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Biomedical subjects

Hideki Yoshikawa

Publications and source records attributed to Hideki Yoshikawa.

At least 55 records · Page 3Linked to original sources
PubMed2006

Serum glucagon-like peptide-2 levels in neonates: comparison between extremely low-birthweight infants and normal-term infants.

BACKGROUND: Glucagon-like peptide-2 (GLP-2) arises from proglucagon within enteroendocrine L cells of the small and large intestines, and its physiological roles have been gradually elucidated. However, the circulating GLP-2 levels in human neonates are still unknown. The aim of the present study was to measure serum GLP-2 levels in extremely low-birthweight (ELBW) infants and normal-term infants, and to compare these values between the two groups. METHODS: Blood samples were collected and serum GLP-2 concentrations measured, from 15 ELBW infants at three stages (stage I, before initial feeding after birth; stage II, point at which milk intake reached 100 mL/kg per day; stage III, corrected 40 weeks of gestation), and from 30 normal-term infants at two stages (stages I and II). RESULTS: No significant difference in basal GLP-2 values at stage I (before initial feeding) was found between ELBW infants and normal-term infants (7.37 +/- 0.95 ng/mL vs 9.47 +/- 0.94 ng/mL). However, in ELBW infants, serum GLP-2 concentrations at stage II were significantly increased, compared with those at stage I (P < 0.0001). In normal-term infants, serum GLP-2 concentrations at stage II were also significantly increased compared with those at stage I (P < 0.001). CONCLUSION: The results suggest that initial feeding stimulates secretion of serum GLP-2 in neonates. In addition, the secretion mechanism of GLP-2 is considered to be established at 24 weeks of gestation at the latest.

Eating↗
PubMed2006

CARM1 regulates proliferation of PC12 cells by methylating HuD.

HuD is an RNA-binding protein that has been shown to induce neuronal differentiation by stabilizing labile mRNAs carrying AU-rich instability elements. Here, we show a novel mechanism of arginine methylation of HuD by coactivator-associated arginine methyltransferase 1 (CARM1) that affected mRNA turnover of p21cip1/waf1 mRNA in PC12 cells. CARM1 specifically methylated HuD in vitro and in vivo and colocalized with HuD in the cytoplasm. Inhibition of HuD methylation by CARM1 knockdown elongated the p21cip1/waf1 mRNA half-life and resulted in a slow growth rate and robust neuritogenesis in response to nerve growth factor (NGF). Methylation-resistant HuD bound more p21cip1/waf1 mRNA than did the wild type, and its overexpression upregulated p21cip1/waf1 protein expression. These results suggested that CARM1-methylated HuD maintains PC12 cells in the proliferative state by committing p21cip1/waf1 mRNA to its decay system. Since the methylated population of HuD was reduced in NGF-treated PC12 cells, downregulation of HuD methylation is a possible pathway through which NGF induces differentiation of PC12 cells.

Animals↗
PubMed2006

Inhibitory effect of ribbon-type NF-kappaB decoy oligodeoxynucleotides on osteoclast induction and activity in vitro and in vivo.

In this study we examined the effect of ribbon-type (circular-type) NF-kappaB decoy oligodeoxynucleotides (RNODN) on osteoclast induction and activity. We extracted bone marrow cells from the femurs of rats and incubated non-adherent cells with receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). First, transfer efficiency into osteoclasts and their precursors, resistance to exonuclease, and binding activity of decoy to NF-kappaB were examined. Next, to examine the effect of RNODN on osteoclast induction and activity, osteoclast differentiation and pit formation assays were performed. RNODN were injected into the ankle joints of rats with collagen-induced arthritis. Joint destruction and osteoclast activity were examined by histological study. The resistance of RNODN to exonuclease and their binding activity on NF-kappaB were both greater than those of phosphorothionated NF-kappaB decoy oligodeoxynucleotides. The absolute number of multinucleate cells scoring positive for tartrate-resistant acid phosphatase was significantly decreased in the RNODN-treated group. The average calcified matrix resorbed area was significantly decreased in the RNODN-treated group. Histological study showed marked suppression of joint destruction and osteoclast activity by intra-articular injection of RNODN. These results suggest the inhibitory effect of RNODN on the induction and activity of osteoclasts. Direct intra-articular injection of RNODN into the joints may be an effective strategy for the treatment of arthritis.

Animals↗
PubMed2006

Four cases of Kawasaki syndrome complicated with myocarditis.

BACKGROUND: Myocarditis frequently occurs in the acute phase of Kawasaki syndrome (KS), and a few severe cases have been reported. Four cases of myocarditis in KS required additional catecholamine treatment because of severe left ventricular dysfunction (LVD). CASE REPORTS: Three cases were relatively older children and 2 cases were complicated with encephalopathy. All 4 developed coronary artery abnormalities during convalescence. There was 1 case of LVD because of prolonged severe inflammation prior to administration of intravenous immunoglobulin (IVIG). The remaining 3 patients had normal values for ejection fraction before the administration of IVIG but decreased values (42-51%) and increased C-reactive protein levels after IVIG administration. These cases demonstrate an association between myocarditis in KS and severe or worsened inflammation. CONCLUSIONS: Even with prior normal echocardiography, careful observation of cardiac function may be necessary for patients with KS, especially older children, when inflammation deteriorates after administration of IVIG.

Catecholamines↗
PubMed2006

Application of femtosecond laser ablation for detaching grown protein crystals from glass capillary tube.

We developed a novel technique for detaching protein crystals from glass capillary tube using the counter diffusion crystallization technique by femtosecond laser irradiation. X-ray diffraction analysis demonstrated that femtosecond laser irradiation has little effect on crystallinity. This technique will contribute to progress in structural genomics as a powerful tool.

Crystallization↗
PubMed2006

Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development.

UNLABELLED: In this study, overexpression of noggin, a BMP antagonist, in developing bone caused significantly decreased osteoclast number as well as bone formation rate, resulting in increased bone mass with immature bone quality. BMP signaling plays important roles in normal bone development and regulation of bone resorption. INTRODUCTION: Bone morphogenetic proteins (BMPs) act on various types of cells. Although involvement of BMP signals in osteoblast differentiation has been studied extensively, the effects of BMPs on osteoclasts have not been widely researched. Consequently, the net effects of BMPs on bone remain unclear. The purpose of this study was to delineate more fully the role of BMPs in skeletal biology. MATERIALS AND METHODS: We generated transgenic mice that express BMP4 or noggin in bone under the control of the 2.3-kb alpha1(I) collagen chain gene (Col1a1) promoter, and analyzed their bone phenotype. We also analyzed bone of transgenic mice expressing BMP4 specifically in cartilage. RESULTS: Mice overexpressing BMP4 in bone developed severe osteopenia with increased osteoclast number. Mice overexpressing noggin, a BMP antagonist, in bone showed increased bone volume associated with decreased bone formation rate and decreased osteoclast number. The noggin-transgenic tibias exhibited reduced periosteal bone formation and reduced resorption of immature bone in marrow spaces, associated with frequent fractures at the diaphysis. Co-culture of primary osteoblasts prepared from noggin-transgenic calvariae and wildtype spleen cells resulted in poor osteoclast formation, which was rescued by addition of recombinant BMP2, suggesting that noggin inhibits osteoclast formation by attenuating BMP activities in noggin-transgenic mice. The expression levels of Rankl were not decreased in primary osteoblasts from noggin transgenic mice. Immunoblot analysis showed increased phosphorylation of Smad1/5/8 in osteoclast precursor cells after 20-minute treatment with BMPs, suggesting that these cells are stimulated by BMPs. Mice overexpressing BMP4 in cartilage had enlarged bones containing thick trabeculae, possibly because of expansion of cartilage anlagen. CONCLUSIONS: Overexpression of noggin in bone revealed that BMP signals regulate bone development through stimulation of osteoblasts and osteoclasts.

Animals↗
PubMed2006

In vivo three-dimensional kinematics of the midcarpal joint of the wrist.

BACKGROUND: The human carpus is a complex joint system. Many problems that arise in the wrist are the result of an alteration of intercarpal motion. Although the midcarpal joint is a major component of the wrist joint, the global kinematics of the midcarpal joint have not been described. The purpose of this study was to provide a simplified description of the motion and function of the midcarpal joint. METHODS: We studied the in vivo three-dimensional kinematics of the midcarpal joint with use of a markerless bone-registration technique. Magnetic resonance images of the wrists of twenty-four healthy volunteers were acquired during a dart-throwing motion or flexion-extension motion of the wrist. Three-dimensional animations of the isolated midcarpal joint were created. Relative midcarpal motions were investigated qualitatively and quantitatively. RESULTS: The direction of the capitate motion relative to the scaphoid was always similar: it was oblique and it extended from radiodorsal to ulnopalmar in radioulnar deviation, in the dart-throwing motion, and in the flexion-extension motion. The directions of the capitate motions relative to the lunate and triquetrum inclined in a similar way, while the ranges of motion were almost unchanged. As the wrist motion changed from radioulnar deviation to flexion-extension motion, the range of the capitate rotation relative to the scaphoid decreased while the range of the lunate rotation relative to the scaphoid increased. Regardless of the type of wrist motion, the loci of the displacement of all of the joint surfaces of the midcarpal joint were located within a midcarpal ovoid space, and a line connecting the centers of the joint surfaces of the midcarpal joint could be schematized as a letter "C" entwining the midcarpal ovoid. CONCLUSIONS: Midcarpal motion is essentially the combined motion of three types of joint systems: (1) the uniaxial joint between the scaphoid and the distal row; (2) the biaxial joint between the lunate and triquetrum and the distal row; and (3) the intercarpal joints of the proximal row, which have an adaptive mechanism that accommodates the above-mentioned two types of joint systems in the midcarpal joint. CLINICAL RELEVANCE: We advocate use of the "ovoid/C" concept to describe the function of the midcarpal joint that contributes to both the stability and the mobility of the wrist, to assist clinicians in achieving a better understanding of the kinematics of the wrist joint.

Adult↗
PubMed2006

Computer-assisted spherical osteotomy with a curved-bladed Tuke Saw.

Techniques for spherical osteotomy, such as rotational acetabular osteotomy, can help orthopaedic surgeons correct bony deformities and remove spherical acetabular components. Curved chisels are used during a spherical osteotomy, but they require skill and have a potential risk of damaging blood vessels or nerves. In order to perform a precise, quick and safe spherical osteotomy, we have developed a novel computer-assisted surgical tool using a vibrating bone saw, the Tuke Saw, with a curved blade that operates under the guidance of an optical navigation system. In this study, the accuracy and ease of use of this curved-bladed Tuke Saw in spherical osteotomy were examined in comparison with the conventional curved chisel. Using these surgical tools, hemispherical osteotomies were performed on rectangular parallelepiped Sawbones blocks and rotational acetabular osteotomies were performed on cadaveric pelves. The distance error with the curved-bladed Tuke Saw was significantly smaller than that with the curved chisel, and the procedure time with the Tuke Saw was approximately half that with the chisel. It can thus be concluded that the curved-bladed Tuke Saw is more accurate and easier to use than the conventional curved chisel.

Acetabulum↗
PubMed2006

[Fracture repair and bone morphogenetic protein (BMP)].

The process of fracture healing involves a number of regenerative mechanisms underlying the skeletal systems, and bone morphogenetic protein (BMP) has been believed to be a key molecule during the reaction. Recent investigations showed that several members of BMPs are induced and activated by the impact of fracture, and play important roles via BMP receptors/Smads pathways. BMPs are newly synthesized by callus-forming cells near the fracture site, and form a "BMP-network" at the fracture callus. The "BMP-network" contributes to the regulation of callus formation, and the network contains noggin, sonic hedgehog (Shh), hepatocyte growth factor (HGF), and vascular endothelial cell growth factor (VEGF). Potential roles of BMPs during fracture repair open the way towards the formulation of new therapeutic strategies for promising fracture management. Recent molecular technologies with use of recombinant BMP and gene therapy will lead to the development of less-invasive and more successful fracture treatment.

Bone Morphogenetic Protein Receptors↗
PubMed2006

[Bone morphogenetic proteins and their related molecules in the skeletal tissue].

Biochemical studies revealed bone morphogenetic protein (BMP) receptors and intracelluar Smad proteins that mediate BMP signals. These pathways are regulated extracelluarly by antagonists such as noggin and intracellularly by Smads 6 and 7. Transgenic and conditional knockout mice have been generated and analyzed to clarify function of these molecules in skeletal tissues by using bone- or cartilage-specific promoter sequences.

Animals↗
PubMed2006

E2F decoy oligodeoxynucleotide ameliorates cartilage invasion by infiltrating synovium derived from rheumatoid arthritis.

This study examined the ability of E2F decoy oligodeoxynucleotides (ODN) to inhibit proliferation of synovial fibroblasts derived from patients with rheumatoid arthritis (RA). The effect of E2F decoy ODN on cartilage invasion by RA synovium in a murine model of human RA was also investigated. E2F decoy ODN were introduced into synovial tissue and synovial fibroblasts derived from patients with RA using hemagglutinating virus of Japan (HVJ)-liposomes. The effect of E2F decoy ODN on synovial fibroblast proliferation was evaluated by MTT assay and by RT-PCR for the cell cycle regulatory genes proliferating-cell nuclear antigen (PCNA) and cyclin-dependent kinase 2 (cdk2). Changes in production of inflammatory mediators by RA synovial tissue following transfection with E2F decoy ODN were assessed by ELISA. Human cartilage and RA synovial tissue transfected with E2F decoy ODN were co-transplanted in severe combined immunodeficient (SCID) mice. After 4 weeks, the mice were sacrificed and the implants histologically examined for inhibition of cartilage damage by E2F decoy ODN. E2F decoy ODN resulted in significant inhibition of synovial fibroblast proliferation, corresponding with reduced expression of PCNA and cdk2 mRNA in synovial fibroblasts. The production of interleukin-1beta (IL-1beta), IL-6 and matrix metalloproteinase (MMP)-1 by synovial tissue was also significantly inhibited by the introduction of E2F decoy ODN. Further, in an in vivo model, cartilage that was co-implanted with RA synovial tissue transfected with E2F decoy ODN exhibited no invasive and progressive cartilage degradation. These data demonstrate that transfection of E2F decoy ODN prevents cartilage destruction by inhibition of synovial cell proliferation, and suggest that transfection of E2F decoy ODN may provide a useful therapeutic approach for the treatment of joint destruction in arthritis.

Animals↗
PubMed2006

[Cartilage formation and regeneration by mechanical stress].

Every cell in our body is subject to mechanical stress and responds to mechanical stimulation. Especially, tissues which function as a supportive tissue such as bone or cartilage utilize these stimulation during tissue formation and maintenance. Several lines of extensive studies have revealed the effects and mechanisms of mechanotransduction in cartilage or three dimensional engineered tissue. Furthermore, these biological responses to mechanical stimulation are thought to enhance cartilage formation or regeneration in vitro . Mechanical stimulation to a cultured tissue is thought to be a feasible strategy to develop a new cartilage therapy.

Animals↗
PubMed2005

An echo-contrast agent, Levovist, lowers the ultrasound intensity required to induce apoptosis of human leukemia cells.

To verify the effect of echo-contrast agent (ECA) on apoptosis induced by ultrasound, leukemia cell lines (Jurkat, Molt-4 and U937) were sonicated at intensities previously shown to induce optimal apoptosis with or without Levovist, an ECA. The results showed that loss of viability and apoptosis can be induced in all three cell lines, apoptosis highest with Molt-4, based on viability and DNA fragmentation assay. Such finding was supported by corresponding increase of cells with low mitochondrial membrane potential, high superoxide production, increased intracellular calcium concentration, and phosphorylation of histone H2AX after sonication. Optimal ultrasound condition was 0.3W/cm(2), 1MHz, 10% duty factor pulsed at 100Hz; but in the presence of Levovist, an apparent shift of cell killing induction was observed at 0.2W/cm(2). While these results further confirmed previous findings on ultrasound-induced apoptosis, they also suggest that use of an enhancing factor, such as addition of ECA, may be useful in cancer therapy when a much lower intensity is desired.

Apoptosis↗
PubMed2005

Cloning and expression pattern of lbx3, a novel chick homeobox gene.

The Drosophila melanogaster genes, ladybird early (lbe) and ladybird late (lbl), encode transcriptional regulators, which play an important role in neurogenesis, myogenesis and cardiogenesis. Here, we report an isolation of a novel ladybird family homeobox gene (lbx3) and its expression during chick development. The open reading frame of lbx3 encodes a predicted protein of 213 amino acids including a homeodomain, a PST motif and a nuclear localization signal. The homeodomain of lbx3 protein has 80% identities with the chick and mouse lbx1 homeodomains, and 75% identity with the mouse lbx2 homeodomain. Both lbx1 and lbx3 are expressed in prospective hypaxial myoblasts at cervical and limb level. In addition, lbx3 transcripts are detected in the medial dermomyotomal lips of somites of all axial levels at stage 23, but not detected in the neural tube.

Amino Acid Sequence↗
PubMed2005

False positive 18F-FDG PET in an ischial chondroblastoma; an analysis of glucose transporter 1 and hexokinase II expression.

We report a rare case of chondroblastoma arising from the ischium which showed an increased (18)F-FDG uptake. Chondroblastoma is an uncommon lesion and usually involves the epiphysis of long bones. However, in this case, the tumor appeared as a well-defined osteolytic lesion in the ischium on radiographs. MR imaging demonstrated two components in the tumor: a solid one and a multilobular cystic component. (18)F-FDG PET imaging revealed an increased uptake in the ischium. The (18)F-FDG uptake resembled the results observed in malignant bone tumors. A histological diagnosis of chondroblastoma was obtained from tissue of an open biopsy. An immunohistochemical analysis demonstrated weak expression of both Glut-1 and HK-II. These findings suggest that Glut-1 and HK-II expression are not strongly related to FDG uptake in chondroblastoma.

Adult↗
PubMed2005

Genomic rearrangement at 10q24 in non-syndromic split-hand/split-foot malformation.

Split-hand/split-foot malformation (SHFM) is a congenital limb malformation characterized by a median cleft of hand and/or foot due to the absence of central rays. Five loci for syndromic and non-syndromic SHFM, termed SHFM1-5, have been mapped to date. Recently, a 0.5 Mb tandem genomic duplication was found at chromosome 10q24 in SHFM3 families. To refine the minimum duplicated region and to further characterize the SHFM3 locus, we screened 28 non-syndromic SHFM families for tandem genomic duplication of 10q24 by Southern blot and sequence analysis of the dactylin gene. Of 28 families, only two showed genomic rearrangements. Representative patients from the two families exhibit typical SHFM, with symmetrically affected hands and feet. One patient is a familial case with a 511,661 bp tandem duplication, whereas the second is a sporadic case arising from a de novo, 447,338 bp duplication of maternal origin. The smaller duplication in the second patient contained the LBX1, BTRC, POLL, and DPCD genes and a disrupted extra copy of the dactylin gene, and was nearly identical to the smallest known duplicated region of SHFM3. Our results indicate that genomic rearrangement of SHFM3 is rare among non-syndromic SHFM patients and emphasize the importance of screening for genomic rearrangements even in sporadic cases of SHFM.

Chromosomes, Human, Pair 10↗