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Biomedical subjects

Hideki Yoshikawa

Publications and source records attributed to Hideki Yoshikawa.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced expression of mRNA for nuclear factor kappaB1 (p50) in CD34+ cells of the bone marrow in rheumatoid arthritis.

Bone marrow CD34+ cells from rheumatoid arthritis (RA) patients have abnormal capacities to respond to tumor necrosis factor (TNF)-alpha and to differentiate into fibroblast-like cells producing matrix metalloproteinase (MMP)-1. We explored the expression of mRNA for nuclear factor (NF)kappaB in RA bone marrow CD34+ cells to delineate the mechanism for their abnormal responses to TNF-alpha. CD34+ cells were purified from bone marrow samples obtained from 49 RA patients and 31 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The mRNAs for NFkappaB1 (p50), NFkappaB2 (p52) and RelA (p65) were examined by quantitative RT-PCR. The expression of NFkappaB1 mRNA in bone marrow CD34+ cells was significantly higher in RA than in OA, whereas there was no significant difference in the expression of mRNA for NFkappaB2 and RelA. The expression of NFkappaB1 mRNA was not correlated with serum C-reactive protein or with the treatment with methotrexate or oral steroid. Silencing of NFkappaB1 by small interfering RNA abrogated the capacity of RA bone marrow CD34+ cells to differentiate into fibroblast-like cells and to produce MMP-1 and vascular endothelial growth factor upon stimulation with stem cell factor, granulocyte-macrophage colony stimulating factor and TNF-alpha without influencing their viability and capacity to produce beta2-microglobulin. These results indicate that the enhanced expression of NFkappaB1 mRNA in bone marrow CD34+ cells plays a pivotal role in their abnormal responses to TNF-alpha and, thus, in the pathogenesis of RA.

Adult↗
PubMed2006

Serious metallosis of a metal head due to fragmented ceramic screws in a cemented THA.

We reported a rare revision case necessitated by massive metallosis of a metal head due to a fragmented ceramic screw which had been extraarticularily used in the primary THA here and reviewed previous literature about metallosis of metal heads associated with ceramic materials. The ceramic screw had been used for the fixation of a bone graft and reattachment of the greater trochanter in the primary THA. Scanning electron microscope analysis revealed large alumina ceramic particles embedded on the bearing surface of the polyethylene. It has previously been pointed out that metallosis of an inner head occurred in bipolar case due to a fracture of the ceramic screws in contact with a proximally migrated outer head. However, this case showed that if a ceramic screw fragmented even though it was used outside of the hip joint, the fragments could migrate into bearing surface and cause serious metallosis of the metal head. Thus, we recommend that surgeons should pay special attention to the radiographic signs of ceramic failure or metallosis such as a change of the metal head contour, if an aseptic loosening or severe osteolysis is observed in a THA in which ceramic materials were used near the hip joint. And, when a surgical revision is planned, the surgeon should be prepared to exchange with a new ceramic head.

Bone Screws↗
PubMed2006

Stimulation of cyclooxygenase-2 expression by bone-derived transforming growth factor-beta enhances bone metastases in breast cancer.

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme of prostaglandin synthesis, has been implicated in invasiveness and distant metastases of cancer. Bone is one of the most common target sites of cancer metastasis. However, the role of COX-2 in bone metastasis is unclear. We examined the surgical specimens of bone metastases from patients with various types of cancers by using immunohistochemistry and observed evident COX-2 expression in these bone metastases. In a nude mouse model of bone metastasis, the MDA-MB-231 human breast cancer cells showed no COX-2 expression at orthotopic sites, whereas these cells, when metastasized to bone, intensely expressed COX-2, suggesting that the bone microenvironment induced COX-2 expression. Consistent with this notion, inhibition of bone resorption by the bisphosphonate ibandronate reduced COX-2 expression in MDA-MB-231 cells in bone. Transforming growth factor-beta (TGFbeta), one of the most abundant growth factors stored in bone, increased COX-2 expression and prostaglandin E2 production in MDA-MB-231 cells in culture. MDA-MB-231 cells overexpressing dominant-negative TGFbeta type II receptors showed decreased bone metastases and reduced osteoclastic bone resorption with impaired COX-2 expression. The COX-2 inhibitors, NS-398 and nimesulide, significantly suppressed bone metastases with decreased osteoclast number and increased apoptosis in MDA-MB-231 cells. These results suggest that bone-derived TGFbeta up-regulates COX-2 expression in breast cancer cells, thereby increasing prostaglandin E2 production, which in turn, stimulates osteoclastic bone destruction, leading to the progression of bone metastases. Our results also suggest that COX-2 is a potential therapeutic target for bone metastases in breast cancer.

Animals↗
PubMed2006

Kinematics of the cervical spine in lateral bending: in vivo three-dimensional analysis.

STUDY DESIGN: Kinematics of the cervical spine during lateral bending were investigated using a novel system of three-dimensional motion analysis. OBJECTIVES: To demonstrate in vivo intervertebral coupled motions of the cervical spine during lateral bending of the neck. SUMMARY OF BACKGROUND DATA: No previous studies have successfully documented in vivo three-dimensional intervertebral motions of the cervical spine during lateral bending. METHODS: Twelve healthy volunteers underwent three-dimensional magnetic resonance imaging (MRI) of the cervical spine in 7 positions with 10 degrees increments of lateral bending. Relative motions of the cervical spine were calculated automatically by superimposing a segmented three-dimensional-MRI of the vertebra in the neutral position over images of each position using volume registration. RESULTS: Mean maximum lateral bending of the cervical spine to one side was 1.6 degrees to 5.7 degrees at each level. Coupled axial rotation opposite to lateral bending was observed in the upper cervical levels (Oc-C1, 0.2 degrees ; C1-C2, 17.1 degrees ), while in the subaxial cervical levels, it was observed in the same direction as lateral bending except for at C7-T1. Coupled flexion-extension motion was small at all vertebral levels (<1.1 degrees). CONCLUSIONS: We succeeded in identifying in vivo coupled motions of the cervical spine in lateral bending for the first time.

Adult↗
PubMed2006

Cloning and regulation of the vertebrate homologue of lin-41 that functions as a heterochronic gene in Caenorhabditis elegans.

The Caenorhabditis elegans gene lin-41 is the one of the heterochronic genes that regulate the timing of many developmental events. MicroRNA let-7 negatively regulates the expression of lin-41 through RNA-RNA interaction on its 3' untranslated region (UTR). Here, we report the isolation of chick and mouse homologues of lin-41 that encode the RBCC-NHL family protein and their expression patterns. C. elegans lin-41 is one of the RBCC-NHL families and the predicted amino acid sequences of isolated two genes encode the same family proteins. Chick and mouse lin-41 expression was also observed in developing limb buds, branchial arches, and tail buds. The 3'UTRs of the mouse and chick lin-41 genes contain multiple let-7 complementary sites. Using luciferase assay, we showed that lin-41 expression can be regulated through let-7 complementary sites.

3' Untranslated Regions↗
PubMed2006

Dual hydroxyapatite composite with porous and solid parts: experimental study using canine lumbar interbody fusion model.

Hydroxyapatite (HA) has been evaluated for use in a variety of applications in bone reconstruction surgery because of its high affinity with host bone and biocompatibility. However, because of the difficulty in combining porosity (for bone ingrowth) and strength in HA, it is generally considered inappropriate to use HA for high-load applications such as spinal interbody fusion. In the present study, we constructed a HA implant for spinal interbody fusion, composed of a dual HA composite (DHC) that combines two HA materials with different porosities: HA with 75% porosity, for bone ingrowth; and HA with 0% porosity, for load bearing. We used a canine lumbar interbody fusion model to evaluate bone conduction of the implant and its efficacy for bony fusion. Six months after the operation, DHC exhibited almost the same efficacy for bony fusion as iliac bone grafts. Moreover, pores of the porous part of the DHC were completely filled with newly formed bone and bone marrow cells. The present findings indicate that DHC is suitable for use as an implant material for spinal interbody fusion as a substitute for iliac bone grafts, which could eliminate the disadvantages associated with autograft harvesting.

Animals↗
PubMed2006

Multidetector-CT evaluation of bone substitutes remodeling after revision hip surgery.

UNLABELLED: We evaluated remodeling of grafted bone substitutes after revision hip arthroplasty using serial examinations of multidetector-row computed tomography imaging. Ten patients (12 hips) had cementless revision surgery with grafting of beta-tricalcium phosphate granules and pastelike calcium phosphate cement in bone defects around the femoral component. At 3 weeks and 1 year postoperatively, the patients were evaluated using multidetector-row computed tomography imaging with a metal artifact minimizing protocol. New bone formation and changes in volume of beta-tricalcium phosphate and calcium phosphate cement were measured. At 1 year postoperatively, beta-tricalcium phosphate had decreased more than calcium phosphate cement. The residual volumes of calcium phosphate cement and beta-tricalcium phosphate were 78% (range, 37%-96%) and 30% (range, 10%-62%) of the initial grafted volume, respectively. The volume of the new bone that formed after absorption of beta- tricalcium phosphate was 34% (range, 11%-76%) of the initial beta-tricalcium phosphate volume. Use of cement in prior operations was an unfavorable factor in graft remodeling after revision surgery. Multidetector-row computed tomography is a promising tool for evaluating bone stock restoration of patients and influential factors of bone remodeling, and for clarifying remodeling patterns of various bone substitutes. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Aged↗
PubMed2006

Does alendronate prevent collapse in osteonecrosis of the femoral head?

UNLABELLED: Progression of collapse in osteonecrosis of the femoral head is related to the repair response, especially bone resorption around the necrotic region. A preliminary clinical study was done to determine whether systemic alendronate would prevent collapse and lead to pain relief in patients with osteonecrosis of the femoral head. Fourteen patients (20 hips) with osteonecrosis of the femoral head received daily administration of 5 mg alendronate (alendronate group) for 1 year. Eight patients (13 hips) with osteonecrosis of the femoral head did not receive alendronate (control group). All patients had measurements of biochemical markers of bone turnover at entry into the study, and the patients in the alendronate group repeated the measurements at 3 months, 6 months, and 12 months. All patients had clinical and plain radiographic examinations at entry into the study and at 3 months, 6 months, and 12 months. The alendronate group showed a greater decrease of biochemical marker of bone resorption than biochemical marker of bone formation. The alendronate group showed a lower frequency of collapse of the femoral head and reported less hip pain than the control group. Our results suggest alendronate has the potential to prevent collapse of the femoral head, even with extensive necrosis, presumably by inhibiting bone resorption in the necrotic region. LEVEL OF EVIDENCE: Therapeutic study, level II (prospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.

Adolescent↗
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

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

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↗
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↗
PubMed2005

Differential and collaborative actions of Rad51 paralog proteins in cellular response to DNA damage.

Metazoan Rad51 plays a central role in homologous DNA recombination, and its activity is controlled by a number of Rad51 cofactors. These include five Rad51 paralogs, Rad51B, Rad51C, Rad51D, XRCC2 and XRCC3. We previously hypothesized that all five paralogs participate collaboratively in repair. However, this idea was challenged by the biochemical identification of two independent complexes composed of either Rad51B/C/D/XRCC2 or Rad51C/XRCC3. To investigate if this biochemical finding is matched by genetic interactions, we made double mutants in either the same complex (rad51b/rad51d) or in both complexes (xrcc3/rad51d). In agreement with the biochemical findings the double deletion involving both complexes had an additive effect on the sensitivity to camptothecin and cisplatin. The double deletion of genes in the same complex, on the other hand, did not further increase the sensitivity to these agents. Conversely, all mutants tested displayed comparatively mild sensitivity to gamma-irradiation and attenuated gamma-irradiation-induced Rad51 foci formation. Thus, in accord with our previous conclusion, all paralogs appear to collaboratively facilitate Rad51 action. In conclusion, our detailed genetic study reveals a complex interplay between the five Rad51 paralogs and suggests that some of the Rad51 paralogs can separately operate in later step of homologous recombination.

Animals↗
PubMed2005

Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification.

Leptin has been suggested to mediate a variety of actions, including bone development, via its ubiquitously expressed receptor (Ob-Rb). In this study, we investigated the role of leptin in endochondral ossification at the growth plate. The growth plates of wild-type and ob/ob mice were analyzed. Effects of leptin on chondrocyte gene expression, cell cycle, apoptosis and matrix mineralization were assessed using primary chondrocyte culture and the ATDC5 cell differentiation culture system. Immunohistochemistry and in situ hybridization showed that leptin was localized in prehypertrophic chondrocytes in normal mice and that Ob-Rb was localized in hypertrophic chondrocytes in normal and ob/ob mice. Growth plates of ob/ob mice were more fragile than those of wild-type mice in a mechanical test and were broken easily at the chondro-osseous junction. The growth plates of ob/ob mice showed disturbed columnar structure, decreased type X collagen expression, less organized collagen fibril arrangement, increased apoptosis and premature mineralization. Leptin administration in ob/ob mice led to an increase in femoral and humeral lengths and decrease in the proportional length of the calcified hypertrophic zone to the whole hypertrophic zone. In primary chondrocyte culture, the matrix mineralization in ob/ob chondrocytes was stronger than that of wild-type mice; this mineralization in both types of mice was abolished by the addition of exogenous leptin (10 ng/ml). During ATDC5 cell differentiation culture, exogenous leptin at a concentration of 1-10 ng/ml (equivalent to the normal serum concentration of leptin) altered type X collagen mRNA expression and suppressed apoptosis, cell growth and matrix calcification. In conclusion, we demonstrated that leptin modulates several events associated with terminal differentiation of chondrocytes. Our finding that the growth plates of ob/ob mice were fragile implies a disturbance in the differentiation/maturation process of growth plates due to depletion of leptin signaling in ob/ob mice. These findings suggest that peripheral leptin signaling plays an essential role in endochondral ossification at the growth plate.

Animals↗