of the LDMF, tissue blood flow of OM was significantly preserved than Control (86.4 +/- 6.5% in OM and 33.6 +/- 3.4% in Control, p < 0.05). Maximal isotonic tension was significantly higher in OM as compared to Control. Microscopic findings of H and E stained specimen from distal part of LDMF showed that muscle fibers were preserved in OM. And in the distal part, VEGF expression of OM was 49.6 +/- 7.9 pg/100 micrograms protein and significantly higher than that of Control. Our results indicated that induced endogenous VEGF expression in the LDMF by the omental flap preserved blood perfusion and muscular strength of the LDMF, and suggested that dynamic cardiomyoplasty might not lose its long-term direct cardiac assistance when an omental flap applied for the latissimus dorsi muscle flap.

Animals↗

Quantitative assessment of peripheral occlusive arterial diseases by color duplex sonography and blood endothelin level.

UNLABELLED: To evaluate peripheral occlusive diseases quantitatively, we performed color duplex sonography and measured the blood endothelin (ET-1) level. MATERIALS AND METHOD: We measured the systolic velocities of the dorsal pedial and the posterior tibial arteries as well as the brachial artery. We also calculated the flow volume, and the ratio of systolic velocities and flow volume of the lower to upper extremity (AVI, AFI). Furthermore we measured the blood ET-1 level and investigated the relationship between this value and clinical symptoms. RESULTS: The value of AVI as well as AFI decreased in the order of Fontaine class I, II, III and IV. In four limbs with a Fontaine class greater than II with a normal ankle pressure index, the values of AVI were low. On the other hand, three limbs with normal values of peak-AVI (> 0.9) and lower API (< 0.75) were in Fontaine class I. The value of the ET-1 level was higher in Fontaine class III and IV than in class II, and decreased after revascularization along with improvement of clinical symptoms. CONCLUSIONS: The new AVI and AFI values showed a better correlation with clinical symptoms than API. The ET-1 level was significantly higher in Fontaine class III and IV, and showed marked regression after arterial reconstruction. Thus, the new AVI and AFI values may provide a novel means of identifying patients with the peripheral occlusive diseases, and the measurement of ET-1 level may be potentially useful in identifying the severity of arteriosclerosis.

Adult↗

Pathological analysis of transmyocardial laser revascularization for acute myocardial ischemia.

Transmyocardial laser revascularization (TMLR) is an alternative surgical procedure for the patients with intractable coronary artery disease. Efficacy of the treatment has been established, however, the mechanism of TMLR is still controversial. In this study, we investigated the effect of TMLR on acute myocardial ischemia with pathological analysis. Under general anesthesia, the hearts of mongrel dogs were exposed. Then, the anterior descending branch of the left coronary artery was ligated to make the ischemic area on the left ventricle. Laser punctures were made 30 minutes after coronary ligation in the TMLR group (n = 5), and no further procedure was performed after coronary ligation in the AMI group (n = 5). One month after these operations, the hearts were extirpated for pathological studies. The avascular area and the viable area in the infarcted area were macroscopically separated by Evans blue dye and triphenyltetrazolium chloride (TTC) staining. Thickness of the left ventricular wall in the infarcted area was also measured and compared. Furthermore, all of the infarcted area and the lased area were microscopically examined with Masson's trichrome stain. The size of the infarcted area in the TMLR group was smaller than that in the AMI group. It was significantly different (p < 0.05) in the basal and apical regions. As a result, the ratio of the viable area by the avascular area was larger in the TMLR group than in the AMI group. It was significantly different (p < 0.05) in the apical region. In the basal region, the thickness of the left ventricle in the AMI group was thinner than that of untreated dogs (normal group: n = 5), and there was no difference between the normal group and the TMLR group. Whereas in the apical region, significant difference of the thickness was found among AMI, TMLR, and normal groups (p < 0.05). In conclusion, our study supported; 1) TMLR reduced overall infarcted size, and increased the viable area in the infarcted area, 2) TMLR prevented the thinning of the left ventricular wall.

Animals↗

Reperfusion in acute ischemic myocardium by transmyocardial revascularization using CO2 laser.

Transmyocardial laser revascularization (TMLR) is currently applied to provide clinical benefits in the patients with end-stage coronary artery disease. However, this method is so far indicated only for chronic status of ischemic heart disease. In this study, we have investigated in the canine model whether acute ischemic myocardium could be reperfused by TMLR using CO2 laser. A CO2 laser was used to create transmural myocardial channels. The ischemic areas of 3 cm in diameter were created on the left ventricle with multiple coronary ligations. Laser procedure was carried out 30 minutes after coronary ligation in TMLR group (n = 6), while laser treatment was not performed after coronary ligation in acute myocardial infarction (AMI) group (n = 6). The level of MB isozyme of creatinine kinase (CK-MB) derived from coronary sinus was measured at 0, 3, 6, 12, 18, 24, and 48 hours after coronary ligations, and the pattern of serial CK-MB changing was analyzed. Animals were sacrificed 48 hours after treatment and histologically investigated. The time to peak level of CK-MB in TMLR group appeared significantly earlier (13.0 +/- 2.4 hours) than that in AMI group (22.0 +/- 3.1 hours). The value of CK-MB of 24 hours after ligation in TMLR group (1985 +/- 805 IU/L) was significantly lower than that in AMI group (4759 +/- 778 IU/L). The channels on the gross section after 48 hours of TMLR were patent with some of fibrin network. Red blood cells were scattered in the lumens. It was suggested that acute ischemic myocardium was directly reperfused through the open laser channels from the left ventricular chamber in the canine model.

Animals↗

Experimental investigations on relationships between myocardial damage and laser type used in transmyocardial laser revascularization (TMLR).

Transmyocardial laser revascularization (TMLR) using a CO2 laser is clinically attempted in end-stage ischemic heart disease that is not treated by conventional bypass grafting or transluminal angioplasty. Besides, clinical trials of TMLR using a Ho:YAG laser have started recently. In this study, we compared the degree of damage to normal myocardium using these 2 types of lasers. Hearts of adult mongrel dogs were exposed under general anesthesia. Dogs were divided into 2 groups; those with channels made in the left ventricle by CO2 laser (CO2 group, n = 5) and those with channels made by Ho:YAG laser (Ho:YAG group, n = 5). The chest was temporarily closed, then serum MB isozyme of creatinine kinase (CK-MB) and troponin T (TnT) were measured sequentially. Twenty-four hours after laser irradiation, hearts were isolated for pathological studies with hematoxylin-eosin and Masson's trichrome stains. The CO2 group produced CK-MB with a peak of 1162.2 +/- 462.2 IU/l and the Ho:YAG group 1804.0 +/- 992.4 IU/l after 12 hours, and there was a significant difference between two groups (p < 0.01). The CO2 group produced TnT with a peak of 1.2 +/- 0.4 ng/ml and the Ho:YAG group 11.6 +/- 4.1 ng/ml after 6 hours, and the peak value in Ho:YAG group was significantly higher than that in the CO2 group (p < 0.001). Thirty channels were confirmed histologically in the CO2 group, and the width of thermal damage layer around the channel lumen was 249 +/- 83 microns. Twenty-seven channels were confirmed histologically in the Ho:YAG group, and the width of thermal damage layer was 760 +/- 288 microns. Thermal damage in the Ho:YAG group was significant greater than that in the CO2 group (p < 0.01). We concluded that TMLR using a CO2 laser is more suitable for end-stage myocardial ischemia than a Ho:YAG laser in terms of myocardial damage.

Aluminum↗

Evaluation of local platelet deposition during laser thermal angioplasty.

Laser thermal angioplasty is one of the brand-new transluminal interventions for arterial occlusive disease. And one of the most important prognostic factors of this intervention is the degree of local platelet deposition which causes the acute platelet thrombus and increases the proliferation of smooth muscle cells. The purpose of this study is to assess the degree of platelet deposition on the laser ablated area and to investigate the optimal conditions of laser ablation from the point of thrombogenesis. First of all, the laser ablations of various delivered energy were carried out on canine femoral arteries, then thrombus formation after laser ablation was evaluated with angioscopy. No thrombus was recognized on all ablated areas in the cases with a laser energy of 16 Joule (J) and 20 J. On the other hand, small thrombus on the ablated area was observed in 1 of 4 cases (25%) with that of 24 J, and in 2 of 4 cases (50%) with that of 30 J. Then, the degree of platelet deposition on the laser ablated area was evaluated with platelet labeled radioimmunoassay. Laser ablations were employed in canine femoral arteries varying delivered laser energy. There were no differences in the numbers of platelet deposition when the laser energy for one shot was within 24 J. The numbers of platelet deposition with a laser energy of 30 J and 45 J were significantly (p < 0.05) higher than those with a laser energy within 24 J. The numbers of platelet deposition were gradually increased related to the frequency of laser ablations, and the numbers of platelet depositions in 10 repeated laser ablations of 16 J and 20 J were significantly (p < 0.05) higher than that in single laser ablation of 16 J and 20 J. From the aspect of local platelet deposition, the optimal laser energy for one shot should be restricted within 24 J and the repeated ablation was the most appropriate method of laser thermal ablation.

Aluminum↗

Cerebral acetylcholine levels and long-term spatial cognitive impairment following middle cerebral artery occlusion in rats.

The behavioral and neurochemical changes in the chronic phase of permanent occlusion of the right middle cerebral artery (MCA) in rats were investigated. Nineteen MCA-occluded rats failed to solve the 8-arm radial maze task (cognitively impaired rats), while 11 MCA-occluded rats could complete it (cognitively unimpaired rats). When a delay of 60 min was imposed in the task, however, 5 cognitively unimpaired rats failed to complete the task. The rats that underwent behavioral testing were studied for any changes in ACh levels in various brain regions using HPLC with electrochemical detection. The ACh levels in the infarcted areas decreased considerably in all MCA-occluded rats, but no region of the infarcted areas correlated with the spatial cognitive deficit. The ACh levels tended to decrease in the frontal cortex of the cognitively impaired rats and greatly increased in both ipsilateral and contralateral parietal cortex of the cognitively unimpaired rats. A significant correlation was observed between the ACh levels and spatial cognitive deficit in the contralateral frontal cortex, and ipsilateral and contralateral parietal cortex. These results suggest that the cholinergic function of the frontal and parietal cortices might play a role in acquiring spatial cognition in MCA-occluded rats.

Acetylcholine↗

[Relationship between hippocampal arachidonic acid content and induction of LTP in aged rats].

There are several lines of evidence indicating that membrane AA correlates with the ability of aged rats to sustain LTP. The age-related decrease in membrane AA seems to be triggered by increased lipid peroxidation, which is involved with the decline of LTP. The chronic treatment of DHA could decrease membrane AA without an increase in lipid peroxidation. We have thus investigated the effect of chronic treatment of DHA on hippocampal LTP to assess whether the decrease in membrane AA could directly affect the induction of LTP. The effects of daily supplementation of DHA for 3 months on membrane AA, LTP, and Ca2+ response were evaluated using hippocampal slices from 26-month-old Wistar rats. Chronic treatment of DHA reduced the hippocampal AA significantly, but did not change the amplitude of LTP. Neither 30 mM K+ nor 500 microM NMDA-induced Ca2+ response was affected by chronic treatment of DHA, while the 500 microM carbachol-induced Ca2+ response was reduced. From these results, the reduction of membrane AA might suppress the carbachol-induced Ca2+ response by inhibiting the muscarinic receptor function, IP3 formation and/or Ca2+ release from Ca2+ stores by IP3. However, the reduction of membrane AA is not likely to be a main causal factor of the decline of LTP.

Aging↗

[Estimated production by the official inspection of coal-tar dyes (including dye aluminum lakes) in fiscal year 1998].

There were 284 official inspections of coal-tar and their lakes in fiscal year 1998, and 283 of the lots qualified, one of the 40 samples of Food Yellow No. 5 was rejected. The quality of coal-tar dyes that passed inspection in Japan in fiscal year 1998 reached 150.3 tons. Coal-tar dye production is summarized by manoth in Table 2 and by manufacturer in Table 3. The food coal-tar dye produced in the largest quantity was Food Yellow No. 4, accounting for 44.1% during this period.

Chemical Industry↗

Effect of oral administration of Pinellia ternata, Zingiberis rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve in the rat.

The effect of taste stimulation of Pinellia temata, Zingiberis rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve was observed in the anesthetized rat. Taste stimulation by Pinellia ternata (50 mg/ml, 10 min) resulted in a suppression in vagal gastric nerve activity. On the contrary, stimulation by Zingiberis rhizoma (50 mg/ml, 10 min) caused a facilitation in efferent activity. The mixture of Pinellia ternata and Zingiberis rhizoma (5:1, 50 mg/ml, 10 min stimulation) demonstrated no suppressive effect on gastric nerve activity. These observations indicate that it is reasonable to prescribe Pinellia ternata with Zingiberis rhizoma in traditional Japanese medicine to prevent suppressive effect of the taste of Pinellia ternata on gastric function.

Administration, Oral↗

Effect of infusion of vasoactive intestinal peptide (VIP)-antisense oligodeoxynucleotide into the third cerebral ventricle above the hypothalamic suprachiasmatic nucleus on the hyperglycemia caused by intracranial injection of 2-deoxy-D-glucose in rats.

We examined the effect of the infusion of a vasoactive intestinal peptide (VIP) antisense oligodeoxynucleotide into the third cerebral ventricle above the hypothalamic suprachiasmatic nucleus (SCN) using osmotic minipump for 3 days (0.2 nmol/ml per h) on the hyperglycemic response to intracerebroventricular injection of 2-deoxy-D-glucose (2DG) (80 micromol) in rats. After the infusion of the VIP antisense the inhibition of VIP expression in the SCN was observed in association with suppressions of the hyperglycemia, hyperglucagonemia and relative hypoinsulinemia due to the 2DG injection. Furthermore, additional intracranial injection of VIP (4 nmol) restored these responses to the 2DG injection in rats treated with the VIP antisense. These findings suggest that VIP neurons in the SCN are involved in the regulation of glucose metabolism.

Animals↗

Molecular cloning and functional expression of a water-soluble chlorophyll protein, a putative carrier of chlorophyll molecules in cauliflower.

A cDNA for a water-soluble chlorophyll (Chl) protein (WSCP) from cauliflower (Brassica oleracea L. var botrys) was cloned and sequenced. The cDNA contained an open reading frame encoding 19 residues for a signal peptide and 199 residues for the mature form of WSCP. The sequence showed extensive homology to drought-stress-related, 22-kDa proteins in some Brassicaceae plants. Functional WSCP was expressed in Escherichia coli as a fusion protein with a maltose-binding protein (MBP). When the recombinant MBP-WSCP was incubated with thylakoid membranes, the MBP-WSCP removed Chls from these membranes. During this process, the monomer of the apo-MBP-WSCP successfully bound Chls and was converted into tetrameric holo-MBP-WSCP. The reconstituted MBP-WSCP exhibited absorption and fluorescent spectra identical to those of the native WSCP purified from cauliflower leaves. The Chl a/b ratio in native WSCP indicates a high content of Chl a, which was mainly due to the higher affinity of MBP-WSCP for Chl a. WSCP is the first example of a hydrophilic protein that can transfer Chls from thylakoid hydrophobic proteins. Possible functions of WSCP are discussed.

Amino Acid Sequence↗

Complex gangliosides are essential in spermatogenesis of mice: possible roles in the transport of testosterone.

Mice, homozygous for disrupted ganglioside GM2/GD2 synthase (EC 2.4. 1.94) gene and lacking all complex gangliosides, do not display any major neurologic abnormalities. Further examination of these mutant mice, however, revealed that the males were sterile and aspermatogenic. In the seminiferous tubules of the mutant mice, a number of multinuclear giant cells and vacuolated Sertoli cells were observed. The levels of testosterone in the serum of these mice were very low, although testosterone production equaled that produced in wild-type mice. Testosterone was found to be accumulated in interstitial Leydig cells, and intratesticularly injected testosterone was poorly drained in seminiferous fluid in the mutant mice. These results suggested that complex gangliosides are essential in the transport of testosterone to the seminiferous tubules and bloodstream from Leydig cells. Our results provide insights into roles of gangliosides in vivo.

Animals↗

Essential roles of Lyn in fibronectin-mediated filamentous actin assembly and cell motility in mast cells.

Although the requirement for c-Src in extracellular matrix (ECM)-mediated fibroblast motility has been well established, the roles of hemopoietic Src family protein tyrosine kinases in leukocyte migration have not been fully elucidated. To address the issue, we analyzed fibronectin (Fn)-mediated adhesion signaling in rat basophilic leukemia (RBL) 2H3 cells overexpressing 1) Csk, 2) a membrane-anchored, gain-of-function Csk (mCsk), and 3) a kinase-defective mCsk (mCsk(-)). Parent RBL2H3 cells, expressing autoactivated c-kit, readily adhered to Fn-coated surface, developed typical leukocyte adhesion machinery (podosome), and migrated toward Fn without cytokine priming, thus provided a simple experimental system to analyze Fn-mediated outside-in signaling. While overexpression of Csk or the Csk mutants did not significantly affect cell adhesion to the Fn surface or alpha5 integrin recruitment to the attachment sites, Csk suppressed and mCsk almost abolished Fn-mediated tyrosine phosphorylation of paxillin, filamentous actin assembly to podosomes, and cell migration, but mCsk(-) did not. Coexpression of LynA devoid of C-terminal negative regulatory tyrosine in mCsk cells successfully restored Fn-mediated podosome formation and cell migration. Coexpression of c-Src lacking the C-terminal tyrosine reconstructed podosomes, but could not restore the cell migration regardless of its expression level. Collectively, these observations provide evidence that Src family protein tyrosine kinases are required, and that Lyn could transmit sufficient signal for Fn-mediated cytoskeletal changes leading to cell locomotion in RBL2H3 cells, and they suggest that Lyn and c-Src are differentially involved in cell motility.

Actins↗

Novel nonsteroidal inhibitor of cytochrome P450(17alpha) (17alpha-hydroxylase/C17-20 lyase), YM116, decreased prostatic weights by reducing serum concentrations of testosterone and adrenal androgens in rats.

BACKGROUND: The purpose of this study was to determine the effects of a nonsteroidal C17-20 lyase inhibitor, 2-(1H-imidazol-4-ylmethyl)-9H-carbazole (YM116), on serum concentrations of androgens and ventral prostatic weight in rats. METHODS: Serum concentrations of testosterone and of dehydroepiandrosterone sulfate and prostatic weights were measured in rats treated with YM116. RESULTS: YM116 inhibited testicular C17-20 lyase competitively (Ki, 0.38 nM), and decreased the serum testosterone concentration in gonadotropin-releasing hormone-treated rats (ED50, 0.7 mg/kg), indicating that YM116 was about 21-24 times more potent than other C17-20 lyase inhibitors such as ketoconazole and liarozole, and was twice as potent as CB7630. YM116 also reduced dehydroepiandrosterone sulfate levels in ACTH-treated castrated rats (ED50, 11 mg/kg). YM116 (40 mg/kg, p.o., for 2 weeks) was almost comparable to bilateral orchiectomy with respect to the time course and magnitude of the reduction in prostatic weight. Each of these two treatments decreased the prostatic weight 3 days following the treatment. Contrarily, leuprolide transiently increased the prostatic weight and then decreased it. YM116 (100 mg/kg) had no effect on the serum cortisol level in guinea pigs, and slightly decreased the serum aldosterone level in rats. CONCLUSIONS: YM116 is a selective C17-20 lyase inhibitor which decreases rat prostatic weight by reducing androgen production in the testes and adrenal glands.

Abiraterone Acetate↗

Diversity of calcium signaling by metabotropic glutamate receptors.

During prolonged application of glutamate (20 min), patterns of increase in intracellular Ca2+ concentration ([Ca2+]i) were studied in HEK-293 cells expressing metabotropic glutamate receptor, mGluR1alpha or mGluR5a. Stimulation of mGluR1alpha induced an increase in [Ca2+]i that consisted of an initial transient peak with a subsequent steady plateau or an oscillatory increase in [Ca2+]i. The transient phase was largely attributed to Ca2+ mobilization from the intracellular Ca2+ stores, but the sustained phase was solely due to Ca2+ influx through the mGluR1alpha receptor-operated Ca2+ channel. Prolonged stimulation of mGluR5a continuously induced [Ca2+]i oscillations through mobilization of Ca2+ from the intracellular Ca2+ stores. Studies on mutant receptors of mGluR1alpha and mGluR5a revealed that the coupling mechanism in the sustained phase of Ca2+ response is determined by oscillatory/non-oscillatory patterns of the initial Ca2+ response but not by the receptor identity. In mGluR1alpha-expressing cells, activation of protein kinase C selectively desensitized the pathway for intracellular Ca2+ mobilization, but the mGluR1alpha-operated Ca2+ channel remained active. In mGluR5a-expressing cells, phosphorylation of mGluR5a by protein kinase C, which accounts for the mechanism of mGluR5a-controlled [Ca2+]i oscillations, might prevent desensitization and result in constant oscillatory mobilization of Ca2+ from intracellular Ca2+ stores. Our results provide a novel concept in which oscillatory/non-oscillatory mobilizations of Ca2+ induce different coupling mechanisms during prolonged stimulation of mGluRs.

Calcium↗