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Biomedical subjects

J Hayashi

Publications and source records attributed to J Hayashi.

At least 91 records · Page 5Linked to original sources
PubMed1999

Transcomplementation between different types of respiration-deficient mitochondria with different pathogenic mutant mitochondrial DNAs.

Two cell lines were used for determination of whether interaction occurred between different types of respiration-deficient mitochondria. One was a respiration-deficient rho- cell line having mutant mitochondrial DNA (mtDNA) with a 5,196-base pair deletion including five tRNA genes (tRNAGly, Arg, Ser(AGY), Leu(CUN), His), DeltamtDNA5196, causing Kearns-Sayre syndrome. The other was a respiration-deficient syn- cell line having mutant mtDNA with an A to G substitution at 4,269 in the tRNAIle gene, mtDNA4269, causing fatal cardiomyopathy. The occurrence of mitochondrial interaction was examined by determining whether cybrids constructed by fusion of enucleated rho- cells with syn- cells became respiration competent by exchanging their tRNAs. No cybrids were isolated in selection medium, where only respiration-competent cells could survive, suggesting that no interaction occurred, or that it occurred so slowly that sufficient recovery of mitochondrial respiratory function was not attained by the time of selection. The latter possibility was confirmed by the observations that heteroplasmic cybrids with both mutant mtDNA4269 and DeltamtDNA5196 isolated without selection showed restored mitochondrial respiration activity. This demonstration of transcomplementation between different respiration-deficient mitochondria will help in understanding the relationship between somatic mutant mtDNAs and the roles of such mutations in aging processes.

Cardiomyopathies↗
PubMed1999

A mitochondrial DNA mutation cosegregates with the pathophysiological U wave.

In a family with long QT syndrome (LQT2), some individuals who did not harbor the HERG mutation had a prolonged QTU interval on electrocardiograms after exercise. It may be determined or modified by other gene(s) or factor(s). The sequence analysis of mtDNA in these individuals of this family showed a candidate pathogenic mutation at 3394 in the ND1 gene. The cybrids (mutation at 3394) showed significantly reduced NADH-CoQ reductase (complex I) activity and O2 consumption to normal levels. These inhibitory effects on respiratory function may result in the depletion of ATP and could possibly produce an increase in Ca2+ concentration in cytosol, and it may lead to the prolongation of the QTU intervals on electrocardiograms. Therefore, we stated that the 3394 mutation in the ND1 gene is pathogenic and could be the cause of prolongation of the QTU intervals or modification of the phenotypes of not only congenital but also so-called "acquired drug-induced long QT syndrome."

Adolescent↗
PubMed1999

Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer's disease.

To determine whether pathogenic mutations in mtDNA are involved in phenotypic expression of Alzheimer's disease (AD), the transfer of mtDNA from elderly patients with AD into mtDNA-less (rho0) HeLa cells was carried out by fusion of platelets or synaptosomal fractions of autopsied brain tissues with rho0 HeLa cells. The results showed that mtDNA in postmortem brain tissue survives for a long time without degradation and could be rescued in rho0 HeLa cells. Next, the cybrid clones repopulated with exogenously imported mtDNA from patients with AD were used for examination of respiratory enzyme activity and transfer of mtDNA with the pathogenic mutations that induce mitochondrial dysfunction. The presence of the mutated mtDNA was restricted to brain tissues and their cybrid clones that formed with synaptosomes as mtDNA donors, whereas no cybrid clones that isolated with platelets as mtDNA donors had detectable mutated mtDNA. However, biochemical analyses showed that all cybrid clones with mtDNA imported from platelets or brain tissues of patients with AD restored mitochondrial respiration activity to almost the same levels as those of cybrid clones with mtDNA from age-matched normal controls, suggesting functional integrity of mtDNA in both platelets and brain tissues of elderly patients with AD. These observations warrant the reassessment of the conventional concept that the accumulation of pathogenic mutations in mtDNA throughout the aging process is responsible for the decrease of mitochondrial respiration capacity with age and with the development of age-associated neurodegenerative diseases.

Aged↗
PubMed1999

Acute exercise causes mitochondrial DNA deletion in rat skeletal muscle.

The present study was conducted to determine the effects of acute overload exercise on mitochondrial DNA and the structure of skeletal muscles. Rats were forced to run for 20 min until reaching complete exhaustion. We detected the large-scale deletion (7052 bp) of mitochondrial DNA by the nested polymerase chain reaction, and also observed mitochondrial ultrastructural changes in the soleus muscle.

Animals↗
PubMed1999

Enhanced IFN-gamma production in vitro by CD8+ T cells in hemophiliacs with AIDS as demonstrated on the single-cell level.

We examined T cells from HIV-infected hemophiliacs under antiviral therapy, on the single-cell level, for cytokine production in vitro in response to stimulation. The percentage of IL-2-producing cells was markedly decreased among both CD3+CD8- and CD3+CD8+ cells, while the proportion of IFN-gamma-producing cells was preserved among CD3+CD8- cells and increased among CD3+CD8+ cells in HIV+ subjects, compared with HIV-uninfected controls. The increase in IFN-gamma-producing CD8+ cells was accounted for by the expansion of CD8+CD28- cells among total CD8+ T cells and by the higher percentage of IFN-gamma-expressing cells among both CD8+CD28+ and CD8+CD28- cells in HIV+ individuals, compared with controls. The enhanced IFN-gamma production in CD8+ cells from individuals in the advanced phase of HIV infection might implicate the host's response to chronic viral infection or senescence of host CD8+ cells.

Acquired Immunodeficiency Syndrome↗
PubMed1999

The effect of fibrin glue on inhibition of pericardial adhesions.

The effect of fibrin glue on inhibition of pericardial adhesions was tested using 26 beagle dogs. Dacron patches were sutured to the heart and tincture of iodine was applied to promote adhesions. Fibrin glue (3 ml) was sprayed over the patches in 15 dogs (test group), and was not separated in the remaining 11 dogs (control group). All animals in the test group had minimal adhesions between the pericardium and the epicardium or patched region, and an accumulation of gelatinous material was found in the subpericardial space. Marked fibrosis and a poor demarcation of the subpericardial space were found in the control group. The adhesion score and the visibility of coronary anatomy in the test group were significantly better than in the control group. The tension strength in the test group was significantly less than in the control group. We concluded, therefore, that fibrin glue may also be useful as an adhesion inhibitor.

Animals↗
PubMed1999

Bioassay development: the implications of cardiac myocyte motility in vitro.

Cardiac myocytes cultured over microfabricated extracellular recording devices can be used to assay bioactive compounds. However, electrophysiological signals recorded from these devices vary in amplitude with time. Theoretically, changes in signal amplitude arise from myocytes being moved over recording sites by cocultured fibroblasts. To test this, neonatal rat cardiac myocytes were cultured at high densities and low densities on fibronectin-coated glass. After 36.5 h, myocytes were identified by their rhythmic contractions and then time-lapse-recorded for 3.5 h. Length, width, and angle of orientation was then determined every 30 min for five cells in low density and five cells in high-density culture. Low-density cells had mean lengths of 65.3 microm and widths of 35.1 microm, whereas cells in high-density culture had greater mean lengths of 74.2 microm and lower mean widths of 24.3 microm. Length, width, and angle of orientation of cells in low- and high-density culture changed by 4.1%, 11.8%, and 2.7 degrees, and 6.4%, 10%, and 4.6 degrees, respectively, every half hour. We found no evidence of myocyte-fibroblast interactions influencing cell position or shape in low density, but in high density, we found evidence that fibroblast-myocyte interactions could transiently influence cell shape. We conclude that fibroblast-independent changes in cell shape are largely responsible for the changes in signal amplitude recorded from cardiac myocytes cultured on microfabricated extracellular recording devices. However, there is some evidence that myocyte-fibroblast interactions may augment this process in high-density culture. The implications of these findings for bioassay development are discussed.

Animals↗
PubMed1999

Experimental application of microwave tissue coagulation to ventricular myocardium.

BACKGROUND: It is difficult to create transmural lesions in a beating, normothermic perfused heart. The aim of this study was to evaluate the effect of microwave tissue coagulation on a beating heart. METHOD: We used a microwave tissue coagulator that emits microwaves of 2,450 MHz. Studies were conducted on 30 mongrel dogs weighing between 9 and 13 kg, and microwave tissue coagulation was performed at the free wall of the left ventricle in a beating heart without cardiopulmonary bypass. RESULTS: Microwave tissue coagulation created transmural degenerated lesions in the left ventricle without risk of ventricular rupture. The lesion width of microwave ablation increased from 10 to 60 seconds. Histologic examinations revealed well-demarcated areas of heat degeneration consisting of coagulation necrosis and contraction band necrosis of the myocardium. The lesion healed to hard scar tissue, which was sharply demarcated from the normal myocardium. No animals had inducible ventricular tachycardia through programmed ventricular stimulation. CONCLUSIONS: Microwave ablation with a monopolar antenna created transmural lesions with only a few proarrhythmic events occurring during ablation.

Animals↗
PubMed1999

Efficacy and safety of extended thymectomy for elderly patients with myasthenia gravis.

BACKGROUND: The number of elderly patients who are diagnosed as myasthenia gravis (MG) is increasing in Japan. Although several factors affecting thymectomy have been well documented, few studies have focused on the efficacy and safety of thymectomy for elderly patients older than 60 years. METHODS: We evaluated 94 patients with MG who underwent extended thymectomy, and divided them into two groups: patients younger than 59 years and patients older than 60 years. Preoperative patient data, pathology of the thymus, complications, and clinical outcome were evaluated. RESULTS: In 69 young patients and 25 elderly patients, we observed no significant differences between the two groups with regard to preoperative data. Thymic hyperplasia was present in 45% of the young group and 16% of the elderly group. Remission and improvement rate were 40% and 57% in the young group and 8% and 75% in the elderly group, respectively. There were no serious complications, except one early death due to gastrointestinal bleeding in the elderly group. CONCLUSIONS: We conclude that thymectomy is a safe and effective alternative for elderly patients with MG.

Adolescent↗
PubMed1999

Biocompatibility of a silicone-coated polypropylene hollow fiber oxygenator in an in vitro model.

BACKGROUND: A silicone-coated microporous hollow-fiber membrane oxygenator has been developed to prevent plasma leakage during long-term use. The objective of this study was to evaluate the biocompatibility of the oxygenator. METHODS: A silicone-coated oxygenator was compared with an uncoated oxygenator in an in vitro model of cardiopulmonary bypass. Simulated circulation was maintained for 6 h at 37 degrees C. RESULTS: Platelet counts decreased significantly (p < 0.05) and leukocyte counts tended to decline; however, the differences between groups were not significant. Concentrations of C3a increased significantly in both groups (p < 0.05), but levels were significantly less in the silicone-coated oxygenator (p = 0.008). In contrast, concentrations of C4a, beta-thromboglobulin, and granulocyte elastase increased significantly (p < 0.05), but the differences between groups were not significant. CONCLUSIONS: Silicone coating over a microporous hollow-fiber membrane may improve biocompatibility by reducing C3a activation.

Coated Materials, Biocompatible↗
PubMed1999

Successful tracheal transplantation using cryopreserved allografts in a rat model.

OBJECTIVES: The purpose of this study was to determine the appropriate cryopreservation period of tracheal allografts based on morphological and immunological findings and to test the possibility of tracheal transplantation in rats using cryopreserved allografts without immunosuppression. METHODS: Morphological and immunological studies were performed to compare the differences between non-cryopreserved grafts and cryopreserved grafts. Orthotopic tracheal transplantation using cryopreserved allografts, non-cryopreserved allografts, and non-cryopreserved autografts was performed and the rejection score of each group was evaluated. RESULTS: Epithelial cells were lost when the grafts were cryopreserved for more than 20 days. Immunohistochemical staining of the trachea revealed that the MHC classII antigen was expressed on normal epithelium. These findings suggest that cryopreservation for more than 20 days decreased the antigeneicity of allografts because of epithelial desquamation. All rats that received allografts cryopreserved for more than 20 days survived until the scheduled sacrifice day. Microscopically, cryopreserved allografts that had been preserved for more than 20 days had a significantly lower rejection score than that of non-cryopreserved allografts (P < 0.05). CONCLUSIONS: We conclude that the appropriate period for cryopreservation of allografts would be 20 days or more, because cryopreservation for more than 20 days depleted epithelium, which possessed the MHC classII antigen. Therefore, a longer period of cryopreservation decreases the antigeneicity of allografts. Rat tracheal transplantations using cryopreserved allografts is possible without immunosuppression when the grafts have been cryopreserved for more than 20 days.

Animals↗
PubMed1999

Differences between interferon-alpha and -beta treatment for patients with chronic hepatitis C virus infection.

To compare virological, biochemical, and immune responses to human lymphoblastoid interferon (IFN-alpha) and human fibroblast interferon (IFN-beta) in patients with chronic hepatitis C virus (HCV) infection, 120 patients were randomly assigned to three groups (group A, 60 patients receiving IFN-alpha, 6 million units (MU) once a day, daily for one month and thrice weekly for five months; group B, 40 patients receiving 6 MU IFN-beta once a day daily for two months; and group C, 20 patients receiving 3 MU IFN-beta twice a day (6 MU/day) daily for two months). Serum soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay. Patients with sustained clearance of serum HCV RNA detected by polymerase chain reaction (PCR) at six months after IFN treatment were defined as having complete response to IFN treatment. A low level of HCV RNA (< or = 10(4) copies/50 microl, measured by competitive PCR) and HCV RNA of genotype 2a were favorable factors for a complete response to both IFNs. Complete response in group A treatment was strongly associated with early HCV RNA clearance, in contrast with group B. A significantly higher HCV RNA negativity at the second week from start of treatment was noted in group C (80.0%), compared with groups A (41.6%) and B (27.5%). sIL-2R levels rose in each group during IFN administration. In group C, alanine aminotransferase (ALT) and IL-6 levels were remarkably elevated. These findings indicate that timing of serum HCV RNA negativity in sustained response differs between IFN-alpha and IFN-beta administrations and that early HCV RNA clearance was induced by twice-a-day IFN-beta treatment.

Antiviral Agents↗
PubMed1999

Heterosexual transmission of GB virus C/hepatitis G virus infection to non-intravenous drug-using female prostitutes in Fukuoka, Japan.

To determine if GB virus C (GBV-C) or hepatitis G (HGV) infection can be transmitted by heterosexual intercourse, we tested serum samples from 234 non-drug-injecting female prostitutes for GBV-C/HGV. We used reverse transcription polymerase chain reaction to test for GBV-C/HGV RNA and ELISA for GBV-C/HGV-E2 antibody. The prevalence of total GBV-C/HGV marker (GBV-C/HGV RNA and/or GBV-C/HGV-E2 antibody) was 58/234 (24.8%) in the prostitutes, and 7/71 (8.9%) in matched controls. The GBV-C/HGV RNA and GBV-C/HGV-E2 antibody concurrence rate was 12.5% for the prostitutes, but was nil in matched controls. Total GBV-C/HGV marker was significantly higher in the prostitutes than in matched controls. Additionally, total GBV-C/HGV marker was associated with the number of years engaged in prostitution after adjusting for age. We found hepatitis B virus and hepatitis C virus infections in prostitutes to be associated with syphilis infection, but GBV-C/HGV infection was not. Thus, it seems likely that GBV-C/HGV can be transmitted by heterosexual intercourse, even in the absence of syphilis.

Adult↗
PubMed1999

Serum soluble interleukin-2 receptor levels before and during interferon treatment in patients with chronic hepatitis B virus infection.

To determine the role of serum soluble interleukin-2 receptor (sIL-2R) in chronic hepatitis B virus (HBV) infection, the level of serum sIL-2R was measured in sera of 105 patients with chronic HBV infection and in 21 healthy controls, using enzyme-linked immunosorbent assay. Serum sIL-2R levels were significantly higher in chronic HBV-infected patients with chronic hepatitis (508+/-310 units/ml) and liver cirrhosis (543+/-283 units/ml) than in healthy controls (331+/-106 units/ml, P < 0.05). Moreover, serum sIL-2R levels were significantly higher in patients with chronic hepatitis or liver cirrhosis than in asymptomatic HBV carriers (341+/-150 units/ml, P < 0.01). There was no difference in serum sIL-2R levels between asymptomatic HBV carriers and healthy controls or between patients with chronic hepatitis and liver cirrhosis. A significant relationship was found between serum sIL-2R and ALT levels (P < 0.05) in patients with chronic HBV infection, although there was no correlation between sIL-2R and HBV DNA levels. Serum sIL-2R levels in most patients decreased to the same level as asymptomatic HBV carriers and healthy controls at 48 weeks after the end of treatment, and serum ALT and HBV DNA levels were decreased to within the normal range at 96 weeks. Thus, serum sIL-2R levels indicate the degree of liver damage among patients with chronic HBV infection. The serum sIL-2R levels one year after interferon administration may be a useful marker of determined at the effectiveness by this treatment.

Alanine Transaminase↗
PubMed1999

Clinical course of chronic hepatitis C virus infection is not influenced by concurrent hepatitis G virus infection.

To determine the effects of hepatitis G virus (HGV) infection on chronic hepatitis C virus infection (HCV) and to evaluate HGV response to interferon, we investigated HGV RNA by polymerase chain reaction in 247 Japanese patients with chronic HCV infection (166 men and 81 women; 124 had chronic hepatitis and 26 cirrhosis, and 97 hepatocellular carcinoma). HGV RNA was detectable in 22 (8.9%) patients, among whom 21 were men: this male predominance was statistically significant (P < 0.01). There were no differences in age, aminotransferase level, stage of liver disease, HCV RNA level by competitive polymerase chain reaction, genotype, or interferon response to HCV RNA between patients with HCV infection alone or with HCV/HGV coinfection. Sustained elimination of HGV RNA was found in 28.6% of the 14 treated patients with HCV/HGV coinfection. In the 14 treated patients, sustained elimination of both viruses was seen in two, HCV alone was eliminated in two, and HGV alone was eliminated in two. Aminotransferase level improvement by interferon treatment was associated with clearance of HCV, but not of HGV. Thus, HGV infection had no apparent effects on HCV infection, and the sensitivity of HGV to interferon is comparable to but independent of HCV.

Antiviral Agents↗
PubMed1999

Surgical management of cardiovascular lesions caused by systemic inflammatory diseases.

BACKGROUND: The surgical treatment of cardiovascular disorders caused by inflammatory diseases presents many difficulties, including suture detachment and progression of vascular lesions. We here report the various surgical procedures used to treat these disorders and their long-term outcomes. METHODS: We operated on 14 patients: eight with Takayasu's disease, three with systemic lupus erythematosus, two with rheumatoid arthritis, and one with Behçet's disease. Patients were divided into three groups as follows; patients (n=7) requiring aortic valve replacement; patients (n = 4) requiring reconstruction of the coronary artery; and patients (n = 3) requiring aortic aneurysm repair. RESULTS: There were no early or late deaths in the postoperative follow-up period of 70 +/- 40 months, but there was one operative death. Three patients received postoperative steroids due to progression of the inflammation. However, there were no major complications such as valve detachment, pseudoaneurysmal formation, or occlusion of the bypass conduit. CONCLUSIONS: We conclude that it is crucial to reduce inflammation pre- and postoperatively, to reinforce the suture line, and to carefully select the operative procedures when treating cardiovascular disorders caused by inflammatory diseases.

Adolescent↗
PubMed1999

A surgical management of aortic insufficiency concomitant with mediastinal well-differentiated liposarcoma.

We present a rare case of a mediastinal liposarcoma concomitant with aortic insufficiency due to myxoid degeneration of the aortic valve. Because the patient's left ventricle was in moderate dilatation and a posterolateral thoracotomy combined with median sternotomy was required in order to perform a complete resection of a mediastinal liposarcoma, it was decided to carry out aortic valve surgery and tumor excision in one operation.

Aortic Valve Insufficiency↗