Association of decreased calcium-sensing receptor expression Expression of vitamin D receptor (VDR) is known to with proliferation of parathyroid cells in secondary hyperparabe decreased in the parathyroid (PT) glands from the thyroidism. early/predialysis stage of chronic renal failure [1]. The Background. The down-regulation of both calcium-sensing expression of VDR negatively correlated with the prolifreceptor (CaSR) and vitamin D receptor (VDR) in parathyroid (PT) glands of secondary hyperparathyroidism (HPT) caused erative activity of the hyperplastic PT glands from paby chronic renal failure has been associated with PT hormone tients with secondary hyperparathyroidism (secondary hypersecretion as well as PT hypergrowth. To clarify the pre-HPT) [2]. An active vitamin D metabolite, 1,25(OH) 2 D 3 , dominance of decreased expression of CaSR and VDR in the which partially restores the VDR expression level, suphigh proliferative activity of PT glands, we examined the relapresses not only PT hormone (PTH) synthesis at the tionship between the expression of both receptors and proliferative activity in human PT glands. mRNA level but also PT cell proliferation through the Methods. Serial sections of 56 PT glands, including 52 glands receptor [3-6]. An intermittent administration of high from secondary HPT and 4 normal PT glands resected together doses of 1,25(OH) 2 D 3 can reduce the serum PTH level with thyroid carcinoma, were examined immunohistochemias well as the volume of the PT gland in many cases cally with specific antibodies against CaSR, VDR, and Ki67. The Ki67-positive cell number was counted and expressed as of secondary HPT [7-9]. However, in some cases, this the Ki67 score. The CaSR and VDR expressions were semi-1,25(OH) 2 D 3 pulse therapy cannot induce the approquantitatively analyzed. priate PTH levels or must be discontinued as a result of Results. The expressions of both CaSR and VDR were side effects, which inevitably include hypercalcemia and markedly decreased in PT glands of secondary HPT, while hyperphosphatemia. This suggests that alterations in the the Ki67 score was significantly higher than it was in normal controls. When hyperplastic glands were classified into two vitamin D-VDR axis might not be the only determinants subgroups, with [N(ϩ)] or without [N(Ϫ)] nodular formation, of the pathological growth of the PT glands in chronic CaSR expression was significantly decreased in N(ϩ), while renal failure. VDR expression was not different. Multiple regression analy-The calcium-sensing receptor (CaSR) plays a crucial ses revealed that the decreased expression of CaSR could contribute significantly to the high proliferative activity, even if role in the regulation of PTH secretion [10]. A loss of VDR expression was taken into account. CaSR function leads to pathological states such as famil-Conclusion. The decrease in CaSR expression is associated ial hypocalciuric hypercalcemia (FHH) and neonatal sewith the high proliferative activity of PT glands in secondary vere hyperparathyroidism (NSHP...

Summary. A cell line designated SKM‐1 was newly established from leukaemic cells of a 76‐year‐old Japanese male patient with monoblastic leukaemia following myelodysplastic syndrome (MDS). The cells were obtained from peripheral blood of the patient when he lost multiple point mutations of ras genes with acquisition of chromosomal abnormalities during disease progression in MDS. The cells grew as a single floating cell, and have been continuously growing with the morphological characteristics of immature monoblasts by serial passages during the past 42 months with a doubling time of about 48 h. By cytochemical analysis. the cloned cells were positive for butyrate esterase, but negative for the Epstein‐Barr virus associated nuclear antigen. Phenotypic analysis revealed the expression of myelomonocyte specific antigens such as CD4, CD13, CD33 and HLA‐DR. Cells from the primary peripheral blood and those from SO passages of the SKM‐1 cell line both possessed no activated ras genes but showed karyotype abnormalities with 46.XY, del(9)(q13;q22), der(17) t(17:?)(p13:?). The SKM‐1 cells have two mutations in p53 gene and overexpress the pS3 products. This cell line may contribute to a better understanding of molecular mechanisms in the progression from MDS to myelogenous leukaemia.

Statins stimulate bone formation partly by inducing osteoblast differentiation, although there is controversy about the effects of statins on bone mineral density and fracture risk. Several studies have revealed that statins suppress bone resorption. However, the mechanism by which statins inhibit bone resorption is still unclear. The present study was performed to clarify the effects of statins on osteoclast formation as well as the levels of osteoprotegerin (OPG) and receptor activator of NFkappaB ligand (RANKL) mRNA in mouse bone-cell cultures by semiquantitative RT-PCR. 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] significantly stimulated osteoclast formation and 10(-6) M statins (mevastatin and simvastatin) significantly antagonized osteoclast formation stimulated by 1,25(OH)2D3 in mouse bone-cell cultures, including both osteoblasts and osteoclasts. 10(-6) M mevastatin and simvastatin increased the level of OPG mRNA in mouse bone-cell cultures. On the other hand, 10(-6) M mevastatin and simvastatin inhibited the level of RANKL mRNA in these cultures. In conclusion, the present study demonstrates that statins inhibit osteoclast formation in mouse bone-cell cultures. Moreover, statins also increased and decreased the levels of OPG and RANKL mRNA expression in these cultures, respectively. The modulation of OPG/RANKL may be involved in the inhibition of osteoclast formation by statins.

Distribution and staining intensities of growth hormone releasing factor (GRF) and somatostatin (SRIF) were examined in young (3 months of age) and old (24 months of age) male rats of Sprague-Dawley strain, using the PAP immunocytochemical procedure. Some animals of each age group were intraventricularly injected with colchicine to demonstrate immunoreactive neuronal perikarya. GRF-immunoreactive intensities of old rats were markedly reduced in the median eminence as compared with those of young rats. No remarkable difference could be detected between SRIF immunoreactivities in the young and old animals, since intensive SRIF immunoreactivities were found in the external layer of the median eminence of both groups of animals. Between two age groups injected with colchicine, we also found no difference in the distribution and staining intensities of immunoreactive perikarya of GRF and SRIF in the hypothalamus and also detected no significant difference in total neuron numbers of each peptide. These findings suggest that the synthesis and/or release of GRF in GRF-containing neurons are decreased, though GRF-containing neurons themselves remain alive and have the capacity to synthesize GRF.