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Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 289 records · Page 16Linked to original sources
PubMed1998

Aluminum taken up by transferrin-independent iron uptake affects the iron metabolism in rat cortical cells.

We previously demonstrated that cultured human fibroblasts internalize iron via transferrin-independent iron uptake (Tf-IU), redox, and receptor-mediated endocytosis uptake systems [Oshiro, S., Nakajima, H., Markello, T., Krasnewich, D., Bernardini, I., and Gahl, W.A. (1993) J. Biol. Chem. 268, 21586 21591]. Of these iron transport systems, the Tf-IU system is involved in the accumulation of transition metals in various mammalian cells. It is also known that in experimental animals fed aluminum (Al), Al at micromolar level selectively accumulates in the brain. In the present study, we examined the effects of Al accumulated in the brain cells on iron transport by the Tf-IU system and iron metabolism, using primary cultures from fetal rat cerebral cortex. Pretreatment of cells with 200 microM Al-nitrilotriacetate upregulated the Tf-IU system for iron. Moreover, of various metals tested, Al markedly upregulated the Tf-IU activity. To examine the influence of Al on iron metabolism, the interaction between Al accumulated in the cells and iron-responsive element binding protein (IRE-BP), a cellular iron regulator, was examined by Northern blot analysis, and activity assay: Al decreased the Tf receptor mRNA level and increased the aconitase activity of IRE-BP. The increase of aconitase activity by Al was also observed in vitro. These results suggest that Al accumulated in cortical cells affects iron metabolism.

Aconitate Hydratase↗
PubMed1998

Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion.

OBJECTIVE: The aim of this study was to report the long-term results of percutaneous isolated liver chemoperfusion with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) in patients with multiple advanced hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The results of conventional chemotherapy including regional and systemic chemotherapy in patients with HCC remain dismal, and long-term survivors after treatment are rare among patients with multiple advanced HCC. In an effort to improve this situation, we previously developed a novel system of percutaneous isolated liver chemoperfusion with HVI-CHP. METHODS: Doxorubicin (60 to 150 mg/m2) was administered via the hepatic artery, under conditions of extracorporeal drug elimination by HVI-CHP in 28 consecutive patients with advanced HCC (39 total treatments). Hepatic venous isolation and charcoal hemoperfusion was accomplished mainly by the single catheter technique using a newly developed 4-lumen-balloon catheter, which was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. RESULTS: Complete remission was achieved in five patients, of which four received repeated treatments (two or three times). Although 1 of 5 patients with complete remission died of pulmonary metastases at 8 months, the other 4 remain healthy and free of disease at 20, 24, 27, and 42 months after the first treatment. Partial responses were observed in 12 patients. Duration of response in responders (complete and partial) with repeated treatments was significantly longer than that with a single treatment (p = 0.01). The overall survival rate by the Kaplan-Meier method was 39.7% at 5 years. The treatments were well-tolerated, and the primary side effects were mild to moderate chemical hepatitis and reversible myelosuppression. CONCLUSIONS: The results suggest that percutaneous isolated liver chemoperfusion with HVI-CHP is an effective palliative treatment in the majority of patients and yields long-term complete remission in some patients with multiple advanced HCC.

Adult↗
PubMed1998

Constitutive and cytokine-inducible expression of prion protein gene in human neural cell lines.

Prion diseases are a group of neurodegenerative disorders characterized by intracerebral accumulation of a protease-resistant prion protein (PrP(Sc)) that causes extensive neuronal degeneration and astrogliosis. The regulation of prion protein (PrP) gene expression by a panel of glial and neuronal cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL-10, and TGF-beta1) was investigated in human neural cell lines by reverse transcription-polymerase chain reaction and Northern blot analysis. The constitutive expression of PrP mRNA was identified in all human neural cell lines and tissues examined including Y79 retinoblastoma, IMR-32 neuroblastoma, SK-N-SH neuroblastoma, U-373MG astrocytoma, KG-1-C glioma, NTera2 teratocarcinoma, NTera2-derived differentiated neurons (NTera2-N), peripheral nerve, and cerebral and cerebellar tissues. In SK-N-SH cells, a 48 hour (h) treatment with 100 ng/ml IL-1beta, 100 ng/ml TNF-alpha, or 100 nM phorbol 12-myristate 13-acetate induced a 2.7- to 4.2-fold increase in the level of PrP mRNA, while the exposure to 100 ng/ml IFN-gamma resulted in a 50% decrease. By contrast, none of these cytokines significantly altered the levels of PrP mRNA in IMR-32, NTera2-N, or U-373MG cells. These results indicate that the PrP gene expression is constitutive in a wide range of human neural cell lines and tissues where it is controlled by cell type-specific regulatory mechanisms.

Astrocytoma↗
PubMed1998

Endothelium-derived hyperpolarizing factor activates Ca2+-activated K+ channels in porcine coronary artery smooth muscle cells.

Although endothelium-derived hyperpolarizing factor (EDHF) activity has been demonstrated in arteries from various species, EDHF has not been chemically identified, nor its mechanism of action characterized. To elucidate this mechanism, we tested the effect of EDHF on large-conductance Ca2+-activated K+ (K(Ca)) channels in porcine coronary artery smooth muscle cells. By using a patch-clamp technique, single-channel currents were recorded in cultured smooth muscle cells; the organ bath also contained a strip of porcine coronary with endothelium, which served as the source of endothelium-derived relaxing factor(s) including EDHF. Exposure of endothelium to 10(-6) M bradykinin activated K(Ca) channels in cultured smooth muscle cells in cell-attached patches. When the experiment was performed in the presence of 10 microM indomethacin and 30 microM N(G)-nitro-L-arginine (L-NNA), which block the generation of prostaglandin I2 (PGI2) and NO, respectively, K(Ca) channel activity was stimulated by bradykinin, indicating the direct involvement of EDHF in K(Ca) channel stimulation. Neither 10 microM methylene blue nor 25 microM Rp-cAMPS inhibited bradykinin-induced K(Ca) channel activity. In inside-out patches, the addition of bradykinin to the solution was without effect on K(Ca) channel activation. However, in the presence of 0.5 mM guanosine triphosphate (GTP) and 1.0 mM adenosine triphosphate (ATP) in the bath solution, K(Ca) channels was activated by bradykinin. In outside-out patches, the addition of bradykinin also increased K(Ca) channel activity, when GTP and ATP were added to the pipette solution. The addition of GDP-beta-S (100 microM) in the cytosolic solution completely blocked the activation K(Ca) channels induced by bradykinin in inside-out and outside-out patches. Pretreatment with 30 microM quinacrine, a phospholipase A2 inhibitor, or 3 microM 17-octadecynoic acid (17-ODYA), a cytochrome P450 inhibitor, in addition to indomethacin and L-NNA, abolished bradykinin-stimulated K(Ca) channel activity in cell-attached patches. Both 14,15-epoxyeicosatrienoic acid (EET) and 11,12-EET increased the open probabilities of K(Ca) channels in cell-attached patches. These results suggest that EDHF, released from endothelial cells in response to bradykinin, hyperpolarizes smooth muscle cells by opening K(Ca) channels. Furthermore, our data suggest that EDHF is an endothelium-derived cytochrome P450 metabolite of arachidonic acid. The effect of EDHF on K(Ca) channels is not associated with an increase of cAMP and cGMP. The activation of K(Ca) channels appears to be due to the activation of GTP-binding protein.

Adenosine Triphosphate↗
PubMed1998

Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein.

The inhibitory effects of SDZ PSC 833 (PSC833), a non-immunosuppressive cyclosporin derivative, on the P-glycoprotein (P-gp)-mediated transport of doxorubicin and vinblastine were compared with those of cyclosporin A (Cs-A). The transcellular transport of the anticancer drugs and PSC833 across a monolayer of LLC-GA5-COL150 cells, which overexpress human P-gp, was measured. Both PSC833 and Cs-A inhibited P-gp-mediated transport of doxorubicin and vinblastine in a concentration-dependent manner and increased the intracellular accumulation of doxorubicin and vinblastine in LLC-GA5-COL150 cells. The values of the 50%-inhibitory concentration (IC50) of PSC833 and Cs-A for doxorubicin transport were 0.29 and 3.66 microM, respectively, and those for vinblastine transport were 1.06 and 5.10 microM, respectively. The IC50 of PSC833 for doxorubicin transport was about 4-fold less than that for vinblastine transport, suggesting that the combination of PSC833 and doxorubicin might be effective. PSC833 itself was not transported by P-gp and had higher lipophilicity than Cs-A. These results indicated that the inhibitory effect of PSC833 on P-gp-mediated transport was 5- to 10-fold more potent than that of Cs-A, and this higher inhibitory effect of PSC833 may be related to the absence of PSC833 transport by P-gp and to the higher lipophilicity of PSC833.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Surgical significance of telomerase activity in noncancerous liver tissue from patients with hepatocellular carcinoma.

Telomerase activity has been detected in tissue from noncancerous liver of patients with chronic liver disease, but its functional significance remains to be elucidated. We therefore evaluated the telomerase activity in surgically obtained noncancerous liver tissue from 20 hepatocellular carcinoma (HCC) patients. Two samples of noncancerous liver tissue were obtained from each patient: one from the parenchyma adjacent to the HCC nodules of the resected specimen; the other from the parenchyma distant from the HCC nodules of the remnant liver. Telomerase activity was assayed by a non-radioisotope quantitative system based on "TRAP-eze." Five samples from the noncancerous liver tissue adjacent to the HCC nodules (25.0%) were telomerase-positive; all such cases showed high-grade malignant potential, such as intrahepatic metastasis and/or portal vascular invasion and infiltration of the fibrous capsule in the corresponding HCC nodules, and telomerase positivity showed neither a relationship with the histological activity index scores nor a correlation with liver function. Interestingly, no telomerase activity was detected in any of the 20 samples obtained from the parenchyma of the remnant liver. These results indicate that telomerase in noncancerous liver tissue is associated not with the hepatic condition accompanying HCC, but with the biological characteristics of the tumor itself, and may derive from infiltrating cancer cells. Determination of telomerase status may aid in designing more effective surgical procedures.

Aged↗
PubMed1998

Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer.

In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinase-type plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P< 0.01) and lymph node metastasis (P< 0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P< 0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P< 0.01), lymph node metastasis and depth of invasion (P< 0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.

Adult↗
PubMed1998

Spontaneous rupture of an intrahepatic bile duct with biloma treated by percutaneous drainage and endoscopic sphincterotomy.

A case of spontaneous rupture of an intrahepatic bile duct with biloma formation treated by percutaneous drainage and endoscopic sphincterotomy is reported. A 73-yr-old woman was admitted with fever and abdominal pain. There was no past history of abdominal surgery, instrumentation, or trauma. Ultrasound and computed tomography revealed a massive fluid collection in the abdominal cavity. Endoscopic retrograde cholangiography demonstrated extravasation of contrast medium from a distal biliary radicle in the left lobe of the liver. After successful treatment by percutaneous drainage and endoscopic sphincterotomy, the patient did well. Ultrasound and computed tomography showed resolution of the biloma. Nontraumatic bilomas are very rare: in fact, only 24 cases of spontaneous biloma have been reported. Endoscopic treatment for patients with spontaneous bilomas can be safe and effective, and should be considered.

Aged↗
PubMed1998

Urokinase type plasminogen activator receptor expression in colorectal neoplasms.

BACKGROUND: The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis. AIMS: To study the involvement of uPAR in colorectal carcinogenesis. METHODS: The cellular expression and localisation of uPAR were investigated in colorectal adenomas and invasive carcinomas by in situ hybridisation, immunohistochemistry, and northern and western blot analyses. RESULTS: uPAR mRNA expression was found mainly in the cytoplasm of dysplastic epithelial cells of 30% of adenomas with mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes' stages A (72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR was detected in dysplastic epithelial cells of 14% of adenomas and in carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and protein concentrations were significantly higher in severe than in mild or moderate dysplasia (p<0.05); they were notably higher in Dukes' stage A than in severe dysplasia (p<0.05), and significantly higher in Dukes' stage B than in stage A (p<0.05), but those in stage B were not different from those in stage C or in metastatic colorectal carcinomas of the liver. CONCLUSIONS: Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer.

Blotting, Northern↗
PubMed1998

The side-to-side differences of bone mass at proximal femur in female rhythmic sports gymnasts.

This cross-sectional study examined the side-to-side differences of the bone mineral density (BMD) at proximal femora in female rhythmic sports gymnasts (RSGs). The hypothesis on which the study is based is that gymnasts use a different leg in take-off (left leg) and in landing (right leg) and therefore differ in the loading for the left and right legs. The gymnasts made up two groups: the regular group, which consisted of 15 regular players who had trained for about 28 h/week, and the substitutes group, which consisted of 8 substitute players who had trained for about 12 h/week. The control group consisted of 10 nonathletic college women who had not participated in any kind of regular sports activity. BMD (g/cm2) was measured in three hip sites using the XR-26 dual-energy X-ray absorptiometer scanner. Muscle strength at knee extensors (EXT) and flexors (FLX) was examined using an isokinetic dynamometer (CYBEX6000), and the vertical ground reaction force was determined with a force platform during take-off and landing movements. In the regular players, the BMDs of the left leg were significantly higher than those of the right leg at the femoral necks, greater trochanters, and Ward's triangles (p < 0.01 to approximately 0.005). The side-to-side differences were 4.7 to approximately 9.6%. Regarding the strength parameters, the left side was greater than the right side significantly at EXT 60 degrees/s (p < 0.01), although the overall side-to-side difference was small. In the substitutes, the BMDs at the three sites mentioned above were also higher in the left leg than the right, but the side-to-side difference was statistically significant only at Ward's triangles (93%, p < 0.05). The side-to-side difference of strength was not significant. In the controls, there were small left-to-right differences of the BMDs, ranging from -1.8 to 0.5%, which was significantly lower than in the regular players at each site. The overall average strength measurements were larger in the right leg than in the left except at the 120 degrees/s. The side-to-side difference was statistically significant at EXT 30 degrees/s and 60 degrees/s (p < 0.05). The peak force was greater in take-off than in landing, and the unit time force during take-off was significantly greater than that during landing (p < 0.001). In conclusion, regarding the side-to-side difference of the BMD at proximal femora, our results demonstrate: that the left leg for take-off had higher measurements than the right leg for landing in both gymnasts' groups, which accounts for the vertical ground reaction force during take-off being greater than that during landing; that the difference in the regular players group was greater than that in the substitute group, which can be explained because the regular players practiced much more than the substitutes did; and that there was no difference in the control group.

Adolescent↗
PubMed1998

Comparison of GAD and ICA512/IA-2 antibodies at and after the onset of IDDM.

OBJECTIVE: Longitudinal changes in GAD antibody (Ab) and ICA512/IA-2 (ICA512) Ab were examined in relation to age at the onset of diabetes and autoimmunity against the thyroid gland. RESEARCH DESIGN AND METHODS: GADAb, ICA512Ab, and antithyroid autoantibody were examined at onset in 40 juvenile-onset IDDM patients (17 males, 23 females, age at onset 9.4 +/- 4.1 years, range 1.7-20). To assess the changes in antibody levels, 29 patients were followed up with sequential serum samples for up to 5 years. RESULTS: At onset, GADAb, ICA512Ab, and antithyroid autoantibody (thyroglobulinAb or thyroid peroxidaseAb) were found in 70, 58, and 25% of the 40 patients, respectively. Prepubertal patients (n = 21) had a significantly higher prevalence and index of ICA512Ab compared with pubertal patients (n = 19) (76 vs. 37%, P = 0.012, and 2.43 +/- 2.36 vs. 0.66 +/- 1.23, P = 0.011), while GADAb was more prevalent in pubertal patients (57 vs. 84%, P = 0.09). A longitudinal analysis of GADAb and ICA512Ab showed that GADAb levels declined more slowly than those of ICA512Ab (P = 0.008). Patients with continuous extremely high levels of GADAb also had high levels of antithyroid autoantibody. CONCLUSIONS: The measurement of ICA512Ab is useful in prepubertal patients, who often show rapid progression of the disease. The presence of autoimmunity against thyroid gland seems to influence the GADAb level but not the ICA512Ab level.

Adolescent↗
PubMed1998

Expression level of G1-cyclins and cell proliferation in human cultured leukemia/lymphoma cell lines.

We observed the expression of wild-type retinoblastoma protein (RB) in all 17 hematologic cultured cell lines tested. However, no p16INK4 expression was detected in any cell line among 16 leukemia/lymphoma cell lines, although an EBV-transformed cell line expressed p16INK4. The expression levels of cyclin D1 and CDK4 varied widely among the cell lines. The correlation coefficient (r2) between doubling time (DT) and cyclin D1 in the 14 cell lines that doubled within 47.2 h was 0.4856, while the r2 between DT and cyclin dependent kinase 4 (CDK4) and that between DT and RB among those cell lines were 0.3761 and 0.0874, respectively. The levels of protein expression in vincristine (VCR)-resistant cell lines was not different from those in corresponding wild-type cell lines. Thus, we concluded that the loss of p16INK4 protein and inactivation of RB protein could be an essential step for oncogenesis of leukemia/ lymphoma, and that cyclin D1 may possibly be a target protein to control cell growth of hematologic cell lines which lack the expression of p16INK4.

Cell Division↗
PubMed1998

Effect of MDR antagonists on the cidal activity of vincristine for cells expressing MDR-1 is superior to those expressing MRP.

In an attempt to identify the target protein, P-GP or mrp, of each MDR antagonist, verapamyl (Ver), dipyridamole (Dip), or cyclosporin A (Cy-A), this study was designed to compare the activity of the three afore-mentioned drugs and to test their combined effect on the cidal activity of vincristine (VCR) in five types of wild and the corresponding VCR-resistant cultured cell lines from human leukemia and lymphoma. Three of the VCR-resistant cell lines are characterized by the overexpression of mdr-1, while two cell lines overexpress mrp. We found that all three antagonists additively to synergistically enhanced the cidal activity of VCR for the five wild-type and VCR-resistant cell lines in a dose dependent manner when used singly. Combinations consisting of a 20% inhibitory concentration (IC20) of VCR plus two antagonists also showed additive to synergistic effects on both wild and VCR-resistant cell lines. It is of interest that the combined effect of IC20 VCR plus MDR antagonists on the three VCR-resistant cell lines expressing mdr-1 was significantly superior to those of the two cell lines expressing the mrp gene. These results suggest that the combined effect of MDR antagonists work better than their single use and that the MDR antagonists work more efficiently in cells showing drug resistance through mdr-1 than in those utilizing mrp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Preoperative examination for estimating the course of the facial nerve].

In surgery for a parotid tumor, facial palsy is the most serious complication. Facial palsy tends to occur in the operation in which the facial nerve runs outside of the parotid tumor. Therefore, we developed the facial nerve electric stimulating test (FNEST) to determine more accurately the relationship between the facial nerve and the tumor. The FNEST diagnosed the condition in half of the patients whose facial nerve ran outside of the parotid tumor. Furthermore, a combination of CT and FNEST increased the diagnostic efficiency. The FNEST was a very efficient preoperative examination for estimating the course of the facial nerve.

Adolescent↗
PubMed1998

[Radiation therapy for non-small cell lung cancer with postoperative intrathoracic recurrence].

We reviewed patients with intrathoracic recurrence of non-small cell lung cancer after surgery, with reference to the feasibility of radiotherapy. The series consisted of 46 patients (39 males and 7 females) treated by radiotherapy from 1982 to 1995. Histology included squamous cell carcinoma (28 patients), adenocarcinoma (17), and large cell carcinoma (1). Clinical stage by UICC classification (1987) was as follows: stage I(2 patients), stage II(1), stage IIIa(13), stage IIIb(23), and stage IV(7). Recurrences were noted in bronchial stump (18 patients) and surgical scar (4). Metastases occurred in hilar-mediastinal lymphnodes (15), lung fields (7), and pleuropericardium (2). The mean interval from surgery to recurrence was 27 months. Delivered dose ranged from 45 to 80 Gy, and 19 patients received combined chemotherapy. Therapeutic results were as follows: complete response in 16 patients, partial response in 27, no response in 12 and progressive disease in 1, Overall 2- and 5-year survival rates were 17% and 11%, respectively, and 10 months in MST. On univariate analysis, significant prognostic factors were sex, stage at recurrence, recurrence pattern, performance status and initial response to radiotherapy, while multivariate analysis showed sex and initial response. From these data, we are encouraged by effective radiotherapy for postoperative intrathoracic recurrence of non-small cell lung cancer, especially in patients with stump or lymphnode recurrence.

Adenocarcinoma↗
PubMed1998

[Results of radiation therapy for limited small-cell lung cancer].

Results of radiotherapy were reviewed in 68 patients with limited small-cell lung cancer from the aspect of local control. Thirty-one patients achieved CR (46%), while the other 31 remained at PR. The 1-, 2-, 3-, and 5-year cumulative survival rates were 57%, 28%, 21%, and 16%, respectively, for 15 months in MST. Thirty-six patients developed local recurrence (53%) and 46 had distant metastasis (68%). The thirty-one patients with CR had a 43% 2-year-survival rate and 23 months in MST. The remaining 37 patients (PR + NC) had respective figures of 13% and 13 months (p < 0.025). There was no statistically significant difference between radiation dose and local thoracic failure among the patients. Of the 31 patients with CR, 28 had achieved CR at 45Gy (17 received 55Gy or more, and 11 less than 55Gy). In the former, the local control rate, 2-year-survival and MST were 94%, 53% and 44 months, while in the latter these were 45%, 27% and 17 months, respectively. Thirty-five patients were irradiated by the shrinking field technique according to tumor reduction; however, this technique did not influence the treatment results. To obtain better results, it is first necessary to achieve CR at initial chemo-radiotherapy. As to irradiation, randomized trials between 50Gy and 60Gy would require patients with CR at 45Gy.

Aged↗