Role of reducing co-factor in cerulenin-insensitivity of 6-hydroxymellein synthase in carrot cell extract.

The activity of 6-hydroxymellein synthase, a multifunctional polyketide biosynthetic enzyme of carrot, was not inhibited by cerulenin in the presence of NADPH. However, cerulenin showed a marked inhibitory activity to the synthase if the reducing co-factor was omitted from the assay mixture. The synthase was also sensitive to the antibiotic even in the presence of NADPH when the acyl condensation site and the reducing domain at the reaction center of the enzyme were dissociated under the high ionic strength condition. In addition, the synthase activity was appreciably inhibited when NADH was employed instead of NADPH. These observations strongly suggest that a phosphate group attached to 2'-position of adenosyl moiety of NADPH molecule plays an important role in the apparent insensitivity of 6-hydroxymellein synthase toward cerulenin.

Inhibition of human telomerase activity by alterperylenol.

Human telomerase is a ribonucleoprotein that maintains telomeres by adding TTAGGG tandem repeat sequences using RNA template of the enzyme. Telomerase activity is highly expressed in immortalized cells but not in most somatic cells, except for some renewal tissues, such as hematopoietic stem cells. Therefore, telomerase can be a target for anticancer drugs. Here we show that a fungus metabolite, alterperylenol, inhibits human telomerase activity. Alterperylenol inhibited telomerase activity (IC50 = 30 microM), but altertoxin I, a structurally related compound, did not affect it at 1 mM. Moreover, alterperylenol did not affect the activity of viral reverse transcriptase at 1 mM.

The 'oral 1,25-dihydroxyvitamin D3 pulse therapy' in hemodialysis patients with severe secondary hyperparathyroidism.

Many hemodialysis patients are still suffering from secondary hyperparathyroidism although 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been used to treat renal osteodystrophy for the last two decades. The main reason for its failure to correct the secondary hyperparathyroidism is that in patients, hypercalcemia occurs before adequate parathyroid hormone (PTH) suppression is obtained when a large daily dose of 1,25(OH)2D3 is started. In this study, the oral dose of 1,25(OH)2D3 (4.0 micrograms) was administered only twice a week at the end of hemodialysis ('oral 1,25(OH)2D3 pulse therapy'), in 19 patients with severe secondary hyperparathyroidism. Serum immunoreactive PTH started to decrease after 6 weeks of therapy, and the original level of 41.2 +/- 7.24 was reduced to 24.4 +/- 6.12 ng/ml by the end of the 6-month therapy (p less than 0.001). Serum alkaline phosphatase also was reduced by 64.4%. Three out of 19 patients suffered from hypercalcemia during the 4th month of therapy. Calcium supplement given to 6 other patients with severe secondary hyperparathyroidism did not lower serum PTH levels significantly after 6 weeks of therapy, although serum calcium levels increased and were sustained above 10 mg/dl for the last 5 weeks. These findings strongly suggest that the suppressive effect of the oral 1,25(OH)2D3 pulse therapy was attained by a direct action of 1,25(OH)2D3 on the parathyroid gland rather than by its ability to elevate serum calcium levels. In conclusion, the oral 1,25(OH)2D3 pulse therapy effectively lowered PTH levels in hemodialysis patients who cannot tolerate large daily doses of 1,25(OH)2D3.

Comparison of different parathyroid hormone radioimmunoassays in uremic patients with secondary hyperparathyroidism.

Parathyroid hormone (PTH) levels of patients with chronic renal failure (CRF) were measured by three different radioimmunoassays (RIA); RIA for mid-region PTH by antibody CH9 (i-PTH) (1), RIA for intact fragments of PTH (intact PTH) and RIA for C-terminal fragments of PTH (PTH-C). PTH levels were higher in CRF patients undergoing hemodialysis therapy (hemodialysis patients) by all three methods. However, PTH levels measured only by i-PTH assay and intact PTH assay were significantly higher in patients with CRF who were not on dialysis (non-dialyzed CRF patients). PTH levels were above normal when creatinine clearance was below 45 ml/min in the intact PTH assay and 66 ml/min in the i-PTH assay. I-PTH levels were well correlated with the severity of osteitis fibrosa evaluated by the degree of periosteal resorption in the digits of hemodialysis patients. Since special handling of the sample is required for the intact PTH assay, i-PTH assay is the most suitable method for diagnosing secondary hyperparathyroidism in patients with CRF.

[Recent advance in diagnostic imaging: NMR].

Application of NMR, whether in imaging or in spectroscopy, is evolving rapidly and its clinical feasibility is to be fully assessed. It is not clear if speculation today will hold true tomorrow, but here present status of NMR in medicine, especially in its roles in research of the central nervous system are discussed as follow; NMR imaging in brain tumors, cerebrovascular diseases, degenerative diseases, trauma, spinal cord diseases, Imaging by surface coil, Contrast material in NMR imaging, Blood flow measurement by NMR, Chemical shift imaging, Studies of metabolism by 31P NMR spectroscopy, Recent advances and possible future role of NMR in medicine.