Biomedical subjects

Hideyuki Koga

Publications and source records attributed to Hideyuki Koga.

14 recordsLinked to original sources

PubMed2006

Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration.

We previously demonstrated that synovium-derived MSCs had greater in vitro chondrogenic ability than other mesenchymal tissues, suggesting a superior cell source for cartilage regeneration. Here, we transplanted undifferentiated synovium-derived MSCs into a full-thickness articular cartilage defect of adult rabbits and defined the cellular events to elucidate the mechanisms that govern multilineage differentiation of MSCs. Full-thickness osteochondral defects were created in the knee; the defects were filled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled MSCs and covered with periosteum. After 4 weeks, although the cell density decreased, transplanted MSCs produced a great amount of cartilage matrix extensively. The periosteum became thinner, and chondroprogenitors in the periosteum produced a small amount of cartilage matrix. In the deeper zone, transplanted MSCs progressed to the hypertrophic chondrocyte-like cells. In the deep zone, some transplanted cells differentiated into bone cells and were replaced with host cells thereafter. In the next phase, the border between bone and cartilage moved upwards. In addition, integrations between native cartilage and regenerated tissue were improved. Chondrocyte-like cells derived from the transplanted MSCs still remained at least after 24 weeks. Histological scores of the MSC group improved continuously and were always better than those of two other control groups. Immunohistological analyses and transmission electron microscopy confirmed that the MSCs produced abundant cartilage matrix. We demonstrated that transplanted synovium-derived MSCs were altered over a time course according to the microenvironments. Our results will advance MSC-based therapeutic strategies for cartilage injury and provide the clues for the mechanisms that govern multilineage differentiation of MSCs.

Animals↗

PubMed2006

Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle.

Mesenchymal stem cells (MSCs) are increasingly being reported as occurring in a variety of tissues. Although MSCs from human bone marrow are relatively easy to harvest, the isolation of rodent MSCs is more difficult, thereby limiting the number of experiments in vivo. To determine a suitable cell source, we isolated rat MSCs from bone marrow, synovium, periosteum, adipose, and muscle and compared their properties for yield, expansion, and multipotentiality. After two passages, the cells in each population were CD11b (-), CD45 (-), and CD90 (+). The colony number per nucleated cells derived from synovium was 100-fold higher than that for cells derived from bone marrow. With regard to expansion potential, synovium-derived cells were the highest in colony-forming efficiency, fold increase, and growth kinetics. An in vitro chondrogenesis assay demonstrated that the pellets derived from synovium were heavier, because of their greater production of cartilage matrix, than those from other tissues, indicating their superiority in chondrogenesis. Synovium-derived cells retained their chondrogenic potential after a few passages. The Oil Red-O positive colony-rate assay demonstrated higher adipogenic potential in synovium- and adipose-derived cells. Alkaline phosphatase activity was greater in periosteum- and muscle-derived cells during calcification. The yield and proliferation potential of rat MSCs from solid tissues was much better than those from bone marrow. In particular, synovium-derived cells had the greatest potential for both proliferation and chondrogenesis, indicating their usefulness for cartilage study in a rat model.

Adipose Tissue↗

PubMed2006

Higher chondrogenic potential of fibrous synovium- and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in humans.

OBJECTIVE: Mesenchymal stem cells from synovium have a greater proliferation and chondrogenic potential than do those from bone marrow, periosteum, fat, and muscle. This study was undertaken to compare fibrous synovium and adipose synovium (components of the synovium with subsynovium) to determine which is a more suitable source for mesenchymal stem cells, especially for cartilage regeneration, and to examine the features of adipose synovium-derived cells, fibrous synovium-derived cells, and subcutaneous fat-derived cells to determine their similarities. METHODS: Human fibrous synovium, adipose synovium, and subcutaneous fat were harvested from 4 young donors and 4 elderly donors. After digestion, the nucleated cells were plated at a density considered proper to expand at a maximum rate without colony-to-colony contact. The surface epitopes, proliferative capacity, cloning efficiency, and chondrogenic, osteogenic, and adipogenic differentiation potentials of the cells were compared. RESULTS: Fibrous synovium- and adipose synovium-derived cells were higher in STRO-1 and CD106 and lower in CD10 compared with subcutaneous fat-derived cells. Cells derived from fibrous and adipose synovium had higher proliferative potential and colony-forming efficiency compared with subcutaneous fat-derived cells, both in mixed-population and in single-cell-derived cultures. In chondrogenic assays, pellets from fibrous synovium- and adipose synovium-derived cells produced more cartilage matrix than did cell pellets from subcutaneous fat. Osteogenic ability was also higher in fibrous synovium- and adipose synovium-derived cells, whereas adipogenic potential was nearly indistinguishable among the 3 populations. Differentiation potential of the cells was similar between young and elderly donors. CONCLUSION: Cells derived from the fibrous synovium and from the adipose synovium demonstrate comparable chondrogenic potential. Adipose synovium-derived cells are more similar to fibrous synovium-derived cells than to subcutaneous fat-derived cells.

Adolescent↗

PubMed2006

A retrospective study of the midterm outcome of two-bundle anterior cruciate ligament reconstruction using quadrupled semitendinosus tendon in comparison with one-bundle reconstruction.

PURPOSE: The objective of the study was to retrospectively compare the outcome of the first series of a 2-bundle anterior cruciate ligament reconstruction technique using quadrupled semitendinosus tendon with that of a 1-bundle reconstruction technique from 1992 through 1996. TYPE OF STUDY: Case-control study. METHODS: The 1-bundle group consisted of 56 patients with a follow-up period of 24 months or more (average, 46.5 months). The 2-bundle group consisted of 79 patients with a follow-up period of 24 months or more (average, 40.8 months). Manual knee laxity tests, anterior stability with KT-1000 (manual maximum), and knee extension and flexion strength by Cybex were evaluated using an average and standard deviation, and data were categorized according to the International Knee Documentation Committee (IKDC) classification. The Lysholm scale and the subjective recovery scale were also evaluated. RESULTS: A statistically greater number of patients in the 1-bundle group were positive (+ or ++) based on the Lachman test (34% in the 1-bundle group and 13% in the 2-bundle group). The average KT-1000 anterior laxity of 2.7 +/- 2.3 mm in the 1-bundle group was statistically greater than the 1.9 +/- 1.9 mm in the 2-bundle group, with a statistical power between 70% and 80%. The total Lysholm knee scale score was 93 points in both groups, and the subjective recovery score was equivalent, 82% in the 1-bundle group and 86% in the 2-bundle group, respectively. CONCLUSIONS: There was no statistical difference based on the IKDC, Lysholm, and subjective analysis. However, there was a statistical difference in the Lachman test, anterior drawer test, and KT-1000 measurements. LEVEL OF EVIDENCE: Level III.

Adolescent↗

PubMed2006

[A case of carcinoma with sarcomatoid elements in the middle mediastinum].

We describe a 63-year-old man who, while under treatment as an outpatient for adult onset Still's disease (AOSD), developed edema of the extremities and mediastinal tumor was observed on a chest X-ray film and a chest CT scan. He was not pathologically diagnosed at first and received radiation therapy with a total dose of 30 Gy. Transbronchial biopsy was carried out because the tumor enlarged, and the tumor invasion was observed in the left lumen of the main bronchus. Histological findings suggested a diagnosis of carcinoma with sarcomatoid elements (CSE). Further radiation therapy with a dose of 20 Gy was unsuccessful; his condition gradually worsened and the patient died. The autopsy findings demonstrated that CSE developed in the middle mediastinum, and the other organs were not involved. From an embryologic standpoint, there seemed to be some possible differential diagnoses, such as a pleomorphic carcinoma as a subtype of lung cancer, and CEA as a metastatic mediastinal lymph node cancer of unknown origin or a primary mediastinal lymph node cancer. Like the present case, tumors developed in the middle mediastinum with rapid progression are rare. We report a case, that was difficult to diagnose and treat.

Carcinoma↗

PubMed2005

Characterisation of patients with frequent exacerbation of asthma.

BACKGROUND: Exacerbation is one of the most significant problems in patients with asthma. Although subpopulation of patients is more susceptible to exacerbations than others, which clinical features characterise susceptibility to exacerbation are not well understood. METHODS: Consecutive non-smoking adult patients with asthma who had multiple exacerbations (ME) despite regular maintenance treatment were compared with those who had at most single exacerbation as control during the previous 1 year. Exacerbation of asthma is defined initiations or escalations of systemic corticosteroid as part of the management for aggravated asthma condition. RESULTS: Patients with ME (n=32, male: 6, mean age: 46.7 years) were characterised by intensive current maintenance treatment (dose of inhaled corticosteroid; 1037.5+/-452.8 vs 621.6+/-257.3 microg, P=0.0005, proportion of oral corticosteroid users; 28.1% vs 2.7%, P=0.008), severe episodes of exacerbation (asthma-related hospitalisations; 71.9% vs 23.4%, P=0.0002, arrival on ambulance; 37.5% vs 8.1%, P=0.008), concomitant chronic sinusitis (34.4% vs 10.8%, P=0.038) and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) (34.4% vs 5.4%, P=0.006) in comparison with controls (n=37, male:11, mean age:44.4). Pulmonary function in patients with ME was characterised by persistent airflow limitation and reduced reversibility. CONCLUSION: Patients with ME are at increased risk for severe exacerbation despite more intensive maintenance anti-inflammatory treatment. Persistent irreversible airflow limitation and complications of chronic sinusitis and/or NSAIDs intolerance are characteristics to this subpopulation.

Adrenal Cortex Hormones↗

PubMed2005

Survey of human immunodeficiency virus (HIV)-seropositive patients with mycobacterial infection in Japan.

OBJECTIVE: To assess DNA polymorphisms in mycobacterial isolates obtained from human immunodeficiency virus (HIV)-seropositive patients with tuberculosis in Japan from 1996 to 2003. METHODS: Restriction fragment length polymorphisms (RFLP) from Mycobacterium tuberculosis and Mycobacterium avium isolates obtained from individual seropositive patients with tuberculosis (n=78) were analysed with the use of IS6110 and (CGG)(5) or IS1245 and IS1311, respectively, as markers. As a control, the same procedures were applied to isolates from HIV-seronegative tuberculosis patients (n=87). RESULTS: Of 86 mycobacterial strains, M. tuberculosis, M. avium and Mycobacterium chelonae were identified in 48 (55.8%), 36 (41.9%) and 2 (2.3%) isolates, respectively. The obtained RFLP patterns of M. tuberculosis isolates from both the HIV-seropositive and -seronegative groups were variable, suggesting no obvious clustering among the isolates. Similar results were obtained in isolates of M. avium. CONCLUSIONS: This is the first report on the molecular epidemiology of Mycobacterium spp. isolated from HIV-seropositive patients in Japan. The results indicate that no particular clones of M. tuberculosis or M. avium prevail in HIV-seropositive patients in Japan. Further monitoring of mycobacterial infection associated with HIV infection in Japan should be continued.

Adolescent↗

PubMed2004

Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is a major interstitial lung disease (ILD). Recently, we established a new mouse model for ILD in which daily administration of interleukin (IL)-18 with IL-2 induces lethal lung injury, suggesting that IL-18 is involved in the pathogenesis of ILD. Here, utilizing immunohistochemistry, we have analyzed IL-18 and IL-18 receptor (IL-18R) alpha expression in the lungs of 18 patients with IPF/UIP and 13 control subjects by using monoclonal anti-IL-18 antibodies and a new monoclonal antibody for IL-18Ralpha (H44). IL-18 was expressed in bronchoalveolar epithelium, alveolar macrophages, and the endothelium of small vessels in control subjects, and was abundantly expressed in the majority of pulmonary cells in patients with IPF. IL-18Ralpha was expressed in bronchoalveolar epithelium and alveolar macrophages in control subjects, and was strongly expressed in interstitial cells in patients with IPF, especially in the fibroblastic foci (FF). Interestingly, IL-18Ralpha expression was only weakly observed in areas showing established fibrosis. Semiquantitative analysis revealed that the histologic FF score was significantly correlated with the IL-18Ralpha expression level in FF lesions. Moreover, IL-18 levels in the serum and bronchoalveolar lavage fluid of patients with IPF were significantly higher than those in control subjects. Our findings suggest IL-18 and IL-18R are involved in the pathogenesis of IPF/UIP.

Adult↗

PubMed2004

Clinical features of acute respiratory infections associated with the Streptococcus milleri group in the elderly.

The Streptococcus milleri group are becoming increasingly recognized as important pulmonary pathogens which may lead to the development of empyema or lung abscesses. Although several small series have been reported, the clinical and laboratory features of Streptococcus milleri infection have yet to be fully characterized in the elderly. We retrospectively examined the clinical features of 19 patients with Streptococcus milleri pulmonary disease who were admitted to our hospital between 2000 and 2002, based on their clinical records and laboratory data. The microbiological diagnosis was based on the results of quantitative sputum culture and other invasive procedures, including transthoracic needle aspiration or bronchoscopic examinations. There were thirteen cases of pneumonia, two of contaminant pneumonia and pleuritis, one of bronchitis, two of pulmonary abscess, and one of empyema. The patients ranged in age from 65 to 91. The most common symptoms at presentation were shortness of breath, coughing, sputum, and weight loss. An underlying disease existed in 14 of the 19 cases. We conclude that the Streptococcus milleri group is a more important cause of pulmonary infections than has been previously recognized.

Acute Disease↗

PubMed2003

Bezold-Jarisch-like reflex during Brockenbrough's procedure for radiofrequency catheter ablation of focal left atrial fibrillation: report of two cases.

Brockenbrough's puncture technique has been widely conducted in the electrophysiologic laboratory. We report here two cases exhibiting a rare complication of this procedure, which arose during the conduct of catheter ablation using radiofrequency energy delivered to the pulmonary vein for the treatment of focal left atrial fibrillation. These cases exhibited marked sinus bradycardia and profound hypotension, suggestive of a Bezold-Jarisch-like reflex, observed immediately after Brockenbrough's procedure but before radiofrequency application. ST elevation in the inferior leads was also observed in spite of normal coronary angiograms. This unanticipated transient complication was treated by intravenous administration of atropine, which had no influence on the ablation procedure or prognosis. This is speculated to be attributable to the elevation of vagal tone caused by the mechanical effects of transseptal puncture on the interatrial vagal network.

Adult↗

PubMed2002

Overexpression of Polycomb-group gene rae28 in cardiomyocytes does not complement abnormal cardiac morphogenesis in mice lacking rae28 but causes dilated cardiomyopathy.

The Polycomb-group genes (PcG) are widely conserved from Drosophila to mammals and are required for maintaining positional information during development. The rae28 gene (rae28) is a member of the mouse PcG. Mice deficient in rae28 (rae28(-/-)) demonstrated that rae28 has a role not only in anteroposterior patterning but also in cardiac morphogenesis. In this study we generated transgenic mice with ubiquitous or cardiomyocyte-specific exogenous rae28 expression. Genetic complementation experiments with these transgenic mice showed that ubiquitous expression of rae28 could reverse the cardiac anomalies in rae28(-/-), whereas cardiomyocyte-specific expression of rae28 could not, suggesting that rae28 is involved in cardiac morphogenesis through a noncardiomyocyte pathway. Interestingly, however, cardiomyocyte-specific overexpression of rae28 caused dilated cardiomyopathy, which was associated with cardiomyocyte apoptosis, abnormal myofibrils, and severe heart failure. Cardiac expression of rae28 was predominant in the early embryonic stage, whereas that of the other PcG members was relatively constitutive. Because rae28 forms multimeric complexes with other PcG proteins in the nucleus, it is presumed that constitutive cardiomyocyte-specific rae28 overexpression impaired authentic PcG functions in the heart. rae28-induced dilated cardiomyopathy may thus provide a clue for clarifying the direct role of PcG in the maintenance of cardiomyocytes.

Animals↗

PubMed2002

The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis.

The Polycomb-group (PcG) gene Rae28 is a mammalian homologue of the Drosophila gene polyhomeotic. PcG genes are known to maintain transcription states, once initiated, probably by regulating chromatin structure. Since homozygous Rae28-deficient (Rae28(-/-)) mice displayed cardiac anomalies similar to congenital heart diseases in humans, we examined the role of Rae28 in cardiac morphogenesis at the molecular level. In Rae28(-/-) embryos, expression of the cardiac selector gene Nkx2.5/Csx (Nkx2.5) was initiated properly but was not sufficiently sustained later in development. This impaired expression of Nkx2.5 in the maintenance phase proved to have a crucial effect on cardiac morphogenesis, as demonstrated by the results of a genetic complementation experiment in which the cardiac anomalies were suppressed by overexpression of human NKX2.5/CSX1 in Rae28(-/-) embryos. Ubiquitous expression of exogenous Rae28 likewise restored the impaired Nkx2.5 expression in Rae28(-/-) embryos, further supporting the notion that Rae28 sustains Nkx2.5 expression in cardiomyocytes. Thus, our data show that a mammalian PcG gene can play a key role in organogenesis by helping to maintain the expression of a selector gene.

Animals↗

PubMed2002

Sick sinus syndrome disclosed by the successful radiofrequency catheter ablation of persistent common atrial flutter.

Sick sinus syndrome was disclosed in a 77 year-old man after a radiofrequency (RF) linear catheter ablation of cavotricuspid isthmus for persistent common atrial flutter. Prolongation of corrected sinus node recovery time, sinoatrial conduction time and AH interval, as observed after RF ablation, suggested binodal (sinus as well as atrioventricular node) dysfunction. Adams-Stokes syndrome due to sinus arrest was encountered on the day of RF ablation and a permanent DDD pacemaker was implanted consequently. Our experience indicates that careful observation is very important after the RF ablation when atrial flutter is associated with sick sinus syndrome. The present case suggests that binodal dysfunction underlies persistent atrial flutter and vice versa.

Aged↗

PubMedDate not supplied

Cholesterol embolization treated with corticosteroids--two case reports.

Cholesterol embolization (CE) is a potentially serious complication associated with invasive arterial maneuvers, in which standard therapy has not been established. We experienced two cases of CE in patients with severe atherosclerosis whose renal function deteriorated within a few months after invasive arterial maneuvers. CE was confirmed either by renal biopsy (case 1) or skin biopsy (case 2). Oral administration of prednisolone at a daily dose of 30 mg (0.4 mg/kg) was effective to improve their renal function. Our observation suggests that corticosteroid therapy may be beneficial in some patients with CE.

Aged↗