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Biomedical subjects

S Komiya

Publications and source records attributed to S Komiya.

At least 37 records · Page 2Linked to original sources

A solitary bone cyst in the spinous process of the cervical spine: a case report.

STUDY DESIGN: A case report. OBJECTIVES: To illustrate a rare case of histologically confirmed solitary bone cyst involving the spinous process of C7. SUMMARY OF BACKGROUND DATA: A solitary bone cyst involving the spine is very unusual. Although four cases of a solitary bone cyst in the spine have been reported in the literature, the current authors have been able to find only one case of solitary bone cyst in the spinous process. All four patients reported in the literature were over 30 years of age. The patient in the current case was a 13-year-old girl with no history of trauma. METHODS: Radiographs and a computed tomography scan of the cervical spine were performed before the operation, as was a histologic examination to make a diagnosis of the lesion. RESULTS: The intraoperative findings from examination of the stagnant fluid within the lesion and the histologic examination indicated the diagnosis of a solitary bone cyst. CONCLUSIONS: A solitary bone cyst in the spine is rare, especially in the young. An osteolytic lesion in the spinous process of the spine tends to be diagnosed as an osteoblastoma or as a giant cell tumor of the bone. A solitary bone cyst of the spine, although rare, must be considered as a differential diagnosis.

Adolescent↗

Increased concentrations of nitrate and nitrite in the cyst fluid suggesting increased nitric oxide synthesis in solitary bone cysts.

The etiology and treatment of a solitary bone cyst have remained undefined. Surgical treatments have not been encouraging, because a less invasive corticosteroid-injection treatment has afforded good results. However, there has been little scientific rationale supporting corticosteroid treatment. In recent reports, bone-resorbing factors, including matrix metalloproteinases, prostaglandins, interleukin-1, and oxygen free radicals, have been demonstrated in the cyst fluid. To better elucidate the pathophysiology of the solitary bone cyst, we examined the activities of nitric oxide and cytokines in the cyst fluid as well as in the cyst membrane. The levels of nitrate and nitrite were significantly higher in the cyst fluid than in serum. Immunostaining of cells in the stroma and lining cells of the cyst wall was strongly positive for inducible nitric synthase. The levels of interleukin-6 and interleukin-1beta in the cyst fluid were elevated, and cells in the cyst membrane were positive for tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. Cultured cells from the cyst membrane were induced in the production of nitrate and nitrite in response to cytokine treatment. These findings suggest that the solitary bone cyst was in a state favorable for the production of nitric oxide.

Adolescent↗

p21 and parathyroid hormone-related peptide in the growth plate.

It is essential for terminal chondrocytes to die before the conversion of calcified cartilage to bone. We have previously demonstrated that apoptosis occurred in the terminal hypertrophic chondrocyte of the growth plate. However, the essential mechanism by which the differentiation of chondrocytes is regulated has not yet been characterized. The purpose of this study was to investigate the mechanism for regulating chondrocyte differentiation. We focused on PTHrP and p21 which regulated the differentiation of chondrocytes and investigated how these factors interacted with each other in chondrocyte differentiation in the growth plate. PTHrP was strongly positive on immunostaining at the interface between the proliferating and the upper zone of the hypertrophic chondrocytes, whereas p21 was negative. On the other hand, p21 was positive in the lower zone of hypertrophic chondrocytes. Furthermore, PTHrP up-regulated the cell proliferation and down-regulated the expression of the p21 messengers in SW-1353 chondrosarcoma cells. These findings indicated that PTHrP might be a negative regulator for p21 in the differentiation of chondrocytes.

Animals↗

Development of a solitary bone cyst--a report of a case suggesting its pathogenesis.

The origin and natural course of solitary bone cysts (SBC) still remain controversial. Knowledge of the process of cyst formation and enlargement would be helpful for investigating its pathogenesis. Only two papers have described a radiodense nidus of the diaphysis as a precursor. Their cases were unique in that the initial lesions were in the diaphysis and that the cysts did not abut onto the epiphyseal line. This study reports a case in a patient with a tiny erosive lesion in the endosteal surface of the humeral metaphysis, which developed expansively into a typical large cyst over 6 years. Serial roentgenograms taken every year demonstrated the process of cyst enlargement. This is the first longitudinal study of a case with SBC documented from its onset.

Bone Cysts↗

Gender differences in body fat of low- and high-body-mass children: relationship with body mass index.

The primary objective of this study was to determine gender differences in total body fat mass (TBFM) and body fat distribution (subcutaneous fat mass, SFM; and internal fat mass, IFM) in a cross-sectional sample of 280 children. Measurements of the body composition of 141 boys and 139 girls, all apparently healthy and aged 3-6 years were made using bioelectrical impedance. Determinations of impedance were made using a four-terminal impedance analyzer (TP-95K; Toyo Physical, Fukuoka, Japan). Lean body mass (LBM) was calculated using a previously published equation [Goran MI, Kaskoun MC, Carpenter WH, Poehlman ET, Ravussin E, Fontvieikke A-M (1993) Estimating body composition of young children by using bioelectrical resistance. J Appl Physiol 75: 1776-1780]. SFM was calculated using a modification of the equation derived by Skerjl [Skerjl B, Brozek J, Hunt EE (1953) Subcutaneous fat and age changes in body build and body form in women. Am J Phys Anthrop 11: 577-580] and Davies [Davies PSW, Jones PRM, Norgan NG (1986) The distribution of subcutaneous and internal fat in man. Ann Hum Biol 13: 189-192]. The main modifications of the equation in the present study were the introduction of: (1) mean thickness of adipose tissue over body surface/2, and (2) skin mass. IFM was calculated as the difference between TBFM and SFM. The body mass index (BMI; kg/m2) was calculated from the formula: body mass/height2. For each gender, the subjects in the lowest and highest 25th percentiles were designated as "low body mass" and "high body mass", respectively. In the present study, no gender differences in absolute TBFM, SFM and IFM were observed in either of these groups. In contrast, gender differences in relative TBFM (%Fat) and SFM (SFM/mass) were evident in girls. However, the four subgroups were similar in terms of relative IFM (IFM/mass). The TBFM was independently related to SFM, IFM and %Fat in both genders after adjustment for BMI; however, there was no significant association of SFM with IFM after adjustment for BMI in any group. Even after adjustment for BMI, IFM was independently related to %Fat in both genders, although SFM was not independently related to %Fat in any group except low-body-mass boys. This study shows that relative TBFM and SFM are higher in high-body-mass groups and tend to be higher in girls than in boys, and that the higher %Fat in high-body-mass girls than in high-body-mass boys appears to be associated with internal adipose tissue deposits. External adipose tissue mass does not appear to be related to the higher %Fat levels in high-body-mass girls. In addition, subcutaneous fat mass appears to be higher in low-body-mass girls than in low-body-mass boys, although this observation needs confirmation using more valid measures of subcutaneous fat such as computerized tomography and magnetic resonance imaging.

Adipose Tissue↗

The turnover of body water as an indicator of health.

Water homeostasis is essential for healthy living. Body water turnover, meaning the replacement of body water that is lost in a given period of time, has been examined in a number of previous studies, and a review of their results has yielded the following findings. Children up to 15 years of age show higher body water turnover than adults, although it is not clear how the aging process influences body water. Among people of similar age, the rate of body water turnover seems to be higher in those who exercise than in those who are sedentary. Therefore we hypothesized that healthy individuals have a higher body water turnover than unhealthy individuals whose metabolic balance, as indicated by water turnover, has broken down, and that a prolonged condition of excessively slow body water turnover may be associated with a lower level of metabolism. If so, body water turnover can be an indicator of human health. However, there is a paucity of information regarding water turnover rates in individuals with various physical characteristics. This study indicates the need for further investigation of body water turnover levels associated with significant changes in physiological condition and metabolic state.

Adult↗

Expression of the SART1 tumor-rejection antigen in human osteosarcomas.

We recently reported a tumor-rejection antigen, SART1259, possessing tumor epitopes capable of inducing cytotoxic T lymphocytes (CTLs). This study investigated the expression of SART1259 antigen in osteosarcoma and other skeletal malignant tumors to explore for a potential molecule for use in specific immunotherapy. The SART1259 antigen was detected in the cytosol fraction of 13 of 21 (62%) osteosarcoma cell lines and 3 of 8 (38%) osteosarcoma tissues, and 3 of 10 (30%) malignant fibrous histiocytoma (MFH) tissues. The HLA-A24+ and SART1259+ osteosarcoma cells were recognized by the HLA-A24 restricted and SART1 specific CTLs. These results raise a possibility that the SART1259 would be an appropriate molecule for use in specific immunotherapy of approximately one-third of HLA-A24+ patients with osteosarcoma and MFH.

Antigens, Neoplasm↗

APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis.

Previously we cloned a novel adaptor protein, APS (adaptor molecules containing PH and SH2 domains) which was tyrosine phosphorylated in response to c-kit or B cell receptor stimulation. Here we report that APS was expressed in some human osteosarcoma cell lines, markedly so in SaOS-2 cells, and was tyrosine-phosphorylated in response to several growth factors, including platelet derived growth factor (PDGF), insulin-like growth factor (IGF), and granulocyte-macrophage colony stimulating factor (GM-CSF). Ectopic expression of the wild type APS, but not C-terminal truncated APS, in NIH3T3 fibroblasts suppressed PDGF-induced MAP kinase (Erk2) activation, c-fos and c-myc induction as well as cell proliferation. In vitro binding experiments suggest that APS bound to the beta type PDGF receptor, mainly via phosphotyrosine 1021 (pY1021). Indeed, tyrosine phosphorylation of PLC-gamma, which has been demonstrated to bind to pY1021, but not that of PI3 kinase and associated proteins, was reduced in APS transformants. PDGF induced phosphorylation of the tyrosine residue of APS close to the C-terminal end. In vitro and in vivo binding experiments indicate that the tyrosine phosphorylated C-terminal region of APS bound to c-Cbl, which has been shown to be a negative regulator of tyrosine kinases. Since coexpression of c-Cbl with wild type APS, but not C-terminal truncated APS, synergistically inhibited PDGF-induced c-fos promoter activation, c-Cbl could be a mechanism of inhibitory action of APS on PDGF receptor signaling.

Adaptor Proteins, Signal Transducing↗

Bone tumors in the pelvis presenting growth during pregnancy.

Among 56 cases of a giant cell tumor of bone (GCT) and 52 cases of chondrosarcoma (CSA) in our series, four patients were discovered to have a tumor in the pelvic bone that grew in size during pregnancy. These four rare cases are described here. They include three cases of a GCT in the sacrum and one case of a CSA in the innominate bone. The dextran-coated charcoal assay and immunohistochemical techniques demonstrated the independence of these tumors from hormonal regulation despite the growth stimulated during pregnancy. It was concluded that the delay in detection of these tumors in the pelvis was just related to the opportunity afforded for unexpected growth during pregnancy. Surgical management was difficult due to the delay in tumor detection. The initial complaints such as pain, discomfort, or numbness around the pelvis were misinterpreted as symptoms of pregnancy. It should be kept in mind that during pregnancy, any pain or numbness in the pelvic region could be the direct result of a tumor in the pelvic bone.

Adult↗

APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl.

We cloned a novel adaptor protein, APS (adaptor molecule containing Pleckstrin homology (PH) and Src Homology-2 (SH2) domains), which was tyrosine phosphorylated in response to c-kit or B cell receptor stimulation. Here, we report that APS was tyrosine phosphorylated by Janus kinase-2 (JAK2) at its C-terminal tyrosine residue and interacted with c-Cbl. Forced expression of APS in an erythropoietin (EPO)-dependent hematopoietic cell line resulted in reduced activation of STAT5 but not cell proliferation in response to EPO. APS bound to the phosphorylated tyrosine residue, Y343 of the erythropoietin receptor cytoplasmic domain. Co-expression of APS and c-Cbl, but not expression of either alone inhibited EPO-dependent STAT5 activation in 293 cells. This required the C-terminal phosphorylation site, as well as PH and SH2 domains of APS. Therefore, one of the major functions of APS is in recruitment of c-Cbl into the receptor/JAK complex, thereby inhibiting JAK signaling activity.

Adaptor Proteins, Signal Transducing↗

Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors by nested reverse transcription-polymerase chain reaction: application to archival paraffin-embedded tumor tissues.

Chromosomal translocations generating unique chimeric genes are highly characteristic of specific sarcomas, and their use as diagnostic markers has been suggested. From a diagnostic pathologic point of view, detection of such cytogenetic or molecular aberrations applicable to routinely processed archival tissue specimens is considered a powerful tool for tumor diagnosis. To assess the feasibility and reliability of the molecular detection of the transcript originating from the chimeric gene in paraffin-embedded tumor specimens, we performed a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the EWS-FLI1 chimeric message in a series of Ewing family tumors. Of 24 paraffin-embedded tumor specimens from 23 cases analyzed, the chimeric message was detectable in 20 (83%) specimens from 20 cases (87%) by this nested RT-PCR assay, whereas none of 7 small round cell tumors not from this family (3 alveolar rhabdomyosarcomas, 2 neuroblastomas, 2 malignant lymphomas) showed detectable chimeric messages. In the sequence analysis of the PCR products, the amplified chimeric messages contained the junctions between exon 7 of the EWS gene and any one of exons 5, 6 and 8 of the FLI1 gene. The detection process was usually completed within 3 days, except for the subseqent sequence analysis. Our results endorse the use of this molecular assay as an ancillary technique in the diagnosis of Ewing family tumors using paraffin-embedded material.

Adolescent↗

Age-related changes in body composition of 3- to 6-year-old Japanese children.

This study was undertaken to establish an approach for the investigation of age-related changes in indices of body composition during childhood in Japan. It provides current reference values for total body fat mass (TBFM) and lean body mass (LBM) as indices of body composition in an urban population of 3- to 6-year-old Japanese children. Moreover, we assessed the age-specific patterns of body fat distribution [subcutaneous fat mass (SFM) and internal fat mass (IFM)] during childhood. Measurements of body composition by bioelectrical impedance were made in 141 boys and 139 girls, all apparently healthy, aged 3-6 years. Determinations of impedance were made using a four-terminal impedance analyzer (TP-95K; Toyo Physical, Inc., Fukuoka, Japan). LBM was calculated using the equation of Kushner et al. (1992) and Goran et al. (1993). SFM was calculated using a modification of the equation derived by Skerjl et al. (1953). IFM was calculated as the difference between TBFM and SFM. From ages 3 through 6 years, the mean LBM increased with age in boys and girls, and showed significant age differences. Between the ages of 3 and 6, the average increment in LBM was 5.1 kg in boys and 4.4 kg in girls. On average, boys gained 0.5 kg of TBFM each year, whereas girls gained 0.4 kg of TBFM each year. Furthermore, both groups gained 0.3 kg of SFM each year. Percentage body fat decreased in both genders until approximately the age of 5, and increased again slightly at the age of 6. The age-specific pattern of fat accumulation during childhood was characterized by an almost linear increase in SFM in girls, but a transient decrease in IFM in boys. We conclude that further research is required, including longitudinal assessment of body composition variables, in order to unravel the dynamics of body composition change in Japanese children.

Adipose Tissue↗

Modulation of fas-mediated apoptosis in osteosarcoma cell lines.

Fas/APO-1 (or CD95) is a 45-kDa cell surface glycoprotein that transduces cellular death signals for apoptosis upon cross-linking with the Fas ligand, which is experimentally replaced by anti-Fas antibodies. We examined the Fas expression at the protein and mRNA levels, and susceptibility to anti-Fas-mediated apoptosis, in 14 osteosarcoma cell lines. Ten of 14 ostesarcoma cell lines constitutively expressed detectable levels of Fas on the cell surface with positive cell rates ranging from 10.2 to 72.4%. Four other cell lines expressed Fas almost exclusively in the cytoplasm. An antibody against Fas was able to induce Fas-mediated cell death only in two cell lines with high levels of surface Fas. In the presence of the protein synthesis inhibitor cyclohexamide, antibody to Fas led to an induction of apoptosis in ten of the osteosarcoma cell lines antibody-concentration dependently. These data suggest that Fas is a potential protein related to apoptosis in osteosarcomas when the sensitizing activity of cyclohexamide on anti-Fas-mediated cytotoxicity was exerted.

Antibodies, Monoclonal↗

CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells.

We have reported JAK-signaling modulators, CIS1 (cytokine-inducible SH2 protein-1), CIS3 and JAB (JAK2 binding protein), which are structurally related. In M1 myeloid leukemia cells, CIS3 was induced by neither interleukin 6 (IL6) nor interferon gamma (IFNgamma), while JAB was induced strongly by IFNgamma and slightly by IL6 and leukemia inhibitory factor (ILF). Forced expression of CIS3 and JAB in M1 cells prevented IL6- or LIF-induced growth arrest and differentiation, even when their expression levels were comparable to endogenous ones in several cell lines such as HEL, UT-7, IFNgamma-treated M1, and CTLL2 cells. Pretreatment of parental M1 cells with IFNgamma but not IFNbeta resulted in suppression of LIF-induced STAT3 activation and differentiation, further supporting that physiological level of JAB is sufficient to inhibit LIF-signaling. However, unlike JAB, CIS3 did not inhibit IFNgamma-induced growth arrest, suggesting a difference in cytokine specificity between CIS3 and JAB. CIS3 inhibited STAT3 activation with slower kinetics than JAB and allowed rapid c-fos induction and partial FcgammaRI expression in response to IL6. In 293 cells, CIS3 as well as JAB bound to JAK2 tyrosine kinase domain (JH1), and inhibited its kinase activity, however, the effect of CIS3 on tyrosine kinase activity was weaker than that of JAB, indicating that CIS3 possesses lower affinity to JAK kinases than JAB. These findings suggest that CIS3 is a weaker inhibitor than JAB against JAK signaling, and JAB and CIS3 possess different regulatory roles in cytokine signaling.

Carrier Proteins↗

Ti/Al multilayer zone plate and Bragg-Fresnel lens.

By using a helicon plasma sputtering technique, a one-dimensional Ti/Al multilayer zone plate with an outermost layer width of 76 nm has been successfully fabricated. A Bragg-Fresnel lens has been made by combining this zone plate with a Ge(422) crystal. Comparison of the Ti/Al multilayer zone plate with the Ag/Al zone plate is discussed in terms of focusing efficiency.

Journal Article↗

Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis.

OBJECTIVE: To examine the occurrence of apoptosis in human osteoarthritis (OA) cartilage, and to determine its relationship to cartilage degradation. METHODS: Knee cartilage was obtained from subjects at autopsy, from a tissue bank, and from OA patients undergoing total joint replacement surgery. Chondrocytes were isolated and the number of apoptotic cells was analyzed by flow cytometry. Apoptotic cells in cartilage sections were identified by the detection of DNA strand breaks. Electron microscopy was applied to demonstrate morphologic changes, and Safranin O staining was performed to analyze the relationship between apoptosis and proteoglycan depletion. RESULTS: Flow cytometry on cell suspensions prepared from collagenase digests of cartilage showed that approximately 22.3% of OA chondrocytes and 4.8% of normal chondrocytes were undergoing apoptosis. Staining of cartilage sections demonstrated the presence of apoptotic cells in the superficial and middle zones. Cartilage areas that contained apoptotic cells showed proteoglycan depletion, and the number of apoptotic cells was significantly correlated with the OA grade. CONCLUSION: These observations demonstrate increased chondrocyte apoptosis in OA cartilage. Chondrocyte apoptosis and proteoglycan depletion are anatomically linked and may be mechanistically related.

Adult↗

Role of glutathione in cisplatin resistance in osteosarcoma cell lines.

This study was designed to examine whether and how glutathione and catalase increase the resistance of osteosarcoma cells to the toxicity of cisplatin. Eight osteosarcoma cell lines were exposed to varying concentrations of cisplatin, and a [3H]thymidine incorporation study then estimated their drug sensitivity. Cells were pretreated with aminotriazole and buthionine sulfoximine to depress catalase and glutathione activities and then entered into the same protocol to assess their sensitivity to cisplatin. Intracytoplasmic levels of catalase and glutathione were measured before and after the treatments. Cisplatin-glutathione conjugates were created to examine how glutathione might depress the toxicity of cisplatin. Although the cell lines differed in the magnitude of their response to cisplatin, there was a statistical correlation between intrinsic glutathione content and cisplatin resistance. Pretreatment with aminotriazole reduced catalase activity by 84% but did not change the sensitivity to cisplatin. Depletion of glutathione activity by 70% increased the sensitivity of the cells to the cytotoxicity of cisplatin. In addition, cisplatin was detoxified following conjugation with glutathione. The increased sensitization to cisplatin toxicity caused by the depletion of glutathione and cisplatin detoxification after the in vitro reaction of glutathione to cisplatin indicated that the formation of the glutathione-cisplatin conjugate was an important mechanism in the cellular resistance to cisplatin. These data also demonstrated that catalase activity did not contribute to resistance to cisplatin and suggested that H2O2-induced oxidative stress did not significantly contribute to the cytotoxicity of cisplatin in osteosarcoma cells.

Adenosine Triphosphate↗