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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 181 records · Page 10Linked to original sources

A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement.

We have analyzed two unrelated Japanese patients with carbonic anhydrase II deficiency born to consanguineous parents. We have identified the same mutation as that reported to be homozygous in a Belgian family and compound heterozygous in an American family. It comprises to C-to-T transition that results in the amino acid substitution of Tyr (TAT) for His (CAT) at position 107. This point mutation creates an AccI site that can be conveniently screened by the polymerase chain reaction/restriction fragment length polymorphism method using a restriction enzyme for gene tracking. Our patients exhibit severe mental retardation, not seen in the Belgian and American patients.

Carbonic Anhydrases↗

Prognosis of hypertrophic cardiomyopathy: assessment by 123I-BMIPP (beta-methyl-p-(123I)iodophenyl pentadecanoic acid) myocardial single photon emission computed tomography.

123I-BMIPP (beta-methyl-iodophenyl pentadecanoic acid) has shown unique properties for potential use in assessing myocardial metabolism. Previous basic and clinical studies demonstrated that the disturbances of myocardial metabolism precede the occurrence of myocardial perfusion abnormalities by using 201Tl in hypertrophic myocardium. The present study was therefore undertaken to determine whether or not 123I-BMIPP myocardial SPECT is useful in predicting the prognosis of hypertrophic cardiomyopathy (HCM) in 65 patients in 6 facilities. There were 33 patients with non-obstructive HCM, 12 with obstructive HCM, 12 with apical HCM and 8 with dilated-phase HCM. Fasted patients at rest received an intravenous injection of 111 MBq of 123I-BMIPP. Twenty to thirty minutes later, myocardial SPECT was carried out. The BMIPP severity score (BMIPP SS) was evaluated semiquantitatively by using representative short axial SPECT images. We followed up the incidence of cardiac events for a mean period of 3.0 +/- 0.6 years. Cardiac events occurred in 13 patients. Of these, 11 developed heart failure and 6 died (4 from heart failure and 2 from sudden death). The BMIPP SS in the dilated-phase HCM was significantly lower than that for the nonsurvivors. The BMIPP SS was particularly high in patients with fatal heart failure. Furthermore, there was a close negative correlation between the BMIPP SS and percent fractional shortening measured by echocardiography (r = -0.49). Finally, the mortality over the three years increased according to the extent of the BMIPP SS. In conclusion, these results indicate that BMIPP SS is useful in evaluating the severity of HCM. We conclude that 123I-BMIPP is a valuable metabolic tracer in predicting the outcome of HCM.

Adult↗

Efficacy and safety of a percutaneous right ventricular assist system.

BACKGROUND: Mechanical right ventricular assistance is necessary in the management of profound right ventricular failure resistant to medical therapy. Conventional right ventricular assistance requires a thoracotomy. We developed a technique for assisting the failing right ventricle without thoracotomy. METHODS: We implanted the percutaneous right ventricular assist system in animals to test its feasibility and safety. A feasibility study was performed in a right ventricular failure model using 12 open chest dogs, and we examined the effects of the system hemodynamically. Next, the system was implanted into 6 goats and driven for 2 to 8 days. RESULTS: Institution of the percutaneous right ventricular assist system revealed overall hemodynamic improvement on right ventricular failure in dogs. In the goat experiment, no animal died from cannula-related complications. No damage to the intracardiac structures and no pulmonary edema were seen. Plasma free hemoglobin concentration did not exceed 10 mg/dL. CONCLUSIONS: The percutaneous right ventricular assist system is safe and effective in the management of right ventricular failure.

Animals↗

Effects of portal venous inoculation with donor splenocytes on lung allograft survival in dogs.

The effects of portal venous inoculation with donor splenocytes on lung allograft survival were evaluated in dogs. Within the dose range examined, portal venous inoculation with donor splenocytes alone did not affect the graft survival time. Although the mean graft survival time was prolonged by FK 506 treatment for 14 days, the transplanted lungs were rejected within 12 days after termination of FK 506 administration. However, when the recipients were given portal venous inoculation with donor splenocytes at the time of transplantation, the graft survival time after termination of FK 506 administration was significantly prolongated. In the recipients that received combined therapy of portal venous inoculation with donor splenocytes and FK 506 treatment, arterial oxygen tension and histologic architecture of the transplanted lungs remained within the normal range for a longer period than these measures did in control animals that received FK 506 treatment alone. Dose-response experiments revealed that 1 x 10(8) cells/recipient was most effective in causing prolonged graft survival after termination of FK 506 treatment. On the basis of these results, perioperative portal venous inoculation with donor splenocytes can enhance the immunosuppressive effect of FK 506 in the canine lung transplantation model.

Animals↗

Clinical manifestations of hypertrophic cardiomyopathy with mutations in the cardiac beta-myosin heavy chain gene or cardiac troponin T gene.

Introduction of molecular genetics has improved our understanding of HCM substantially, but has simultaneously raised further important questions. Studies on HCM are revealing a more complex picture than might have been expected on clinical grounds. Further extensive studies are warranted to elucidate the pathogenesis and pathophysiology of HCM, and to establish therapeutic strategies to cure or prevent the development of the disease.

Adult↗

Development and cytolytic function of intestinal intraepithelial T lymphocytes in antigen-minimized mice.

Intraepithelial T lymphocytes in the small intestine (IEL) consist of alpha beta T-cell receptor (TCR)-bearing T cells (alpha beta-IEL) and gamma delta TCR-bearing T cells (gamma delta-IEL). Development and cytolytic activation of alpha beta-IEL sharply attenuate in germ-free (GF) mice fed a natural diet (Nat-GF), but the number and cytotoxicity of gamma delta-IEL are comparable between conventional (CV) and Nat-GF mice. In this report, we compared the properties of IEL in Nat-GF mice and GF mice fed antigen-minimized diet (AgM-GF mice) of C57BL/6 strain to evaluate an influence of gut antigenic load on IEL development. Numbers of alpha beta-IEL and gamma delta-IEL in AgM-GF mice were less by 1.9- and 1.4-fold than those in Nat-GF mice, respectively. Significant decreases in the proportions of CD4+8-, CD4-8 alpha beta +, and CD4+8+ subsets and a resultant increase in the ratio of CD4-8 alpha alpha + subset were evident in alpha beta-IEL of Nat-GF mice compared with CV mice, but the subset constitution of alpha beta-IEL was similar between Nat-GF and AgM-GF mice. In contrast, relative composition of gamma delta-IEL was not different between CV, Nat-GF, and AgM-GF mice. alpha beta-IEL displayed low cytolytic activity in Nat-GF mice and were almost deprived of their cytotoxicity under the antigen-minimized condition. While gamma delta-IEL were strongly cytolytic in Nat-GF mice their cytolytic activity was remarkably reduced in AgM-GF mice. These results indicate that gamma delta-IEL are activated independently of microbial colonization in the gastrointestinal tract but their activation occurs in response to the exogenous antigenic substances other than live micro-organisms.

Animals↗

Aeropyrum pernix gen. nov., sp. nov., a novel aerobic hyperthermophilic archaeon growing at temperatures up to 100 degrees C.

A novel aerobic hyperthermophilic archaeon was isolated from a coastal solfataric vent at Kodakara-Jima Island, Japan. The new isolate, strain K1, is the first strictly aerobic organism growing at temperatures up to 100 degrees C. It grows optimally at 90 to 95 degrees C, pH 7.0, and a salinity of 3.5%. The cells are spherical shaped and 0.8 to 1.2 microns in diameter. Various proteinaceous complex compounds served as substrates during aerobic growth. Thiosulfate stimulates growth without producing H2S. The core lipids consist solely of C25-isopranyl archaeol (glycerol diether). The G + C content of the genomic DNA is 67 mol%. Phylogenetic analysis based on 16S rRNA sequence indicates that strain K1 is a new member of Crenarchaeota. On the basis of our results, the name Aeropyrum pernix gen. nov., sp. nov. is proposed (type strain: K1; JCM 9820).

Archaea↗

Xanthine oxidase mediates cyclic flow variations in a canine model of coronary arterial thrombosis.

We investigated the hypothesis that xanthine oxidase (XO) mediates platelet aggregation and cyclic flow variations (CFVs) in stenosed canine coronary arteries. CFVs were produced by an external constrictor placed at the site of the coronary artery with the injured endothelium. The severity of CFVs was evaluated by a pulsed Doppler flow probe. If CFVs developed, dogs intravenously received allopurinol, a specific XO inhibitor. The transcardiac gradient (difference between coronary vein and left atrium) of purine metabolites was determined during CFVs and after allopurinol administration. Allopurinol significantly reduced CFVs (from 8 +/- 1 to 1 +/- 1 cycles/h, P < 0.01, n = 14), whereas saline did not (from 8 +/- 1 to 7 +/- 1 cycles/h, n = 7). In seven dogs with CFVs, the transcardiac gradient of xanthine and uric acid concentrations significantly increased after the establishment of CFVs and significantly decreased after the administration of allopurinol. In vitro platelet studies showed that XO enhanced (from 30.9 +/- 2.0 to 47.6 +/- 1.5%, P < 0.0001, n = 10) and allopurinol inhibited ADP-induced platelet aggregation (from 48.3 +/- 1.3 to 24.8 +/- 1.5%, P < 0.0001, n = 10). Our results indicate that allopurinol inhibits platelet aggregation in vitro and provides a protection against CFVs in vivo. Thus XO may be an important mediator in this model.

Allopurinol↗

Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis.

The plasma levels of phenol, p-cresol, and indican are markedly increased in uremic patients, and cannot be efficiently reduced by hemodialysis. Such uremic toxins, which are produced in the intestine as bacterial putrefactive metabolites, accumulate to a great degree in the feces of hemodialysis patients. Oral administration of Lebenin, a preparation consisting of antibiotic-resistant lactic acid bacteria, reduced the levels of fecal putrefactive metabolites to levels comparable with those of healthy subjects. Moreover, the plasma level of indican also significantly decreased in these Lebenin-treated patients. An analysis of the fecal microflora revealed that a disturbed composition of the microflora characterized by an overgrowth of aerobic bacteria is restored to normal by oral administration of Lebenin in hemodialysis patients. These results thus demonstrate that oral administration of lactic acid bacteria in uremic patients is effective in reducing the levels of uremic toxins, especially that of indican, in the blood by inhibiting bacterial production by means of correcting the intestinal microflora.

Administration, Oral↗

Chronic L-arginine administration attenuates cardiac hypertrophy in spontaneously hypertensive rats.

Nitric oxide inhibits proliferation and migration of vascular smooth muscle cells and contractility of cardiomyocytes in vitro. In spontaneously hypertensive rats (SHR), evidence suggests intrinsic abnormalities of the L-arginine-nitric oxide axis, such as low cGMP-dependent protein kinase in the heart and abnormal L-arginine metabolism. To investigate the in vivo effect of L-arginine on cardiac hypertrophy, 30 SHR and 30 Wistar-Kyoto rats (WKY) were randomly grouped to receive L-arginine (7.5 g/L in drinking water) or vehicle for 12 weeks. L-Arginine treatment did not affect body weight or arterial pressure in either strain. In vehicle-treated animals, the heart/body weight ratio was significantly higher in SHR than in WKY (P < .01). L-Arginine treatment decreased the heart/body weight ratio in SHR (P < .05) but did not affect it in WKY. Expression of skeletal alpha-actin mRNA, known to be expressed in the hypertrophied myocardium, was attenuated in L-arginine-treated SHR compared with vehicle-treated SHR. Cardiac cGMP content and nitrate/nitrite content were less in SHR than WKY. L-Arginine treatment increased these levels only in SHR, suggesting enhanced nitric oxide production. Thus, chronic L-arginine administration attenuated cardiac hypertrophy independently of blood pressure and increased myocardial content of cGMP and nitrate/nitrite. Our results suggest that abnormality of the cardiac L-arginine-nitric oxide axis may play an important role in the pathogenesis of cardiac hypertrophy in SHR.

Actins↗

The visual estimation of intraoperative myocardial ischemia.

We report a case who had myocardial ischemia after release of the aortic cross clamp during mitral valve replacement. Myocardial ischemia was visually estimated by use of intraoperative MCE (myocardial contrast echocardiography). After appropriate treatment the ischemic area disappeared and the patient showed a good postoperative course. MCE is a useful method with which to detect visually the wash out pattern of cardioplegia from myocardium after reperfusion during open heart surgery.

Cardioplegic Solutions↗