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Biomedical subjects

Yasuo Imanishi

Publications and source records attributed to Yasuo Imanishi.

At least 19 recordsLinked to original sources
PubMed2007

Annual change in bone mineral density in predialysis patients with chronic renal failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D.

Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The aim of this study was to examine how a decrease in renal function affects annual bone mineral density (BMD) changes in predialysis CRF patients and to examine the factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF patients (age, 61.3 +/- 10.8 years; serum creatinine 2.7 +/- 1.2 mg/dl) was measured by peripheral quantitative computed tomography (pQCT) twice with a 1-year interval. The total BMD of the radius significantly decreased over a year (P < 0.001), and both trabecular and cortical BMD showed a significant decrease. Significant positive correlations with BMD changes were found for estimated creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)(2)D (r = 0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger reductions in creatinine clearance and serum 1,25(OH)(2)D. Of several bone metabolic markers examined, baseline serum osteocalcin was significantly positively correlated with annual BMD changes (r = -0.276, P < 0.05). Multiple regression analysis showed that baseline serum 1,25(OH)(2)D (beta = 0.434) was a significant predictor of decreases in total and trabecular BMD (R (2) = 0.188, P < 0.01; and R (2) = 0.207, P < 0.01), independent of other confounding factors. These results indicate that BMD decreases as renal function deteriorates in predialysis CRF patients, and that osteocalcin is a clinically useful marker associated with the decrease in BMD. The serum 1,25(OH)(2)D level is the principal factor affecting BMD of the radius, suggesting that supplementation with an active form of vitamin D is of importance for predialysis CRF patients.

Aged↗
PubMed2006

Direct in vitro evidence of the suppressive effect of cinacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels.

Clinical studies have been performed to determine the effect of cinacalcet HCl (cinacalcet), an allosteric modulator of the calcium-sensing receptor (CaR), on primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism of uremia (SHPT). However, no in vitro studies on human parathyroid cells have been reported to date. In this study, the inhibitory effect of cinacalcet on PTH secretion was analyzed in primary cultured parathyroid cells obtained from patients. The investigation involved three PHPT and three SHPT patients subjected to therapeutic parathyroidectomy. Notably, all SHPT patients were resistant to intravenous vitamin D analogue therapy. Removed parathyroid tumors were used for immunohistochemistry and parathyroid cell primary culture. Immunohistochemical analyses revealed diminished expression of CaR and vitamin D receptor (VDR) in all parathyroid tumors. PTH secretion from cultured parathyroid cells of PHPT and SHPT patients was suppressed by extracellular Ca2+ and cinacalcet in a dose-dependent manner. Rates of suppression of PTH secretion in PHPT and SHPT by cinacalcet (1000 nmol/l) were 61% +/- 21% and 61% +/- 19%, respectively. Cinacalcet demonstrates significant potency in the suppression of PTH secretion in primary cultured human parathyroid cells in vitro, despite reduced levels of the target protein, CaR. Data from this in vitro analysis support the clinical application of cinacalcet in PHPT and SHPT therapy.

Cinacalcet↗
PubMed2006

Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism.

OBJECTIVE: While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT)-PCR and immunohistochemistry. RESULTS: FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23. CONCLUSIONS: Serum calcium may regulate circulating FGF-23 levels in PHPT.

Calcium↗
PubMed2006

[Bone and bone related biochemical examinations. Hormone and hormone related substances. The measurement of circulating fibroblast growth factor 23 (FGF-23)].

Fibroblast growth factor 23 (FGF-23) is a phosphaturic peptide involving in the development of hypophosphatemic rickets/osteomalacia. FGF-23 assays are known to be useful for the diagnosis of hypophosphatemia. Now three different two-site enzyme-linked immunosorbent assays a C-terminal human FGF23 enzyme-linked immunosorbent assay (ELISA) (Immunotopics, California), an intact human FGF23 ELISA (Immunotopics, California), and another intact human FGF23 ELISA (Kainos Laboratories, Japan) are available for the diagnosis.

Enzyme-Linked Immunosorbent Assay↗
PubMed2006

[Activate vitamin D3 or bisphosphonate in glucocorticoid-induced osteoporosis].

Glucocorticoid therapy is associated with bone loss starting soon after the therapy is initiated and an increased risk of fracture. Activated forms of vitamin D(3), which are frequently prescribed for postmenopausal osteoporosis in Japan, are one of a useful agent to prevent glucocorticoid-induced osteoporosis. In this review, the effect of activate form vitamin D(3) is compared with plain vitamin D or bisphosphonate.

Bone Density Conservation Agents↗
PubMed2005

Positive correlation of serum bio-intact PTH(1-84) but not intact PTH with parathyroid gland size in hemodialysis patients.

To evaluate the usefulness of newly-developed bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH(1-84) molecule, serum PTH level determined by Bio-PTH assay, in comparison with second-generation intact PTH (I-PTH) assay, was examined for its correlation with parathyroid gland size. Serum PTH was determined in 46 male HD patients, together with bone formation markers bone alkaline phosphatase, intact osteocalcin, N-terminal propeptide of type I collagen, and bone resorption markers deoxypyridinoline, pyridinoline, beta-crossLaps. Maximal diameter of parathyroid gland was determined with ultrasonography as the parathyroid gland size. Serum Ca and Pi correlated significantly with parathyroid gland size rationalizing our method to define parathyroid gland size. Serum Bio-PTH was correlated significantly in a positive manner with parathyroid gland size (R = 0.308, P = 0.0474), whereas serum I-PTH did not. Furthermore, parathyroid gland size did not exhibit a significant correlation with any of bone formation markers or bone resorption markers. The lack of correlation between bone markers and parathyroid gland size in HD patients may be explained by the occurrence of refractoriness of bone to PTH. In conclusion, serum Bio-PTH assay could provide a better assay than I-PTH assay to estimate parathyroid function in HD patients, due mainly to its exclusive correlation with parathyroid gland size.

Alkaline Phosphatase↗
PubMed2005

Expression of FGF23 is correlated with serum phosphate level in isolated fibrous dysplasia.

Fibrous dysplasia (FD) patients sometimes suffer from concomitant hypophosphatemic rickets/osteomalacia, resulting from renal phosphate wasting. It was recently reported that FD tissue in the patients with McCune-Albright syndrome (MAS) expressed fibroblast growth factor-23 (FGF-23), which is now known to be as a pathogenic phosphaturic factor in patients with oncogenic osteomalacia and X-linked hypophosphatemic rickets. Since it remains controversial whether serum phosphate levels are influenced by FGF23 expressions in FD tissue, isolated FD patients without MAS syndrome were examined for the relationship between FGF23 expressions, circulating levels of FGF-23 and phosphate to negate the effects of MAS-associated endocrine abnormalities on serum phosphate. Eighteen paraffin embedded FD tissues and 2 frozen tissues were obtained for the study. Sixteen of 18 isolated FD tissues were successfully analyzed GNAS gene, which exhibited activated mutations observed in MAS. Eight of 16 FD tissues, which exhibited GNAS mutations, revealed positive staining for FGF-23. These evidence indicate that postzygotic activated mutations of GNAS is necessary for the FD tissue formation by mosaic distribution of mutated osteogenic cell lineage, but is not sufficient to elevate FGF23 expression causing generalized osteomalacia with severe renal phosphate wasting. The expression level of FGF23 in isolated FD tissue with hypophosphatemic osteomalacia determined by real-time PCR was abundant close to the levels in OOM tumors. Osteoblasts/osteocytes in woven bone were predominant source of circulating FGF-23 in FD tissues by immunohistochemistry. A negative correlation of the intensity of FGF-23 staining with serum inorganic phosphate levels indicated that the expression of FGF23 in focal FD tissues could be a prominent determinant of serum phosphate levels in isolated FD patient. These data provide novel insights into the regulatory mechanism of serum inorganic phosphate levels in isolated FD patients and extend the notion that FGF-23 originating from FD tissue may cause hypophosphatemia not only in isolated FD patients but also in the patients with MAS syndrome.

Adolescent↗
PubMed2005

Associations between physical activity, peripheral atherosclerosis and bone status in healthy Japanese women.

The aim of this cross-sectional study was to investigate whether physical activity and bone status may affect arterial thickening and stiffening in healthy Japanese women. Healthy women (n = 149; mean age, 54 years) were recruited from those who participated in a local health check program at the Osaka City University Hospital. Physical activity was assessed by physical functioning score of SF-36, and bone status by bone mineral density (BMD) in lumbar spine and calcaneus osteo-sono index (OSI). Arterial wall thickening assessed by intima-media thickness (IMT) in common carotid artery (CA) and femoral artery (FA), and arterial wall stiffening by peak wave velocity (PWV) in heart-carotid (hc) and heart-femoral (hf) as central segment and in heart-brachial (hb) and femoral-ankle (fa) as peripheral segment, respectively. By Spearman Rank correlation, lumbar spine BMD was correlated negatively with CA IMT (rho = -0.225, p < 0.05) and FA IMT (rho = -0.215, p < 0.05), and calcaneus OSI with FA IMT (rho = -0.330, p < 0.0001) but not CA IMT (rho = -0051, p = 0.5335). Both lumbar spine BMD and calcaneus OSI correlated negatively with PWV in all segments (all p < 0.05). Physical functioning score correlated weakly but significantly in a negative manner with all PWV segments (all p < 0.05) but not IMT. Multiple regression analyses revealed a significant association of calcaneus OSI (beta = -0.240, p = 0.0039) but not lumbar spine BMD (beta = -0.067, p = 0.4541) with FA IMT, although neither lumbar spine BMD nor calcaneus OSI was associated with CA IMT. Furthermore, physical functioning score was independently associated with hb and fa PWV but not hc and hf PWV, suggesting the preferential association with peripheral segment including lower extremities. Neither lumbar spine BMD nor calcaneus OSI was associated with any segment of PWV. In conclusion, it was suggested that calcaneus OSI might be associated with arterial wall thickening preferentially in femoral artery, and that physical activity may be associated with arterial wall stiffening in peripheral segment including lower extremity but not in central segment in healthy Japanese women.

Atherosclerosis↗
PubMed2005

Serum levels of 1-84 and 7-84 parathyroid hormone in predialysis patients with chronic renal failure measured by the intact and bio-PTH assay.

BACKGROUND: The intact parathyroid hormone (PTH) assay detects both PTH(1-84) and the PTH(7-84)-like fragment, which is reported to be an antagonist of the biological action of PTH(1-84). It is debatable which of the two assays is clinically more useful, the intact or bio-PTH assay, the latter of which only detects PTH(1-84). It is also unknown whether serum levels of the PTH(7-84)-like fragment have clinical significance. METHODS: Serum PTH concentrations in 104 predialysis patients with chronic renal failure (CRF; serum creatinine 3.53 +/- 1.93; 62 males and 42 females; 61.0 +/- 11.5 years old) were measured using both the intact and bio-PTH assays, and the concentration of the PTH(7-84)-like fragment was calculated by subtracting bio-PTH from intact PTH. Three bone formation and three bone resorption markers were measured simultaneously. RESULTS: The PTH values measured using the two assays were strongly positively correlated (r = 0.959, p < 0.0001), and were also significantly positively correlated with the three bone formation and three bone resorption markers to a similar degree. The PTH(7-84)-like fragment was significantly positively correlated with both the intact and bio-PTH (r = 0.855, p < 0.0001 for intact PTH; r = 0.672, p < 0.0001 for bio-PTH), and was also significantly positively correlated with each of the six bone metabolism markers. There is no significant relationship between the bio-PTH/PTH(7-84)-like fragment ratio and clinical parameters including bone metabolic markers. CONCLUSION: From the strong relationship between the two assays, and the similar degree of the relationship between each PTH assay and each of the six bone metabolism markers, it is considered that the bio-PTH and intact PTH assays have similar clinical significance in predialysis CRF patients. Serum levels of the PTH(7-84)-like fragment seem to increase as serum PTH(1-84) increases. The results suggest that the serum PTH(7-84)-like fragment has little specific clinical effect on bone metabolism, even when assessed by the ratio of bio-PTH/PTH(7-84)-like fragment.

Blood Chemical Analysis↗
PubMed2005

Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells.

CONTEXT: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process. OBJECTIVE: Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro. METHODS: The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies. RESULTS: The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+. CONCLUSIONS: These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells.

Calcium↗
PubMed2005

The role of fibroblast growth factor 23 for hypophosphatemia and abnormal regulation of vitamin D metabolism in patients with McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia and abnormally low levels of 1,25(OH)(2)D in the presence of hypophosphatemia. Recently, fibroblast growth factor 23 (FGF-23) was reported as a phosphaturic and a causal factor of abnormal vitamin D metabolism. This abnormal phosphate and vitamin D metabolism is well known to be found in oncogenic and X-linked hypophosphatemia. We furthermore reported increased circulating plasma FGF-23 levels in patients with oncogenic and X-linked hypophosphatemia. To determine whether FGF-23 may be involved in the pathogenesis of MAS, we measured plasma FGF-23 levels in six MAS patients. As a control for hypophosphatemia, we also investigated the plasma FGF-23 levels in two patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We also investigated the correlation of plasma FGF-23 levels with serum phosphate and 1,25(OH)(2)D levels after short-term pamidronate therapy in three MAS patients. Plasma FGF-23 levels were significantly increased in patients with MAS compared to normal controls, whereas they were not increased in HHRH patients. Serum phosphate levels of the MAS patients were significantly lower than those observed in normal controls. Plasma FGF-23 levels showed significant negative correlation with serum phosphate concentrations. In three MAS patients, pamidronate therapy decreased plasma FGF-23 levels, which showed significant negative correlation with serum 1,25(OH)(2)D concentrations. These data suggested that FGF-23 is a possible causal factor for hypophosphatemia and abnormal vitamin D metabolism in MAS.

Adolescent↗
PubMed2005

Cimetidine-induced tubulointerstitial nephritis with both MPO-ANCA and PR3-ANCA.

We describe a 75-year-old man with tubulointerstitial nephritis (TIN) with myeloperoxidase (MPO)-antineutrophil antibody (ANCA) and proteinase-3 (PR3)-ANCA. He had a slight fever and eruption with itching after taking cimetidine (prescribed after gastrectomy for gastric cancer) and he was admitted to a nearby hospital. There, he showed proteinuria, serum creatinine (sCr) of 2.9 mg/dl, and creatinine clearance (Ccr) of 44 ml/min per 1.73 m2. His MPO-ANCA titer was 267 EU, and PR3-ANCA titer was 112 EU. Abnormal concentrations in bilateral kidneys were found by gallium scintigraphy. For these reasons, he was transferred to our hospital. Percutaneous renal biopsy was performed after admission. Severe tubular atrophy, mild interstitial fibrosis, and severe mononuclear cell infiltration of the interstitium were noted. Drug-induced renal impairment was suspected, and cimetidine administration was withdrawn. Lymphocyte stimulation tests (DLSTs) were performed. The cimetidine titer was positive, at 2,537 cpm. After the withdrawal of cimetidine, the PR3-ANCA titer was reduced gradually, and, next, the MPO-ANCA titer was also reduced. The sCr level was reduced to 1.2 mg/dl. In summary, we report herein the first case of cimetidine-induced TIN associated with both MPO-ANCA and PR3-ANCA.

Aged↗
PubMed2005

Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism.

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet's effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93-99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.

Aging↗
PubMed2005

Hypercalcemia in a patient with primary hyperparathyroidism and acromegaly: distinct roles of growth hormone and parathyroid hormone in the development of hypercalcemia.

We herein report a case of primary hyperparathyroidism associated with acromegaly. Although serum parathyroid hormone (PTH) levels increased after the resection of a pituitary adenoma, levels of serum 1a, 25-dihydroxyvitamin D [1, 25(OH)2D] decreased but remained above the normal upper limit. After resection of a parathyroid adenoma, serum PTH, 1, 25(OH)2D, calcium (Ca), and phosphate were all normalized. Since serum 1, 25(OH)2D levels decreased in spite of the increase in serum PTH levels after normalization of levels of growth hormone (GH), GH may have contributed to the elevation of serum 1, 25(OH)2D. It is therefore suggested that the mechanism by which elevation of serum 1, 25(OH)2D occurred in the present case may involve an increase in serum GH distinct from the PTH-mediated pathway.

Acromegaly↗
PubMed2005

[Strontium Ranelate as a new therapeutic agent for osteoporosis].

Strontium ranelate is a new chemical entity, which was recently demonstrated to reduce the fracture risk in osteoporosis patients. This unique compound has both stimulatory effect of osteoblast-mediated bone formation and inhibitory effect of osteoclast-mediated bone resorption, leading to increased bone mass.

Bone Density↗
PubMed2005

[Correlation of serum Bio-intact PTH (1-84) and parathyroid gland size in hemodialysed patients].

Bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH (1-84) molecule, provides a better assay for estimating parathyroid function in hemodialysis (HD) patients, whereas intact PTH (I-PTH) assay cross-react with PTH (7-84) as well as PTH (1-84). We have found that PTH (7-84) accumulated into serum of hemodialysis patients due probably to its impaired excretion into urine. We have reported that parathyroid gland size is one of major predictor for vitamin D responsiveness in secondary hyperparathyroidism. Therefore, we investigated whether serum Bio-PTH, in comparison with serum I-PTH, may provide a relevant assay to estimate parathyroid function as evidence by its correlation with parathyroid gland size on ultrasound examination.

Biomarkers↗