Biomedical subjects

K Yudoh

Publications and source records attributed to K Yudoh.

At least 37 records · Page 2Linked to original sources

PubMed1999

Biochemical effect of intra-articular injections of high molecular weight hyaluronate in rheumatoid arthritis patients.

OBJECTIVE: The purpose of this study was to analyze the biochemical characteristics of synovial fluids after treatment of patients with rheumatoid arthritis (RA) with intra-articularly injected hyaluronate (HA). TREATMENT: In a double-blind study, 13 patients received intra-articular injections of 1% HA in phosphate buffered saline (PBS) while 13 other patients were injected 0.01% HA in PBS, as the control group. Injections were administered once a week for five weeks. METHODS: Clinical efficacy and characteristics of synovial fluid were compared between groups. RESULTS: Significant clinical improvement was observed in the HA-treated group compared to the control group. The viscosity of retained synovial fluid increased. Stringing and HA concentration increased significantly whereas the concentrations of protein and chondroitin sulfate 4 and 6 decreased significantly. The HA molecular weight remained the same in both groups. CONCLUSION: Intra-articular HA injection altered the properties of synovial fluid and proved efficacious for patients with RA.

Arthritis, Rheumatoid↗

PubMed1999

1alpha,25-dihydroxyvitamin D3 inhibits in vitro invasiveness through the extracellular matrix and in vivo pulmonary metastasis of B16 mouse melanoma.

We investigated the role of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) in modulating tumor cell invasiveness through the extracellular matrix (ECM) and pulmonary metastasis in B16 mouse melanoma. The pretreatment of B16 cells for 48 hours with 1alpha,25(OH)2D3 significantly inhibited in vitro invasiveness through the ECM by a mechanism that is not directly correlated with the inhibition of cell proliferation. When cells were treated with 1alpha,25(OH)2D3 for only 8 hours during the assay, no inhibitory effect was observed, suggesting that pretreatment with the hormone for more than 8 hours is necessary to inhibit the invasive potential of B16 cells. The activity of B16 cells to adhere to reconstituted basement membrane (Matrigel) and type IV collagenolysis was inhibited by pretreatment of the cells with 1alpha,25(OH)2D3 for 48 hours. Cell motility was not influenced by the hormone. Mice were inoculated subcutaneously with 3 x 106 B16 cells and were given 1alpha,25(OH)2D3 (0.5 microg/kg) or vehicle daily for 28 days, beginning 1 day after tumor inoculation. In the 1alpha,25(OH)2D3-treated group, no significant inhibition in exponential tumor growth, body weight, and serum level of calcium was observed until the twenty-eighth day. The mean serum concentration of the hormone was about 50 ng/mL, and there were no significant changes in its concentration during the treatment period. In both spontaneous and experimental metastasis models of tumor-bearing mice, treatment with 1alpha,25(OH)2D3 inhibited pulmonary metastasis. These findings suggest that 1alpha,25(OH)2D3 acts on B16 cells, inhibiting invasiveness through the ECM that is caused by the inhibition of cell adhesion to the ECM and the degradation of the ECM by the cells. 1alpha,25(OH)2D3 may have the potential to inhibit metastasis by a mechanism that is not exclusively based on its anti-cell proliferative effect.

Animals↗

PubMed1998

Tirapazamine is metabolized to its DNA-damaging radical by intranuclear enzymes.

Tirapazamine (TPZ), a new anticancer drug that is currently in Phase II and III clinical trials, has a unique mechanism of action. Its cytotoxicity is selective for hypoxic cells in solid tumors and results from DNA damage produced by a free radical, which is generated by enzymatic reduction of the parent molecule. However, there is no agreement as to which enzyme(s) are involved. Here, we have measured both DNA damage and TPZ metabolism in A549 human lung cancer cells and in isolated nuclei derived from the cells. We show that, although the nuclei metabolize TPZ at a rate that is only 20% of that of whole cells, they have levels of DNA damage that are similar to those of the cells. We also show that TPZ radicals that are formed outside nuclei do not contribute to intranuclear DNA damage. Thus, essentially all of the DNA damage from TPZ results from radicals generated within the nucleus, and the 80% of the drug metabolism that occurs in the cytoplasm is probably irrelevant for the activity of this drug in killing hypoxic cells.

Antineoplastic Agents↗

PubMed1998

Familial predisposition for lumbar degenerative disc disease. A case-control study.

STUDY DESIGN: A case-control study using magnetic resonance imaging and plain radiography to evaluate whether a family history of lumbar disc herniation is a risk factor for disc degeneration. OBJECTIVES: To evaluate the significance of a family history of operated lumbar disc herniation in the development of lumbar disc degeneration and lumbar disc herniation. SUMMARY OF BACKGROUND DATA: There are only a few epidemiologic studies indicating that a family history of intervertebral disc herniation is a risk factor for juvenile disc herniation. Recently, similarities in degenerative findings of the lumbar spine between identical twins have been reported. METHODS: In the case group, 24 patients who were the immediate relatives of patients who had undergone surgery for disc herniation and who presented or had a history of low back pain and/or unilateral leg pain were included. Control individuals included 72 age- and gender-matched outpatients who reported low back pain and/or leg pain without a family history of operated disc herniation. The incidence, level, and topographic location of disc herniation/diffuse bulge; the incidence and grade of disc degeneration observed on magnetic resonance images; and degenerative changes suggesting disc degeneration observed on plain radiographs were compared between the relatives of patients with disc herniation (cases) and the controls. RESULTS: The incidence of disc degeneration at L4-L5 and L5-S1 in cases (L4-L5, 18/24; L5-S1, 18/24) and controls (L4-L5, 45/72; L5-S1, 43/72) was similarly high. However, the grade of disc degeneration according to magnetic resonance imaging signal intensity on the T2-weighted sagittal image using Schneiderman's four-grade classification was significantly more severe in cases (L4-L5: Grade 1, 6/24; Grade 2, 4/24; Grade 3, 13/ 24; Grade 4, 1/24; L5-S1: Grade 1, 6/24; Grade 2: 3/24, Grade 3: 12/24, Grade 4: 3/24) than in controls (L4-L5: Grade 1, 27/72; Grade 2, 24/72; Grade 3, 20/72; Grade 4, 1/72; P = 0.034; L5-S1: Grade 1, 29/72; Grade 2, 23/72; Grade 3, 13/72; Grade 4, 7/72; P = 0.023; Mann-Whitney U test). The incidence of disc herniation/diffuse bulge at L4-L5 (16/24) and L5-S1 (11/24) in cases was higher than that in controls (L4-L5, 33/72; P = 0.07; L5-S1, 17/ 72; P = 0.04; chi-square test). CONCLUSION: The current study provided evidence that a family history of operated lumbar disc herniation has a significant implication in lumbar degenerative disc disease. There may be a genetic factor in the development of lumbar disc herniation as an expression of disc degeneration.

Adolescent↗

PubMed1998

Cystic spinal cord tumors: magnetic resonance imaging correlated to histopathological findings.

We report the characteristics of magnetic resonance imaging (MRI) of cystic intradural extramedullary spinal cord tumors (cystic neurilemmoma, epidermoid cyst, and enterogenous cyst). T1-weighted MRI enhanced with gadolinium-DTPA clearly demonstrated the rim morphology of these tumors. The comparison between the rim enhancement pattern and histopathological findings offered possible qualitative diagnosis of these cystic spinal cord tumors by MRI.

Adult↗

PubMed1997

Stable translocations detected by fluorescence in situ hybridization: a rapid surrogate end point to evaluate the efficacy of a potentiator of tumor response to radiotherapy.

Testing potential modifiers of the response of tumors to radiation therapy requires large, expensive, and time-consuming clinical trials. It would, therefore, be of value to have a rapid surrogate end point of tumor response that could be used to evaluate such modifiers. We here propose that radiation-induced stable chromosome translocations measured by fluorescence in situ hybridization (FISH) could fulfill this purpose. The assay requires that the ratio of nonlethal stable translocations to lethal dicentric aberrations be unity and not change with radiation dose and that radiation-induced stable translocations remain in the tumor cell population essentially indefinitely after irradiation. We have tested these assumptions with four human tumor cell lines in vitro at doses of 1-5 Gy and found them to be valid. We also modified the response to fractionated irradiation of a human tumor xenograft in three different ways and quantitated the tumor response using clonogenic cell survival and using the FISH stable translocation assay. Both assays gave similar values for the extent of radiation modification. These data suggest that this assay could allow clinical evaluation of potential radiation sensitizers with fewer patients and in shorter times than is the case with conventional clinical trials.

Animals↗

PubMed1997

Nitric oxide induced by tumor cells activates tumor cell adhesion to endothelial cells and permeability of the endothelium in vitro.

Human fibrosarcoma HT1080 cell surface phenotype analysis revealed the expression of "cluster of differentiation 15" (CD15) antigen and to a lesser extent, of "very late antigen-4" (VLA-4). Expression of "endothelial-leukocyte adhesion molecule-1" (ELAM-1) was negligible on resting human umbilical vascular endothelial cells (HUVECs), but its expression could be induced by HT1080 conditioned medium. HT1080 cell adhesion to HUVECs was partially dependent on CD15/ELAM-1 adhesion molecules. HT1080 cell adhesion to HUVECs induced the enhancement of nitric oxide (NO) production from HUVECs. Exogenous NO and NO from HUVECs enhanced ELAM-1 expression on HUVECs, HT1080 cell adhesion to HUVECs, permeability of the HUVEC monolayer, and HT1080 cell invasion through the HUVEC monolayer. These enhancements were not induced by NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). These results suggest that NO expression induced by tumor cells via the CD15/ELAM-1 adhesion system may contribute to enhancement of tumor cell adhesion to endothelial cells and hyperpermeability of the endothelium, facilitating tumor cell invasion.

Capillary Permeability↗

PubMed1997

Evaluation of the prognosis of cancer patients with metastatic bone tumors based on serial bone scintigrams.

We counted the lesions at the time of detection of bone metastases and calculated the rate of increase in the number of bone metastases from changes in serial bone scintigrams, and investigated the usefulness of serial scintigrams as a prognostic indicator in patients with metastatic bone tumors. Subjects were 112 patients with bone metastases from four types of primary lesion: 21 with prostate cancer, 27 breast cancer, 39 lung cancer and 25 stomach cancer. Of these, 18 (prostate), 19 (breast), nine (lung) and eight (stomach) underwent serial bone scintigrams in which bone metastases were first detected and identified as progressing. The numbers of lesions at the time of detection of bone metastases for prostate and stomach cancers were significantly greater than those for lung cancer. The rate of increase in the number of bone metastases for stomach cancer was significantly higher than that for prostate or breast cancers. There was no correlation between the survival time after the detection of bone metastases and the number of lesions at the time of detection in the four types of cancer. However, in prostate cancer, a negative correlation existed between the survival time after the detection of bone metastases and the rate of increase in the number of bone metastases. Thus, in patients with bone metastases from prostate cancer, it appears that the rate of increase in the number of bone metastases, estimated from serial bone scintigrams, was indicative of prognosis.

Adult↗

PubMed1997

Effects of 1,25-dihydroxyvitamin D3 on tumor cell invasion to the extracellular matrix in human fibrosarcoma HT1080 cells and its correlation with laminin.

We investigated the role of the active form of vitamin D, 1,25-dihydroxyvitamin D3[1,25(OH)2D3], in promoting tumor cell invasiveness through the extracellular matrix, and showed that 1,25(OH)2D3-induced reduction of laminin production by the cells was correlated with the inhibitory effect of the hormone on tumor cell invasiveness. 1,25(OH)2D3 significantly inhibited invasiveness through the matrix, type IV collagenolytic and migratory activity, but not cell attachment to the matrix in human fibrosarcoma HT1080 cells. The 1,25(OH)2D3-induced inhibition showed the same dose dependency and magnitude for invasiveness as for the effects on type IV collagenolysis and cell migration. 1,25(OH)2D3 inhibited laminin production from the cells in a dose-dependent manner. The inhibitory effects of 1,25(OH)2D3 on the invasiveness, type IV collagenolysis and cell migration appeared to parallel the hormone-induced reduction of laminin production. Antilaminin monoclonal antibody, blocking the activity of laminin in the culture medium, inhibited HT1080 cell invasiveness. In the presence of exogenous laminin, 1,25(OH)2D3-induced inhibition of invasion was not observed. These findings suggest that 1,25(OH)2D3 acts on HT1080 cells, inhibiting the expression of laminin from the cells, and that the reduced laminin expression leads to the inhibition in the type IV collagenolytic and migratory activity of the cells, and consequently, to the inhibition of invasiveness through the extracellular matrix.

Calcitriol↗

PubMed1997

Regulation of gelatinase production and invasiveness by organ-specific fibroblasts in high- and low-metastatic clones from murine RCT sarcoma.

Regulation of gelatinase production, invasiveness and migration activity by organ-specific fibroblasts from embryo, subcutaneous and lung tissues of mice were investigated in high-metastatic RCT+ and low-metastatic RCT- clones established from a poorly differentiated murine sarcoma. In the conditioned media of RCT+ cells, mouse skin fibroblasts (MSF) obtained from the tissue of tumor origin (orthotopic) stimulated the production of the 105-kD gelatinase more than C3H/ 10T1/2 clone 8 (C3H/10 T1/2 CL8) or mouse lung fibroblasts (MLF). In the conditioned media of RCT- cells, however, cocultivation with fibroblasts showed only slight stimulatory effects on the production of the 105-kD gelatinase. In the invasion assay, using a reconstituted basement membrane (matrigel), RCT+ cells cocultivated with MSF showed significantly higher invasiveness than those cocultivated with C3H/10T1/2 CL8 or MLF. However, no significant differences were shown in the invasiveness of RCT- cells in cocultivation with three types of fibroblasts and in cultivation without fibroblasts. There was no significant difference in migration activity between RCT+ and RCT- cells cultivated alone. But in the cocultivation of both clones with MSF, the migration activity of RCT+ cells was significantly higher than that of RCT- cells. These findings suggest that MSF might delineate the difference in characteristics related to the metastatic potential of RCT+ and RCT- cells through regulation by organ-specific factors.

Animals↗

PubMed1997

Effects of ethane-1-hydroxy-1, 1 diphosphonate on Dunn osteosarcoma cells.

We investigated the effects of ethane-1-hydroxy-1, 1 diphosphonate (EHDP) on Dunn osteosarcoma cells in vivo and in vitro. In in vivo study, an increase of tumor volume was significantly suppressed in the EHDP administered groups compared with the control group. Histologically, Dunn osteosarcoma cells' viability was maintained after EHDP administration. However, fatty degeneration of tumor tissue was suspected in two of eight mice in the 5.0 mg/kg EHDP administered group. In vitro study, EHDP inhibited DNA synthesis and induced morphological changes, such as pycnotic cells. These findings show that the growth of Dunn osteosarcoma cells is inhibited by EHDP.

Alkaline Phosphatase↗

PubMed1997

Effects of dibutyryl cyclic adenosine monophosphate on nucleolar organizer regions and epidermal growth factor receptor of Dunn osteosarcoma cells.

We investigated the characteristics of nucleolar organizer regions (NORs) and epidermal growth factor receptor (EGFR) on differentiated Dunn osteosarcoma in response to dibutyryl cyclic adenosine 3',5'-monophosphate (Bt2cAMP). In the presence of 3 mM Bt2cAMP, the mean number of NORs was significantly decreased in 24 hrs and 48 hrs compared with the untreated group. Also, EGFR affinity was decreased and the EGFR number was increased in response to the cellular differentiation by Bt2cAMP. The decrease in EGFR affinity might be considered as an indicator of differentiation or the mature state of the cells. Thus, the present study provides a new clue to support differentiation of osteosarcoma cells from the viewpoint of NORs findings and EGFR analysis as a differentiation marker.

Animals↗

PubMed1996

Autocrine/paracrine mechanism of insulin-like growth factor-1 secretion, and the effect of insulin-like growth factor-1 on proteoglycan synthesis in bovine intervertebral discs.

The present study was undertaken to investigate the effect of insulin-like growth factor-1 on proteoglycan synthesis and the autocrine/paracrine mechanism involving insulin-like growth factor-1 in the bovine coccygeal intervertebral disc. Insulin-like growth factor-1 stimulated proteoglycan synthesis in cultured cells of the nucleus pulposus of bovine intervertebral discs in a dose-dependent manner, and the effect was inhibited by an anti-insulin-like growth factor-1 monoclonal antibody. In situ hybridization histochemistry revealed the expression of insulin-like growth factor-1 mRNA in the cultured cells, and its production in these cells was demonstrated by radioimmunoassay. Insulin-like growth factor-1 receptor in the cultured cells was also demonstrated immunohistochemically. Scatchard analysis using an [125I]insulin-like growth factor-1 binding assay showed that the cells cultured in monolayer had a single type of insulin-like growth factor-1 receptor, whose affinity and number were estimated to be 7.38 x 10(8)/M and 9.27 x 10(4)/cell, respectively. These results suggest that insulin-like growth factor-1 stimulates proteoglycan synthesis in cells of the nucleus pulposus and that these cells in culture have an insulin-like growth factor-1 autocrine/paracrine mechanism. The expressions of insulin-like growth factor-1 mRNA and insulin-like growth factor-1 receptor in disc tissue were greater in cells of the nucleus pulposus of fetal bovine intervertebral discs than in those of the adult discs. These findings suggest that the action of autocrine/paracrine insulin-like growth factor-1 is more active in cells of the young nucleus pulposus than in cells of mature subjects.

Age Factors↗

PubMed1996

Significance of serum levels of type I procollagen peptide and intact osteocalcin and bone mineral density in patients with ossification of the posterior longitudinal ligaments.

This study was performed to evaluate the correlation between serum biochemical marker levels of bone metabolism and bone mineral density (BMD) in patients with ossification of the posterior longitudinal ligaments (OPLL). In addition, the efficacy of these markers in the prediction of the progression of OPLL was also examined. In 40 patients with OPLL, and in age- and gender-matched controls (n = 36), the levels of C-terminal extension peptide of type I procollagen (PICP) and intact osteocalcin were quantitated by a sandwich enzyme-linked immunosorbent assay as serum markers of bone formation. BMD of the whole body was measured using dual-energy X-ray absorptiometry. Serum PICP and intact osteocalcin levels were significantly increased in patients with OPLL. There was a significant correlation between serum bone formation marker levels and BMD in both the OPLL and the control groups. Patients with radiological progression of OPLL showed a level higher than the mean + 2 SD of controls in PICP, intact osteocalcin, and BMD. In addition, the levels of serum PICP and intact osteocalcin increased in correspondence with the progression of OPLL without statistical significance. In patients without any growth of OPLL, however, all the parameters were below the mean + 2 SD of controls. Thus, aggravation of bone formation activity was suggested to be closely correlated with the development of OPLL. In addition, serial measurements of these parameters might be useful for estimating the progression of OPLL.

Adult↗

PubMed1996

Malignant fibrous histiocytoma secondary to fibrous dysplasia. A case report.

A man of 50 years of age had a malignant fibrous histiocytoma secondary to asymptomatic fibrous dysplasia of the proximal femur. Radiographs showed ill-defined osteolytic changes near to the fibrous lesion which had a ground glass appearance. The histology was of a malignant fibrous histiocytoma concomitant with fibrous dysplasia. An extensive resection of the tumour was carried out and chemotherapy given, but the patient died from a liver metastasis 9 months later. The possibility of malignancy should be considered if a patient with fibrous dysplasia has any progressive symptoms.

Cell Transformation, Neoplastic↗

PubMed1996

Prognostic value of the doubling time of serum C-reactive protein and alkaline phosphatase levels in primary bone and soft tissue tumors.

We investigated the clinical relevance of doubling time (DT) of serum laboratory data obtained in routine clinical examination of patients with primary bone and soft tissue tumors, in comparison with major clinical and pathological parameters (age at presentation, sex, tumor size, location, clinical stage and histologic grade) by uni- and multivariate analyses. In 64 patients with primary bone and soft tissue tumors (primary bone tumors: 39, primary soft tissue tumors: 25) and 68 cancer patients, the pretreatment DT values of serum C-reactive protein (CRP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium (Ca), phosphate (P) levels were measured, as well as the erythrocyte sedimentation rate (ESR: mm/60 min); these values were then compared with overall survival, local recurrence-free survival and metastasis-free survival. Only DT of CRP and ALP (CRP-DT, ALP-DT) were found to be correlated with disease outcome in patients with primary bone and soft tissue tumors. In cancer patients, only CRP-DT showed a relation with clinical stage and histologic grade, but the ALP-DT in patients with bone metastasis was significantly shorter than that in patients with metastases at other sites or in those with no metastasis. Among all tumor patients, those with bone metastasis showed the shortest ALP-DT compared with those with lung, liver and brain metastasis. Univariate analysis showed that shorter CRP-DT and ALP-DT are associated with poor overall survival, and the development of local recurrence and metastasis. These findings suggest that pretreatment CRP- and ALP-DT could be additional prognostic parameters for disease outcome in patients with primary malignant bone and soft tissue tumors. However, in multivariate analysis, only ALP-DT, but not CRP-DT, was an independent prognostic parameter for these disease outcomes.

Adult↗

PubMed1996

Significance of serum laminin and type IV collagen levels for metastasis in murine RCT sarcoma.

We investigated in vivo the correlation between pulmonary metastasis and serum concentrations of laminin and type IV collagen in high-metastatic RCT(+) and low-metastatic RCT(-) clones established from poorly differentiated RCT sarcoma in C3H/He mice. The in vitro invasiveness of these cell clones through the extracellular matrix was also studied. In the in vitro invasion assay, high-metastatic RCT(+) cells showed significantly more invasiveness than low-metastatic RCT(-) cells. The different invasiveness of these cloned cells was associated with their different ability to attach to and degrade the matrix. In mice inoculated with RCT(+) cells, serum levels of laminin and type IV collagen rose with the increase in the number of pulmonary metastatic nodules. Serum levels of these extracellular matrix components started to rise when pulmonary metastatic nodules were macroscopically observed in the RCT(+) group. In mice bearing RCT(-) cells with lower metastatic ability, there were no significant increases in serum extracellular matrix levels. These findings suggested that serum concentrations of laminin and type IV collagen might be useful markers for the early detection of metastasis.

Animals↗

PubMed1996

Characteristics of high and low laminin-adherent Dunn osteosarcoma cells selected by adhesiveness to laminin. Correlation between invasiveness through the extracellular matrix and pulmonary metastatic potential.

We investigated the invasiveness through the extracellular matrix and pulmonary metastatic potential in high laminin-adherent [LN(+)] and low laminin-adherent [LN(-)] Dunn oseosarcoma cells selected for adhesiveness to laminin. In the invasion assay using a reconstituted basement membrane (matrigel) in a Boyden chamber, LN(+) cells proved to be more invasive than LN(-) and the parental Dunn cells. Pulmonary metastatic potential was correlated with invasiveness through the matrigel in three cell types. The ability of LN(+) cells to attach to laminin and the matrigel was significantly higher than that of LN(-) or the parental Dunn cells. LN(-) cells showed much lower attachment ability compared to the other cells. There were no significant differences in type IV collagenolysis and cell migration among the three cell types. In LN(+) and the parental Dunn cells, laminin significantly stimulated type IV collagenolytic and migration activities. LN(-) cells showed no significant differences of type IV collagenolysis and cell migration in response to laminin. These findings suggested that the different invasiveness of these cells was associated with the difference in the abilities of cell attachment to laminin and type IV collagenolysis and cell migration activities stimulated by laminin. YIGSR inhibited not only the laminin-mediated cell attachment but also the type IV collagenolysis and cell migration induced by the cell attachment to laminin. The amount of laminin receptor of LN(+) cells was about fourfold that of LN(-) and twofold that of the parental Dunn cells, suggesting the stimulatory effect of laminin on the invasiveness through the matrix is associated with the level of laminin receptor expression in these cells. The present study provides several findings suggesting that laminin has important roles in invasiveness through the extracellular matrix and metastasis formation in Dunn osteosarcoma cells.

Animals↗