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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 19 recordsLinked to original sources
PubMed1996

Protection of isolated lung from reperfusion injuries by rinsing with high colloidal osmotic solution with deferoaxmine.

We examined the efficacy of rinsing isolated lungs subjected to prolonged hypothermic storage with a high colloidal osmotic pressure solution prior to ex vivo blood reperfusion in order to preserve physiologic functions, suppress peroxidation of mitochondrial membranes, and inhibit infiltration of neutrophils. Isolated rabbit lungs were flushed with a Rinse-1 solution (289 mOsm/kg H2O) to remove remaining blood and immersed in physiologic saline at 8 degrees C for 24 hr. The control group received blood reperfusion immediately after storage; the Rinse-1 group was rinsed with Rinse-1 solution before blood reperfusion and the Rinse-2 group with Rinse-2 solution (312 mOsm/kg H20) including deferoxamine. Reperfused blood was passed through an artificial membranous lung to reduce oxygen tension (PO2) to the venous level, and time-dependent changes in airway pressure (AWP), pulmonary artery pressure (PAP), and PO2, as a measure of gas-exchange capability were examined. We estimated the lipid peroxide level in mitochondrial membranes as thiobarbituric acid-reactive substances (TBARS), i.e., malonedialdehyde, and neutrophil infiltration into lung tissue by measuring myeloperoxidase activity after 60 min of blood reperfusion. The PO2 was significantly higher in both rinsed groups compared with the control, while neither AWP nor PAP was significantly different in the three treatment groups. Both mitochondrial TBARS and myeloperoxidase activity were significantly higher in the control group compared with either rinsed group. These results indicate that rinsing stored lungs with a solution of high colloidal osmotic pressure prior to blood reperfusion was effective in preserving physiologic function and inhibiting neutrophil infiltration. Addition of deferoxamine was markedly effective in reducing TBARS formation and lessening reperfusion injury of stored lungs.

Animals↗
PubMed1996

Extracellular ATP activates mast cells via a mechanism that is different from the activation induced by the cross-linking of Fc receptors.

In this study, the extracellular ATP (ATPo)-induced biochemical events were elucidated by comparing them with either the Fc epsilon RI- or Fc gamma R-induced events in the mouse mast cell line MC9. The omission of extracellular Ca2+ almost completely abolished the elevation of intracellular Ca2+ ([Ca2+]i) in the ATPo-stimulated cells, but only suppressed the second phase of the increase of [Ca2+]i in FcR-stimulated cells, thus suggesting that the ATPo-induced elevation of [Ca2+]i is totally dependent on the entry of extracellular Ca2+. Pretreatment with genistein, which inhibits protein kinases, especially protein tyrosine kinase, inhibited the FcR-triggered increase of [Ca2+]i, but not the ATPo-triggered one; however, such pretreatment did suppress both ATPo- and FcR-mediated beta-hexosaminidase release. An immunoblot analysis revealed that both ATPo and the cross-linking of FcRs led to tyrosine phosphorylation of 44- and 110-kDa proteins, which thus suggested that these tyrosine-phosphorylated proteins are involved in a modulation of the degranulation process following an elevation of [Ca2+]i. Pretreatment with PMA inhibited the FcR-induced [Ca2+]i increase, while not inhibiting the ATPo-induced one, thus suggesting that ATPo can mobilize [Ca2+]i even when protein kinase C (PKC) has already been activated. Pretreatment of calphostin C, a specific PKC inhibitor, had little effect on the ATPo-mediated beta-hexosaminidase secretion, thus indicating that the ATPo-induced degranulation is not mediated by PKC. Taken together, these results demonstrate that ATPo activates MC9 mast cells by a mechanism that is different from the activation induced by the cross-linking of FcRs.

Adenosine Triphosphate↗
PubMed1996

Biologic characteristics of esophageal epithelial dysplasia assessed by proliferating cell nuclear antigen.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) correlates with the cell proliferative state. Using a PCNA specific monoclonal antibody, various malignant neoplasms have been assessed for cell proliferation and malignant potential. However, there are few studies regarding the expression of PCNA in esophageal dysplasia. METHODS: PCNA expression was immunohistochemically determined in resected specimens from 27 patients with superficial esophageal carcinoma that contained areas with various degrees of dysplasia, carcinoma in situ (CIS), and carcinoma invading the mucosal layer. The authors estimated the cell proliferative activity and biologic characteristics of the basal and parabasal cells of these esophageal epithelial disorders. RESULTS: The degrees of PCNA labeling index (PCNA LI) of the basal layers were lower than those of the parabasal layers in normal epithelium and dysplastic lesions, respectively, whereas no difference in CIS was recognized between the two layers. The proportion of PCNA LI in the basal layer of moderate dysplasia was lower than that in the basal layer of severe dysplasia. Conversely, there were no statistical differences between severe dysplasia and CIS in both basal and parabasal layers. In terms of lymphocytic infiltration beneath the dysplasia, there was a close relationship between the degree of lymphocytic infiltration and the PCNA index of the basal and parabasal layers. CONCLUSIONS: PCNA expression may be a useful marker to reflect the biologic characteristics of esophageal dysplasia, suggesting that a high grade of dysplasia is as serious a lesion as esophageal carcinoma.

Biomarkers↗
PubMed1996

Mitochondrial DNA and RNA processing in MELAS.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a maternally inherited disorder, is usually associated with a point mutation in mitochondrial DNA (mtDNA) at position 3,243 in the tRNA Leu(UUR) gene. To further study the pathogenesis of MELAS, we analyzed tissues from 8 MELAS-3,243 patients. Southern blot analysis showed an increase in the ratio of mtDNA to nuclear DNA in almost all tissues examined, implying that mitochondrial proliferation is ubiquitous and is not confined to ragged-red fibers in muscle. By northern blot analysis, we demonstrated increased steady-state levels of RNA 19, a polycistronic transcript corresponding to the 16S rRNA + tRNA Leu(UUR) + ND1 genes (which are contiguous in the mtDNA) in heart, kidney, and muscle. These results provide further evidence that altered mitochondrial nucleic acid metabolism may have pathogenic significance in MELAS.

Adult↗
PubMed1996

DNA typing of HLA class II genes in Japanese patients with rheumatic heart disease.

To study further the association between HLA and rheumatic valvular disease, DNA typing HLA class II genes (DRB1, DQA1, DQB1 and DPB1) was performed in 72 unrelated Japanese patients with predominant mitral stenosis and 525 unrelated Japanese healthy controls, based on the polymerase chain reaction in combination of dot-blot hybridization with sequence-specific oligonucleotide probes. As compared with controls. Patients with mitral stenosis showed increased frequencies of DQA1*0104 (18.1% v 7.2%; RR = 2.82, P = 0.002, Pc = 0.03) and DQB1*05031 (13.9% v 4.8%: RR = 3.23, P = 0.002, Pc = 0.05). In contrast, no significant deviation in the frequencies of DRB1, DPA1 or DPB1 alleles was observed in the patients. These observations suggest that the susceptibility to mitral stenosis is in part controlled by a gene (or genes) in close linkage disequilibrium with HLA-DQA1*0104 and DQB1*05031, i.e. the susceptibility gene may be mapped within the HLA-DQ region.

Adult↗
PubMed1996

Development of a de novo tumorous necrotic lesion in the liver after transcatheter arterial embolization combined with iodized oil infusion: report of a case.

We report herein the case of a 69-year-old woman in whom a hepatic tumorous necrotic lesion was discovered following transcatheter arterial embolization combined with iodized oil infusion (Lp-TAE) for a hepatoma. The lesion, which had not been evident prior to the Lp-TAE, was resected and analyzed pathologically. The portal area distribution in the necrotic lesion was the same as that in the surrounding hepatic tissue, suggesting that the lesion was derived from the nonneoplastic hepatic tissue. Moreover, extensive wall thickening and obstruction were observed in the intrahepatic portal vein and hepatic artery. These findings suggest that the lesion was a focus of hepatic infarction triggered by Lp-TAE.

Aged↗
PubMed1996

Successful treatment of bronchial mucoepidermoid carcinoma in an 11-year-old boy by bronchoplasty: report of a case.

We report herein the rare case of an 11-year-old boy in whom mucoepidermoid carcinoma of the right upper lobe bronchus was successfully treated by bronchoplasty. The patient underwent bronchoscopy to investigate the cause of relapsing respiratory infections over the past 2 years, which revealed a tumor at the orifice of the right upper lobe bronchus. Thus, a right upper sleeve lobectomy was effectively carried out, preserving right pulmonary function. The tumor was observed to partially invade the bronchial wall, but not the lung parenchyma. Histological examination confirmed a diagnosis of mucoepidermoid carcinoma, classified as grade 2 by Conlan's classification. The patient has been well and free of recurrence for 3 years postoperatively.

Anastomosis, Surgical↗
PubMed1996

An event-related potential study on the impairment of automatic processing of auditory input in schizophrenia.

Mismatch negativity (MMN) and P300 to auditory stimuli was carried out using global field power (GFP) in 25 schizophrenics and 25 normal controls. The peak latencies of MMN and P300 were significantly longer in schizophrenics than in normal controls, and the differences in MMN were marked in the frontal regions. The peak amplitudes of MMN and P300 were significantly smaller in schizophrenics. The scalp distribution of MMN to 1050 Hz tone differed between the two groups, although that to 1100 Hz was similar to each other. The results indicate an impairment in the automatic discrimination process of auditory input in schizophrenics.

Acoustic Stimulation↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗