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Yasuaki Nakagawa

Publications and source records attributed to Yasuaki Nakagawa.

At least 19 recordsLinked to original sources
PubMed2007

The effect of surface incongruity of grafted plugs in osteochondral grafting: a report of five cases.

Although grafted osteochondral plugs should ideally have a smooth surface for mosaicplasty, surface incongruity is sometimes evident at the time of surgery. There may be no problem if there is depression of the grafted plugs, but graft protuberance may have an adverse effect. We studied five knees in five patients who had incongruity (protuberance or depression) of grafted osteochondral plugs at the time of mosaicplasty. The mean age at surgery was 36.6 years (range, 15-65 years), and the mean follow-up period was 32.9 months (range, 24-49 months). All patients underwent second-look arthroscopy after a mean post-surgical period of 14.8 months (range, 3-18 months). We divided the cases so that there were two in the protuberant group (P) and three in the depressed group (D). In P, all patients had a catching sensation about 4 months after surgery, and sometimes pain in the knee joint. Second-look arthroscopy revealed fissuring of the plugs and fibrillation around the recipient site. In D, there were no symptoms due to the depressed plugs. Second-look arthroscopy showed that the depressed areas were covered with fibrocartilage-like tissue, and that the joint surface was smooth. In conclusion, our clinical results and second-look arthroscopic evaluation suggest that isolated osteochondral plug depressions of not greater than 1 mm could still promote acceptable cartilage healing leading to good clinical outcomes. However, plug protuberance at mosaicplasty should always be avoided.

Adolescent↗
PubMed2006

Class II HDACs mediate CaMK-dependent signaling to NRSF in ventricular myocytes.

We recently reported that a transcriptional repressor, neuron-restrictive silencer factor (NRSF), represses expression of fetal cardiac genes, including atrial and brain natriuretic peptide (ANP and BNP), by recruiting class I histone deacetylase (HDAC) and that attenuation of NRSF-mediated repression contributes to the reactivation of fetal gene expression during cardiac hypertrophy. The molecular mechanism by which the activity of the NRSF-HDAC complex is inhibited in cardiac hypertrophy remains unresolved, however. In the present study, we show that class II HDACs (HDAC4 and 5), which are Ca/calmodulin-dependent kinase (CaMK)-responsive repressors of hypertrophic signaling, associate with NRSF and participate in NRSF-mediated repression. Blockade of the CaMK-class II HDAC signaling pathway using a CaMK-resistant HDAC5 mutant, a CaMK inhibitor (KN62) or a dominant-negative CaMK mutant inhibited ET-1-inducible ANP and BNP promoter activity, but that inhibitory effect was abolished by mutation of the neuron-restrictive silencer element (NRSE) within the ANP and BNP promoter. In addition, adenovirus-mediated expression of a dominant-negative NRSF mutant abolished the inhibitory effect of KN62 on ET-1-inducible endogenous ANP gene expression in ventricular myocytes. Finally, the interaction between NRSF and class II HDACs was decreased in both in vitro and in vivo models of cardiac hypertrophy. These findings show that ET-1-induced CaMK signaling disrupts class II HDAC-NRSF repressor complexes, thereby enabling activation of ANP and BNP gene transcription in ventricular myocytes, and shed light on a novel mechanism by which the fetal cardiac gene program is reactivated.

Animals↗
PubMed2006

Mechanical and biochemical effect of monopolar radiofrequency energy on human articular cartilage: an in vitro study.

BACKGROUND: There are growing concerns about thermal chondroplasty using radiofrequency energy to treat partial-thickness cartilage defects. However, most studies emphasize effects on chondrocyte viability, and other factors such as mechanical properties are less studied. HYPOTHESIS: Radiofrequency energy may cause significant effects on articular cartilage other than chondrocyte viability. STUDY DESIGN: Controlled laboratory study. METHODS: Human osteoarthritic cartilage samples were obtained from total knee arthroplasty, and monopolar radiofrequency energy was applied using commercially available equipment. Material properties (compressive stiffness, surface roughness, and thickness) just before and after thermal treatment were determined using ultrasound. A series of biochemical analyses were also performed after explant culture of the samples. RESULTS: The cartilage surface became smoother by radiofrequency energy, whereas cartilage stiffness or thickness was not altered significantly. Collagen fibrils, especially in the superficial layers, were converted to denatured form, whereas proteoglycan contents released in the media as well as retained in the tissue remained unchanged. The concentrations of matrix metalloproteinases (MMP-1 and MMP-2) were reduced remarkably. CONCLUSION: Radiofrequency energy is able to create a smooth cartilage surface and reduce catabolic enzymes at the cost of collagen denaturation and chondrocyte death in the superficial layers. The stiffness of the cartilage is not changed at time zero. CLINICAL RELEVANCE: Further animal as well as clinical studies will be necessary to fully evaluate the long-term effects of radiofrequency energy.

Aged↗
PubMed2006

A retrospective review of bone tunnel enlargement after anterior cruciate ligament reconstruction with hamstring tendons fixed with a metal round cannulated interference screw in the femur.

PURPOSE: To assess bone tunnel enlargement after anterior cruciate ligament (ACL) reconstruction with the use of hamstring tendons fixed with a round cannulated interference (RCI) screw in the femur. METHODS: A consecutive series of 30 ACL reconstructions performed with hamstring tendons fixed with an RCI screw in the femur and with staples via Leeds-Keio ligament in the tibia was retrospectively reviewed. The clinical outcome was evaluated through the Lysholm score. Anterior instability was tested by Telos-SE (Telos Japan, Tokyo, Japan) measurement. The location and angle of each femoral and tibial tunnel were measured with the use of plain radiographs, and bone tunnel enlargement greater than 2 mm detected any time 3, 6, 12, and 24 months postoperatively was defined as positive. Each factor (location and angle of the tunnels, sex, affected side, age, Lysholm score, and Telos-SE measurement) was compared between enlarged and nonenlarged groups. RESULTS: Positive enlargement of the bone tunnel (>2.0 mm) was observed in 36.7% (11 of 30) on the femoral side and 33.3% (10 of 30) on the tibial side, and in 6 knees of both sides. Half of patients (15 of 30) had an enlarged tunnel on the femoral or the tibial side until 1 year postoperatively. In most cases, enlargement reached maximum at 6 months postoperatively. Female patients tended to have an enlarged tunnel, especially on the femoral side (P < .05). Tunnel enlargement was not correlated with location and angle of the tunnels. Moreover, no difference was found in Lysholm score and Telos-SE measurement between enlarged and nonenlarged groups, although the nonenlarged group tended to exhibit higher Lysholm score and lesser instability. CONCLUSIONS: Bone tunnel enlargement of the femoral or tibial side was observed in half of patients (6 in both sides, 5 only in the femur, and 4 only in the tibia) after ACL reconstruction was performed with a hamstring tendon fixed with an RCI screw. Female patients had a greater chance for enlargement of the femoral tunnel than did males. This enlargement had no significant impact on patient activity and on anterior instability of the knee 1 year after surgery. LEVEL OF EVIDENCE: Level IV, Therapeutic case series.

Adolescent↗
PubMed2006

[Mosaicplasty].

Basic science and clinical results of autogenous osteochondral graft were reviewed. The operative technique of osteochondral graft gave no bad effect on the grafted plug cartilage in respect of the mechanical properties. In rabbit, the stiffness of grafted cartilage at postoperative 8 weeks was significantly lower than the normal cartilage stiffness, the stiffness at postoperative weeks 12 and 24 was the same as normal cartilage and the stiffness at postoperative 52 weeks was significantly higher than the normal cartilage. In human, the stiffness at postoperative 1 year was the same as normal cartilage. The indication of this procedure was traumatic cartilage defect, osteochondritis dissecans, osteonecrosis and the early stage of osteoarthritis, and the elbow and ankle joints as well as knee joints were also included. The short-term clinical result of this procedure was good, and we had no symptoms on the donor site. However, the long-term follow-up of this procedure is needed.

Animals↗
PubMed2005

Ability of zirconia double coated with titanium and hydroxyapatite to bond to bone under load-bearing conditions.

As a preclinical study, we evaluated the ability of hydroxyapatite and titanium on zirconia (HTOZ) to bond to bone under load-bearing conditions in animal experiments. HTOZ, HA, and Ti on Co-Cr alloy (HTOC) and Ti on Co-Cr alloy (TOC) were implanted into the weight-bearing portion of the femoral condyles of nine beagle dogs. Femurs were extracted 4, 12, and 52 weeks after implantation and examined mechanically by pullout testing, and histologically by toluidine blue staining, SEM, and calculation of the affinity index. The interfacial shear strengths (mean+/-SD) of the HTOZ, HTOC, and TOC groups were 4.42+/-0.453, 3.90+/-0.903, and 4.08+/-0.790 MPa at 4 weeks; 6.82+/-2.64, 6.00+/-1.88, and 6.63+/-1.63 MPa at 12 weeks; and 13.98+/-1.94, 11.95+/-1.51, and 10.78+/-0.83 MPa at 52 weeks. There were no significant differences in the interfacial shear strengths between the three groups at any time. Affinity indices (mean+/-SD) obtained from SEM images of the HTOZ, HTOC, and TOC groups were 49.6+/-6.52%, 43.3+/-10.43%, and 23.7+/-3.95% at 4 weeks; 55.0+/-6.72%, 51.5+/-3.07%, and 28.6+/-4.09% at 12 weeks; and 59.1+/-6.73%, 63.0+/-6.40%, and 34.3+/-6.72% at 52 weeks. HA-coated implants (HTOZ, HTOC) had significantly higher affinity indices than non-HA-coated implants (TOC) at all times. HTOZ has the ability to bond to bone equivalent to HTOC and TOC. HTOZ is an excellent material for components of cementless joint prostheses.

Adhesiveness↗
PubMed2005

Role of natriuretic peptide receptor guanylyl cyclase-A in myocardial infarction evaluated using genetically engineered mice.

Although plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated early after myocardial infarction (MI), the significance is not fully understood. We therefore investigated the function of natriuretic peptides after induction of MI in knockout (KO) mice lacking the natriuretic peptide receptor guanylyl cyclase-A, the receptor for ANP and BNP. KO and wild-type (WT) mice were subjected to left coronary artery ligation and then followed up for 4 weeks. Irrespective of genotype, almost all deaths occurred within 1 week after induction of MI. KO mice showed significantly higher mortality because of a higher incidence of acute heart failure, which was associated with diminished water and sodium excretion and with higher cardiac levels of mRNAs encoding ANP, BNP, transforming growth factor-beta1, and type I collagen. By 4 weeks after infarction, left ventricular remodeling, including myocardial hypertrophy and fibrosis, and impairment of left ventricular systolic function were significantly more severe in KO than WT mice. Notably, the enhanced myocardial fibrosis seen in KO mice was virtually absent in infarcted double-KO mice, lacking guanylyl cyclase-A and angiotensin II type 1a receptors, although there was no improvement in survival and no attenuation of cardiac hypertrophy. Thus, guanylyl cyclase-A activation by endogenous cardiac natriuretic peptides protects against acute heart failure and attenuates chronic cardiac remodeling after MI. These beneficial effects are mediated partly through inhibition of the renin-angiotensin system (RAS), although RAS-independent protective actions of guanylyl cyclase-A are also suggested.

Animals↗
PubMed2005

Bony lesion recurrence after mosaicplasty for osteochondritis dissecans of the talus.

Autogenous osteochondral grafts have recently become popular for use in small, isolated, contained articular cartilage defects. We treated a 26-year-old man who had a cartilage defect measuring 10 x 20 mm in the anteromedial area of the right talus. We performed multiple osteochondral grafting of the lesion with medial malleolar osteotomy from a donor site in the ipsilateral knee joint. Two years after the operation, the patient's ankle pain recurred and the bony lesion in the talus also became osteolytic. Because we believed that only the cartilaginous portions of the osteochondral plugs grafted 2 years previously were fully fixed and viable, and that recurrence had occurred at the bony portions, at reoperation we performed curettage of the bony lesions and grafted iliac bone into the lesions with fenestration of the inferomedial ankle joint cartilage, not grafted plug cartilage. Therefore, probably because of overuse, the bony lesion in the talus had recurred 2 years after the first operation, but the grafted hyaline cartilage had survived. Autogenous osteochondral grafting into the talus, unlike the knee joint, should be done with care to ensure there is no sclerotic bone surrounding the lesion in patients with long-standing symptoms and recurrence of bony lesions.

Adult↗
PubMed2005

Transforming growth factor-beta1 mediates the effects of low-intensity pulsed ultrasound in chondrocytes.

Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing, but the precise mechanism is still unknown. We used aggregate chondrocyte culture system to analyze LIPUS-induced effects on chondrocytes. First, Northern analyses revealed that LIPUS maintained higher expression levels of type II collagen and aggrecan mRNA and delayed the appearance of type X collagen mRNA expression. We also showed that DNA content was increased and that alkaline phosphatase activity was maintained low by daily treatment. Moreover, LIPUS significantly promoted transforming growth factor (TGF)-beta1 mRNA expression and the protein production at 2 h and 12 h after the treatment, respectively. Furthermore, recombinant TGF-beta1 protein mimicked the LIPUS effect and anti-TGF-beta1 neutralizing antibody reversed all these changes induced by the LIPUS treatment. These results indicate that LIPUS promotes the proliferation and retains the differentiation state of chondrocytes in the aggregate culture and that TGF-beta1 plays an important role in mediating the LIPUS effects in chondrocytes.

Aggrecans↗
PubMed2005

SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo.

BACKGROUND: Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of cytokine signaling whose expression is induced in the rat heart by cardiotrophin-1 (CT-1). Sepsis-induced myocardial depression results from the expression of inducible nitric oxide synthase (iNOS) evoked by inflammatory cytokines. METHODS AND RESULTS: The effect of CT-1 on lipopolysaccharide (LPS)-induced cardiac dysfunction was examined in a rat model of sepsis. In the absence of CT-1, LPS (1 mg/kg ip) elicited a reduction of systolic function and dilation of the ventricular cavity within 3-6 h after administration. These physiological effects were accompanied by increased ventricular phosphorylation of signal transducers and activators of transcription (STAT) 1 and STAT3, activation of nuclear factor-kappaB and expression of iNOS mRNA. Notably, administration of CT-1 (20 microg/kg iv) immediately prior to LPS significantly inhibited all of these LPS-induced changes. To determine whether SOCS1 expression in cardiomyocytes is sufficient to inhibit LPS- and cytokine-induced expression of iNOS mRNA, the effects of forced expression of SOCS1 in cultured neonatal cardiomyocytes were investigated using an adenovirus-mediated transfection system. Forced expression of SOCS1 significantly inhibited iNOS transcription induced by LPS, tumor necrosis factor-alpha or interferon-gamma. CONCLUSIONS: CT-1-mediated expression of SOCS1 in cardiomyocytes may be a useful target for preventing sepsis-induced myocardial depression.

Animals↗
PubMed2004

Hypertrophic responses to cardiotrophin-1 are not mediated by STAT3, but via a MEK5-ERK5 pathway in cultured cardiomyocytes.

gp130-dependent signaling is known to play a critical role in the onset of heart failure. In that regard, cardiotrophin-1 (CT-1) activates several signaling pathways via gp130, and induces hypertrophy in neonatal rat cardiomyocytes. Among the mediators activated by CT-1, STAT3 is thought to be important for induction of cell hypertrophy, though its precise function in the CT-1 signaling pathway is not fully understood. In the present study, therefore, to better understand the significance of STAT3 activity in CT-1 signaling, we infected cultured cardiomyocytes with adenoviral vectors harboring a dominant-negative STAT3 mutant or one of two endogenous negative regulators of cytokine signaling via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways [suppressor of cytokine signaling (SOCS) 1 and 3] and then examined their effects on three indexes of CT-1-induced cell hypertrophy: protein synthesis, secretion of brain natriuretic peptide and changes in cell surface area. In control cells, CT-1-induced both STAT3 phosphorylation and cell hypertrophy. Overexpression of dominant-negative STAT3 mutant suppressed CT-1-induced STAT3 phosphorylation, but did not affect cell hypertrophy. On the other hand overexpression of SOCS1 or SOCS3 inhibited both CT-1-induced STAT3 phosphorylation and cell hypertrophy. CT-1 also induced phosphorylations of ERK1/2 and ERK5 in cardiomyocytes, and those, too, were suppressed by overexpression of SOCSs. CT-1-induced cell hypertrophy was suppressed by overexpression of a dominant-negative MEK5 mutant, and not by overexpression of a dominant-negative MEK1 mutant. These findings indicate that the major pathway responsible for the hypertrophic responses to CT-1 is not JAK-STAT3 pathway nor MEK1-ERK1/2 pathway, but MEK5-ERK5 pathway.

Animals↗
PubMed2004

Overexpression of brain natriuretic peptide facilitates neutrophil infiltration and cardiac matrix metalloproteinase-9 expression after acute myocardial infarction.

BACKGROUND: Recent clinical trials have shown that systemic infusion of nesiritide, a recombinant human brain natriuretic peptide (BNP), improves hemodynamic parameters in acutely decompensated hearts. This suggests that BNP exerts a direct cardioprotective effect and might thus be a useful therapeutic agent with which to treat acute myocardial infarction (MI). In the present study, we used BNP-transgenic (BNP-Tg) mice with elevated plasma BNP to determine whether and how BNP contributes to left ventricular remodeling and healing after MI. METHODS AND RESULTS: We examined the accumulation of neutrophils and the expression and activation of matrix metalloproteinase (MMP)-9 in the ventricles of male BNP-Tg mice and their nontransgenic (non-Tg) littermates during the early phase after acute MI. The numbers of neutrophils infiltrating the infarcted area were significantly increased in BNP-Tg mice 3 days after MI. In addition, both the gene expression and zymographic activity of MMP-9, but not MMP-2, were significantly higher in BNP-Tg than non-Tg mice. Double immunostaining revealed that neutrophils are the main source of the MMP-9, although doxycycline, an MMP inhibitor, had no effect on neutrophil infiltration of the infarcted area in BNP-Tg mice. CONCLUSIONS: These results demonstrate that elevated plasma BNP facilitates neutrophil infiltration of the infarcted area after MI and increases the activity of the MMP-9 they produce. This suggests that BNP plays a key role in the processes of extracellular matrix remodeling and wound-healing during the early phase after acute MI.

Animals↗
PubMed2004

Acoustic stiffness and change in plug cartilage over time after autologous osteochondral grafting: correlation between ultrasound signal intensity and histological score in a rabbit model.

We investigated quantitative changes over time in ultrasound signal intensity (an index of stiffness), signal duration (an index of surface irregularity), and interval between signals (an index of thickness) of plug cartilage in an animal model of autologous osteochondral grafting. A full-thickness osteochondral plug was surgically removed and replaced in male Japanese white rabbits (n = 22). Specimens obtained at day 0 and weeks 2, 4, 8, 12 and 24 postoperatively were assessed using an ultrasound system and by macroscopic and histological evaluation (modified Mankin's score). Histology revealed that the plug sank until 2 weeks postoperatively, and that newly formed cartilage-like tissue covered the plug, but at 24 weeks the tissue detached. The plug itself survived well throughout the period of observation. Although the signal intensity at the plug site was same as that in the sham operated contralateral knee at day 0, from 2 to 24 weeks postoperatively it was less than that in the sham knee. At 8 weeks, this difference was significant (P < 0.05). Modified Mankin's score revealed early degenerative changes at the site, but macroscopic examination did not. Signal intensity correlated significantly with score (both at day 0 and at the five postoperative time points [P < 0.05, r = -0.91] and as a whole [P < 0.05, r = -0.36]). Signal intensity also significantly correlated with the individual subscores for 'cartilage structure' (P < 0.05, r = -0.32) and 'cartilage cells' (P < 0.05, r = -0.30) from the modified Mankin's score, but not significantly with subscores for 'staining' and 'tidemark'. Signal duration correlated significantly with total score (as a whole [P < 0.05, r = 0.34]), but not significantly with the score for cartilage structure (P = 0.0557, r = 0.29). The interval between signals reflected well the actual thickness of the plug site. The significant relationships between ultrasound signal intensity and scores suggest that early degenerative changes in plug cartilage and cartilage-like tissue, especially in the superficial layer, are detectable by high-frequency ultrasound assessment.

Animals↗
PubMed2004

Osteochondral grafting for cartilage defects in the patellar grooves of bilateral knee joints.

Autogenous osteochondral grafts have become popular recently for use in small, isolated, contained articular cartilage defects. We treated a 35-year-old man who had cartilage defects, which were the same shape and probably the result of overuse, in the patellar grooves of both knee joints. The left side was 30 x 25 mm, and the right side was 17 x 17 mm in his right patellar groove, and 15 x 7 mm in his right medial femoral condyle. Therefore, we performed multiple osteochondral grafting of the bilateral lesions. Thirty-two months after his right knee operation (37 months after his left one), he had no pain or symptoms in his left knee and occasional mild pain and catching in his right knee. At second-look arthroscopy, the joint surface of the articular cartilage in the bilateral patellar groove was almost completely smooth. However, the whole of the weight-bearing area around the grafted plugs in the medial femoral condyle showed cartilage degeneration. Approximately 3 years after implantation of osteochondral grafts into similarly shaped cartilage lesions in the bilateral patellar grooves, the operative results were good. However, careful follow up is needed.

Adult↗
PubMed2003

NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function.

Reactivation of the fetal cardiac gene program is a characteristic feature of hypertrophied and failing hearts that correlates with impaired cardiac function and poor prognosis. However, the mechanism governing the reversible expression of fetal cardiac genes remains unresolved. Here we show that neuron-restrictive silencer factor (NRSF), a transcriptional repressor, selectively regulates expression of multiple fetal cardiac genes, including those for atrial natriuretic peptide, brain natriuretic peptide and alpha-skeletal actin, and plays a role in molecular pathways leading to the re-expression of those genes in ventricular myocytes. Moreover, transgenic mice expressing a dominant-negative mutant of NRSF in their hearts exhibit dilated cardiomyopathy, high susceptibility to arrhythmias and sudden death. We demonstrate that genes encoding two ion channels that carry the fetal cardiac currents I(f) and I(Ca,T), which are induced in these mice and are potentially responsible for both the cardiac dysfunction and the arrhythmogenesis, are regulated by NRSF. Our results indicate NRSF to be a key transcriptional regulator of the fetal cardiac gene program and suggest an important role for NRSF in maintaining normal cardiac structure and function.

Actins↗
PubMed2003

Androgen contributes to gender-related cardiac hypertrophy and fibrosis in mice lacking the gene encoding guanylyl cyclase-A.

Myocardial hypertrophy and extended cardiac fibrosis are independent risk factors for congestive heart failure and sudden cardiac death. Before age 50, men are at greater risk for cardiovascular disease than age-matched women. In the current studies, we found that cardiac hypertrophy and fibrosis were significantly more pronounced in males compared with females of guanylyl cyclase-A knockout (GC-A KO) mice at 16 wk of age. These gender-related differences were not seen in wild-type mice. In the further studies, either castration (at 10 wk of age) or flutamide, an androgen receptor antagonist, markedly attenuated cardiac hypertrophy and fibrosis in male GC-A KO mice without blood pressure change. In contrast, ovariectomy (at 10 wk of age) had little effect. Also, chronic testosterone infusion increased cardiac mass and fibrosis in ovariectomized GC-A mice. None of the treatments affected cardiac mass or the extent of fibrosis in wild-type mice. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, TGF-beta1, TGF-beta3, angiotensinogen, and angiotensin converting enzyme in the ventricles of male GC-A KO mice was substantially decreased by castration. The gender differences were virtually abolished by targeted deletion of the angiotensin II type 1A receptor gene (AT1A). Neither castration nor testosterone administration induced any change in the cardiac phenotypes of double-KO mice for GC-A and AT1A. Thus, we suggest that androgens contribute to gender-related differences in cardiac hypertrophy and fibrosis by a mechanism involving AT1A receptors and GC-A.

Androgen Receptor Antagonists↗