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Biomedical subjects

H Matsuda

Publications and source records attributed to H Matsuda.

At least 109 records · Page 6Linked to original sources

Effect of hemodilution on the adequacy of cerebral perfusion under hypothermic cardiopulmonary bypass.

OBJECTIVE: Open heart surgery without transfusion has been performed even in children. However, the critical limit of the hemoglobin level has not yet been ascertained. Here, we have assessed experimentally the effect of the hemoglobin level on brain metabolism under hypothermic cardiopulmonary bypass. METHODS: Brain tissue pH was measured in 14 rabbits that were put on bypass with a different degree of hemodilution. Cardiopulmonary bypass was started at 37 degrees C and cooled down to 25 degrees C. After maintaining the bypass at 25 degrees C for 60 minutes, the animal was rewarmed to 37 degrees C for 30 minutes and then kept on-bypass for another 30 minutes. The perfusion flow was maintained as 10 ml/kg/min. RESULTS: The lowest hemoglobin level in each rabbit was from 2.5 through 8.5 g/dl. During hypothermic bypass, brain tissue pH increased from 7.21 +/- 0.16 (mean +/- SD, at the normothermic baseline) to 7.55 +/- 0.27 except 2 cases (6.91 +/- 0.16) whose hemoglobin level was lower than 3.0 g/dl. The brain tissue pH after 60 minutes on hypothermic bypass had a good correlation with the hemoglobin level (r = 0.831). After rewarming for 60 minutes, the brain tissue pH was decreased to 7.18 +/- 0.31. In 4 rabbits with less than 4.0 g/dl of hemoglobin, the brain tissue pH (6.67 +/- 0.24) was lower than the baseline level. In the other 10 rabbits, the brain tissue pH (7.22 +/- 0.16) was almost the same as the baseline level. The correlation coefficient between the brain tissue pH and the hemoglobin level after rewarming for 60 minutes was 0.778. CONCLUSIONS: These results indicated that severe hemodilution in cardiopulmonary bypass promoted acidosis in brain even during hypothermia.

Animals↗

Cerebral blood flow and metabolic abnormalities in Alzheimer's disease.

In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease. In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E genotype has been investigated. Especially, the APOE epsilon4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the epsilon4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single epsilon4 allele. On the contrary the relation of epsilon4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection or statistical parametric mapping instead of a conventional regions of interest technique.

Alleles↗

Novel and convenient methods for Candida tropicalis gene disruption using a mutated hygromycin B resistance gene.

We established a novel and convenient method to construct a ura3 strain (ura3/ura3) of the asporogenous and diploid yeast, Candida tropicalis, that produces dicarboxylic acid. One copy of the URA3 gene was disrupted using a mutated hygromycin B resistance gene (HYG#). The obtained hygromycin-resistant strain was further transformed with a URA3 disruption cassette and selected on a plate containing 5-fluoroorotic acid. The obtained strains were analyzed and the disruption of the gene was confirmed by PCR and Southern blot analysis. The results showed that the strains were obtained in which allelic URA3 genes were simultaneously disrupted. Furthermore, we established a cotransformation method for this gene disruption, using HYG# in C. tropicalis. In order to disrupt the allelic POX4 genes (encoding acyl-CoA oxidase) of dicarboxylic acid-producing strains, the ARS plasmid (which contained HYG#) and a POX4 disruption cassette (which carried the LAC4 gene encoding beta-galactosidase of Kluyveromyces lactis) were simultaneously introduced by transformation. As a result, the allelic POX4 gene was successfully disrupted.

Anti-Bacterial Agents↗

A major determinant quantitative-trait locus responsible for atopic dermatitis-like skin lesions in NC/Nga mice is located on Chromosome 9.

NC/Nga (NC) is a newly discovered model mouse for human atopic dermatitis, NC mice showing specific symptoms such as dermatitis and overproduction of IgE. To detect the loci responsible for the onset of dermatitis in the mice, backcross (N2) progeny between (NCxMSM/MS)F1 and NC were generated, where MSM/MS is an inbred strain from Japanese wild mice, Mus musculus molossinus. Linkage disequilibrium between dermatitis and various chromosome-specific microsatellite markers was then examined in the N2 segregants with severe dermatitis. The analysis revealed that the locus of the major determinant (designated here as derm1) was tightly linked to D9Mit163, D9Mit72, D9Mit143, D9Mit103, D9Mit207, and D9Mit209, because these markers showed the highest and most significant chi2 values. Since no recombination was observed among the markers in our linkage map, a radiation hybrid (RH) panel was applied to locate the derm1 locus more precisely. The markers were separated on the RH map, and their order was D9Mit163-D9Mit72-D9Mit143-D9Mit103-D9Mit207-D9Mit209 from the centromere. Several functional candidate genes are located near the locus derm1. These candidates are Thy1, Cd3d, Cd3e, Cd3g, Il10ra, 1118, and Csk, all of which could be involved in allergic responses through effects on T-cell function. Of these candidates, Csk is the strongest for NC dermatitis, since its map position was most tightly linked to the derm1 locus.

Animals↗

Repression of fatty-acyl-CoA oxidase-encoding gene expression is not necessarily a determinant of high-level production of dicarboxylic acids in industrial dicarboxylic-acid-producing Candida tropicalis.

The synthesis of dicarboxylic acids (DCAs) in Candida tropicalis is thought to be induced by a decrease in fatty acyl-CoA-oxidase activity. However, in the present study we demonstrate that repression of the POX4 gene, encoding fatty acyl-CoA oxidase, does not directly lead to high-level production of DCAs. No fatty acyl-CoA-oxidase activity was detected if the POX4 gene of C. tropicalis strain 1098 (wild-type strain) was disrupted. Furthermore, introduction of the POX4 gene from C. tropicalis strain M1210A3, which is a mutant derived from strain 1098 and is used as an industrial DCA-producing strain, still exhibited low-level fatty acyl-CoA-oxidase activity. Nevertheless, production of DCA was not observed in either case. Furthermore, the increase in acyl-CoA-oxidase activity by expression of the POX4 gene in strain M1210A3 did not reduce high-level production of DCA. These results suggest that alterations in acyl-CoA-oxidase activity are not necessarily related to production of DCA in industrial DCA-producing C. tropicalis M1210A3.

Acyl-CoA Oxidase↗

Inhibition of cardiac delayed rectifier K+ currents by an antisense oligodeoxynucleotide against IsK (minK) and over-expression of IsK mutant D77N in neonatal mouse hearts.

The IsK (minK or KCNE1) protein is known to co-assemble with the KvLQT1 (KCNQ1) protein to form a channel underlying the slowly activating delayed rectifier K+ current (IKs). Controversy remains as to whether the IsK protein assembles with ERG (the ether-a-go-go-related gene) products to form or modulate the channel-underlying the rapidly activating delayed rectifier K+ current (IKr). We investigated the effects of antisense oligodeoxynucleotides (AS-ODN) against IsK and its mutant D77N [which underlies a form of long QT syndrome (LQT5) in humans] on the delayed rectifier K+ current (IK) of neonatal mouse ventricular myocytes in primary culture. Patch-clamp experiments on these cells showed that IK consists of IKs and IKr. IK was not recorded from ventricular cells transfected with AS-ODN, while it was recorded from cells transfected with the corresponding sense oligodeoxynucleotides (S-ODN). IK was not recorded from cells transfected with the D77N mutant, and the action potential duration was much longer than in cells transfected with wild-type IsK. Furthermore, HERG could not induce currents in COS-1 cells co-expressed with the D77N mutant and HERG (the human form of ERG). These results indicate that the IsK protein associates with both KvLQT1 and ERG products to modulate IKr and IKs in cardiac myocytes.

Action Potentials↗

An analysis of video-assisted thoracoscopic resection for mediastinal masses in 150 cases. An overview of the pansternal approach, histology, and complications.

BACKGROUND: To clarify the usefulness of the diagnosis and treatment of mediastinal masses, by video-assisted thoracoscopic surgery (VATS), we performed a retrospective multi-institutional study to delineate the type of approach, histopathology, and complications associated with these entities. METHODS: We analyzed 150 patients who underwent the VATS procedure at several institutions between 1991 and 1999. RESULTS: VATS resections were performed using various combinations of the "pansternal approach." The unilateral thorax approach was applied in 135 patients, the bilateral thorax approach combined with the suprasternum approach in seven patients, the unilateral thoracic approach combined with the supraclavicular approach in three patients, the infrasternal approach in three patients, and the bilateral thoracic approach combined with both the infrasternal and the suprasternal approaches in two patients. Thoracoscopic resections or biopsies diagnosed 140 benign and 10 malignant mediastinal masses. There were operative complications in nine patients (6%). Eight patients (5.3%) were converted to conventional thoracotomy. CONCLUSION: VATS is a safe, effective, minimally invasive technique that can facilitate the resection of mediastinal masses when the pansternal approach is applied as appropriate for the location of the tumor.

Adolescent↗

Anterior capsular contraction after cataract surgery in vitrectomized eyes.

PURPOSE: To assess the contraction of continuous curvilinear capsulorhexis after cataract surgery in eyes with past pars plana vitrectomy. METHODS: In a prospective study, 16 eyes of 16 patients underwent phacoemulsification and implantation of a foldable acrylic intraocular lens after pars plana vitrectomy. Eyes after intensive or repeated vitrectomy were not included. Twenty eyes of 19 patients served as age-matched controls. Aqueous flare intensity was measured using the laser flare-cell meter 1 year after surgery. The area of anterior capsular opening (ACO) was determined by diaphanoscopy using the anterior eye segment analysis system EAS-1000 at 1 day and 1 year postoperatively. RESULTS: There was no significant difference in the mean ACO area between the vitrectomy and control groups both at 1 day and 1 year postoperatively. Aqueous flare intensity 1 year after surgery was slightly higher in the vitrectomy group, but the difference was not statistically significant. CONCLUSION: Eyes after simple vitrectomy are not at a higher risk of ACO contraction following cataract surgery.

Aged↗

A novel strategy of decoy transfection against nuclear factor-kappaB in myocardial preservation.

BACKGROUND: Nuclear factor-kappaB (NFkappaB) is critical for the transcription of multiple genes involved in myocardial ischemia-reperfusion injury. Therefore, we hypothesized that blocking NFkappaB would attenuate ischemia-reperfusion injury after prolonged myocardial preservation, resulting in an improvement in cardiac function. METHODS: Double-stranded oligodeoxynucleotides with a specific affinity for NFkappaB (NFkappaB decoy group) or a scrambled decoy group were transfected into rat hearts using a hemagglutinating virus of Japan-liposome method. After 16 hours of preservation in Euro-Collins solution at 4 degrees C, the cardiac grafts were heterotopically transplanted into recipient rats of the same strain. RESULTS: Fluorescein isothiocyanate staining showed introduction of double-stranded oligonucleotides into the nuclei of endothelial cells and cardiomyocytes. After 1 hour of reperfusion the NFkappaB decoy group showed significantly higher degrees of recovery of left ventricular function as well as significantly lower levels of serum creatine phosphokinase, myocardial water content, tissue IL-8, and neutrophil infiltration than did the scrambled decoy group (p < 0.05). CONCLUSIONS: Gene transfection of the NFkappaB decoy attenuates ischemia-reperfusion injury after prolonged heart preservation. As a result, this method appears to be a novel strategy for enhanced myocardial preservation.

Animals↗

Change of c-Myc expression and cardiac hypertrophy in patients with aortic valve replacement.

BACKGROUND: Long-term volume overload to the left ventricle (LV) due to aortic regurgitation (AR) tends to cause severe impairment in LV function that cannot be reversed even with aortic valve replacement (AVR). Recently, we reported that the protooncogene c-myc is related to the onset of the cardiac hypertrophy and LV dysfunction in patients with chronic AR. However, it is still unclear whether c-myc is related to reversibility of the cardiac hypertrophy or LV dysfunction after AVR. METHODS AND RESULTS: Twenty patients with isolated chronic AR who underwent AVR were included in this study. LV function was calculated before and after AVR. After AVR, end-systolic volume index (ESVI) and enddiastolic volume index (EDVI) were improved, but not mass index (LVMI). However, normalization of ESVI and EDVI was observed only in 12 and 9 patients, respectively. Preoperatively, c-Myc protein was expressed in the myocardium of 16 out of 20 patients with an average point count of 35+/-30%. After AVR, c-Myc protein was observed only in 2 patients. Preoperative ejection fraction (EF), ESVI, and postoperative end-systolic stress (ESS)/ESVI had significant correlation to postoperative cell diameter (CD). Percent c-Myc protein expression before the operation was significantly correlated to postoperative CD, ESVI, and ESS/ESVI. Average c-Myc expression was higher in patients who showed normalization of CD and ESS/ESVI after AVR than the patients who did not. CONCLUSIONS: These data suggest that preoperative expression of c-Myc can be indicative of the reversibility of myocardial cellular hypertrophy and LV dysfunction.

Adult↗

Efficacy of a new coating material, PMEA, for cardiopulmonary bypass circuits in a porcine model.

BACKGROUND: A new coating material, poly-2-methoxyethyl acrylate (PMEA), was developed to improve the biocompatibility of cardiopulmonary bypass (CPB) circuits. METHODS: To investigate the efficacy of the PMEA coating for CPB circuits, we compared PMEA-coated circuits (group P, n = 6) with uncoated circuits (group C, n = 6) and heparin (covalent-bonded heparin, Hepaface)-coated circuits (group H, n = 6) in a porcine CPB model. RESULTS: Platelet counts were significantly preserved in groups P and H compared with those in group C (P versus C, p < 0.05). The plasma levels of thrombin-antithrombin complex and bradykinin were significantly lower at 120 minutes in groups P and H than in group C (thrombin-antithrombin: P versus C, p < 0.05; bradykinin: P versus C, p < 0.05). The amount of fibrinogen adsorbed onto the hollow fibers was markedly less in group P than in groups C and H. CONCLUSIONS: The PMEA coating was equal to heparin coating in preventing reactions induced by CPB circuits, and might be superior to heparin coating in suppressing the adsorption of plasma proteins such as fibrinogen. Thus, PMEA coating may be a suitable means for improving the biocompatibility of CPB circuits.

Acrylates↗

Inducible nitric oxide production is an adaptation to cardiopulmonary bypass-induced inflammatory response.

BACKGROUND: Cardiopulmonary bypass (CPB) increases nitric oxide (NO) production by the activation of NO synthases (NOS). However, the role of NO from inducible NOS (iNOS) in CPB-induced inflammatory response remains unclear. We examined the effect of a selective iNOS inhibitor, aminoguanidine, on CPB-induced inflammatory response in a rat-CPB model. METHODS: Adult Sprague-Dawley rats underwent 60 minutes of CPB (100 mL x kg(-1) x min(-1), 34 degrees C). Group A (n = 10) received 100 mg/kg of aminoguanidine intraperitoneally 30 minutes before the initiation of CPB, and group B (n = 10) served as controls. RESULTS: There were significant time-dependent changes in plasma interleukin (IL)-6, IL-8, nitrate + nitrite, the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr, an indicator of peroxynitrite formation), and respiratory index (RI). Three hours after CPB termination, IL-6, IL-8, and RI were significantly higher in group A (IL-6, 397.5+/-80.6 pg/mL; IL-8, 26.99+/-6.57 ng/mL; RI, 1.87+/-0.31) than in group B (IL-6, 316.5+/-73.9 pg/mL, p <0.05; IL-8, 17.21+/-3.12 ng/mL, p < 0.01; RI, 1.57+/-0.24, p < 0.05) although nitrate + nitrite (31.8+/-4.1 micromol/L) and %NO2-Tyr (1.15%+/-0.20%) were significantly lower in group A than in group B (nitrate + nitrite, 50.2+/-5.0 micromol/L, p < 0.01; %NO2-Tyr, 1.46%+/-0.21%, p < 0.01). Western immunoblot analysis from lung tissue of group A identified marked iNOS inhibition without inhibiting endothelial-constitutive NOS, and neutrophil accumulation in the lung specimens was significantly greater in group A (6.5+/-0.7/alveoli) than in group B (4.4+/-0.4/alveoli, p < 0.01). CONCLUSIONS: These results suggest that NO production from iNOS may be an adaptive response for attenuating the CPB-induced inflammatory response.

Animals↗

Peroxynitrite formation from human myocardium after ischemia-reperfusion during open heart operation.

BACKGROUND: Current experimental studies have demonstrated that peroxynitrite (ONOO-) has both cytotoxic and cytoprotective effects on myocardial ischemia-reperfusion injury. However, even myocardial ONOO- formation has not yet been investigated in humans undergoing open heart operation. We measured plasma nitrotyrosine as an indicator of ONOO- formation during open heart operation and examined its association with myocardial ischemia-reperfusion injury. METHODS: Twenty adult patients undergoing mitral valve replacement under cardiopulmonary bypass between 1997 and 1998 were enrolled in this study (6 men and 14 women). Arterial blood (Ao) and coronary sinus effluent (CS) were obtained: (1) before the initiation of cardiopulmonary bypass, (2) just after aortic unclamping, (3) at 5 minutes, (4) at 10 minutes, (5) at 15 minutes, and (6) at 20 minutes after aortic unclamping. RESULTS: At every sampling point after reperfusion, plasma nitrate and nitrite was significantly lower in CS than in Ao, and the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr; an index of ONOO- formation) was significantly higher in CS than in Ao. The CS-Ao difference in %NO2-Tyr, myocardium-derived ONOO-, reached its peak at 5 minutes after reperfusion (2.17+/-0.74%), which was significantly correlated with the peak CS-Ao difference in plasma malondialdehyde, and with postoperative maximum creatine kinase-MB. CONCLUSIONS: These results first demonstrate that ONOO- is produced from human myocardium after ischemia-reperfusion during open heart operation, and myocardium-derived ONOO- can be determined by the CS-Ao difference in %NO2-Tyr.

Adult↗

A potential cardioprotective role of hepatocyte growth factor in myocardial infarction in rats.

OBJECTIVE: Cardiotrophic growth factors with anti-cell death actions on cardiac myocytes have gained attention for treatment of patients with myocardial infarction. Hepatocyte growth factor (HGF) plays a role in tissue repair and protection from injuries, however, the physiological role of HGF in the myocardium has not been well defined. We asked if HGF would afford to the infarcted myocardium. METHODS AND RESULTS: Mature cardiac myocytes prepared from adult rats expressed barely detectable levels of the c-Met/HGF receptor, however, c-Met receptor expression increased during cultivation, which meant that cardiac myocytes are potential targets of HGF. Addition of hydrogen peroxide remarkably decreased the number of viable mature cardiac myocytes in primary culture, whereas treatment with HGF enhanced survival of the cells subjected to the oxidant stress. Although very low levels of c-Met/HGF receptor and HGF mRNA expression were seen in normal rat hearts, both c-Met/HGF receptor and HGF mRNA levels rapidly increased to much higher levels than normal, when the rats were subjected to myocardial infarction. Immunohistochemical analysis of the c-Met receptor indicated that this receptor was expressed in cardiomyocytes localized in the border regions of the viable myocardium and in non-infarcted regions following myocardial infarction. CONCLUSION: The c-Met/HGF receptor is induced in cardiomyocytes following myocardial infarction and HGF exhibits protective effect on cardiomyocytes against oxidative stress. Our working hypothesis is that HGF may afford myocardial protection from myocardial infarction.

Animals↗

Interleukin-3 and stem cell factor modulate cell cycle regulatory factors in mast cells: negative regulation of p27Kip1 in proliferation of mast cells induced by interleukin-3 but not stem cell factor.

OBJECTIVE: Interleukin-3 (IL-3) and stem cell factor (SCF) are able to promote survival and proliferation of mast cells. However, the precise signal transduction cascades leading to mast cell proliferation are not clearly understood. Thus, we sought to define the mechanism of mast cell proliferation induced by IL-3 and SCF. MATERIALS AND METHODS: We treated murine bone marrow-derived cultured mast cells (BMCMC) with recombinant IL-3 (rIL-3) or recombinant SCF (rSCF) and examined the effects of rIL-3 and rSCF on cell cycle regulatory factors. RESULTS: Both rIL-3 and rSCF suppressed apoptosis of BMCMC. rSCF induced great proliferation of BMCMC with elevation of the proportions of cells in S and G2/M phases, whereas most BMCMC incubated with rIL-3 were arrested in the G1 phase. The G1/S phase transition is initiated by phosphorylated retinoblastoma protein (pRb), which was prominent in cells stimulated with rSCF. In contrast, rIL-3 relatively increased a dephosphorylated form of pRb in BMCMC. Compared with rIL-3, rSCF induced greater expression of cyclin-dependent kinase (CDK) 2 and CDK4, which are able to phosphorylate pRb, and cyclin D3, a partner of CDK4. BMCMC treated with rIL-3 contained a high amount of a CDK inhibitor p27Kip1 that was suppressed by pretreatment with Ro31-7549, a protein kinase C inhibitor, whereas rSCF induced weak expression of p27Kip1 in BMCMC. CONCLUSION: The results suggest that IL-3 and SCF exert their respective mitogenic effects on mast cells by modulating the expression of pRb, CDK, cyclin, and p27Kip1.

Animals↗

A case of schwannoma on the nasal septum.

We present a case of nasal septal schwannoma. The patient was a 62-year-old female complaining of bilateral nasal obstruction. Anterior rhinoscopy revealed a smooth-surfaced mass arising from the nasal septum in both nasal cavities. Computed tomography scan showed a mass with enhancement in the two nasal cavities and the ethmoid sinuses, and this mass extended to the skull base. Lateral rhinotomy was performed under general anesthesia. The tumor arose from the nasal septum, occupied both nasal cavities, and extended to the anterior ethmoid sinuses. It was encapsulated and could be totally removed en bloc. Pathological examination of the excised specimen showed that it was an Antoni type A schwannoma. The tumor cells were immunoreactive for S-100 protein. The patient is doing well with no evidence of recurrence.

Adult↗

Antioxidant constituents from rhubarb: structural requirements of stilbenes for the activity and structures of two new anthraquinone glucosides.

The methanolic extracts from five kinds of rhubarb were found to show scavenging activity for DPPH radical and .O2-. Two new anthraquinone glucosides were isolated from the rhizome of Rheum undulatum L. together with two anthraquinone glucosides, a naphthalene glucoside, and 10 stilbenes. In the screening test for radical scavenging activity of rhubarb constituents, stilbenes and a naphthalene glucoside showed activity, but anthraquinones and sennosides did not. In addition, most stilbenes inhibited lipid peroxidation of erythrocyte membrane by tert-butyl hydroperoxide. Detailed examination of the scavenging effect on various related compounds suggested the following structural requirements; 1) phenolic hydroxyl groups are essential to show the activity; 2) galloyl moiety enhances the activity; 3) glucoside moiety reduces the activity; 4) dihydrostilbene derivatives maintain the scavenging activity for the DPPH radical, but they show weak activity for .O2-. In addition, several stilbenes with both the 3-hydroxyl and 4'-methoxyl groups inhibited xanthine oxidase.

Animals↗