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Hirotaka Haro

Publications and source records attributed to Hirotaka Haro.

13 recordsLinked to original sources
PubMed2005

In vitro evaluation of low-intensity pulsed ultrasound in herniated disc resorption.

Herniated disc (HD) is often resolved spontaneously without surgical intervention. HD resorption (HDR) is associated with abundant vascularization and infiltration of macrophages (Mphi) into the intervertebral disc (ID), as well as with high levels of matrix metalloproteinases (MMPs). Low-intensity pulsed ultrasound (LIPUS) accelerates bone fracture healing in clinical studies, and angiogenic factors are involved in the mechanism of action. In the present study, we examined the effects of LIPUS on HDR in a rat in vitro HD model. HDR was enhanced by LIPUS as measured by the change in the wet weight of the cultured ID. The secretion of tumor necrosis factor-alpha (TNF-alpha) and macrophage chemoattractant protein-1 (MCP-1) from Mphi into the culture medium was stimulated by LIPUS. LIPUS also enhanced matrix metalloproteinase-3 (MMP-3) maturation. Moreover, many apoptotic cell death were observed in the HDR groups with LIPUS exposure. These results suggest that LIPUS enhanced the HDR via MMP-3 activation through TNF-alpha and MCP-1 pathways. Although animal studies and clinical trial are needed to understand the LIPUS effects on HDR, LIPUS treatment might be an effective treatment for accelerating HDR.

Animals↗
PubMed2005

Experimental studies on the effects of recombinant human matrix metalloproteinases on herniated disc tissues--how to facilitate the natural resorption process of herniated discs.

PURPOSE: Recently, MMP-7 and MMP-3 have been found to play a crucial role in the natural resorption process of herniated discs. We therefore examined the role of these recombinant human matrix metalloproteinases (rh MMPs) in the treatment of herniated discs. METHODS: (a) Surgical samples of herniated disc were cultured in the presence or absence of rh MMPs, and wet weight was measured 24h later. (b) The rh MMPs were administered into normal rabbit intervertebral discs, and after 1 week spine samples were stained with Safranin O. (c) The rh MMPs were administered into canine herniated discs in vivo. Myelography and MRI were performed prior to and 1 week after administration. Spine samples were examined histologically. Whole disc tissue was collected, total protein was extracted, and Western blot analysis was performed. RESULTS: (a) Proteoglycan degradation was found in MMP-7, MMP-3, and chymopapain-treated samples. MMP-7 and chymopapain-treated samples displayed a significant loss in wet weight (p<0.01). (b) Normal disc tissues after administration of rh MMP-7, MMP-3, and chymopapain showed an extensive loss of Safranin O staining. (c) The rh MMP-7-treated discs had a marked decrease in protruded herniation by MRI. Herniated discs after administration of MMP-7 and chymopapain showed a significant decrease in protruded mass 7 days after administration compared with saline-treated discs when evaluated by myelography (p<0.01). The rh MMP-7-treated discs displayed a clear loss of Safranin O staining in the nucleus pulposus. Proteoglycan expression was barely detectable in disc tissues after MMP-7 administration, whereas obvious expression was obtained in saline-treated or untreated disc tissues. CONCLUSIONS: Exposure to rh MMP-7 resulted in promising proteoglycan loss in human surgical samples, normal rabbit intervertebral discs, and natural canine herniated discs. Administration of rh MMP-7 may facilitate the resorption process of herniated discs.

Adult↗
PubMed2005

[The basic research of lumbar herniated disc].

Various genes are reported as one of a key gene for lumbar intervertebral disc degeneration. The cross-talk between inflammatory cells and disc cells results in generation of many inflammatory cytokines, growth factors, and proteinases. In near future, a new strategy for the treatment of disc degeneration and herniated disc should be developed based on current evidences.

Humans↗
PubMed2004

Sequential dynamics of inflammatory cytokine, angiogenesis inducing factor and matrix degrading enzymes during spontaneous resorption of the herniated disc.

Intervertebral disc herniation (HD) is one of the most common orthopaedic conditions. MRI analysis of HD has revealed a spontaneous resorption mechanism related with neo-vascularization. It appears that the interaction of activated macrophages with disc tissues leads to the generation of inflammatory cytokines. Moreover, inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) is required for the induction of angiogenesis inducing factors such as vascular endothelial growth factor (VEGF) or matrix degrading enzymes such as MMP-3, MMP-7 and plasmin. We hypothesized that these molecules play a crucial role during spontaneous HD resorption. In this study, we have examined the sequential expression of these molecules using a co-culture system which is composed of the interaction of activated macrophages and disc tissues as a model of the acute response of inflammation occurred in HD. We have also considered the mechanism of activating latent MMPs during HD resorption process. Current our results indicate that upregulation of both TNF-alpha mRNA and protein expressions occur first in the inflammation induced by HD. VEGF upregulation follows the increased level of TNF-alpha expression. Both plasmin and MMP-3 are upregulated at later time points. We also demonstrate that both TNF-alpha and VEGF induce upregulated expression of urokinase-type plasminogen activator (u-PA). Our previous work has demonstrated that TNF-alpha could upregulate the expression of VEGF, MMP-3 and MMP-7 in the co-culture system. It has been reported that plasmin could affect to activate latent MMPs. Based on these findings, we suggest that TNF-alpha acts as the initiator of inflammation following contact between macrophages and disc chondrocytes and that plasmin and u-PA play a crucial role in activation of MMPs. We propose a spontaneous HD resorption cascade. Further understanding of the resorption process may provide future novel therapies for HD.

Animals↗
PubMed2004

Long-term outcomes of surgical treatment for tethered cord syndrome.

SUMMARY: Surgical outcomes for tethered spinal cord syndrome (TCS) associated with low-lying conus medullaris were evaluated. We investigated the long-term results of untethering the spinal cord and dural plasty in surgical patients with a wide age range. Improvement of bladder dysfunction and suppression of leg deformity progression were noted in two pediatric patients. However, severe urinary dysfunction generally remained postoperatively. Adult patients commonly showed low back or leg pain as clinical manifestations. In seven adult patients, urinary dysfunction also improved. Neurologic findings and urinary deficits showed a favorable improvement mostly in adult TCS in comparison with natal or juvenile onset of TCS. A short duration from onset to surgery and cranial movement of the conus medullaris as assessed by postoperative magnetic resonance imaging were factors indicating a favorable prognosis.

Adolescent↗
PubMed2003

Changes in FGF-2 expression in the distal spinal cord stump after complete cord transection: a comparison between infant and adult rats.

STUDY DESIGN: Expression patterns of fibroblast growth factor-2 (FGF-2) in distal transected spinal cord in infant and adult rats were determined by reverse-transcription polymerase chain reaction (RT-PCR) and immunostaining. OBJECTIVE: To reveal the expression pattern of FGF-2 in distal transected cord of infant and adult rats. SUMMARY OF BACKGROUND DATA: Descending fibers in the spinal cord of infant and adult rats show different regenerative capacity. One explanation is that different levels of FGF-2, an important neurotrophic factor for promoting neurite outgrowth and repair, are expressed in the distal transected cords of the rats, providing different levels of support for severed axons. MATERIALS AND METHODS: Spinal cords of infant and adult rats were completely transected. At 12, 24, and 72 hours and at 1 week, segments of distal spinal cord tissues were removed and expression of FGF-2 mRNA was evaluated by RT-PCR. The distribution of FGF-2 and the phenotype of FGF-2-positive cells were determined by immunostaining. RESULTS: Expression of FGF-2 mRNA was shown to be up-regulated in the distal cord of infant rats but not adult rats. Immunohistochemical analysis showed that neurons in distal cord of infant rats were rich in FGF-2 immunoreactivity (IR), whereas in adult rat neurons FGF-2 IR was hardly observed at all, although a few FGF-2-positive astrocytes were observed in the white matter. CONCLUSION: After complete spinal cord transection, the expression of FGF-2 in the distal cord of infant rats was high compared with that of adults. This may provide neurotrophic support for axonal extension and functional recovery.

Age Factors↗
PubMed2003

Induction of apoptosis of articular chondrocytes and suppression of articular cartilage proteoglycan synthesis by heat shock.

We investigated cellular and matrix responses of articular cartilage to heat shock. Rat articular cartilage was pretreated at 37 degrees C for 24 h before being exposed to 48 degrees C for 10 min and subsequently incubated at 37 degrees C for 1, 2, 4, 7, 10, and 14 days. Following heat shock, a terminal deoxynucleotidyl transferase nick end labeling assay showed that articular chondrocyte apoptosis appeared at day 1, peaked at day 7, and declined by day 14. Analysis by transmission electron microscopy confirmed that the chondrocytes had characteristic morphological features of apoptosis; immunohistochemical staining revealed that caspase-3 activity in chondrocytes increased, 3-B-3-positive articular chondrocytes decreased in number, and the expression of 3-B-3 native epitope in articular chondrocytes was reduced. Safranin-O staining revealed that depletion of proteoglycans in the matrix was not found in any group. Morphological and biochemical evidence from this study suggested that heat shock at 48 degrees C induced articular chondrocyte apoptosis and suppressed proteoglycan synthesis of articular cartilage in vitro. This study thus provides evidence of the onset of osteoarthritis induced by heat shock and a basis for choosing a temperature at which malignant bone tumor cells can be killed with minimal damage to articular cartilage.

Animals↗
PubMed2002

Surgical treatment of cervical spondylotic myelopathy associated with athetoid cerebral palsy.

After a mean follow-up period of 7 years (range 4-17 years), we reviewed the cases of 14 patients who underwent surgical treatment for cervical spondylotic myelopathy associated with athetoid cerebral palsy. All of the patients who underwent anterior decompression and arthrodesis showed degeneration and increased range of motion of the adjacent disc despite halo-vest immobilization postoperatively. Laminoplasty is useful in cases in which physiological lordosis is present preoperatively, whereas a case with preoperative kyphotic deformity showed increased neurological symptoms and deterioration of activities of daily living postoperatively due to increased kyphotic deformity and canal stenosis. Anterior decompression and arthrodesis following posterior fusion with lateral mass plating and posterior wiring is a favorable option for patients with highly kyphotic deformity and canal stenosis, as it preserves neurological status and cervical alignment postoperatively.

Adolescent↗
PubMed2002

Factors predicting the prognosis of lumbar radiculopathy due to disc herniation.

This study was designed to determine the prognostic factors in unilateral lumbar radiculopathy due to herniated nucleus pulposus (HNP); this was done by prospectively investigating the clinical course of consecutive patients with HNP. The study population consisted of 131 patients who complained primarily of unilateral leg pain, and who were examined by magnetic resonance imaging (MRI) to establish a definite diagnosis. Patients with a questionable diagnosis were excluded. The initial assessment was done within the first 2 months of presentation, according to conventional surgical indications. Surgery was performed only in patients who gave their informed consent for the procedure. Questionnaires were sent to patients twice, in 1994 and 1996, to assess the clinical outcome in those patients who did not meet the surgical indications and in those who met the indications, but who refused surgery. Clinical outcomes were classified into three categories based on the patients' own assessment. Fifty patients met the surgical indication criteria, and 25 were actually operated on. Neither these patients' profiles nor their MRI findings correlated with the results of the initial assessment. Patient age was significantly correlated with outcome only at the time of the first follow-up. The type of HNP and the result of the initial assessment were correlated with outcome at the times of both follow-ups, but the significance of these correlations had decreased at the second follow-up. In conclusion, initial assessment and type of HNP on MRI are major prognostic factors. However, the conventional manner of treatment selection is inadequate for the appropriate management of lumbar disc herniation.

Adult↗
PubMed2002

Vascular endothelial growth factor (VEGF)-induced angiogenesis in herniated disc resorption.

Intervertebral disc herniation is a major cause of low back pain and sciatica. Spontaneous resorption of herniated disc (HD) is frrequently detected by magnetic resonance imaging (MRI). Marked infiltration by macrophages and neo-vascularization are observed upon histogical examination of HD. In addition, enhanced MRI studies suggest that HD resorption occurs more frequently in those completely exposed to the epidural space and that this correlates with their degree of vascularization. We have postulated that the angiogenic factor, vascular endothelial growth factor (VEGF), may be implicated in the neo-vascularization of HD tissues. Here we demonstrate that VEGF and its receptors VEGFR-1 and VEGFR-2 are expressed in human surgical samples of HD. Using a co-culture system comprised of murine peritoneal macrophages and intervertebral disc tissue as a model of the acute phase of HD developed previously, an increase in macrophage VEGF protein and mRNA expression was observed upon exposure to disc tissue. Tumor necrosis factor alpha (TNF-alpha) was required for this induction of VEGF. Use of a novel angiogenesis assay revealed that addition of the conditioned media from the co-culture system resulted in an increase of vascular tubule formation. This effect was strongly inhibited by anti-VEGF antibody, but augmented by recombinant VEGF. We conclude that VEGF induction, under the co-culture conditions tested can result in neo-vascularization of intervertebral disc tissue and may thus play a role in the resorption of HD.

Adult↗
PubMedDate not supplied

Evaluation of hyaluronic acid sheet for the prevention of postlaminectomy adhesions.

BACKGROUND CONTEXT: Various materials have been tested for their ability to maintain a barrier between muscles and epidural space in order to physically or chemically inhibit scar ingrowths. Hyaluronic acid (HA) solution and gel have been reported to be effective in preventing adhesions postlaminectomy; however, neither has been used clinically after spinal surgery. PURPOSE: To determine the efficacy of HA sheet for the prevention of postlaminectomy adhesions compared with that of HA gel or another sheet. STUDY DESIGN/SETTING: An animal model of lumbar laminectomy in rabbits was used to study postoperative scar tissue formation around the spinal cord. The histologic effects of HA sheet were compared with those of Gelfoam (GF) and further evaluated by an inflammation model using rhTNF-alpha. PATIENT SAMPLE: Rabbit. OUTCOME MEASURES: Histologic examination. METHODS: Five rabbits were killed at 2, 4, 8, and 24 weeks after laminectomy, respectively. Another 18 rabbits were examined in an environment of active inflammation experimentally induced by rhTNF-alpha to compare the effects of HA sheet with those of GF or HA gel. Histologic examination was performed to quantitatively assess invasive scar formation or inflammation postlaminectomy, and then, the histologic effects of HA sheet were compared with those of GF or HA gel. RESULTS: In the HA group, significantly, the area of subarachnoid space was larger, distance from the surface of dura to scar tissues was greater, the number of inflammatory cells in the scar tissues at the site of laminectomy was less, and enlargement of dura was suppressed. Using an inflammation model, we also demonstrated the efficacy of HA sheet treatment. CONCLUSIONS: In an experimental laminectomy model, HA sheet formed a solid interpositional membrane barrier and exhibited anti-inflammatory activity. Further investigations will be needed for HA sheet to be used clinically.

Animals↗
PubMedDate not supplied

New interdisciplinary approach for removing large clivus and upper cervical spine tumors.

We have developed a new interdisciplinary approach for removing large clivus and upper cervical spine tumors. This approach is a combination of the Le Fort I osteotomy, midfacial degloving, and median labiomandibular glossotomy. Our approach gives an excellent, wide surgical field from the nasopharynx, including the base of the skull, to the base of the tongue and permits sufficiently safe extirpation of clivus and upper cervical spine tumors that may not be removed by transoral or transcervical approaches. Our approach not only incorporates the merits of each approach but also creates a larger surgical field that may be modified or expanded to accommodate the removal of more bulky tumors in this region. This novel approach will facilitate more successful resection of tumors arising between the nasopharynx, including the skull base, and the retropharyngeal area.

Adult↗