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Biomedical subjects

Takami Miki

Publications and source records attributed to Takami Miki.

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

[Strontium ranelate].

Strontium ranelate, which has dual effects of decreasing bone resorption and increasing bone formation, is a new orally active drug to treat osteoporosis. Although the clinical values are scientifically proved and the governments admit as one of the treatment for osteoporosis in many countries, the clinical trial is still undergoing in Japan.

Aged↗
PubMed2006

[Bisphosphonate or Raloxifene?: which drug we can choose for osteoporotic patients?].

Raloxifene is preferred because of free from empty stomach and amelioration of lipid metabolism in spite of the significant effect of bisphosphonate on BMD and metabolic markers. As compliance is essential for the prevention of fracture, physicians should discuss about the treatment with their patients. There are no scientific evidences which drug is more suitable to osteoporotic patients. Therefore, bisphosphonate is recommended to the patients with severe osteoporosis, recognition of the disease, and/or expectation for the prevention of hip fracture by the treatment, on the condition that patients are not vitamin D deficiency. Raloxifene is recommended to the patients with mild osteoporosis, poor recognition of the disease, and/or low risk of the new fracture (s). The hyperlipidemic patients with osteoporosis are another candidates for raloxifene.

Bone Density↗
PubMed2006

[Metabolic markers of bone--post-guideline].

Metabolic markers of bone are common clinical parameters for the evaluation of the pathophysiologic conditions and efficacy of the treatment, although they are not helpful for differential diagnosis of osteoporosis. The guideline published officially is helpful for practitioners and non-experts in the field. The distributions of urinary NTX and bone specific alkaline phosphatase are essentially same between primary osteoporotic postmenopausal women less than 70 years old and those over 70 years. No differences were found in the other metabolic markers between these groups. Although clinical evidence for patients over 85 years old is not enough, we do not have to think of age in the clinical application of metabolic markers of bone, if renal functions are within normal ranges.

Aged↗
PubMed2006

[Biochemical markers of bone in steroid (glucocorticoid)-induced osteoporosis (GIOP)].

The pathogenesis of steroid (glucocorticoid)-induced bone loss is still unclear. But, bone formation is known to be quickly decreased in early stage of steroid administration, followed by reduction of bone resorption. The reductions of bone resorption markers are small if low dose of steroid is administered, and the changes are accelerated dose dependently, probably due to secondary hyperparathyroidism. The short term intravenous administration of steroid induces transient suppression of bone turnover even in high dose administration. Therefore, it seems that the degree of changes in bone turnover markers induced by steroid is affected not only by the dosage but also by the period of steroid administration. The reduction of osteocalcin is more sensitive than bone alkaline phosphatase for the detection of the suppression of bone formation, although metabolism of osteocalcin induced by steroid may influence the change.

Alkaline Phosphatase↗
PubMed2006

Implementation and evaluation of standardized patient observation master to the nursing directions system in health facilities for recuperation.

In this study we developed the observation item list from the evaluation of Nursing Observation Master published by MEDIS-DC with the aim of implementing a nursing observation ordering system for convalescent wards in a general hospital. After development, the nursing observation item list and observation ordering system based on it were implemented in clinics and evaluated by clinical staffs.

Humans↗
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

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

A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial.

CONTEXT: ED-71 has been shown to increase lumbar bone mineral density (BMD) in osteoporotic subjects. However, vitamin D insufficiency might have influenced the effect of ED-71 on BMD. OBJECTIVE: Our objective was to examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation. DESIGN, SETTING, AND PATIENTS: We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49-87 yr of age). INTERVENTIONS: Subjects were randomly assigned to receive placebo or 0.5, 0.75, or 1.0 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D(3). MAIN OUTCOME MEASURES: We assessed changes in lumbar and hip BMD and bone turnover markers from baseline. RESULTS: Lumbar BMD increased with ED-71 treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8% vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 microg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 microg ED-71 (-0.8, 0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 microg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in 7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively, but none of them developed sustained hypercalcemia. CONCLUSIONS: These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.

Absorptiometry, Photon↗
PubMed2005

Altered relationship between body fat and plasma adiponectin in end-stage renal disease.

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.

Adiponectin↗
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↗