Background: The construct validity of alexithymia and its assessment using the 20-item Toronto Alexithymia Scale in Japan is unknown. Low reliability has been found for the third factor of the TAS-20 in some cultures, and the factor structure for psychosomatic disorder patients has not been adequately investigated. Although alexithymia most likely has certain developmental aspects, this has infrequently been investigated.

To examine the effects of serum calcium concentrations on PTH biosynthesis, rats were made hyper-(serum total calcium, -3.5 mM) or hypocalcemic (-1.25 mM) and steadystate levels of PTH mRNA in parathyroid cells were measured by the primer extension method using a 32P-labeled synthetic oligomer. PTH mRNA levels increased about twofold in the rats made slightly hypocalcemic by infusion of calcium-free solution and decreased slightly in those made hypercalcemic by CaCI2 infusion (120-150 gmol/h) compared with the levels present in nonfasting control rats. Infusion of calcitonin (0.5 U/h) or EGTA (90 gmol/h) with calcium-free solution increased PTH mRNA levels further (two-to sevenfold) above the levels present in animals infused with calcium-free solution alone. These changes in PTH mRNA levels were observed after 48-but not 24-h infusion, and there was an inverse correlation between PT1H mRNA levels and serum calcium concentrations. The results suggest that changes in serum calcium concentrations in the near physiological range regulate the biOsynthesis of PTH by affecting steady-state levels of PTH mRNA when hypercalcemia or hypocalcemia continues for a relatively long period.

To clarify the mechanism of secondary hyperparathyroidism in chronic renal failure at the parathyroid hormone (PTH) synthesis level, we measured PTH messenger RNA (mRNA) levels in parathyroid glands in a rat model of chronic renal failure. Four weeks after 7/8 nephrectomy, hyperplasia of parathyroid glands was evident and serum PTH levels were elevated. Serum concentration of calcium, inorganic phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)2D) of rats with chronic renal failure were not detectably different from those of sham-operated rats. In chronic renal failure rats, PTH mRNA levels were elevated both per RNA and per DNA of parathyroid cells, suggesting increased PTH mRNA levels per cell. The elevated levels of PTH mRNA were returned to normal levels by achieving supraphysiological concentrations of 1,25(OH)2D3 given i.p. twice at 24 and 48 hours before sacrifice, although this was attended by slight hypercalcemia. A synthetic analogue of vitamin D, 22-oxa-1,25(OH)2D3, also suppressed PTH mRNA to normal levels, but without hypercalcemia. These data suggest that secondary hyperparathyroidism in early chronic renal failure may be due in part to the resistance of parathyroid cells to the physiological concentration of 1,25(OH)2D in circulation on PTH synthesis and that 22-oxa-1,25(OH)2D3 may be useful in the management of secondary hyperparathyroidism of chronic renal failure.

Through the specific binding of a negative calciumresponsive element to its binding protein in response to extracellular Ca (Ca by interacting with a redox factor protein, REF1. Although sequence-nonspecific DNA binding activity of the Ku antigen has been well characterized, the mechanism of its sequence-specific DNA binding remained obscure. Here, we report that the specific binding of the Ku antigen to another protein, REF1, leads to DNA-protein complex formation with a novel sequence specificity and thereby regulates gene expression.The Ku antigen (KuAg), 1 which consists of two subunits, p70 and p80 (p86), plays a crucial role in double-stranded break repair of DNA (1-6). In this process, its ability to bind to DNA ends nonspecifically is postulated to be related to subsequent actions such as DNA recombination or unwinding (1-3). Furthermore, such binding has been reported to be directly coupled with DNA-dependent protein kinase activity, which is elicited by the putative catalytic unit of KuAg, p350 (7,8). On the other hand, sequence-specific binding of KuAg has been demonstrated in some genes, such as the small nuclear RNA (9), T cell receptor (10), transferrin receptor (11), collagenase (12), ribosomal RNA (13, 14), and heat shock protein genes (15, 16). Although expression of most of these genes is stimulated by KuAg, transcription of the latter two is repressed by KuAg (14 -16). However, neither common KuAg-responsive DNA elements nor detailed domain structure of KuAg were identified in either type of gene regulation (9 -16). In this regard, it is of note that multimer formation of KuAg with another proteins was suggested to be involved in some of the above examples of sequence-specific gene regulation by KuAg (12,15,16) We previously reported that two DNA elements located far upstream of the human parathyroid hormone gene mediated negative gene regulation by extracellular Ca (Ca 2ϩ e ). These DNA elements (negative calcium-responsive elements (nCaREs)) bound to common nuclear proteins (nCaRE binding proteins (nCaREBs)) in a sequence-specific and Ca 2ϩ e -dependent manner (17,18). We further demonstrated that a redox factor protein, REF1, was one component of nCaREB by using the protein-DNA binding (Southwestern) assay (19). REF1 was first identified as a mammalian homologue of bacterial apurinic endonuclease/repair enzyme (20). Subsequently, it was reported to potentiate DNA binding activity of several transcription factors such as AP1 and NFB by modifying the redox state of these proteins (21). In addition to such activities of REF1, we first reported that it also possessed the sequencespecific transcriptional repressor function of nCaRE (19). However, REF1 alone could not explain all the characteristics of nCaREB activity, and we predicted the existence of another nuclear protein(s) that functions as nCaREB by cooperating with REF1 (19). By employing an oligonucleotide affinity column (22) and amino acid microsequencing (23), we demonstrate here that both subunits of KuAg interact with REF1 to bind t...