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Biomedical subjects

S Komiya

Publications and source records attributed to S Komiya.

At least 55 records · Page 3Linked to original sources
PubMed1998

Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.

The reciprocal translocation t(X;18)(p11;q11) is known to be highly characteristic of synovial sarcoma, and its consequence, an SYT-SSX fusion gene, is expected to be a diagnostic molecular marker. In this study, we conducted a reverse transcription-polymerase chain reaction-based assay to detect the SYT-SSX fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens from a series of 32 synovial sarcoma cases including 6 tumors found in unusual anatomical sites. The SYT-SSX fusion transcripts could be detected in 30 of 32 paraffin-embedded specimens (94%). A subsequent sequence analysis using the polymerase chain reaction products confirmed that the detected messages were derived from either the SYT-SSX1 (22 cases) or SYT-SSX2 (8 cases) fusion gene. Of 23 SYT-SSX-positive monophasic tumors, 16 tumors had an SYT-SSX1 fusion transcript. Fusion transcripts were detectable in all the 7 biphasic tumors analysed, one of which had an SYT-SSX2 fusion transcript. All of the six tumors at unusual locations (lung; 3, metastasis to the abdominal cavity from a tumor of retroperitoneal origin; 1, sacral region; 1, iliopsoas muscle; 1) contained detectable messages. Our results indicate that this molecular assay can be applied to archival formalin-fixed, paraffin-embedded tumor tissues as a feasible and reliable molecular technique for the diagnosis of synovial sarcoma.

Adolescent↗
PubMed1998

IL-6 in a pleomorphic type of malignant fibrous histiocytoma presenting high fever.

We describe a rare case of pleomorphic type of malignant fibrous histiocytoma (MFH) in the buttock that presented a systemic involvement. The case was of a 58-year-old woman presenting hepatic dysfunction and inflammatory reactions including fever, positive C-reactive protein (CRP), an elevated erythrocyte sedimentation rate, and high levels of platelets and ferritin. The fever of 3 months duration subsided on the first postoperative day. The MFH resection also brought rapid normalization in CRP, platelets, and leukocytes. The local and systemic productions of cytokines induced by this tumor were evaluated. In vivo and in vitro production of interleukin (IL)-6, IL-1beta, and tumor necrosis factor alpha by tumor cells were measured using enzyme-linked immunosorbent assay. Blood samples taken preoperatively, tumor tissues, and the primary culture medium showed extraordinarily high IL-6 levels. The plasma IL-6 level was normalized postoperatively. Immunohistochemistry showed the positivity of tumor cells for IL-6. The IL-6 produced by the tumor was concluded to have been responsible for the systemic illness.

Buttocks↗
PubMed1998

Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell liposarcomas by nested reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.

The reciprocal translocation t(12;16)(q13;p11) has been shown to be highly characteristic of myxoid and round cell subtypes of liposarcoma, and the TLS/FUS-CHOP fusion gene that resulted from the translocation is expected to be a diagnostic molecular marker of these sarcomas. In this study, we conducted a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the TLS/FUS-CHOP fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens. Of 18 paraffin-embedded specimens from 16 myxoid and round cell liposarcoma cases, the fusion transcripts could be identified in 16 (89%) specimens from 15 (94%) cases. A sequence analysis using the PCR products confirmed that the detected messages were derived from either type I or type II TLS/FUS-CHOP fusion gene, the latter of which was predominant (80%). The results were consistent in primary and recurrent lesions of the same patients and in paraffin-embedded and snap-frozen samples from the same tumors. In two negative specimens, transcripts of the beta-actin gene could not be detected by RT-PCR, and intact mRNA including the fusion messages might have been degraded. No fusion transcripts were detected in snap-frozen or paraffin-embedded material of other types of tumors with myxoid morphology (seven myxoid malignant fibrous histiocytomas and four lipomas with myxoid change). These results indicate that this molecular assay can be applied to formalin-fixed, paraffin-embedded tumor tissues as a diagnostic aid for these subtypes of liposarcoma.

Adolescent↗
PubMed1997

Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation.

Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation of a number of proteins, which leads to a cascade of biochemical changes that initiates B cell proliferation and differentiation or growth inhibition. A novel cDNA, designed APS, encoding an adaptor protein with a Pleckstrin homology (PH) domain, Src homology 2 (SH2) domain, and a tyrosine phosphorylation site was cloned from a B cell cDNA library using a yeast two hybrid system. APS is structurally similar to SH2-B, an SH2 protein that potentially binds to the immunoreceptor tyrosine-based activation motif (ITAM) as well as Lnk which is postulated to be a signal transducer that links T-cell receptor to phospholipase Cgamma, Grb2 and phosphatidylinositol 3-kinase. APS expressed only in human Burkitt's lymphoma cells among cell lines we examined and tyrosine phosphorylated in response to BCR stimulation. APS bound to Shc irrespective of stimulation and bound to Grb2 after stimulation, suggesting that it plays a role in linkage from BCR to Shc/Grb2 pathway. These results indicate that APS, SH2-B and Lnk form a new adaptor family that links immune receptors to signaling pathways involved in tyrosine-phosphorylation.

Adaptor Proteins, Signal Transducing↗
PubMed1997

A new protein containing an SH2 domain that inhibits JAK kinases.

The proliferation and differentiation of cells of many lineages are regulated by secreted proteins known as cytokines. Cytokines exert their biological effect through binding to cell-surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases. Cytokine-induced receptor dimerization leads to the activation of JAKs, rapid tyrosine-phosphorylation of the cytoplasmic domains, and subsequent recruitment of various signalling proteins, including members of the STAT family of transcription factors, to the receptor complex. Using the yeast two-hybrid system, we have now isolated a new SH2-domain-containing protein, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain. JAB is structurally related to CIS, a cytokine-inducible SH2 protein. Interaction of JAB with Jak1, Jak2 or Jak3 markedly reduces their tyrosine-kinase activity and suppresses the tyrosine-phosphorylation and activation of STATs. JAB and CIS appear to function as negative regulators in the JAK signalling pathway.

Amino Acid Sequence↗
PubMed1997

Expression of MAGE genes in osteosarcoma.

Expression of MAGE genes that encode tumor-rejection antigens recognized by cytotoxic T lymphocytes with major histocompatibility complex class-I antigens was investigated in human osteosarcomas (20 cell lines and eight fresh tumor tissues). MAGE-1, 2, 3, 4, and 6 genes were expressed at the mRNA level in 11 (52.4%), 10 (47.6%), 10 (47.6%) one (4.8%), and 10 (47.6%) of 21 tumor cell lines, respectively, and in five (62.5%), six (75%), five (62.5%), one (12.5%), and five (62.5%) of eight fresh tumor tissues as determined by the reverse transcription-polymerase chain reaction method. MAGE-1 or 4 protein was detected by immunoblot analysis in eight of 11 or one of one tumor cell lines, respectively, where it was expressed at the mRNA level. Major histocompatibility complex class-I antigens were expressed in 19 of 21 tumor cell lines. These results suggest that MAGE tumor-rejection antigens are expressed in substantial numbers of osteosarcomas in a major histocompatibility class-I-restricted manner.

Antigens, Neoplasm↗
PubMed1997

Correlation between vitamin D receptor genotypes and bone mineral density in Japanese patients with osteoporosis.

In order to better understand the pathogenesis of osteoporosis, we investigated the correlation between the vitamin D receptor (VDR) genotypes defined by BsmI restriction enzyme, as well as other related factors, and the bone mineral density (BMD) at the lumbar spine in 90 Japanese patients with osteoporosis. The same study was performed in 36 patients with osteoarthrosis of the hip joint and 92 healthy volunteers. The majority of the VDR genotypes were bb, and a few of the population showed either the BB or Bb genotype in all three groups. There was no statistical difference in the frequencies of these VDR genotypes in the three groups. The mean age-matched value of BMD (Z scores) at the lumbar spine in patients with osteoporosis was significantly lower than that in patients with osteoarthrosis or healthy volunteers. The mean Z scores of the healthy volunteers with bb genotype were significantly higher than those with BB genotype, whereas those of the osteoporosis patients with BB genotype were significantly higher than those with Bb genotype. There was no significant difference in the mean Z scores between bb and Bb genotypes in patients with osteoporosis and healthy volunteers. No significant difference was seen in the mean Z scores in patients with osteoarthrosis regardless of genotype. On the other hand, body weight significantly correlated with BMD in patients with osteoporosis by simple- and multiple-regression analysis. These results indicate that the BMD at the lumbar spine in Japanese patients with osteoporosis is affected by body weight, and might be affected partially by the VDR genotypes defined by BsmI.

Adult↗
PubMed1996

Morphological and biochemical evidence for apoptosis in the terminal hypertrophic chondrocytes of the growth plate.

The purpose of this study was to investigate the mechanism of cell death in chondrocytes of the growth plate. In the degenerative chondrocyte zone of the growth plate, apoptotic chondrocytes were defeated by the in situ nick end labelling method, by DNA analysis in agarose gel, and by electron microscopy. The results of the in situ nick end labelling method and the occurrence of a ladder pattern of DNA in agarose gel analysis indicated the activation of endogenous endonucleases, resulting in DNA fragmentation. Electron micrographs showed the early morphological changes associated with apoptosis. This report presents both morphological and biochemical evidence for apoptosis in the terminal hypertrophic chondrocytes of the growth plate. These data suggest that apoptosis of degenerative chondrocytes may play an important role in the control of normal and pathological endochondral ossification.

Animals↗
PubMed1996

P-glycoprotein is expressed in the mineralizing regions of the skeleton.

Using oligonucleotide primers specific for the human MDR 1 gene, we were able to identify a specific amplicon using RT-PCR from total bovine growth plate chondrocyte RNA. The identification of MDR mRNA in growth plate chondrocytes led us to examine the precise distribution of MDR P-glycoprotein in bone and cartilage. We applied two monoclonal antibodies (C219 and C494) to human fetal, neonatal, and childhood growth plates and bone. In growth plates, P-glycoprotein was detected at high levels in a perilacunar distribution in the calcifying zone and at lower levels in hypertrophic, but not proliferative or reserve zone, chondrocytes. P-glycoprotein was also observed in perichondrial chondrocytes, in perivascular chondrocytes and matrix in the fetal cartilage anlage, and in osteoblasts and the surface osteoid matrix of newly formed bone trabeculae in the primary spongiosa. The recently described chloride channel of P-glycoprotein suggests a potential role of P-glycoprotein in growth plate chondrocyte hypertrophy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Interleukin-4 stimulates rheumatoid synovial fibroblasts to express matrix metalloproteinase-1 (tissue collagenase) and histamine H1 receptor mRNA.

In the present study, we investigated the effect of interleukin-4 (IL-4) on metalloproteinase 1 (MMP-1/tissue collagenase) production in human rheumatoid synovial fibroblasts. Northern blot analysis revealed that addition of IL-4 with or without histamine stimulated the cells to increase the amount of proMMP-1 mRNA, and the IL-4 with histamine addition resulted in a 3.3-fold increase compared with histamine only. Furthermore, IL-4 itself stimulated the expression of histamine H1 receptor mRNA. These results suggest that IL-4 may play an important role in joint destruction in RA.

Arthritis, Rheumatoid↗
PubMed1996

Body size and composition in different somatotypes of Japanese college-aged women.

The purpose of this study was to determine differences in body size, composition and structure between three somatotypes of Japanese college-aged women. The study sample consisted of 30 sedentary female college students between 18 and 20 years of age. Ten subjects had an endomorphic ectomorph somatotype (mean weight 41.95 kg), 10 had an endomorph-ectomorph somatotype (mean weight 47.12 kg) and the remaining subjects had a mesomorphic endomorph somatotype (mean weight 55.37 kg). The mean heights for these groups did not differ significantly. The mesomorphic endomorph group had a higher gross weight and a higher percentage of all adipose variables than the other two groups, though these measurements were not significantly different between the endomorph-ectomorph and the endomorphic ectomorph groups. The mean lean body weight (LBW) for the mesomorphic endomorph group was significantly larger than that of the other two groups. The endomorph-ectomorph group had the next largest LBW, and the mean for the endomorphic ectomorph group was significantly smaller than that of the other two groups. Inversely, mean values of LBW/weight(WT), LBW/total adipose tissue weight (TATW) ratio and total body water/WT were significantly lower for the mesomorphic endomorph group than for the other two groups. Furthermore, the ratios of internal adipose tissue to weight (IATW)/WT and subcutaneous adipose tissue to IATW (SATW)/IATW did not differ significantly between groups. In conclusion, college-aged women of different somatotypes within the same age and height range varied in body composition. Consequently, the notion of a small frame is incorrect. An accurate assessment of the human body's composition may provide a valuable insight into the ideal weight for optimal physiologic function.

Adolescent↗
PubMed1995

Histamine-stimulated production of matrix metalloproteinase 1 by human rheumatoid synovial fibroblasts is mediated by histamine H1-receptors.

The purpose of this study was to investigate the role of histamine in human rheumatoid synovial fibroblasts in the production of factors responsible for tissue remodelling and cartilage breakdown in rheumatoid arthritis. We examined the effects of histamine of tritiated thymidine incorporation, production of matrix metalloproteinase-1 (MMP-1), histamine H1-receptor expression, phosphoinositide metabolism and intracellular calcium ion concentration ([Ca2+]i) in human rheumatoid synovial fibroblasts. Tritiated thymidine incorporation studies demonstrated that histamine markedly stimulated the proliferation of rheumatoid synovial fibroblasts. Immunofluorescence and Northern blot analyses revealed that proMMP-1 production was also stimulated by histamine. The levels of inositol phosphates and [Ca2+]i in the cells were elevated in response to histamine, indicating that the cells expressed histamine H1-receptors; and Northern blot analysis indicated that these H1-receptors were up-regulated by histamine. In in situ hybridization, large amounts of histamine H1-receptor mRNA were also detected in rheumatoid synovial tissue. These results suggest that the interaction between H1-receptor expression in rheumatoid synovial fibroblasts and histamine secretion by mast cells and macrophages in the affected sites is an important event responsible for tissue remodelling and joint destruction in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1995

p53 overexpression in Ewing's sarcoma/primitive neuroectodermal tumour is an uncommon event.

Aim-To determine the presence of p53 overexpression in Ewing's sarcoma/primitive neuroectodermal tumours (ETs) and to assess whether p53 accumulation has any prognostic value.Methods-From a prospectively compiled database of 76 patients with ETs, suitable tumour tissue was available for 38. The monoclonal antibody pAb1801 was used to detect p53 nuclear protein overexpression. Results-Nuclear staining was detected in the tumours of three (8%) of the 38 patients. Where tumours stained positively, over 10% of the tumour nuclei were postively stained. All three patients whose tumours overexpressed p53 died and in a relatively short time compared with the patients who did not overexpress p53 (mean 3.7 months compared with a mean of 38.7 months in the p53 negative group).Conclusion-Overexpression of p53 in ETs is an uncommon event. Overexpression of p53 has repeatedly been shown to correlate closely with p53 point missense mutations and therefore this oncogenic event appears not to be of primary pathogenic importance in ETs. There is a tentative indication that those uncommon ETs in which p53 overexpression can be detected may be-have more aggressively.

Journal Article↗
PubMed1994

Oxygen scavengers in simple bone cysts.

Simple bone cyst is a fluid-filled, cystic lesion that occurs in the metaphysis of the long bones of children and adolescents. The chemical characteristics of the cyst fluid of the simple bone cyst are similar to those of serum. The existence of the cyst fluid itself may be an obstacle to cyst healing, and, in part, this may be because the cyst fluid contains bone destructive factors. Oxygen-free radicals, which are cytotoxic and cause connective tissue damage, are known to be generated under ischemic conditions. Blockage to the drainage of interstitial fluid within the metaphysis has been suggested as the possible primary cause of simple bone cyst, thus causing an ischemic state in which free radicals are generated. The precise measurement of free radical levels is difficult to obtain because of their extremely short half-lives. High levels of oxygen-free radicals induce high levels of oxygen scavengers locally to protect cells from the harmful effects of the free radicals. Therefore, the activity of the oxygen scavengers, superoxide dismutase and catalase, was measured in the cyst fluid of 9 cases of simple bone cyst as an indicator of high oxygen-free radical content in the cyst. Serum from the patients with simple bone cyst and joint fluid from patients with osteoarthritis were used for comparison with the intracystic levels of oxygen scavengers. Superoxide dismutase activity was directly measured at room temperature using an electron spin resonance spin-trapping technique with 5,5'-dimethyl-1-pyrroline-N-oxide as a trapping agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of lipid peroxide on production of matrix metalloproteinase 1 (tissue collagenase) and 3 (stromelysin) and tissue inhibitor metalloproteinase 1 by human rheumatoid synovial fibroblasts.

The effects of linoleic acid hydroperoxide on the production of matrix metalloproteinases (MMPs) including MMP-1 (tissue collagenase), -2 ("type IV collagenase"), and -3 (stromelysin) and of tissue inhibitor of metalloproteinase 1 (TIMP-1), as well as DNA synthesis were investigated in rheumatoid synovial fibroblasts. Our results demonstrated that the levels of proMMP-1 and -3 and TIMP-1 were extremely elevated when 0.5-2.0 nmole/ml of linoleic acid hydroperoxide was added to cultures of rheumatoid synovial fibroblasts. DNA synthesis, however, was inhibited by linoleic acid hydroperoxide. These results indicate that lipid peroxide causes the disruption of extracellular matrix macromolecules and the inhibition of cell repair in synovial tissue. Therefore, they also suggest that an elevated level of oxygen free radical and/or lipid peroxides in synovial fluid may play an important role in the process of rheumatoid arthritis, resulting in the disruption of the joint.

Arthritis, Rheumatoid↗
PubMed1993

Cementation in the treatment of giant cell tumor of bone.

This study was designed to review the clinical experience of cementation in the treatment of giant cell tumor of bone and to clarify its biologic basis. Eleven patients treated by this technique had results rated excellent. No recurrences of the tumor were found. Serious complications, including infection, late fracture, or secondary osteoarthrosis, did not occur. The possibility of immediate fixation and stabilization of large defects is the most valuable point of this method. Local recurrence seems to be easily detectable by magnetic resonance imaging. A cell line of mononuclear cells from giant cell tumor of bone was examined for its response to hyperthermic exposure. Hyperthermic treatment was carried out at temperature of 60 degrees for 10 min and in other conditions. The numbers of cells surviving after heat treatment were counted, and flow cytometry was used to analyze the positive rate of surface antigens of the cells and the pattern of DNA distribution at the different temperatures. The heat treatment caused a fair number of the cells to fall into S-phase, and the tetraploid value was very low. The higher the temperature and the longer the time, the fewer cells survived and the less the expression of the monocytic phenotype. No cells survived after heating at 60 degrees for 10 min. Cementation seemed to have a hyperthermic effect to the cells of giant cell tumor of bone.

Adult↗