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Biomedical subjects

E Ogata

Publications and source records attributed to E Ogata.

At least 91 records · Page 5Linked to original sources
PubMed1994

Reduction of functioning parathyroid cell mass by ethanol injection in chronic dialysis patients.

Recent data suggest that the larger parathyroid glands are more resistant to calcitriol therapy than the smaller glands due to more severe reduction of calcitriol receptor number. To control severe secondary hyperparathyroidism resistant to calcitriol pulse therapy in chronic dialysis patients, we introduced repeatable and quantitative ethanol injection(s) into the largest parathyroid gland under ultrasonographic guidance with a specifically modified needle. Efficacy of each injection and the recurrence of hyperparathyroidism were confirmed by color Doppler ultrasonography and could undergo additional ethanol injection(s) into the optimal site. When the ethanol injection(s) into the largest gland was not sufficient to control PTH hypersecretion, we injected ethanol into the next largest gland. We performed 32 injections into 16 parathyroid glands in nine dialysis patients. PTH decreased to less than 200 pg/ml after the final injection in seven patients and they remained controlled either by the following conventional oral active vitamin D or calcitriol pulse therapy. The other two patients, whose PTH decreased but not to less than 200 pg/ml, also became controllable with the following calcitriol pulse therapy. Recurrent nerve palsy was encountered in 2 out of 32 injections, but only transiently. Our data suggest that the measurement of the size of parathyroid glands is an important factor in the management strategy of secondary hyperparathyroidism in chronic dialysis patients, and that ethanol injection(s) into the largest parathyroid gland(s) could be an effective and safe strategy to restore the responsiveness to calcitriol therapy, by reducing the functioning parathyroid cell mass most resistant to calcitriol.

Adult↗
PubMed1994

Serial evaluation of parathyroid size by ultrasonography is another useful marker for the long-term prognosis of calcitriol pulse therapy in chronic dialysis patients.

To clarify whether the changes of parathyroid size have any correlations with the long-term prognosis of calcitriol pulse therapy, we examined the time course of serum levels of parathyroid hormone (PTH) and size of parathyroid glands in 14 chronic dialysis patients during and after the oral calcitriol pulse therapy. In 5 patients without any detectable glands, secondary hyperparathyroidism was easily controlled by calcitriol pulse therapy and then by conventional oral active vitamin D therapy. In 2 patients with detectable gland(s) in whom size of all parathyroid glands as well as PTH hypersecretion regressed to normal by calcitriol pulse therapy, secondary hyperparathyroidism could then remain controlled at least for 12 months after switching to conventional oral active vitamin D therapy. In contrast, in 7 patients in whom size of all parathyroid glands did not regress to normal by calcitriol pulse therapy, secondary hyperparathyroidism relapsed after switching to the conventional therapy, even if PTH hypersecretion could be controlled temporarily. Our findings suggest that the time course of parathyroid hyperplasia detected by ultrasonography is an important determinant of the efficacy and the prognosis of calcitriol pulse therapy. Thus, the change of parathyroid gland size as well as PTH hypersecretion should be taken into account for the management of secondary hyperparathyroidism.

Administration, Oral↗
PubMed1994

A rise in antineutrophil cytoplasmic antibody in a patient with systemic vasculitis in remission.

We report a 42-year-old man who showed alveolar hemorrhage and glomerulonephritis as well as episcleritis and skin rash. He had an extremely high titer of cytoplasm-staining antineutrophil cytoplasmic antibody (C-ANCA) and was diagnosed as having systemic vasculitis based on histological findings of kidney and skin biopsies. After immunosuppressive therapy clinical manifestations resolved within several weeks and C-ANCA titers commensurably declined. C-ANCA titers, however, increased again and remained high despite clinical remission. In general, there is a close relationship between ANCA titers and clinical activities in ANCA-associated diseases, but they displayed a large discrepancy in this patient. Indeed, the serum of the patient in remission contained the antibody against 29-kD neutrophil extracts which was detected by immunoblot analysis. These findings suggest that C-ANCA may not necessarily be, by itself, pathogenetic for the development of the vasculitis.

Adult↗
PubMed1994

Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin-diabetic rats.

The effect of local application of recombinant human basic fibroblast growth factor (rhbFGF) on fracture repair was examined using normal rats and streptozotocin-diabetic rats with impaired repairing ability. Immediately after fracturing the fibula, rhbFGF was applied by a single injection to the fracture site. Application of rhbFGF increased the volume and mineral content of callus in a dose-dependent manner in both normal and diabetic rats, and callus formation of diabetic rats was stimulated to levels similar to those in nontreated normal rats. The marked effect of rhbFGF on fracture repair was associated with an improvement in the mechanical properties of the healing fibula in both normal and diabetic rats. Immunohistochemical staining showed that endogenous bFGF was widely distributed in normal rats 1 and 3 weeks after fracture, especially in the soft callus and periosteum, whereas much less bFGF was detected in diabetic rats. Insulin treatment of diabetic rats restored the immunostaining for bFGF. These results demonstrate that bFGF is expressed during the early stage of fracture repair, and that the impaired fracture-repairing ability in diabetic rats is associated with reduced expression of bFGF at the fracture site. A single application of bFGF immediately after fracture not only facilitates the repair process in normal rats, but also recovers the impaired repairing ability in diabetic rats. These results suggest that local application of bFGF may facilitate bone union in patients with impaired as well as normal repairing ability.

Animals↗
PubMed1994

Treatment of malignancy-associated hypercalcemia with YM175, a new bisphosphonate: elevated threshold for parathyroid hormone secretion in hypercalcemic patients.

The effect of a new third generation bisphosphonate, YM175 (cycloheptylamino-methylene bisphosphonate), on serum calcium (Ca) and intact PTH levels was examined in 79 malignancy-associated hypercalcemia patients with serum Ca levels higher than 2.75 mmol/L. A single infusion of 2.5, 5, and 10 mg YM175 reduced serum Ca levels in a dose-dependent manner. YM175 was about 6 times more potent than 3-amino-hydroxypropylidene-1,1-bisphosphonate. Among 23 patients treated with 10 mg YM175, serum Ca decreased by more than 0.5 mmol/L in 20 patients and was normalized in 11 patients. Serum intact PTH was subnormal in all of these patients before treatment and remained subnormal in 12 patients (suppressed PTH group), but was elevated to normal or high levels after treatment in the remaining 11 patients (responsive PTH group). Serum Ca was significantly higher throughout the study period in the suppressed PTH group, and mean serum Ca at the nadir did not decrease below 2.90 mmol/L in this group. However, the rate or magnitude of reduction in serum Ca was not different in the two groups. Polynomial regression analysis revealed that the threshold of serum Ca for PTH secretion was elevated to 2.75 mmol/L in the responsive PTH group, whereas it was about the upper limit of normal when both groups were combined (2.59 mmol/L). Furthermore, in the responsive PTH group, the threshold for PTH secretion during the decreasing serum Ca phase (days 4 and 6) was higher than that during the increasing serum Ca phase (days 10 and 14). The changes in the threshold for PTH secretion were also observed in patients treated with lower doses of YM175. These results demonstrate that YM175 is one of the most potent currently available bisphosphonates, and that the threshold for PTH secretion is elevated in at least some malignancy-associated hypercalcemia patients. In addition, there appears to be a difference in the threshold for PTH secretion between the decreasing and increasing serum Ca phases similar to the previously reported hysteresis phenomenon.

Adult↗
PubMed1994

A case of ectopic ACTH syndrome associated with Zollinger-Ellison syndrome: long-term survival with chemical adrenalectomy.

The female patient in this report was suffering from a pancreatic islet cell tumor which exhibited ectopic ACTH syndrome associated with Zollinger-Ellison syndrome. When this combined syndrome was diagnosed, there were already multiple metastasis to the liver. Zollinger-Ellison syndrome was treated with a histamine-H2-receptor blocker, and ectopic ACTH syndrome was controlled with trilostane, metyrapone and o,p'-DDD. She survived more than 6 years after the diagnosis, mostly as an outpatient. During treatment she became cachexic. After she died, an autopsy was done. Immunohistochemical staining established that tumor cells contained ACTH- and gastrin-like immunoreactivity. Our treatment suggested the efficacy of chemical adrenalectomy in managing ectopic ACTH syndrome associated with Zollinger-Ellison syndrome.

ACTH Syndrome, Ectopic↗
PubMed1994

Healing of chronic gastric ulcer depends on gastric mucosal prostaglandin synthesis.

In the present study, the role of endogenous prostanoid synthesis in gastric mucosa in the healing of chronic gastric ulcers was investigated. Nineteen patients were divided into two groups in accordance with healing state after one month of treatment with cimetidine only: "healed group" and "unhealed group". Biopsy specimens taken from the mucosa around the ulceration (damaged gastric mucosa) and at a distance from the ulceration (normal gastric mucosa) at endoscopy prior to treatment were homogenized, and the mucosal prostanoid synthesis was determined using [14C]arachidonic acid. The mean value of prostaglandin E2 synthesis in the normal gastric mucosa of the healed group was 60% higher than in that of the unhealed group, but the difference was not significant. However, prostaglandin E2 synthesis in the damaged gastric mucosa of the healed group was 117% higher than in that of the unhealed group. The same tendency was observed for prostaglandin D2 and 6-keto prostaglandin F1 alpha synthesis as for prostaglandin E2. In our study it was demonstrated that there is a good correlation of prostaglandin synthesis in the damaged mucosa with healing of chronic gastric ulceration. Furthermore, our study indicated that prostaglandin synthesis, especially in damaged mucosa, might be important in the healing of gastric ulceration.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Conversion of G-protein specificity of insulin-like growth factor II/mannose 6-phosphate receptor by exchanging of a short region with beta-adrenergic receptor.

The 14-residue peptide (peptide 14) corresponding to Arg2410-Lys2423 of the insulin-like growth factor II receptor (IGF-IIR) can activate the adenylate cyclase-inhibitor guanine nucleotide-binding protein Gi, and the 15-residue beta III-2 peptide Arg259-Lys273 of the beta 2-adrenergic receptor (beta 2AR) can activate the stimulatory protein Gs. In phospholipid vesicles, IGF-IIR and beta 2AR activate Gi and Gs in response to IGF-II and isoproterenol, respectively. We constructed a chimeric IGF-II receptor (beta III-2/IGF-IIR) by converting its native peptide 14 sequence to the beta III-2 sequence. In cells expressing beta III-2/IGF-IIR, membrane adenylate cyclase activity markedly increased without IGF-II and was further promoted by IGF-II. This was verified by measuring chloramphenicol acetyltransferase (CAT) activity in beta III-2/IGF-IIR cells with cotransfection of a cAMP response element-CAT construct. This study shows not only the conversion of G-protein specificity of a receptor from Gi to Gs but also the simulation of G protein-coupled receptor signals by using a short receptor region and intact cells. These findings indicate that the G protein-activation signals are interchangeable, self-determined structural motifs that function in the setting of either a single-spanning or multiple-spanning receptor.

Adenylyl Cyclases↗
PubMed1993

GTP-binding protein-activator sequences in the insulin receptor.

Some functions of the insulin receptor (insR) are assumed to be mediated by pertussis toxin-sensitive Gi/G(o) proteins. Here we have located G-protein-activator domains in the cytoplasmic region of the human insR. We searched the sequence of insR and found three candidate regions at residues 1039-1061, 1147-1168 and 1325-1345, referred to as ISRP1, ISRP2 and ISRP3, respectively. Among them, the Gi/G(o)-activating function was observed only in peptide ISRP3. ISRP1 specifically activated Gs, whereas ISRP2 had no effect on G proteins. ISRP2 and ISRP3 contained five of six autophosphorylated tyrosine residues in insR. After tyrosine phosphorylation, ISRP2 showed specific Gi-activating function, and ISRP3 potentiated its ability and became capable of activating G proteins generally. This is the first study that specifies G-protein-activator domains in insR and describes their modification by autophosphorylation.

Amino Acid Sequence↗
PubMed1993

22-Oxacalcitriol, a noncalcemic analogue of calcitriol, suppresses both cell proliferation and parathyroid hormone-related peptide gene expression in human T cell lymphotrophic virus, type I-infected T cells.

Human T cell lymphotrophic virus, type I (HTLV-I)-infected T cells overproduce parathyroid hormone-related peptide (PTHRP) and cause hypercalcemia in patients with adult T cell leukemia. The present study was undertaken to test whether 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and its noncalcemic analogue, 22-oxa-1,25-(OH)2D3 (OCT), could suppress cell proliferation and PTHRP gene expression in an HTLV-I-infected T cell line, MT-2. OCT as well as 1,25-(OH)2D3 inhibited the proliferation of MT-2 cells in a time- and dose-dependent manner. Cell cycle analysis revealed that OCT, like the parent compound, caused a transition delay of cells through the G1 phase. OCT and 1,25-(OH)2D3 decreased the steady state levels of PTHRP mRNA, and nuclear runoff assays demonstrated that the effect of OCT occurred at a transcription level. As a result, OCT caused a reduction in PTHRP concentrations in the conditioned medium by approximately 50%. OCT inhibited not only the basal secretion but also the stimulation of PTHRP secretion by interleukin-2 or cAMP, which we had identified as two important stimulators. Northern blot analysis and the specific uptake of [3H]1,25-(OH)2D3 revealed unexpectedly that the vitamin D receptor was abundantly expressed in MT-2 cells. These results suggest that OCT, as well as 1,25-(OH)2D3, has the potential to suppress both cell proliferation and PTHRP gene expression through binding to the vitamin D receptor overexpressed in HTLV-I-infected T cells.

Calcitriol↗
PubMed1993

Antitumor effect of 22-oxa-calcitriol, a noncalcemic analogue of calcitriol, in athymic mice implanted with human breast carcinoma and its synergism with tamoxifen.

The antitumor effect of 22-oxa-calcitriol (OCT), a newly developed noncalcemic analogue of calcitriol, was examined in vivo in athymic mice implanted with human breast carcinoma with or without estrogen receptor (ER). In ER-positive MCF-7 tumor, the growth of which was dependent on exogenous estrogen, administration p.o. of OCT as well as the antiestrogen tamoxifen five times a week for 4 weeks suppressed tumor growth in a dose-related fashion. The antitumor effect of 1.0 microgram/kg body weight (BW) OCT (mean +/- SEM of tumor weight in 6 mice: 28 +/- 4% of vehicle-treated group) was comparable to that of 2.0 mg/kg BW tamoxifen (25 +/- 6% of control group). In addition, a synergistic antitumor effect of submaximal doses of OCT and tamoxifen was observed in MCF-7 tumor in vivo as well as in ER-positive breast carcinoma cell lines (MCF-7 and ZR-75-1) in vitro. Administration of OCT p.o. three times a week for 4 weeks also suppressed the growth of ER-negative MX-1 tumor in a dose-dependent manner without raising serum calcium concentrations. The antitumor effect of 1.0 microgram/kg BW OCT (mean +/- SEM of tumor weight in 10 mice: 44 +/- 6% of vehicle-treated group) was greater than that of 500 micrograms/kg BW Adriamycin (71 +/- 6% of control group). These results indicate that OCT suppresses the growth of ER-negative as well as ER-positive breast carcinoma in vivo without causing hypercalcemia and that the antitumor effect of OCT can be enhanced by tamoxifen in an ER-positive tumor. It is suggested that OCT may provide a new strategy, either alone or in combination with other anticancer drugs, for systemic adjuvant therapy of breast carcinoma regardless of ER status.

Animals↗
PubMed1993

Role of calcium entry and protein kinase C in the progression activity of insulin-like growth factor-I in Balb/c 3T3 cells.

We previously reported that insulin-like growth factor-I (IGF-I) stimulated calcium entry (Kojima, I., Matsunaga, H., Kurokawa, K., Ogata, E., and Nishimoto, I. (1988) J. Biol. Chem. 263, 16561-16567) and production of 1,2-diacylglycerol in IGF-responsive "primed competent" Balb/c 3T3 cells (Kojima, I., Kitaoka, M., and Ogata, E. (1990) J. Biol. Chem. 265, 16846-16850). The present study was conducted to determine a role of protein kinase C (PKC) in the progression activity of IGF-I. To monitor the activity of PKC in intact cells, we measured phosphorylation of a synthetic KRTLRR peptide, a substrate of PKC, immediately after the permeabilization of the cells with digitonin. When 1 nM IGF-I was added to primed competent cells, KRTLRR peptide phosphorylation was augmented. IGF-I induced more than 2-fold increase in KRTLRR peptide phosphorylation that was blocked by PKC19-36, a pseudosubstrate of PKC, which blocks the activity of the kinase, and Ro31-8220, an inhibitor of PKC. The phosphorylation remained elevated for up to 6 h. To assess the role of PKC in cell cycle progression, IGF-I-induced nuclear labeling was measured in the presence of Ro31-8220. Ro31-8220 reduced the rate of entrance into S phase when added in the first quarter of the G1 phase, but did not affect cell cycle progression when added at the second quarter or later. In contrast, reduction of extracellular calcium completely blocked cell cycle progression when done in the first, second, and third quarter but had no effect in the last quarter. These results indicate that IGF-I persistently activates PKC in primed competent cells, but the activation is required only for the initiation of progression. We conclude that IGF-I promotes cell cycle progression by calcium-dependent mechanisms that are largely independent of PKC.

3T3 Cells↗
PubMed1993

Estrogen stimulates the elaboration of cell/matrix surface-associated inhibitory factor of osteoclastic bone resorption from osteoblastic cells.

Osteoblast-like UMR106 cells secreted bone resorption-stimulating activity (BRSA) under stimulation by human parathyroid hormone 1-34. Most of BRSA was associated with cell/matrix surface and could be extracted by 2 M NaCl. Pretreatment with 17 beta-estradiol (E2) reduced BRSA by enhancing the elaboration of an inhibitory factor of BRSA in a dose-dependent manner, and 10(-9) M 17 beta-E2 showed a significant effect. Neither 17 alpha-E2 nor dihydrotestosterone showed a similar effect. The inhibitory factor of BRSA was also bound to cell/matrix surface, showed affinity for heparin, and was trypsin- and heat-sensitive. Furthermore, this factor could also inhibit resorption pit formation stimulated by 1,25-dihydroxyvitamin D3, interleukin (IL)-1 alpha and IL-6. Elaboration of such an inhibitory factor of bone resorption from osteoblasts may play an important role in the protective effect of estrogen against bone resorption.

Animals↗
PubMed1993

Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o)

The most characteristic change in progressive dementia of Alzheimer's type is a tissue deposit of amyloid beta/A4 protein, which is derived from its precursor protein APP (ref.2). Structural alterations of APP are implicated in the pathogenesis of Alzheimer's disease, but it is not known how they cause the disease. Although APP has a receptor-like architecture, is located on the neuronal surface, and has a conserved cytoplasmic domain, no receptor function has been demonstrated for APP. Here we report that APP forms a complex with G(o), a major GTP-binding protein in brain. The cytoplasmic APP sequence His 657-Lys 676 shows a specific G(o)-activating function and is necessary for complex formation. G(o) protein treated with GTP-gamma S lost the ability to associate with APP. This suggests that APP is a receptor coupled to G(o) and that abnormal APP-G(o) signalling is involved in the Alzheimer's disease process.

Amino Acid Sequence↗
PubMed1993

Transcription of the gene for parathyroid hormone-related peptide from the human is activated through a cAMP-dependent pathway by prostaglandin E1 in HTLV-I-infected T cells.

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), and hypercalcemia frequently associated with ATL is mediated by parathyroid hormone-related peptide (PTHRP). The present study was undertaken to clarify the role of cAMP second messenger system in the regulation of human PTHRP gene expression in ATL cells, using an HTLV-I-infected T-cell line, MT-2. Forskolin and dibutyryl cAMP (Bt2cAMP) caused a marked and transient increase in the steady-state level of PTHRP mRNA. The effects of these agents were dose-dependent, and the maximal effects were observed at 3 h. Nuclear runoff transcription assay showed that forskolin and Bt2cAMP caused an increase in the transcription rate of the human PTHRP gene. In contrast, the stability of PTHRP mRNA was only modestly increased by these agents. Forskolin and Bt2cAMP also increased the secretion of PTHRP by MT-2 cells, as determined by both a newly established immunoradiometric assay using two antibodies against human PTHRP-(1-34) and PTHRP-(50-83) and a radioimmunoassay using an antibody against human PTHRP-(109-141). Prostaglandin E1 (PGE1) caused a marked stimulation of intracellular cAMP production in MT-2 cells, whereas PGE2 and PGF2 alpha had only modest effects. The ability of these PGs to stimulate cAMP production correlated well with their ability to increase PTHRP mRNA level and the secretion of PTHRP. Indomethacin did not affect the basal level of cAMP production or PTHRP mRNA, suggesting that endogenous PG was not involved in the basal production of cAMP or PTHRP. When PGE1 was given to MT-2 cells together with interleukin 2, which is another stimulator of PTHRP gene expression, PTHRP secretion was synergistically stimulated. These results suggest that the transcription of the human PTHRP gene is enhanced through a cAMP-dependent pathway by PGE1 and that PGE1, as well as interleukin 2, plays an important role in the overexpression of the human PTHRP gene in HTLV-I-infected T cells leading to the development of hypercalcemia in ATL patients.

Alprostadil↗
PubMed1993

Effects of transforming growth factor beta 1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells.

Proteoglycans synthesized by osteoblasts are incorporated into bone matrix and thought to play a role in bone metabolism. Transforming growth factor (TGF) beta affects the synthesis of matrix proteins, including proteoglycans, in various stromal cells, and proteoglycans, especially decorin, are associated with matrix collagen. In the present study, the effects of TGF-beta 1 and L-ascorbate, a factor essential for collagen synthesis, on the synthesis and distribution of proteoglycans were examined using murine osteoblast-like MC3T3-E1 cells. TGF-beta 1 stimulated the synthesis of proteoglycans in MC3T3-E1 cells. Among various proteoglycans, the synthesis of decorin was preferentially enhanced by TGF-beta 1, and the effect was more pronounced on secreted decorin compared to that associated with the cell/matrix layer. TGF-beta 1 also stimulated the initiation and elongation of the dermatan sulfate glycosaminoglycan chain, resulting in a larger molecular size of decorin. TGF-beta 1 influenced the synthesis of a heparan sulfate proteoglycan only slightly. L-ascorbate had no effect on the synthesis of proteoglycans, but increased those associated with the cell/matrix layer. Furthermore, when L-ascorbate was added to the culture along with TGF-beta 1, the percentage of proteoglycans associated with the cell/matrix layer increased from 25.8 +/- 1.0 to 41.0 +/- 0.5%. These data demonstrate that TGF-beta 1 markedly stimulates the synthesis of proteoglycans, especially decorin, mainly as a secreting form, that the accumulation of decorin into matrix is enhanced by L-ascorbate, and that the effects of TGF-beta 1 and L-ascorbate are additive.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1993

Effect of 24R,25-dihydroxyvitamin D3 on the formation and function of osteoclastic cells.

Previous reports demonstrated that the administration of large doses of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] to animals with normal vitamin D supply causes an increase in bone volume with reduced bone resorption and decreased osteoclast number. The present study was undertaken to clarify if 24R,25(OH)2D3 has any inhibitor effect on the formation and function of osteoclasts. The effect of 24R,25(OH)2D3 on the formation of osteoclastic cells was examined by measuring the number of tartrate-resistant acid phosphatase-positive multinucleated cells (MNCs) formed from hemopoietic progenitor cells obtained from spleens of 5-fluorouracil-treated mice. Treatment with 1,25(OH)2D3 or parathyroid hormone fragment 1-34 [PTH(1-34)] stimulated osteoclast-like MNC formation in a dose-dependent manner. Addition of 24R,25(OH)2D3 alone showed a weak stimulatory effect on MNC formation at 10(-6) M, which appeared to be due to its binding to 1,25(OH)2D3 receptors. In contrast, when 24R,25(OH)2D3 was added together with 1,25(OH)2D3 or PTH(1-34), it inhibited osteoclast-like MNC formation stimulated by these hormones. A significant inhibition of MNC formation was observed with 10(-7) M 24R,25(OH)2D3, and the stimulatory effect of 1,25(OH)2D3 or PTH(1-34) was almost completely eliminated with 10(-6) M 24R,25(OH)2D3. Neither 24S,25(OH)2D3 nor 25(OH)D3 exhibited a similar inhibitory effect. The effect of 24R,25(OH)2D3 on the resorptive function of osteoclasts was examined by measuring the formation of resorption pits by mouse bone cells on dentine slices. Treatment with 24R,25(OH)2D3 also inhibited the resorption pit formation stimulated by 1,25(OH)2D3 or PTH(1-34) with similar dose response.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗