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Biomedical subjects

Hisashi Kurosawa

Publications and source records attributed to Hisashi Kurosawa.

At least 19 recordsLinked to original sources
PubMed2007

A simple combined floating and anchored collagen gel for enhancing mechanical strength of culture system.

In this study, a simple combined method consisting of floating and anchored collagen gel in a ligament or tendon equivalent culture system was used to produce the oriented fibrils in fibroblast-populated collagen matrices (FPCMs) during the remodeling and contraction of the collagen gel. Orientation of the collagen fibrils along single axis occurred over the whole area of the floating section and most of the fibroblasts were elongated and aligned along the oriented collagen fibrils, whereas no significant orientation of fibrils was observed in normally contracted FPCMs by the floating method. Higher elasticity and enhanced mechanical strength were obtained using our simple method compared with normally contracted floating FPCMs. The Young's modulus and the breaking point of the FPCMs were dependent on the initial cell densities. This simple method will be applied as a convenient bioreactor to study cellular processes of the fibroblasts in the tissues with highly oriented fibrils such as ligaments or tendons.

Animals↗
PubMed2006

Involvement of TNF-like weak inducer of apoptosis in the pathogenesis of collagen-induced arthritis.

TNF-like weak inducer of apoptosis (TWEAK) is a type II membrane protein belonging to the TNF family that regulates apoptotic cell death, cellular proliferation, angiogenesis, and inflammation. However, the role of TWEAK in the pathogenesis of rheumatoid arthritis (RA) remains unclear. In this study, we have investigated the effect of neutralizing anti-TWEAK mAb on the development of collagen-induced arthritis (CIA), a well-established murine model of RA. Administration of anti-TWEAK mAb significantly ameliorated paw swelling, synovial hyperplasia, and infiltration of inflammatory cells. The levels of proinflammatory chemokines such as MCP-1 and MIP-2 in serum and knee joints were reduced by this treatment. Consistently, recombinant TWEAK enhanced the proliferation of MCP-1 and MIP-2 production by synovial cells from CIA mice in vitro. Histological examination also revealed that the treatment with anti-TWEAK mAb suppressed the development of small vessels in synovial tissues. These results indicated anti-inflammatory and antiangiogenic effects of the TWEAK blockade in CIA, which may be also beneficial for the treatment of RA.

Animals↗
PubMed2006

Oxidative stress causes heart failure with impaired mitochondrial respiration.

Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role in the development of heart failure, no direct evidence has been documented so far. In order to investigate the pathological significance of oxidative stress in the heart, we generated heart/muscle-specific manganese superoxide dismutase-deficient mice. The mutant mice developed progressive congestive heart failure with specific molecular defects in mitochondrial respiration. In this paper, we showed for the first time that the oxidative stress caused specific morphological changes of mitochondria, excess formation of superoxide (O(2)(*)(-)), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility. Accordingly, administration of a superoxide dismutase mimetic significantly ameliorated the symptoms. These results implied that O(2)(*)(-) generated in mitochondria played a pivotal role in the development and progression of heart failure. We here present a bona fide model for human cardiac failure with oxidative stress valuable for therapeutic interventions.

Animals↗
PubMed2006

Osteopontin is associated with nuclear factor kappaB gene expression during tail-suspension-induced bone loss.

Osteoporosis due to unloading-induced bone loss is a critical issue in the modern aging society. Although the mechanisms underlying this phenomenon are largely unknown, osteopontin (OPN) is one of the critical mediators required for unloading-induced bone loss [M. Ishijima, S.R. Rittling, T. Yamashita, K. Tsuji, H. Kurosawa, A. Nifuji, D.T. Denhardt, and M. Noda, Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin, J Exp Med, 193 (2001) 399-404]. To clarify the molecular bases for OPN actions, we carried out microarray analyses on the genes expressed in the femoral bone marrow cells in wild type and OPN-/- mice. The removal of the mechanical load induced bone loss in wild type, but not in OPN-/- mice, as previously reported. Expression analysis of 9586 cDNAs on a microarray system revealed that OPN deficiency blocked tail-suspension-induced expression of ten genes (group A). This observation was confirmed based on semi-quantitative RT-PCR analyses. On the other hand, expression of four genes (group B) was not altered by tail suspension in wild type but was enhanced in OPN-deficient mice. NF-kappaB p105 subunit gene (Nfkb1) was found in group A and Bax in group B. p53 gene expression was upregulated by tail suspension in wild type mice, but it was no longer observed in OPN-/- mice. These data indicate that OPN acts to mediate mechanical stress signaling upstream to the genes encoding apoptosis-related molecules, and its action is associated with alteration of the genes.

Animals↗
PubMed2006

Original methods to move femoral head medially and caudally after rotational acetabular osteotomy: especially to use ceramic spacer.

The operative procedures chosen to treat arthrosis in patients with severe acetabular dysplasia vary among orthopaedic surgeons, particularly in younger patients. We operated on 450 hips with acetabular dysplasia by using the rotational acetabular osteotomy (RAO) method of Ninomiya and Tagawa by Ninomiya (Clin Orthop 247:127-137, 1989). In this report, we describe our technique of performing RAO with hydroxyapatite tricalcium phosphate-composite (HAP-TCP) blocks to achieve good acetabular coverage and the results of this procedure in 16 hips with severe dysplasia, including nine with advanced arthrosis. Adequate coverage of the osteotomized acetabulum was maintained and symptoms, especially pain, showed marked improvement at the latest follow up.

Acetabulum↗
PubMed2006

Activation of genes for growth factor and cytokine pathways late in chondrogenic differentiation of ATDC5 cells.

The mouse embryonal carcinoma cell line ATDC5 provides an excellent model system for chondrogenesis in vitro. To understand better the molecular mechanisms of endochondral bone formation, we investigated gene expression profiles during the differentiation course of ATDC5 cells, using an in-house microarray harboring full-length-enriched cDNAs. For 28 days following chondrogenic induction, 507 genes were up- or down-regulated at least 1.5-fold. These genes were classified into five clusters based on their expression patterns. Genes for growth factor and cytokine pathways were significantly enriched in the cluster characterized by increases in expression during late stages of chondrocyte differentiation. mRNAs for decorin and osteoglycin, which have been shown to bind to transforming growth factors-beta and bone morphogenetic proteins, respectively, were found in this cluster and were detected in hypertrophic chondrocytes of developing mouse bones by in situ hybridization analysis. Taken together with assigned functions of individual genes in the cluster, interdigitated interaction between a number of intercellular signaling molecules is likely to take place in the late chondrogenic stage for autocrine and paracrine regulation among chondrocytes, as well as for chemoattraction and stimulation of progenitor cells of other lineages.

Animals↗
PubMed2006

Proteomic signatures corresponding to histological classification and grading of soft-tissue sarcomas.

We performed a global protein expression study on soft-tissue sarcoma in order to develop novel diagnostic biomarkers and allow molecular classification. 2-D difference gel electrophoresis was used to generate the global protein expression profiles of 80 soft-tissue sarcoma samples with seven different histological backgrounds. We found that 67 protein spots distinguished the subtypes of soft-tissue sarcoma. Hierarchical clustering with these 67 protein spots resulted in the grouping of all 80 sarcoma samples corresponding to the histological classification. We found that the expression pattern of tropomyosin isoforms was different in conventional and pleomorphic leiomyosarcomas. We also identified five proteins, including alpha-1-antitrypsin, alpha-actinin 1, HSP27, and elongation factor 2, that could differentiate between malignant fibrous histiocytomas and leiomyosarcomas in grade III into low-risk and high-risk groups, which differed significantly with respect to survival. These results establish proteomics as a powerful tool to develop novel biomarkers for diagnosis and molecular classification of soft-tissue sarcomas. Identification of proteins associated with survival in grade III sarcoma will allow delineation of a high-risk group that may benefit from adjuvant therapy and the exclusion of low-risk patients in whom additional therapies are unlikely to exhibit clinical benefit.

Biomarkers↗
PubMed2006

Randomized prospective study on prophylactic antibiotics in clean orthopedic surgery in one ward for 1 year.

BACKGROUND: At present in Japan, there are neither reports on antibiotic prophylaxis regardless of underlying diseases nor precise guidelines on prophylactic antibiotics in orthopedic surgery. Therefore, the preventive effect of antimicrobial agents on surgical site infection (SSI) after clean orthopedic surgery was studied to control the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in our ward and to reduce SSI caused by MRSA. METHODS: Regardless of the type of operation or underlying disease, a regimen of prophylaxis that is of shorter duration than before was conducted in 419 patients admitted to our orthopedic ward (one ward) and who underwent clean orthopedic surgery between 2001 and 2002. RESULTS: The annual usage of beta-lactam antibiotics in the ward decreased by 960.9 g, the isolation rate of MRSA in the ward decreased to 50% (the lowest isolation rate in the past 4 years), and SSIs caused by MRSA were found in 3 of 419 (0.71%) patients in one year compared with 6 of 470 (1.28%) during the previous year. Comparison of two antibiotics revealed that SSI caused by MRSA did not occur in any of the 187 patients receiving sulbactam/ampicillin as prophylaxis but did occur in 1.29% (3/232) patients receiving cefazolin. Concerning all SSIs caused by any organisms, they occurred in 0.53% of patients receiving sulbactam/ampicillin and in 2.16% of patients receiving cefazolin. The difference in the SSI rates between the two groups was not statistically significant. CONCLUSIONS: Although there is statistically no significant difference in the incidence of SSI caused by MRSA, we were able to decrease the isolation rates of MRSA and prevent MRSA from spreading owing to the reduced antibiotic usage in this study. Sulbactam/ampicillin can be recommended, as well as cefazolin, for antibiotic prophylaxis in clean orthopedic surgery.

Adolescent↗
PubMed2006

Early failure of modern metal-on-metal total hip arthroplasty using a Wagner standard cup.

In 54 patients (1 man and 53 women), 55 hips underwent primary metal-on-metal total hip arthroplasty (Metasul) with a Wagner standard cup (44-48 mm in outer diameter) and were followed for a minimum of 3 years. All patients received the same type of cementless femoral component (Natural Hip Stem) and femoral head (28 mm in diameter). Twelve (21.8%) of the 55 Wagner standard cups showed aseptic loosening over a mean period of 31 months postoperatively, and there were no bone anchors on the outer surface of the 9 retrieved cups. From our experience, the small Wagner standard cup does not achieve sufficient osteointegration and we do not recommend use of this cup, especially for dysplastic hips.

Adult↗
PubMed2005

The effect of initial graft tension on postoperative clinical outcome in anterior cruciate ligament reconstruction with semitendinosus tendon.

INTRODUCTION: The goal of this study is to establish the influence of tensioning the graft during anterior cruciate ligament (ACL) reconstruction, with a semitendinosus tendon graft, on postoperative stability. TYPE OF STUDY: Prospective controlled clinical trial. MATERIAL AND METHODS: Forty-eight patients were randomly allocated to three groups in which three different tensions, 8, 12, or 15 kg force, was applied on the reconstructed ACL during the operation. The patients were observed for 1 year or more after surgery (min. 1 year, max. 2 years 8 months). Clinical outcome was evaluated using the visual analogue scale, anterior knee laxity (using the KT2000 arthrometer) and the torque of the knee extensor. RESULTS: Postoperatively, the average side-to-side differences in anterior laxity were 1.3 mm in the 8 kg group, 2.1 mm in the 12 kg, and 2.4 mm in the 15 kg group. The visual analogue scale averaged 84, 83, and 79 mm, respectively. There were no significant differences among the three groups. There were also no significant differences between the groups for muscle strength recovery during isokinetic and isometric contraction at 1 year postoperatively. CONCLUSION: There were no significant differences among the groups in subjective clinical results, anterior laxity, and knee extensor strength in the ACL reconstructions that used the autogenous semitendinosus tendon graft.

Adult↗
PubMed2005

Primary pleomorphic liposarcoma of bone: MRI findings and review of the literature.

Primary liposarcoma of bone is exceedingly rare. We report a case of primary pleomorphic liposarcoma in the humerus of a 38-year-old female. Radiographs demonstrated an expansile and osteolytic lesion extending from the head to the proximal part of the shaft in the right humerus. MR study showed a defined lesion in the humerus. The lesion had an iso-signal intensity and partial high-intensity lesion on T1-weighted images and a heterogeneous high signal intensity on T2-weighted images. Wide resection and proximal humeral endoprosthesis replacement were performed. Final pathological diagnosis of the lesion was pleomorphic liposarcoma. This is the second reported case of pleomorphic liposarcoma of the bone, and the first case presenting MRI findings for liposarcoma of bone.

Adult↗
PubMed2005

Estrogen, insulin, and dietary signals cooperatively regulate longevity signals to enhance resistance to oxidative stress in mice.

To investigate the biological significance of a longevity mutation found in daf-2 of Caenorhabditis elegans, we generated a homologous murine model by replacing Pro-1195 of insulin receptors with Leu using a targeted knock-in strategy. Homozygous mice died in the neonatal stage from diabetic ketoacidosis, whereas heterozygous mice showed the suppressed kinase activity of the insulin receptor but grew normally without spontaneously developing diabetes during adulthood. We examined heterozygous insulin receptor mutant mice for longevity phenotypes. Under 80% oxygen, mutant female mice survived 33.3% longer than wild-type female mice, whereas mutant male mice survived 18.2% longer than wild-type male mice. These results suggested that mutant mice acquired more resistance to oxidative stress, but the benefit of the longevity mutation was more pronounced in females than males. Manganese superoxide dismutase activity in mutant mice was significantly upregulated, suggesting that the suppressed insulin signaling leads to an enhanced antioxidant defense. To analyze the molecular basis of the gender difference, we administered estrogen to mutant mice. It was found that the survival of mice under 80% oxygen was extended when they were administered estradiol. In contrast, mutant and wild-type female mice showed shortened survivals when their ovaries were removed. The influence of estrogen is remarkable in mutant mice compared with wild-type mice, suggesting that estrogen modulates insulin signaling in mutant mice. Furthermore, we showed additional extension of survival under oxidative conditions when their diet was restricted. Collectively, we show that three distinct signals; insulin, estrogen, and dietary signals work in independent and cooperative ways to enhance the resistance to oxidative stress in mice.

Animals↗
PubMed2005

The medium-term results of treatment with hydroxyapatite implants.

Although the short-term results of implants with synthetic hydroxyapatite (HA), a bioactive material, have been favorable, few reports have been published concerning medium-term outcomes for this therapy. The authors recently analyzed data supplied by 37 medical facilities nationwide concerning the outcomes of synthetic HA implants [Bonfil (BF); Mitsubishi Materials Corporation, Tokyo] in 138 patients followed up for at least 5 years after treatment. When the data were analyzed, the patients were divided into two groups: the disease site-filling group (62 cases where bone defects created by disease were filled with synthetic HA) and the donor site-filling group (76 cases where bone defects created by bone donation were filled with synthetic HA). In the disease site-filling group, synthetic HA was used in combination with autologous bone or autogenous bone marrow donated from the same patient in 77% of cases. In the donor site-filling group, only synthetic HA was used in most cases. The average follow-up period after implantation was 7.9 years in the disease site-filling group and 9.1 years in the donor site-filling group. Therapy was rated radiographically as "very effective" or "effective" in 81% of patients in the disease site-filling group and in 89% of patients in the donor site-filling group. The therapy was not rated as "ineffective" in any case from either group. These results suggest that synthetic HA may serve as a very useful substitute for cancellous bone if used carefully, with its initial strength taken into account.

Acetabulum↗
PubMed2005

Development and application of an inside-to-out drill bit for anterior cruciate ligament reconstruction.

We report a novel drilling device for anterior cruciate ligament (ACL) reconstruction that has been developed. We invented a special inside-to-out drill bit that can make a bone socket in an inside-to-out fashion. A blade at the tip of a 4.5-mm diameter drill bit closes when the drill bit is in orthograde rotation, but the blade opens when the drill bit is in reverse rotation. The special drill bit is introduced into the joint through a 4.5-mm diameter bone tunnel rotating the bit in the orthograde direction. Then the drill bit is switched to reverse rotation and is pulled backward so that it bores the bone from the inside out. We have used this special drill bit in treating 31 ACL-injured knees and have experienced no problems or complications with the procedure.

Adult↗
PubMed2005

Analysis of the risk factors regarding anterior cruciate ligament reconstruction using multiple-looped semitendinosus tendon.

The purpose of this study was to investigate the risk factors regarding anterior cruciate ligament (ACL) reconstruction using autogenous semitendinosus tendon by subjective evaluation of the patients. We studied 63 patients who had been followed for 18 months or longer after surgery. They comprised 31 men and 32 women aged 15-45 (mean, 25.5) years. The patients were divided into two groups by subjective scores. Subjective clinical evaluation was performed using 100 mm visual analogue scale (VAS). In the high score group (group H), the VAS score was 80 mm or higher, and in the low score group (group L), the score was less than 80 mm. Forty three patients were in group H and 20 patients were in group L. The parameters examined were age, gender, sports activity level, preoperative period, complicated meniscus injury, articular cartilage status, graft tendon size, joint stability, and knee extension muscle strength. There were 26 men and 17 women in group H, and 5 men and 15 women in group L. There were significantly more women in group L (p<0.01). The mean preoperative period after injury was 23+/-38 months in group H, and was 52+/-67 months in group L (p<0.05). The average side-to-side differences in anterior laxity were 1.3+/-1.0 mm in group H and 2.2+/-1.6 mm in group L (p<0.01). There were no significant differences in other parameters between the two groups. In this study the risk factors for poor subjective outcome following hamstring ACL surgery was female gender and prolonged delay from injury to operation.

Adolescent↗