Biomedical subjects

S Komiya

Publications and source records attributed to S Komiya.

At least 19 recordsLinked to original sources

PubMed2005

Delayed segmental motor paralysis following laminoplasty: two case reports.

STUDY DESIGN: Two patients who experienced the onset of segmental motor paralysis several years after laminoplasty are presented. OBJECTIVES: To discuss the mechanism of development of delayed segmental motor paralysis following laminoplasty. SETTING: A department of orthopaedic surgery in Japan. METHODS: One patient experienced motor weakness in his deltoid and biceps muscles on the left side 5 years after laminoplasty. The other patient noticed motor weakness in his deltoid and biceps on the right side 7 years after laminoplasty. CT myelography revealed posterior spur formation and hypertrophic facet joints on the hinged side at the C4-C5 level in both patients. RESULTS: Posterior foraminotomy was performed at the C4-C5 level on the hinged side in both patients. Postoperatively, motor weakness in the deltoid and biceps muscles was improved in both patients. CONCLUSIONS: Although spondylotic changes, including spur formation and disc herniation, have occasionally developed in operated segments after laminoplasty, few patients have required additional surgery for treatment of relapse of neurological deficits. It has been believed that spinal cord is rarely compressed by the spondylotic changes since it shifts posteriorly in the enlarged spinal canal. However, laminoplasty disturbs the facet joints since the medial portion of dorsal cortex and cancellous bone in facet joints is drilled out to make a trough. Facet joints disturbed in this fashion undergo degeneration over time after surgery. Nerve roots may occasionally be compressed by degenerated facet joints and spurs that have developed at the entrance of root canal, resulting in segmental motor paralysis several years after laminoplasty. Careful long-term observation is necessary after this procedure.

Aged↗

PubMed2005

An efficient construction of conditionally replicating adenoviruses that target tumor cells with multiple factors.

Despite the enormous potential of conditionally replicating adenoviruses (CRAs), the time-consuming and laborious methods required to construct CRAs have hampered both the development of CRAs that can specifically target tumors with multiple factors (m-CRA) and the efficient analysis of diverse candidate CRAs. Here, we present a novel method for efficiently constructing diverse m-CRAs. Elements involving viral replication, therapeutic genes, and adenoviral backbones were separately introduced into three plasmids of P1, P2, and P3, respectively, which comprised different antibiotic resistant genes, different ori, and a single loxP (H) sequence. Independently constructed plasmids were combined at 100% accuracy by transformation with originally prepared Cre and specific antibiotics in specific Escherichia coli; transfection of the resulting P1+2+3 plasmids into 293 cells efficiently generated m-CRAs. Moreover, the simultaneous generation of diverse m-CRAs was achieved at 100% accuracy by handling diverse types of P1+2 and P3. Alternatively, co-transfection of P1+3 and P2 plasmids into Cre-expressing 293 cells directly generated m-CRA with therapeutic genes. Thus, our three-plasmid system, which allows unrestricted construction and efficient fusion of individual elements, should expedite the process of generating, modifying, and testing diverse m-CRAs for the development of the ideal m-CRA for tumor therapy.

Adenoviridae↗

PubMed2004

Increased expression of humanin peptide in diffuse-type pigmented villonodular synovitis: implication of its mitochondrial abnormality.

OBJECTIVES: To define the pathogenesis of pigmented villonodular synovitis (PVNS), by searching for highly expressed genes in primary synovial cells from patients with PVNS. METHODS: A combination of subtraction cloning and Southern colony hybridisation was used to detect highly expressed genes in PVNS in comparison with rheumatoid synovial cells. Northern hybridisation was performed to confirm the differential expression of the humanin gene in PVNS. Expression of the humanin peptide was analysed by western blotting and immunohistochemistry. Electron microscopic immunohistochemistry was performed to investigate the distribution of this peptide within the cell. RESULTS: 68 highly expressed genes were identified in PVNS. Humanin genes were strongly expressed in diffuse-type PVNS, but were barely detected in nodular-type PVNS, rheumatoid arthritis, or osteoarthritis. Humanin peptide was identified in synovium from diffuse-type PVNS, and most of the positive cells were distributed in the deep layer of the synovial tissue. Double staining with anti-humanin and anti-heat shock protein 60 showed that humanin was expressed mainly in mitochondria. Electron microscopy disclosed immunolocalisation of this peptide, predominantly around dense iron deposits within the siderosome. CONCLUSIONS: Increased expression of the humanin peptide in mitochondria and siderosomes is characteristic of synovial cells from diffuse-type PVNS. Humanin is an anti-apoptotic peptide which is encoded in the mitochondrial genome. Present findings suggest that mitochondrial dysfunction may be the principal factor in pathogenesis of diffuse-type PVNS and that humanin peptide may play a part in the neoplastic process in this form of PVNS.

Arthritis, Rheumatoid↗

PubMed2004

Primary malignant peripheral nerve sheath tumor of the cauda equina in a child case report.

STUDY DESIGN: A case report of primary malignant peripheral nerve sheath tumor (MPNST) of the cauda equina in a child is presented, and the literature is reviewed. OBJECTIVE: To discuss the problems involved in the treatment of primary intradural MPNSTs. SETTING: A department of orthopaedic surgery in Japan. METHODS: A 4-year-old boy complained of low-back pain radiating to the left calf. MRI revealed an intradural tumor at L3-L5 level. Following laminectomy of L3, L4 and L5, the tumor was removed en bloc. Based on pathological and immunohistological findings, the tumor was diagnosed as an MPNST. RESULTS: Although adjuvant chemotherapy was administered local recurrence and cerebral and spinal metastases of the tumor were found 6 months after the operation. Following additional incomplete removal of the recurrent tumor, radiation therapy was administered. Although recurrent and metastatic tumors disappeared or diminished in size by radiation, tumors increased in size thereafter, despite additional adjuvant chemotherapy. At 21 months after the first operation, he died of pneumonia. CONCLUSIONS: Reported clinical outcomes for patients with primary intradural MPNST are very poor. Although no gold standard for the treatment of tumors has been established yet, surgical removal of tumors combined with postoperative high-dose radiation may be recommended.

Brain Neoplasms↗

PubMed2001

Traumatic injury-induced BMP7 expression in the adult rat spinal cord.

It has been reported that bone morphogenetic proteins (BMPs) are involved in the generation of the central nervous system during development. However, the roles of BMPs in mature spinal cord have not been clarified. We examined the expression of BMP7 mRNA before and after traumatic injury of the adult rat spinal cord. BMP7 mRNA was already detectable at a relatively low level in uninjured spinal cord, but was dramatically increased after injury. Semiquantitative RT-PCR study further confirmed upregulation of BMP7 mRNA in injured spinal cord. In situ hybridization indicated that expression of BMP7 mRNA was present only in glial cells in uninjured spinal cord. After injury, the number of BMP7-expressing glial cells was increased, BMP7 expression also became apparent in motor neurons. It has been suggested that BMPs promote survival of subventricular zone cells in adult rats. Thus, our results suggest that increase in the expression of BMP7 promotes survival of neurons and glial cells after acute traumatic injury. In contrast, there is increasing evidence that BMPs inhibit neurogenesis and alternatively promote gliogenesis of neural progenitors, which are also present in adult spinal cord, suggesting that injury-upregulated BMP7 may regulate differentiation of glial cells from neural progenitors and may induce gliosis after central nervous system injury.

Age Factors↗

PubMed2001

Spred is a Sprouty-related suppressor of Ras signalling.

Cellular proliferation, and differentiation of cells in response to extracellular signals, are controlled by the signal transduction pathway of Ras, Raf and MAP (mitogen-activated protein) kinase. The mechanisms that regulate this pathway are not well known. Here we describe two structurally similar tyrosine kinase substrates, Spred-1 and Spred-2. These two proteins contain a cysteine-rich domain related to Sprouty (the SPR domain) at the carboxy terminus. In Drosophila, Sprouty inhibits the signalling by receptors of fibroblast growth factor (FGF) and epidermal growth factor (EGF) by suppressing the MAP kinase pathway. Like Sprouty, Spred inhibited growth-factor-mediated activation of MAP kinase. The Ras-MAP kinase pathway is essential in the differentiation of neuronal cells and myocytes. Expression of a dominant negative form of Spred and Spred-antibody microinjection revealed that endogenous Spred regulates differentiation in these types of cells. Spred constitutively associated with Ras but did not prevent activation of Ras or membrane translocation of Raf. Instead, Spred inhibited the activation of MAP kinase by suppressing phosphorylation and activation of Raf. Spred may represent a class of proteins that modulate Ras-Raf interaction and MAP kinase signalling.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Src-catalyzed phosphorylation of c-Cbl leads to the interdependent ubiquitination of both proteins.

The protooncogene c-Cbl has recently emerged as an E3 ubiquitin ligase for activated receptor tyrosine kinases. We report here that c-Cbl also mediates the ubiquitination of another protooncogene, the non-receptor tyrosine kinase c-Src, as well as of itself. The c-Cbl-dependent ubiquitination of Src and c-Cbl requires c-Cbl's RING finger, Src kinase activity, and c-Cbl's tyrosine phosphorylation, probably on Tyr-371. In vitro, c-Cbl forms a stable complex with the ubiquitin-conjugating enzyme UbcH7, but active Src destabilizes this interaction. In contrast, Src inhibition stabilizes the c-Cbl. UbcH7.Src complex. Finally, c-Cbl reduces v-Src protein levels and suppresses v-Src-induced STAT3 activation. Thus, in addition to mediating the ubiquitination of activated receptor tyrosine kinases, c-Cbl also acts as a ubiquitin ligase for the non-receptor tyrosine kinase Src, thereby down-regulating Src.

Binding Sites↗

PubMed2001

Unusual magnetic susceptibility anisotropy in untwinned La2-xSr(x)CuO4 single crystals in the lightly doped region.

We present a study of the magnetic susceptibility chi in carefully detwinned La 2-xSr(x)CuO4 single crystals in the lightly doped region (x = 0-0.03), which demonstrates a remarkable in-plane anisotropy of the spin system. This anisotropy, chi(a)/chi(b), is found to persist after the long-range antiferromagnetic (AF) order is destroyed by hole doping, suggesting that doped holes break the AF order into domains in which the spin alignment is kept essentially intact. It turns out that the freezing of the spins taking place at low temperatures is also notably anisotropic, implying that the "spin-glass" feature is governed by the domain structure as well.

Journal Article↗

PubMed2001

Mobility of the doped holes and the antiferromagnetic correlations in underdoped high- Tc cuprates.

The emergence and the evolution of the metallic charge transport in the La2-xSrxCuO4 system from lightly to optimally doped samples (x = 0.01-0.17) are studied. We demonstrate that in high-quality single crystals the in-plane resistivity shows a metallic behavior for all values of x at moderate temperatures and that the hole mobility at 300 K changes only by a factor of 3 from x = 0.01 to 0.17, where its x dependence is found to be intriguingly similar to that of the inverse antiferromagnetic correlation length. We discuss an incoherent-metal picture and a charged-stripe scenario as candidates to account for these peculiar features.

Journal Article↗

PubMed2001

Quality of life in elderly patients with ossification of the posterior longitudinal ligament.

STUDY DESIGN: A longitudinal cohort study of 216 elderly patients with ossification of the posterior longitudinal ligament for an average of 13 years was performed. OBJECTIVE: To know the quality of life experienced by patients after treatment. SUMMARY OF BACKGROUND DATA: No report is available on the quality of life experienced by elderly patients with ossification of the posterior longitudinal ligament. Because the life prognosis of patients with this condition is relatively good, the quality of life experienced by elderly patients with this disease is an important subject. METHODS: The study participants were 216 elderly patients with ossification of the posterior longitudinal ligament. Conservative therapy was performed for 126 patients, and surgical therapy for 90 patients. Surgery was basically indicated for patients with myelopathy, who were classified using Nurick's grading system. The cumulative survival rate of these patients and their disabilities in daily living were reviewed. The occurrence of fracture resulting from osteoporosis was surveyed, and the relation of such fractures to bone mineral density was examined. RESULTS: The cumulative survival rate of 70-year-old patients exhibiting Nurick Grade 5 severe myelopathy before treatment was 20%, whereas that of patients without myelopathy or those with Grades 1, 2, 3, or 4 myelopathy before treatment was 80%. Patients who underwent surgical therapy for Grade 3 or 4 myelopathy were statistically more likely to be independent of assistance with activities of daily living than those with similar degrees of myelopathy who underwent conservative therapy. The final quality of life was poor for patients with Grade 5 myelopathy at the first examination, regardless of therapeutic method. The prevalence of complication by fracture in patients with ossification of the posterior longitudinal ligament was 1.4% for men and 8.6% for women. The bone mineral density in these patients without myelopathy was significantly higher than in healthy subjects of the same age. CONCLUSION: The study data suggest that surgical treatment should be chosen for patients exhibiting moderate myelopathy to obtain satisfactory quality of life for them over a long period.

Absorptiometry, Photon↗

PubMed2001

Intraneural monophasic synovial sarcoma: a case report.

STUDY DESIGN: A case report. OBJECTIVES: To illustrate a rare case of synovial sarcoma arising within a peripheral nerve. SUMMARY OF BACKGROUND DATA: A synovial sarcoma arising within a peripheral nerve is very unusual. Only five cases of primary synovial sarcoma within a peripheral nerve have been reported. This is the first case with involvement of the nerve root. The authors diagnosed the tumor arising within the S1 nerve root as synovial sarcoma using cytogenetic analysis that detected the chimeric SYT/SSX gene. METHODS: In addition to the immunohistochemical study, a reverse transcription-polymerase chain reaction (RT-PCR) assay was conducted for the SYT-SS10 fusion gene using archival formalin-fixed paraffin-embedded tumor specimens. RESULTS: Computed tomography scan, magnetic resonance imaging performed before surgery, and the intraoperative findings showed that the tumor was embedded within the S1 nerve root. Although the histologic findings were suggestive of a malignant peripheral nerve sheath tumor, the results of the cytologic study confirmed its diagnosis of synovial sarcoma. CONCLUSION: Primary intraneural synovial sarcoma, although rare, must be distinguished from malignant peripheral nerve sheath tumor. The molecular assay of the detection of the SYT/SSX fusion gene is useful to make a definite diagnosis of monophasic synovial sarcoma.

Female↗

PubMed2001

Gender-specific haplotype association of collagen alpha2 (XI) gene in ossification of the posterior longitudinal ligament of the spine.

Among Japanese, ossification of the posterior longitudinal ligament of the spine (OPLL) is a leading cause of myelopathy, showing ectopic bone formation in the paravertebral ligament. We have provided genetic evidence that the collagen alpha2 (XI) (COL11A2) locus of chromosome 6 constitutes susceptibility for OPLL. Five distinct single nucleotide polymorphisms (SNPs), identified in COL11A2, were combined to construct possible haplotypes by the use of a maximum likelihood program. Estimated haplotype frequency was compared in OPLL patients and non-OPLL controls. We report a gender-specific association of the COL11AA2 haplotvpe with OPLL. The frequency of the most commonly observed haplotype was significantly higher in male patients (P = 0.0003) compared with controls, but not in female patients (P = 0.21). OPLL is predominantly observed in males. with a prevalence ratio of 2:1, and our gender-specific associations indicate that genetic factors involving COL11A2 play a specific role in the etiology of OPLL exclusively in males.

Aged↗

PubMed2001

Osteosarcoma cell apoptosis induced by selenium.

An essential nutrient selenium has been reported to be a potential cancer preventive and inhibitory agent, although no exact mechanism has yet been proposed. Since little is known about the anti-proliferative effect of selenium on osteosarcoma, this issue was addressed in the present study in vitro using three osteosarcoma cell lines, and in vivo using an osteosarcoma transplantable to nude mice. Selenium inhibited the tumor growth in vitro and morphological changes indicative of apoptosis were demonstrated. Osteosarcomas in nude mice were inhibited in growth by selenium with no cytotoxic change in normal tissues. The findings suggested that selenium may offer a novel therapeutic modality for osteosarcoma.

Animals↗

PubMed2001

Expression of a newly defined tumor-rejection antigen SART3 in musculoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytes by SART3-derived peptides.

We recently reported that a SART3 tumor-rejection antigen possessing tumor epitopes is capable of inducing HLA class 1-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients. We studied the expression of the SART3 protein in musculoskeletal tumors to find a molecule for potential use in tumor-specific immunotherapy. The SART3 was detected at protein levels in 100% of the osteosarcoma cell lines (n = 20), in 50% of the musculoskeletal tumor tissue specimens (n = 32), and at notable levels in 67% of osteosarcoma tissues (n = 9) and malignant fibrous histiocytosis tissues (n = 9), respectively. SART3-derived peptides at positions 109-118 and 315-323 induced HLA-A24-restricted tumor-specific cytoxic T lymphocytes from peripheral blood mononuclear cells of patients with osteosarcoma or malignant fibrous histiocytosis. These peptide-induced cytotoxic T lymphocytes recognized HLA-A24+ SART3+ osteosarcoma cells but not HLA-A24 or SART3 cells. These results suggest that the SART3 protein and its derived peptides could be molecules appropriate for use in specific immunotherapies for approximately 60% of HLA-A24+ patients with osteosarcoma or malignant fibrous histiocytosis.

Antigens, Neoplasm↗

PubMed2001

Transcriptional activation of p21 by vitamin D(3) or vitamin K(2) leads to differentiation of p53-deficient MG-63 osteosarcoma cells.

p21 (WAF1/CIP1) is a downstream effector of p53 and mediates growth arrest by inhibiting the action of G(1) cyclin-dependent kinases. However, it has been reported that the p21 expression was triggered by multiple differentiation-inducing agents by a p53-independent pathway. These agents induced expression of p21 by binding to specific DNA elements and modulating transcriptional initiation. We demonstrated that the gene encoding p21 was not only a vitamin D(3) target gene but also a vitamin K(2) target gene in the cells and that their differentiation was well related to the transcriptional activation of the p21 gene. Transient overexpression of p21, using adenovirus-driven p21 expression plasmid, in MG-63 cells in the absence of vitamins D(3) and K(2) resulted in their differentiation. The transcriptional activation of p21 by vitamin D(3) or vitamin K(2) in p53-deficient osteosarcoma cells demonstrated the p53-independent role of p21 in human osseous differentiation. HUM PATHOL 32:410-416.

Bone Neoplasms↗

PubMed2001

Release property of progesterone from a mixed-base suppository consisting of Witepsol W35 and Witepsol E85.

The mechanism of drug release from progesterone suppositories that consist of two types of hard fat (Witepsol W35 and Witepsol E85) was investigated. The strength, the thermodynamic characteristics, the surface structures, the drug release property, methylene blue penetration into suppositories, and change of surface structure after the dissolution test were employed for detecting characteristics of progesterone suppositories. The formulation with a mixing ratio of Witepsol W35 and Witepsol E85 at a 1:1 ratio showed the maximum strength value. The peak temperature of the suppositories showed a tendency to increase with increases in the ratio of Witepsol E85. The maximum height of the profiles measured with laser microscopy, from 20.8 microm to 29.2 microm, reached a maximum after 3 h of the dissolution test. When the suppositories were immersed in pH 7.4 phosphate buffer containing 0.5% methylene blue at 37 degrees C, the penetrating area increased with time. The weight of the suppositories also increased with time. According to these findings, it was suggested that the release of drug from a mixed type of suppository containing progesterone was via the matrix and pores.

Adjuvants, Pharmaceutic↗

PubMed2001

Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis.

Immune and inflammatory systems are controlled by multiple cytokines, including ILs and INFs. These cytokines exert their biological functions through Janus tyrosine kinases and STAT transcription factors. One such cytokine, IL-6, has been proposed to contribute to the development of rheumatoid arthritis (RA). We found that STAT3 was strongly tyrosine phosphorylated in synovial tissue of RA patients, but not those with osteoarthritis. Blockade of the IL-6-gp130-JAK-STAT3-signaling pathway might therefore be beneficial in the treatment of RA. We show here that the mRNA for the endogenous cytokine signaling repressor CIS3/SOCS3 is abundantly expressed in RA patients. To determine whether CIS3 is effective in treating experimental arthritis, a recombinant adenovirus carrying the CIS3 cDNA was injected periarticularly into the ankle joints of mice with antigen-induced arthritis or collagen-induced arthritis (CIA). Periarticular injection of CIS3 adenovirus drastically reduced the severity of arthritis and joint swelling compared with control groups. CIS3 was more effective than a dominant-negative form of STAT3 in the CIA model. Thus, induction of CIS3 could represent a new approach for effective treatment of RA.

Animals↗

PubMed2001

Functional impact of human collagen alpha2(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is the leading cause of myelopathy in Japan. In earlier studies, we provided genetic linkage and allelic association evidence of distinct differences in the human collagen alpha2(XI) gene (COL11A2) that might constitute inherited predisposition to OPLL. In the present study, a strong allelic association with non-OPLL (p = 0.0003) was observed with an intron 6 polymorphism [intron 6 (-4A)], in which the intron 6 (-4A) allele is more frequently observed in non-OPLL subjects than in OPLL patients. In addition, a newly identified polymorphism in exon 6 [exon 6 (+28A)] was in linkage disequilibrium with the intron 6 (-4A). The functional impact of the polymorphisms was analyzed by comparing the differences in messenger RNA (mRNA) splicing by reverse-transcription polymerase chain reaction (RT-PCR) analysis in cultured cells from the interspinous ligament and an in vitro exon trapping study. The intron 6 (-4A) allele resulted in skipping exon 6 and retaining exon 7, while the exon 6 (+28A) allele was not associated with alteration in mRNA splicing. Similar mRNA species were observed in undifferentiated osteoblast (Ob) cells and in cells from posterior longitudinal ligament of non-OPLL subjects. The region containing exons 6-8 is an acidic subdomain presumably exposed to the surface that could interact with molecules of the extracellular matrix. Accordingly, retaining exon 7 together with removal of exon 6 observed in intron 6 (-4A) could play a protective role in the ectopic ossification process because the same pattern was observed in undifferentiated Ob cells and nonossified posterior longitudinal ligament cells.

Alternative Splicing↗