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Hiroaki Nakamura

Publications and source records attributed to Hiroaki Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

The structure and diversity of alpha1-acid glycoprotein/orosomucoid gene in Africans.

Human orosomucoid (ORM), or alpha(1)-acid glycoprotein, is known to be controlled by duplicated and triplicated genes on chromosome 9, encoding ORM1 and ORM2 proteins. In this study, the structure and diversity of the ORM gene were investigated in 16 Sub-Saharan Africans, who originated from widely dispersed locations in Africa. The duplicated ORM1-ORM2 gene was observed in all 16 samples. ORM1*S1(2), characterized by an ORM2 gene-specific sequence in intron 5, was common in Africans. Three Africans showed the duplication of the ORM1 gene. The organization of the triplicated ORM1A-ORM1B-ORM2 gene was established in two Africans. The recombination breakpoints resulting in the ORM1 duplication lay within a small genomic interval around exon 1 of the ORM1B gene. The duplication of the ORM2 gene reported previously was not detected in this population sample. Several single-nucleotide polymorphisms were observed in the ORM2 gene. The rearrangement of the ORM gene is likely to occur often in Africans.

Alu Elements↗
PubMed2006

Endometrial thickness in Japanese women with hypertension or/and type 2 diabetes mellitus.

OBJECTIVES: The purpose of this study was: (a) to examine whether the endometrium of postmenopausal women with hypertension (HT) and/or type 2 diabetes mellitus (DM) was thicker than that of healthy controls (HC) and (b) whether endometrial thickness (ET) was associated with endometrial cancer risk factors. STUDY DESIGN: A total of 242 postmenopausal women were included in this study. Thirty women with type 2 DM, 49 women with HT, 23 women with DM and HT and 140 HCs were studied. Clinical evaluation of all women was done using TVS and endometrial cytology. RESULTS: In the 140 HCs, the mean ET of nulliparous women was larger than multiparous women (3.0 mm versus 1.6 mm, p = 0.017). However, there was no significant relationship between ET and other clinical parameters such as a history of sterility or BMI. There was no significant difference in ET amongst the four groups. The relationship between ET, age, pregnancy history, menopause age, BMI and presence of DM or HT were analyzed using stepwise multivariate analysis. There was no significant relationship between these risk factors and ET (p = 0.063). CONCLUSIONS: The risk factors such as age, pregnancy history, menopause age, BMI and presence of DM or HT were not related to ET in Japanese women.

Adult↗
PubMed2006

[Vertebroplasty for osteoporotic vertebral fracture].

Vertebroplasty for osteoporotic vertebral fracture has been published to enhance fractured vertebra and to reduce severe pain after the fracture. Bone cement such as Polymethylmethacrylate or calcium phosphate cement has been used for this procedure. However, serious neurological complication and pulmonary embolism might occur following the leakage of the cement. In order to avoid these serious complications, it seems to be important to make an enough space in the vertebral body before injecting bone cement. For this purpose, we utilized balloon inflation and endoscopic resection of connective tissue for pseudoarthrosis following osteoporotic vertebral fracture. With this procedure, severe pain after the fracture improved dramatically. So far, we did not have any serious systemic complications.

Bone Cements↗
PubMed2005

Transvaginal ultrasonography of the endometrium in postmenopausal Japanese women.

AIMS: To determine the cut-off level of endometrial thickness for detecting endometrial disease on a large scale of screening and to examine the usefulness of transvaginal ultrasonography (TVS) for endometrial disease screening in asymptomatic postmenopausal Japanese women. METHODS: The study involved 1,400 postmenopausal women in whom endometrial thickness was measured with TVS, and then compared with the histopathological diagnosis of endometrial specimens. RESULTS: The prevalence of endometrial disease in asymptomatic and symptomatic cases was 2.3 and 21%. In symptomatic cases, at a cut-off limit of 3 mm for endometrial thickness, the sensitivity for detecting endometrial disease was 94%, specificity 70% and positive predictive value 46%. With an endometrial thickness < or = 3 mm, the probability that endometrial disease would be overlooked was 0.025. In asymptomatic cases, the corresponding figures at a cut-off limit of 3 mm were 90, 84, 12% and 0.003. CONCLUSIONS: TVS does not appear to be an effective screening method in asymptomatic postmenopausal Japanese women because of the low prevalence of endometrial disease in this population. We recommend a normal cut-off level for endometrial thickness of 4 mm in symptomatic postmenopausal Japanese women.

Adult↗
PubMed2005

Transcytosis of calcium from bone by osteoclast-like cells evidenced by direct visualization of calcium in cells.

'Transcytosis' of calcium (Ca) from bone by osteoclasts was identified by using a newly developed method that uses fixed or living osteoclast-like cells previously differentiated in vitro, a Ca-specific cell-membrane-impermeable fluorescent dye, and confocal laser scanning microscopy. This method, called the cell-membrane-impermeable dye method, revealed that in fixed osteoclast-like cells, a large quantity of Ca was confined within vacuoles and transported toward the apical cell membrane in the cells. These Ca-confined vacuoles were co-localized with marker proteins of both ruffled border and lysosome. The vacuoles were disrupted when treated with an inhibitor of ruffled border ATPase. In living osteoclast-like cells, Ca-confined vacuoles were again preferentially located at the central region and near the apical cell membrane. These results suggest actual transcytosis of Ca from bone by osteoclasts, and are the first direct evidence of the significant role of osteoclasts in the entire process of Ca metabolism in bone.

Adenosine Triphosphatases↗
PubMed2005

Experimental spinal fusion with recombinant human bone morphogenetic protein-2 delivered by a synthetic polymer and beta-tricalcium phosphate in a rabbit model.

STUDY DESIGN: An experimental animal study to achieve posterolateral intertransverse process spine fusion with recombinant bone morphogenetic protein in combination with a new delivery system. OBJECTIVE: To evaluate the efficacy of a new synthetic biodegradable bone-inducing material containing recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone-graft substitute for posterolateral intertransverse process fusion in a rabbit model. SUMMARY OF BACKGROUND DATA: rhBMP-2, a powerful bone-inducing cytokine, has been used as a bone graft substitute in combination with animal-derived collagen to achieve spinal fusion in animal models. However, the minimum dose of rhBMP-2 required to obtain solid posterolateral intertransverse process fusion was high on the basis of previous reports (>100 microg in rabbit models). To improve the efficacy, performance of rhBMP-2, and the safety of the delivery system for this protein, a more sophisticated system is required. METHODS: To fabricate one implant for one-side L4-L5 intertransverse process fusion, beta-tricalcium phosphate (beta-TCP) powder (300 microg), a polymer gel (PLA-DX-PEG block copolymer; 300 microg) and rhBMP-2 (7.5, 15, or 30 microg) were mixed and manually shaped to resemble a rod. Through a posterolateral approach, two implants were placed on both sides (1 per side) by surgery so as to bridge the transverse processes of adult New Zealand white rabbits (n = 27). In control animals, implants without rhBMP or autogenous cortico-cancellous bone chips from the iliaccrest were placed in a similar location. The lumbar vertebrae were recovered 6 weeks after surgery. The posterolateral fusion was examined by manual palpation, radiography, biomechanical testing, and histology. RESULTS: Rabbits that received 15 or 30 microg of rhBMP-2 showed consistent fusion. However, solid fusion was seen in 2 of 5 rabbits with autografting and rabbits that received 7.5 microg of rhBMP-2. Fusion was not observed in the rabbits that did not receive rhBMP-2. CONCLUSIONS: Consistent spinal fusion was obtained by implanting a biodegradable bone-inducing implant composed of beta-TCP, PLA-DX-PEG, and rhBMP-2 within a period of 6 weeks. The rhBMP-2 doses required for the spinal fusion were significantly lower than those reported previously.

Animals↗
PubMed2005

Objective assessment of reduced invasiveness in MED. Compared with conventional one-level laminotomy.

Microendoscopic discectomy (MED) has been accepted as a minimally invasive procedure for lumbar discectomy because of the small skin incision and short hospital stay required for this surgery. However, there are few objective laboratory data to confirm the reduced systemic responses in the early phase after this procedure. In order to substantiate the reduced invasiveness of MED compared to microdiscectomy (MD) or procedures involved in one-level unilateral laminotomy, the invasiveness of each surgical procedure was evaluated by measuring serum levels of biochemical parameters reflective of a post-operative inflammatory reaction and damage to the paravertebral muscles. Thirty-three patients who underwent lumbar discectomy or one-level unilateral laminotomy (MED in 15 cases, MD in 11 cases and one-level unilateral laminotomy in 7 cases with lumbar spinal canal stenosis) were included in this study. The serum levels of C-reactive protein (CRP) and creatine phosphokinase (CPK) were measured at 24 h after operation. Interleukin-6 (IL-6) and Interleukin-10 (IL-10) were measured at 2, 4, 8 and -24 h following the surgery to monitor the inflammatory response to the respective surgery. The post-operative serum CRP levels from both the MD and MED groups were significantly lower than those from the open laminotomy group. However, there was no significant difference in these serum levels between the MED and MD groups. The levels of IL-6 and IL-10 in the MED group during the first post-operative day were also significantly lower than those in the laminotomy group. When the MED and MD groups were compared, the IL-6 levels in the MED group were lower than in MD group at 2, 4 and 8 h after surgery, but the differences were not statistically significant. However, the level was significantly lower in the MED group at 24 h after surgery. In terms of IL-10, no significant difference was noted between the MED and MD groups over the study period. The changes in serum levels of post-operative inflammatory: markers (CRP, IL-6 and IL-10) in the early phase indicated reduced inflammatory reactions in MED as well as in MD when compared with classical open unilateral laminotomy. These data draw a direct link between the lower level of the inflammatory response and reduced invasiveness of MED. However, an indicator for muscle damage (CPK) appeared not to be affected by the type of surgical procedure used to correct disc herniation.

Adult↗
PubMed2005

Pharmacological and pharmacokinetic study of olmesartan medoxomil in animal diabetic retinopathy models.

A close relationship between the renin-angiotensin system and the pathophysiology of diabetic retinopathy has been suggested, several angiotensin II type 1 receptor (angiotensin AT1 receptor) antagonists being effective in animal models. Therefore, we examined the efficacy of an angiotensin AT1 receptor antagonist, olmesartan medoxomil (CS-866), in animal retinopathy models. In diabetic stroke-prone spontaneously hypertensive (SHRSP) rats, 4-week treatment with CS-866 prevented the elongation of oscillatory potential peaks dose-dependently which almost normalized at 3 mg/kg/day. Next, in oxygen-induced retinopathy mice, CS-866 at 1 mg/kg significantly prevented the retinal neovascularization. In these animal models, plasma concentrations of CS-866 were comparable to the in vitro IC50 value of the angiotensin AT1 receptor. In summary, our data demonstrated that CS-866 was effective in early and late stage retinopathy models through the inhibition of the angiotensin AT1 receptor. These findings suggest the possibility of CS-866 as a therapeutic agent for diabetic retinopathy.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Ultrastructural and immunohistochemical studies of medullary bone calcification, with special reference to sulphated glycosaminoglycans.

Histochemical, immunohistochemical and electron energy-loss spectroscopic studies were performed to examine the relationship between sulphated glycosaminoglycans and medullary bone calcification using oestrogen-injected male Japanese quail. Sulphated glycosaminoglycans, detected by high iron diamine (HID) or HID-thiocarbohydrazide-silver protein (HID-TCH-SP) methods, were distributed throughout the matrix of medullary bone, some periphery and extending tips of the trabeculae stained weakly, and the globular structures at osteoid areas were exclusively positive for HID-TCH-SP stain. Immunohistochemistry identified keratan sulphate located in the globular structures at osteoid areas and calcified matrix, but chondroitin-4 sulphate and chondroitin-6 sulphate were not detected in the matrix. Using electron spectroscopic imaging, sulphur was determined to be localized in the globular structures. These results demonstrate that medullary bone matrix accumulates keratan sulphate in the globular structures, which are the foci for calcification, and eventually in the calcified areas. This suggests that keratan sulphate containing sulphur is maintained in the calcified matrix. These results indicate a unique process of calcification exists in medullary bone.

Animals↗
PubMed2005

Immunolocalization of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in Meckel's cartilage compared with developing endochondral bones in mice.

We examined the immunolocalization of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in areas of resorption caused by osteoclasts/chondroclasts on embryonic days 14-16 (E14-16) in Meckel's cartilage, and compared the results with those in endochondral bones in mice. Intense RANKL and OPG immunoreactivity was detected in the chondrocytes in Meckel's cartilage. On E15, when the incisor teeth were closest to the middle portion of Meckel's cartilage, tartrate-resistant acid phosphatase (TRAP)-positive cells appeared on the lateral side of the cartilage. Furthermore, the dental follicle showed moderate immunoreactivity for RANKL and OPG, whereas osteoblasts derived from perichondral cells were immunonegative for RANKL and OPG in that area. On E16, cartilage resorption by TRAP-positive cells had progressed at the differential position, and intensely immunoreactive products of RANKL were overlapped on and found to exist next to TRAP-positive cells in the resorption area. In developing metatarsal tissue, OPG immunoreactivity was intense in periosteal osteoblasts, whereas RANKL was only faintly seen in some of the periosteal cells. In epiphyseal chondrocytes of the developing femur, RANKL immunoreactivity was moderate, and OPG scarcely detected. These results indicate a peculiarity of RANKL and OPG immunolocalization in resorption of Meckel's cartilage. Growth of the incisor teeth may be involved in the time- and position-specific resorption of Meckel's cartilage through local regulation of the RANKL/OPG system in dental follicular cells and periosteal osteoblasts, whereas RANKL and OPG in chondrocytes seem to contribute to resorption through regulation of the chondroclast function.

Animals↗
PubMed2005

Localization of CD44 (hyaluronan receptor) and hyaluronan in rat mandibular condyle.

CD44 is a multifunctional adhesion molecule that binds to hyaluronan (HA), type I collagen, and fibronectin. We investigated localization of CD44 and HA in mandibular condylar cartilage compared with the growth plate and the articular cartilage, to clarify the characteristics of chondrocytes. We also performed Western blotting using a lysate of mandibular condyle. In mandibular condyle, CD44-positive cells were seen in the surface region of the fibrous cell layer and in the proliferative cell layer. Western blotting revealed that the molecular weight of CD44 in condyle was 78 to 86 kD. Intense reactivity for HA was detected on the surface of the condyle and the lacunae of the hypertrophic cell layer. Moderate labeling was seen in cartilage matrix of the proliferative and maturative layer. Weak labeling was also seen in the fibrous cell layer. In growth plate and articular cartilage, HA was detected in all cell layers. However, chondrocytes of these cartilages did not exhibit reactivity for CD44. These results suggest that chondrocytes in the mandibular condylar cartilage differ in expression of CD44 from those in tibial growth plate and articular cartilage. Cell-matrix interaction between CD44 and HA may play an important role in the proliferation of chondrocytes in the mandibular condyle.

Animals↗
PubMed2005

Distribution of actin filaments, non-muscle myosin, M-Ras, and extracellular signal-regulated kinase (ERK) in osteoclasts after calcitonin administration.

Scanning electron microscopy (SEM) was employed to study the effect of calcitonin on the distribution of actin filaments in osteoclasts obtained from rat tibiae. Fluorescent microscopy was also applied to examine calcitonin-induced changes in the distribution of actin filaments, non-muscle myosin, M-Ras, and extracellular signal-regulated kinase (ERK) to clarify the role of ERK in the cytoskeleton of osteoclasts. SEM of control osteoclasts revealed a ring-like structure in the peripheral region. Labeled actin filaments and non-muscle myosin were detected in the peripheral region and exhibited a ring-like pattern. Immunoreactivity indicating M-Ras and ERK was also detected in the vicinity of the actin ring. After calcitonin treatment, many osteoclasts exhibited a retracted appearance and lacked a discernible actin ring. Numerous retraction fibers were found at the edge of calcitonin-treated osteoclasts. Actin filaments and non-muscle myosin were concentrated in the cytoplasm of calcitonin-treated osteoclasts, and exhibited a filamentous pattern. Labeled M-Ras and ERK also accumulated in the central region of these osteoclasts. These findings suggest that actin-myosin interaction plays an essential role in the retraction of osteoclasts induced by calcitonin. ERK may play a role in this interaction by activating myosin light chain kinase, as previously observed in smooth muscle cells.

Actins↗
PubMed2004

MATP polymorphisms in Germans and Japanese: the L374F mutation as a population marker for Caucasoids.

Inference of the population and ancestry to which an individual belongs is important in forensic individualization and personal identification. In this study, five polymorphisms of the membrane-associated transporter protein (MATP) gene were investigated in German and Japanese populations. The L374F mutation was present at an allele frequency as high as 0.96 in the German population, whereas it was completely absent in the Japanese population. This extreme difference in allele frequency suggests that the L374F mutation is valuable as a population and ancestry informative marker for Caucasoids.

Antigens, Neoplasm↗
PubMed2004

Potential risk factors for prolonged recovery following whiplash injury.

A retrospective analysis of insurance data was made of 600 individuals claiming compensation for whiplash following motor vehicle accidents. Three hundred randomly selected claimants who had settled their injury claims within 9 months of the accident were compared with 300 who had settled more than 24 months after the accident. We compared the two groups to identify possible risk factors for prolonged recovery, for which settlement time greater than 24 months was a marker. Variables considered included demographic factors, type of collision, degree of vehicle damage, workers compensation, prior claim or neck disability, treatment and time to settlement. Consulting a solicitor was associated with a highly significant, four-fold increase of late settlement of the claim. A concurrent workers' compensation claim, prior neck disability and undergoing physiotherapy or chiropractic treatment were weakly associated with late settlement. The degree of damage to the vehicle (as indicated by cost of repairs) was not a significant predictor of late settlement. Late settlement may be the direct effect of legal intervention, independent of the severity of the injury. Whilst the financial benefit to the claimant of consulting a solicitor is apparent, the benefit of prolonged disability is not. It may be to the advantage of both insurers and claimants if those likely to proceed to late settlement could be recognised early and their claims settled expeditiously.

Accidents, Traffic↗
PubMed2004

Different type and localization of CD44 on surface membrane of regenerative renal tubular epithelial cells in vivo.

BACKGROUND: CD44 is a transmembrane glycoprotein comprising an extracellular domain, a transmembrane domain, and a cytoplasmic tail. Previous studies demonstrated that CD44 was generally restricted to lateral-basal plasma membrane (PM) of epithelial cells, whether it localized on apical PM in vivo has not been clarified. METHODS: In this study, we used a gentamicin-induced acute tubular necrosis (ATN) and spontaneous recovery model in rats and two distinct antibodies, an anti-rat distal extracellular domain (OX49) of standard CD44 (CD44-OX49) and an anti-rat CD44 cytoplasmic tail (CD44CPT), to survey the localization of CD44-OX49 and CD44CPT on the PM in renal tubular epithelial cells in different recovery stages after ATN with immunohistochemistry and immunoelectron-microscopic examinations. RESULTS: CD44-OX49 was localized not only on the lateral-basal PM in tubular epithelial cells, but also on the apical surface membrane in PCNA-positive newly regenerative tubular epithelial cells in early recovery stages after ATN. However, CD44CPT was only localized on the lateral-basal PM. The immunoelectron-microscopic results showed that CD44-OX49 localization was changed from the apical to lateral to basal surface membrane in renal tubular epithelial cells during the recovery process after ATN, finally disappearing from basal PM when normal polarized epithelial cells formed. CONCLUSIONS: These results suggest that there were two types of CD44 including CD44 without a cytoplasmic tail localizing on the apical surface membrane related to newly regenerative epithelial cells, and CD44 with a cytoplasmic tail localizing on the lateral-basal PM related to establishment of tubular epithelial cell polarity after ATN in vivo.

Animals↗
PubMed2004

Expression of the Ellis-van Creveld (Evc) gene in the rat tibial growth plate.

Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplasia characterized by short limbs, postaxial polydactyly, natal teeth, and dysplastic nails. The Ellis-van Creveld (EVC) gene, which is mutated in patients with EvC syndrome, has been identified by positional cloning. However, the physiological roles of the EVC gene have not been elucidated. Histopathological analyses of EvC syndrome have shown disturbed chondrocytic phenotypes during cartilage development. We therefore postulated that the EVC gene is a critical factor for chondrocytes during endochondral ossification. The present study focuses on the relationship between the Evc gene and chondrocytes, and examines Evc gene expression in the rat tibial growth plate at the mRNA and protein levels. Evc mRNA in tibial epiphyseal cartilage was expressed at postnatal day (P) 1, P28, and P56 by RT-PCR. Immunohistochemical analyses localized the Evc protein mainly in prehypertrophic and hypertrophic chondrocytes of the epiphyseal growth plate in the tibia during the embryonic and postnatal periods. Evc mRNA was also detected in prehypertrophic and hypertrophic chondrocytes by in situ hybridization. These results indicate that the Evc gene functions mainly in the prehypertrophic and hypertrophic chondrocytes of the epiphyseal growth plate. The data presented here are important for future studies of the underlying mechanism of chondrodysplasia in EvC syndrome.

Animals↗
PubMed2004

Expression of tbx20 RNA during chick heart development.

The T-box gene family encodes a set of transcription factors that are involved in various developmental processes. We isolated tbx20 gene from chick embryos and examined in detail its expression patterns during heart development. In situ hybridization showed that tbx20 was expressed in the lateral plate mesoderm and subsequently in the primitive heart tube. At stages of looped heart, tbx20 was localized in the outflow tract (OT) and atrioventricular (AV) canal, in which valvuloseptal endocardial cushion develops. At later stages, although tbx20 was expressed predominantly in the nascent right ventricle, transcripts of tbx20 were down-regulated in the left ventricle. These results suggest that tbx20 may play important roles in a variety of developmental processes in cardiogenesis, such as chamber-specification and septation.

Animals↗