Biomedical subjects

H Moriya

Publications and source records attributed to H Moriya.

At least 55 records · Page 3Linked to original sources

PubMed2001

Spatial and temporal gene expression in chondrogenesis during fracture healing and the effects of basic fibroblast growth factor.

Chondrogenesis is an essential component of endochondral fracture healing, though the molecular and cellular events by which it is regulated have not been fully elucidated. In this study, we used a rat model of closed fracture healing to determine the spatial and temporal expression of genes for cartilage-specific collagens. Furthermore, to determine the effects of basic fibroblast growth factor (bFGF) on chondrogenesis in fracture healing, we injected 100 microg recombinant human bFGF into the fracture site immediately after fracture. In normal calluses, pro-alpha1(II) collagen mRNA (COL2A1) was detected in proliferative chondrocytes beginning on day 4 after the fracture, and pro-alpha1(X) collagen mRNA (COL10A1) in hypertrophic chondrocytes beginning on day 7. In FGF-injected calluses, the cartilage enlarged in size significantly. On day 14, both COL2A1- and COL10A1-expressing cells were more widely distributed, and the amounts of COL2A1 and COL10A1 mRNAs were both approximately 2-fold increased when compared with uninjected fractures. Temporal patterns of expression for these genes were, however, identical to those found in normal calluses. The number of proliferating cell nuclear antigen-positive cells was increased in the non-cartilaginous area in the bFGF-injected calluses by day 4. The present molecular analyses demonstrate that a single injection of bFGF enhances the proliferation of chondroprogenitor cells in fracture callus, and thus contributes to the formation of a larger cartilage. However, maturation of chondrocytes and replacement of the cartilage by osseous tissue are not enhanced by exogenous bFGF, and this results in the prolonged cartilaginous callus phase. We conclude that, in the healing of closed fractures of long bones, exogenous bFGF has a capacity to enlarge the cartilaginous calluses, but not to induce more rapid healing.

Animals↗

PubMed2001

Spatial and temporal gene expression for fibroblast growth factor type I receptor (FGFR1) during fracture healing in the rat.

Recent experiments have shown that exogenous basic fibroblast growth factor (bFGF) enlarges fracture callus and accelerates the healing of osteotomized long bones. The actions of bFGF are mediated by four different transmembrane receptors (FGFR1-4). Among them, FGFR1 has a high affinity for bFGF, and gain-of-function mutations of the FGFR1 gene cause craniosynostosis in humans. Gene expression for FGFR1 has been analyzed in embryogenesis; however, in skeletal repair, detailed expression of FGFR1 has not been fully established. In the present study, a rat model of closed femoral fracture healing was used to quantify mRNA encoding the FGFR1 and to characterize cells expressing FGFR1 by in situ hybridization. Gene expression for FGFR1 was rapidly upregulated after fracture; its mRNA level on day 1 was 3.4-fold higher than that of unfractured femora. At this stage, a moderate signal for FGFR1 was detected in periosteal osteoprogenitor cells, inflammatory cells near fracture sites, and cells among muscle layers. FGFR1 mRNA reached peak expression when callus remodeling actively progressed (6.8-fold on day 14), and remained elevated even in the later stages of healing (6.3-fold on day 28). During the intermediate stage of fracture healing, a strong signal for FGFR1 was diffusely distributed in mature osteoblasts in the hard callus, and mature osteoclasts also expressed a weak signal for FGFR1. These results suggest that FGF/FGFR1 signaling has multifunctional roles during fracture healing and may regulate both osteoblasts and osteoclasts, contributing to bone formation and callus remodeling.

Animals↗

PubMed2001

Production of monoclonal antibodies against mammalian Ring1B proteins.

The Polycomb group (PcG) genes play a role of transcriptional repressor for long-term maintenance of the Hox cluster gene expression. Recently two structurally similar gene products, Ring1A and Ring1B, were identified. Genetic evidence has indicated that Ring1A has Pc-G properties, however, Ring1B functions are still unknown. To gain functional insights for Ring1B, we raised the mouse monoclonal antibodies (MAbs) against murine Ring1B protein. Using these antibodies, we have detected specifically mouse, human and monkey Ring1B gene products from whole cell extracts in immunoblot and immunoprecipitation analyses. Immunofluorescent staining by the antibodies has shown that endogenous Ring1B proteins clearly co-localize with Ring1A at the pattern of diffuse nuclear speckles. Together with their sequence similarity, Ring1B also may function as a Pc-G protein. Finally, we have proposed that the anti-Ring1B would be useful for biochemical and cytological analyses of Ring1B and Pc-G complex.

Animals↗

PubMed2001

Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment.

OBJECTIVES: To investigate the actual time of onset of osteonecrosis (ON) after high dose corticosteroid treatment in systemic lupus erythematosus (SLE). METHODS: 72 patients with active SLE, who received high dose corticosteroid for the first time, for the development of ON at hips and knees were monitored by magnetic resonance imaging for at least 12 months. RESULTS: ON lesions were detected in 32/72 patients (44%) between one and five months (3.1 months on average) after starting high dose corticosteroid treatment. No osteonecrotic lesion was newly detected from the sixth month of treatment until the end of the follow up period. CONCLUSION: The findings suggested that the actual time of onset of ON in SLE is within the first month of high dose corticosteroid treatment.

Adolescent↗

PubMed2001

An unusual cause of sciatic pain.

We describe a 47-year-old woman with sciatic neuropathy caused by compression of the sacral plexus by posterior shift of the uterus.

Diagnosis, Differential↗

PubMed2001

Natural history of scoliosis in children with syringomyelia.

We performed a retrospective review of 27 scoliotic patients with syringomyelia using MRI. Their mean age at the first MRI examination was 10.9 years, and at the final review 15.8 years. The mean ratio of the diameter of the syrinx to the cord on the midsagittal MRI (S/C ratio) decreased from 0.49 to 0.24; 14 patients showed a decrease of 50% or more (reduction group). In this reduction group, the cerebellar tonsillar herniation decreased from a mean of 11.3 mm to 6.0 mm, and some improvement in dissociated sensory disturbance was seen in nine of 13 patients. The scoliosis improved by 5 degrees or more in six patients in the reduction group. Our results indicate that spontaneous shrinkage of syringomyelia in children is not unusual and is associated with improvement in the tonsillar herniation, the scoliosis and the neurological deficit.

Adolescent↗

PubMed2001

Differential effects of oxidised and non-oxidised polyethylene particles on human monocyte/macrophages in vitro.

Sterilisation by gamma irradiation in the presence of air causes free radicals generated in polyethylene (PE) to react with oxygen, which could lead to loss of physical properties and reduction in fatigue strength. Tissue retrieved from failed total hip replacements often has large quantities of particulate PE and most particles associated with peri-implant osteolysis are oxidised. Consequently, an understanding of the cellular responses of oxidised PE particles may lead to clarification of the pathogenesis of osteolysis and aseptic loosening. We have used the agarose system to demonstrate the differential effects of oxidised and non-oxidised PE particles on the release of proinflammatory products such as interleukin-1beta (IL-1beta), IL-6, and tumour necrosis factor-alpha (TNF-alpha) from monocytes/macrophages (M/M). Oxidised PE particles were shown to stimulate human M/M to phagocytose and to release cytokines. Oxidation may alter the surface chemistry of the particles and enhance the response to specific membrane receptors on macrophages, such as scavenger-type receptors.

Cells, Cultured↗

PubMed2001

Spatial and temporal collagen gene expression in lumbar intertransverse fusion in the rabbit.

We have examined the process of fusion of the intertransverse processes and bone graft in the rabbit by in situ hybridisation and evaluated the spatial and temporal expression of genes encoding pro-alpha1 (I) collagen (COL1A1), pro-alpha1 (II) collagen (COL2A1) and pro-alphal (X) collagen (COL10A1). Beginning at two weeks after operation, osteogenesis and chondrogenesis occurred around the transverse process and the grafted bone at the central portion of the area of the fusion mass. Osteoblasts and osteocytes at the newly-formed woven bone expressed COL1A1. At the cartilage, most chondrocytes expressed COL2A1 and some hypertrophic chondrocytes COL10A1. In some regions, co-expression of COL1A1 and COL2A1 was observed. At four weeks, such expressions for COLlA1, COL2A1 and COL10A1 became prominent at the area of the fusion mass. From four to six weeks, bone remodelling progressed from the area of the transverse processes towards the central zone. Osteoblasts lining the trabeculae expressed a strong signal for COL1A1. At the central portion of the area of the fusion mass, endochondral ossification progressed and chondrocytes expressed COL2A1 and COL10A1. Our findings show that the fusion process begins with the synthesis of collagens around the transverse processes and around the grafted bone independently. Various spatial and temporal osteogenic and chondrogenic responses, including intramembranous, endochondral and transchondroid bone formation, progress after bone grafting at the intertransverse processes. Bone formation through cartilage may play an important role in posterolateral spinal fusion.

Animals↗

PubMed2001

MRI study of talonavicular alignment in club foot.

We studied in vivo the talonavicular alignment of club foot in infants using MRI. We examined 26 patients (36 feet) with congenital club foot. The mean age at examination was 9.0 months (4 to 12). All analyses used MRI of the earliest cartilaginous development of the tarsal bones in the transverse plane, rather than the ossific nucleus. The difference in the mean talar neck angle (44.0 +/- 8.1 degrees) in club foot was statistically significant (p < 0.001) when compared with that of the normal foot (30.8 +/- 5.5 degrees). The difference between the mean angles in the group treated by operation (47.9 +/- 6.7 degrees) and those treated conservatively (40.1 +/- 7.5 degrees) was also statistically significant. The anatomical relationship between the head of the talus and the navicular was divided into two patterns, based on the position of the mid-point of the navicular related to the long axis of the head. In the operative group, 18 feet were classified as having a medial shift of the navicular and none had a lateral shift. In the conservative group, 12 showed a medial shift of the navicular and six a lateral shift. All nine unaffected normal feet in which satisfactory MRI measurements were made showed a lateral shift of the navicular. Club feet had a larger talar neck angle and a more medially deviated navicular when compared with normal feet. This was more marked in the surgical group than in the conservative group.

Bone Malalignment↗

PubMed2001

Neurones in the dorsal root ganglia of T13, L1 and L2 innervate the dorsal portion of lower lumbar discs in rats. A study using diI, an anterograde neurotracer.

Based on a study using a retrograde neurotracer, we have previously found that the dorsal portion of the L5/6 disc in the rat is multisegmentally innervated by dorsal root ganglia (DRG) from the level of T13 to L6, and that sensory nerve fibres from DRG of T13, L1 and L2 pass through the paravertebral sympathetic trunks. In this study in newborn rats, we injected crystals of 1,1'-dioctadecyl-3,3,3',3'-tetramethylinedocarbocyanine perchlorate (DiI) into the DRG of T13, L1 and L2 and showed DiI-labelled sensory nerve fibres in the dorsal portion of the discs from the level of T13/L1 to L5/6. Our results show that the dorsal portion of the lumbar discs is innervated by the DRG from levels T13 to L2.

Animals↗

PubMed2001

Results of degenerative spondylolisthesis treated with posterior decompression alone via a new surgical approach.

OBJECT: The purpose of this study was to assess radiologically demonstrated results and clinical outcomes in patients with degenerative spondylolisthesis who underwent posterior decompressive surgery via a new (unilateral) approach. This approach allows surgeons to perform central and bilateral decompression while only stripping the muscles unilaterally, thus preserving the posterior osteoligamentous complexes. METHODS: The authors evaluated 51 consecutive patients in whom surgery was performed between 1987 and 1996. The mean follow-up period was 4.7 years. There was no statistically significant difference between the pre- and postoperative measurements in percentage of vertebral slippage. Postoperative dynamic angulation statistically decreased compared with its preoperative value (p < 0.05). Improvement of an average of 67% was shown on the Japanese Orthopaedic Association scale, and in 78% of these patients, good to excellent results were demonstrated. Secondary fusion was required in only three patients (5.9%). CONCLUSIONS: This new surgical technique offers a potential alternative for the treatment of degenerative spondylolisthesis in a minimally invasive manner, avoiding the risk of causing or aggravating postoperative spinal instability.

Adult↗

PubMed2001

Sensory disturbance of the thigh after renal transplantation.

PURPOSE: Although sensory disturbance of the anterior and/or lateral thigh often develops after renal transplantation, this complication is overlooked because of the minor degree of disability. We evaluated the rate of sensory disturbance of the thigh after renal transplantation. MATERIALS AND METHODS: We examined neurological deficits of the thigh on the operated side in 61 patients who underwent renal transplantation, including 48 using the internal and 13 using the external iliac artery. RESULTS: We noted sensory disturbance in 23 of the 61 cases, including 20 of the 48 in which the internal iliac artery was used. One patient had complete femoral nerve palsy involving motor weakness. Sensory disturbance was in the anterior thigh in 15 patients, in the lateral thigh in 3, and on the anterior and lateral thigh in 2. Postoperatively there was sensory disturbance of the thigh in 3 of the 13 patients in whom the external iliac artery was used. Sensory disturbance persists in all 3 cases at the time of this report, including in the anterior thigh in 1, and in the anterior and lateral thigh in 2. CONCLUSIONS: The rate of sensory disturbance of the thigh after renal transplantation is high. Therefore, we should inform patients of the possibility of sensory disturbance before renal transplantation surgery is performed.

Femoral Nerve↗

PubMed2001

[A case of retroperitoneal malignant fibrous histiocytoma with marked response to cisplatin, ifosfamide and doxorubicin].

A 61-year-old man was admitted to our hospital in December 1994 for a suspected retroperitoneal tumor. Systemic imaging investigations demonstrated retroperitoneal solid tumor, which was diagnosed as malignant fibrous histiocytoma (MFH) by immunohistochemistry for alpha 1-antitrypsin. In March 1995, he was treated with 3 courses of systemic chemotherapy with cisplatin, ifosfamide and doxorubicin followed by the same therapy in March 1996, without serious side effects. MFH is known to be resistant to ordinary chemotherapy. However, the CT showed a marked decrease in the size of the tumor, and the tumor disappeared within 2 months after the first treatment. The patient also recovered rapidly from abdominal pain, for which complete remission has been achieved for more than 5 years. The present chemotherapy may be an effective treatment for retroperitoneal MFH.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

[A novel neurotransmitter, DAN, mediates pain sensation in the spinal dorsal horn].

Differential screening-selected gene aberrative in neuroblastoma(DAN) belongs to a novel gene family(DAN family) that includes the head-inducing factor, Cerberus, and dorsaling factor, Gremlin. It has been suggested that DAN family members control diverse processes in growth, development and the cell cycle. Here, we demonstrate that DAN is produced in the small neurons of the dorsal root ganglion(DRG) and transported to the nerve terminals in the spinal dorsal horn in adult rats. Furthermore, intrathecal injection of an antibody to DAN suppressed pain sensations induced by the application of complete Freund's adjuvant and carageenan into the rat hindpaw, and the amount of DAN mRNA in the DRG neurons and of DAN in the spinal dorsal horn were increased in the inflammatory models. These data suggest that DAN in a novel neurotransmitter and/or modulator in the primary sensory nerve fibers for pain sensation.

Animals↗

PubMed2000

Substance P and calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the lumbar facet joints in rats.

The rat L5/6 facet joint is innervated from L1 to L5 dorsal root ganglions (DRGs) multisegmentally. Sensory fibers from L1 and L2 DRGs were reported to innervate nonsegmentally through the paravertebral sympathetic trunks, while those from L3 to L5 DRGs segmentally innervate the L5/6 facet joint. The presence of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive (ir) nerve fibers has been demonstrated in the lumber facet joints, but their ratios have not been determined. Fluoro-gold (F-G) labeled neurons innervating the L5/6 facet joint were distributed throughout the DRGs for levels L1 to L5. Of the F-G labeled neurons, the ratios of SP-ir L1, L2, L3, L4 and L5 DRG neurons were 13, 15, 29, 31 and 30%, respectively, and those of CGRP-ir neurons were 17, 24, 44, 56 and 50%, respectively. The ratios of SP and CGRP-ir neurons in L1 and L2 DRGs were significantly less than those in L3, L4 or L5 DRGs. In conclusion, the neurons of L3, L4 and L5 DRGs may have a more significant role in pain sensation of the facets than L1 and L2 DRG neurons.

Animals↗

PubMed2000

Overexpression of DAN causes a growth suppression in p53-deficient SAOS-2 cells.

It has been shown that the expression of DAN as well as Drm/Gremlin, a member of DAN/Cerberus family, is significantly down-regulated in rodent fibroblasts transformed with various oncogenes and overexpression of DAN results in the phenotypic reversion of the transformed phenotypes. In the present study, we examined the expression levels of DAN, BMP-2, BMP-4, and BMPRs (BMP receptors) in five human cell lines derived from bone and soft tissue tumors. Northern blot analysis revealed that DAN mRNA was detected in OS-KH and RMS-NK cells, but was not detectable in SAOS-2, NOS-1, and ASPS-KY cells. Transient overexpression of DAN in SAOS-2 cells, which lack functional p53 and pRB, resulted in a remarkable growth suppression without the induction of p21(Waf1). Interestingly, overexpression of DAN was associated with a reduction of alkaline phosphatase activity in SAOS-2 cells. Stable transfection of DAN in SAOS-2 cells caused a significant reduction of numbers of drug-resistant colonies, whereas the truncated form of DAN which lacked a possible signal peptide, completely lost this capability. Our results suggest that the secreted form of DAN exerts its growth-suppressive function in SAOS-2 cells in a p53-independent manner.

Alkaline Phosphatase↗

PubMed2000

CYP3A is responsible for N-dealkylation of haloperidol and bromperidol and oxidation of their reduced forms by human liver microsomes.

We studied the biotransformation of haloperidol, bromperidol and their reduced forms by human liver microsomes. Nifedipine oxidation (CYP3A) activity correlated significantly with N-dealkylation rates of haloperidol and bromperidol and oxidation rates of their reduced forms, while neither ethoxyresorufin O-deethylation (CYP1A2) activity nor dextromethorphan O-deethylation (CYP2D6) activity did. In chemical and immunoinhibition studies, only troleandomycin and anti-CYP3A4 serum inhibited both formation rates of 4-fluorobenzoylpropionic acid, a metabolite of haloperidol and bromperidol, and back oxidation rates. Among 10 recombinant isoforms examined, only CYP3A4 showed catalytic activity. The Vmax and Km values of N-dealkylation of bromperidol and reoxidation of reduced bromperidol were similar to those of haloperidol and reduced haloperidol, respectively. The present study indicates that CYP3A plays a major role in N-dealkylation of and oxidation back to bromperidol as well as haloperidol and suggests that modification of in vivo CYP3A activity by inhibition or induction may affect the pharmacokinetics and therapeutic effects of haloperidol and bromperidol.

Aryl Hydrocarbon Hydroxylases↗

PubMed2000

Fos expression in the rat brain and spinal cord evoked by noxious stimulation to low back muscle and skin.

STUDY DESIGN: Acute noxious stimulation delivered to lumbar muscles and skin of rats was used to study Fos expression patterns in the brain and spinal cord. OBJECTIVES: The present study was conducted to determine the differences in Fos expression in the brain and spinal cord as evoked by stimuli delivered to lumbar muscles and skin in rats. SUMMARY OF BACKGROUND DATA: Patients with low back pain sometimes show psychological symptoms, such as quiescence, loss of interest, decreased activities, appetite loss, and restlessness. The pathway of deep somatic pain to the brain has been reported to be different from that of cutaneous pain. However, Fos expression has not been studied in the central nervous systems after stimulation of low back muscles. METHODS: Rats were injected with 100 L of 5% formalin into the multifidus muscle (deep pain group; n = 10) and into the back skin of the L5 dermatome (cutaneous pain group; n = 10). Two hours after injection, the distribution of Fos-immunoreactive neurons was studied in the brain and spinal cord. RESULTS: Fos-immunoreactive neurons were observed in laminae I-V in the spinal cord in the cutaneous pain group, but they were not seen in lamina II in the deep pain group. In the brain, Fos-immunoreactive neurons were significantly more numerous in the deep pain group than in the cutaneous pain group in the piriform cortex, the accumbens nucleus core, the basolateral nucleus of amygdala, the paraventricular hypothalamic nucleus, the ventral tegmental area, and the ventrolateral periaqueductal gray. CONCLUSION: The finding that Fos-immunoreactive neurons were absent from lamina II of the spinal cord in the deep pain group is similar to that of the projection pattern of the visceral pain pathway. Fos expression in the ventrolateral periaqueductal gray in the deep pain group may represent a reaction of quiescence and a loss of interest, activities, or appetite. Furthermore, the detection of large numbers of Fos-immunoreactive neurons in the core of accumbens nucleus, basolateral nucleus of amygdala, paraventricular hypothalamic nucleus, and ventral tegmental area in the deep pain group may suggest a dominant reaction of dopaminergic neurons to stress, and a different information processing pathway than from that of cutaneous pain.

Animals↗