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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 451 records · Page 25Linked to original sources
PubMed1996

Hypoxia regulates vascular endothelial growth factor receptor KDR/Flk gene expression through adenosine A2 receptors in retinal capillary endothelial cells.

PURPOSE: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic factor that serves an important role in numerous ischemic retinopathies. The authors studied the hypoxic gene regulation of two known VEGF receptors (KDR and Flt) and its mechanism in cultured bovine retinal endothelial cells (BREC). METHODS: Confluent monolayers of BREC were exposed to various oxygen concentrations using a computer-controlled, infrared, water-jacked CO2 incubator with reduced oxygen control. Northern blot analysis and 125I-VEGF binding analysis were used to identify hypoxia-induced alterations of VEGF receptor at mRNA and protein levels. RESULTS: KDR was detectable by Northern blot analysis in BREC, whereas Flt was not. Hypoxia decreased KDR gene expression in a dose-and time-dependent manner with maximal inhibition to 0.5 +/- 0.2% (P = 0.019) of normoxic control observed after 24 hours exposure to 0% oxygen and with significant inhibition at oxygen concentrations below 5%. Blockade of oxygen respiration decreased KDR mRNA expression to 58% +/- 7.1% of control (P = 0.001) after 3 hours. CPA, a stable adenosine A1 receptor (A1R) agonist, did not affect KDR mRNA expression at A1R stimulatory concentrations, but it decreased KDR mRNA levels to 30% +/- 4.9% (P = 0.002) of control at higher concentrations that react with A2R. DPMA, an adenosine A2 receptor (A2R) agonist, decreased KDR mRNA in a dose-dependent manner with an EC50 of 5 to 10 nM. A1R antagonists, 8-cyclolentyl-1,3-dipropylxanthine and 8-phenyltheophylline, did not inhibit the hypoxic response of KDR mRNA at A1R inhibitory concentrations but did inhibit the response at A2R effective doses (P = 0.001). The A2R antagonist, CSC, inhibited the KDR hypoxic response by 42% +/- 7.8% (P = 0.008) at 10 microM. Specific VEGF binding to BREC was decreased from 15.1% +/- 0.3% to 12.7% +/- 0.4% per milligram protein (P < 0.001) after exposure to 1% oxygen for 24 hours. In contrast, long-term exposure to 1% oxygen (72 hours) resulted in an increase of VEGF binding from 13.5% +/- 1.1% to 18.3% +/- 0.8% per milligram protein (P < 0.001). Scatchard analysis detected a decrease of receptor binding sites without change in binding affinity after 30 hours of exposure to hypoxia but demonstrated an increase in specific binding sites (4.2 +/- 0.6 x 10(4) sites/cell to 6.7 +/- 1.0 x 10(4) sites/cell, P = 0.049) with unaltered receptor affinity after 72 hours of hypoxic exposure. CONCLUSIONS: These data suggest that hypoxia induces an initial decline in KDR mRNA levels and VEGF binding sites as mediated through adenosine binding to the A2R. Exposure to prolonged periods of hypoxia, however, results in an increase in VEGF binding sites by an as yet unidentified mechanism.

Adenosine↗
PubMed1996

Factors affecting graft function in cadaveric renal transplantation from non-heart-beating donors using a double balloon catheter.

Experiences in 145 cadaveric kidney transplantation from non-heart-beating donors showed that not only donor age and WIT but also recipient body weight and duration of hemodialysis dependency were the determining factors affecting posttransplant kidney function analyzed with the use of a stepwise logistic regression model. This suggests that the fluid burden on the graft provides an additional insult on the recovery of the grafts from ischemic injury.

Adenosine↗
PubMed1996

[Measurement of serum tissue polypeptide antigen (TPA) in patients with malignant tumor using prolifigen TPA-M "Daiichi" kit].

Serum tissue polypeptide antigen (TPA) was measured using a newly developed Prolifigen TPA-M "Daiichi" kit in 1,236 healthy subjects, 2,867 patients with malignant tumors, and 901 with benign diseases. Because 94.0% of healthy subjects had serum TPA under 70 U/l, the cut-off value was set at 70 U/l. Serum TPA was elevated in more than 50% of patients with head and neck cancer, lung cancer, liver cancer, gallbladder or bile duct cancer, pancreatic cancer, colorectal cancer, ovarian cancer, and prostate cancer. The overall positive rate in malignant tumors was 55.5%. Serum TPA was higher in advanced cancer than in earlier stage cancer, and decreased after the resection of the tumor. The false positive rate in benign diseases was 31.3%. ROC analysis revealed the usefulness of TPA as a tumor marker in many cancers. The correlation coefficient between TPA and CYFRA 21-1, and between TPA and TPSA, was 0.747 and 0.694, respectively. In conclusion, measurement of serum TPA using the new kit is useful in the management of patients with various malignant tumors.

Antigens, Neoplasm↗