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Biomedical subjects

Toshitsugu Sugimoto

Publications and source records attributed to Toshitsugu Sugimoto.

At least 19 recordsLinked to original sources
PubMed2006

Acromegaly associated with monoclonal gammopathy of undetermined significance (MGUS).

Here we report the case of a 65-year-old woman with acromegaly complicated with monoclonal gammopathy of undetermined significance (MGUS). The patient visited Shimane University Hospital for treatment of spinal canal stenosis, and was diagnosed as acromegaly with GH 43.1 ng/ml, insulin-like growth factor (IGF)-I 510 ng/ml and the detection of a pituitary adenoma by MRI. She was also diagnosed as MGUS with IgG 2208 mg/dl, the existence of IgG-kappa type monoclonal protein, and 5.6% plasma cells in bone marrow. After a pituitary adenoma was operatively removed by transsphenoidal approach, IgG levels, as well as GH and IGF-I levels, decreased spontaneously and simultaneously. We suspect a pathogenetic link between acromegaly and MGUS in this case, because both GH and IGF-I are known to directly promote immunoglobulin production from plasma cells, thus inducing the proliferation of the cells in vitro.

Acromegaly↗
PubMed2006

Parathyroid hormone increases beta-catenin levels through Smad3 in mouse osteoblastic cells.

PTH, via the PTH/PTH-related protein receptor type 1 that couples to both protein kinase A (PKA) and protein kinase C (PKC) pathways, and the canonical Wnt-beta-catenin signaling pathway play important roles in bone formation. In the present study we have examined the interaction between the PTH and Wnt signaling pathways in mouse osteoblastic MC3T3-E1 cells. PTH dose- and time-dependently increased the concentrations of beta-catenin. The PKA activator, forskolin, and the PKC activator, phorbol 12-myristate-13-acetate, as well as the PTH analog, [Nle(8,18),Tyr(34)]human PTH-(3-34)amide, all increased beta-catenin levels. Both H-89, a specific PKA inhibitor, and PKC inhibitors, staurosporine and calphostin C, antagonized PTH stimulation of beta-catenin levels. TGF-beta as well as transfection of the TGF-beta-signaling molecule, Smad3, enhanced beta-catenin levels, and this was antagonized by transfection of a dominant-negative Smad3. The transcriptional activity of transfected dominant-active beta-catenin was enhanced by PTH, an effect that was antagonized by cotransfection of a dominant-negative Smad3. PTH as well as LiCl(2), which mimics the effects of the Wnt-beta-catenin pathway, rescued the dexamethasone- and etoposide-induced apoptosis of osteoblastic cells. In conclusion, the data demonstrate that PTH stimulates osteoblast beta-catenin levels via Smad3, and that both PKA and PKC pathways are involved. The canonical Wnt-beta-catenin pathway is likely to be involved in the antiapoptotic actions of PTH by acting through Smad3 in osteoblasts.

Animals↗
PubMed2006

A paranasal tumor associated with tumor-induced osteomalacia.

BACKGROUND: Tumor-induced osteomalacia (TIO) is an extremely rare paraneoplastic syndrome associated with mesenchymal tumors in the craniofacial region. METHODS: We treated a 24-year-old Japanese woman with paranasal sinus tumor and a low serum phosphate level who presented with nasal obstruction and systemic bone fractures. Serum fibroblast growth factor 23 (FGF-23) was measured before and after surgery. RESULTS: After surgery, her symptoms were resolved and the serum phosphate and FGF-23 levels became normalized. CONCLUSION: FGF-23 is thought to be a useful diagnostic marker in patients with craniofacial tumors associated with multiple systemic fractures.

Adult↗
PubMed2006

Expression and functional analysis of menin in a multiple endocrine neoplasia type 1 (MEN1) patient with somatic loss of heterozygosity in chromosome 11q13 and unidentified germline mutation of the MEN1 gene.

In some patients with multiple endocrine neoplasia type 1 (MEN1) it is not possible to identify a germline mutation in the MEN1 gene. We sought to document the loss of expression and function of the MEN1 gene product, menin, in the tumors of such a patient. The proband is an elderly female patient with primary hyperparathyroidism, pancreatic islet tumor, and breast cancer. Her son has primary hyperparathyroidism. No germline MEN1 mutation was identified in the proband or her son. However, loss of heterozygosity at the MEN1 locus and complete lack of menin expression were demonstrated in the proband's tumor tissue. The proband's cultured parathyroid cells lacked the normal reduction in proliferation and parathyroid hormone secretion in response to transforming growth factor- beta. This assessment provided insight into the molecular pathogenesis of the patient and provides evidence for a critical requirement for menin in the antiproliferative action of transforming growth factor-beta.

Aged↗
PubMed2006

The threshold of bone mineral density for vertebral fracture in female patients with glucocorticoid-induced osteoporosis.

Glucocorticoid (GC)-induced osteoporosis (GIO) is a serious problem for patients taking GC therapy. GC increases risk for fracture. However, there are controversies regarding the threshold of bone mineral density (BMD) in patients with GIO. The present study aimed to examine the relationship between the presence or absence of vertebral fracture and various indices including BMD in 136 female Japanese patients treated with oral GC (102 patients with autoimmune diseases). Moreover, we analyzed the cut-off values of BMD for incidence of vertebral fracture in patients with oral GC use and compared these values with those in control subjects. BMD was measured by dual-energy X-ray absorptiometry of the lumbar spine, femoral neck, and distal one third of radius. We compared various indices between patients taking oral GC with and without vertebral fracture. Age, body height, and body weight were significantly greater, shorter, and lower in the group with vertebral fracture, respectively. As for BMD, age-matched BMD seemed lower in the fracture group, although the differences were significant between both groups only at the femoral neck. Duration of GC treatment was longer in the fracture group. Cut-off values of BMD at lumbar spine, femoral neck, and distal radius were higher in patients with GC treatment compared with those of control group [GC vs control (g/cm(2)): 0.807 vs 0.716 at lumbar spine; 0.611 vs 0.581 at femoral; 0.592 vs 0.477 at radius]. The sensitivity and specificity were lower in patients with GC treatment compared with those of control group. The present study demonstrated that the thresholds of BMD for vertebral fracture were higher in Japanese female patients with oral GC treatment at any site compared with postmenopausal subjects. The factors other than BMD were considered to affect bone strength and vertebral fracture risk.

Absorptiometry, Photon↗
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

[Treatment of primary osteoporosis in men].

Primary osteoporosis in men occurs less frequently and thus tends to be less noticed than that in women. However, once a femoral neck fracture occurs in men, patients are more likely to be disabled than women. Thus, implementing treatments of osteoporosis before the occurrence of femoral neck fractures is important in terms of men's quality of life. Several studies have shown that bisphosphonate is a mainstay of the treatment of the disorder, by increasing bone mineral density and reducing the risk of vertebral fractures.

Bone Density Conservation Agents↗
PubMed2006

[Calcium homeostasis and diabetes mellitus].

Diabetes mellitus is associated with various organ dysfunctions through hyperglycemia, insulin deficiency, or advanced glycation end products, which can also cause impaired calcium homeostasis such as the reductions of parathyroid hormone secretion, vitamin D receptor (VDR) number, and 25- (OH) vitamin D-1 alpha-hydroxylase activity in the parathyroid gland, intestine, and kidney, respectively. On the contrary, abnormal calcium homeostasis such as vitamin D deficiency/insensitivity and hyperparathyroidism can cause glucose intolerance or diabetes. Vitamin D deficiency/insensitivity induces type 2 diabetes through impaired insulin secretion involving VDR on pancreatic beta cells, as well as type 1 diabetes through the reduction in immuno-modulatory action of 1,25 (OH)(2) vitamin D. Primary hyperparathyroidism induces glucose intolerance via insulin resistance due to elevated intracellular calcium in the targeted organ of insulin.

Animals↗
PubMed2006

[Increased fracture rate in patients with type 2 diabetes mellitus is independent of its bone mineral density].

Several large-scale clinical studies have recently revealed that both type 1 and type 2 diabetic patients are at higher risk for some fractures than those without diabetes. The fracture rate of type 1 diabetic patients has been reported to increase due to decreased bone mineral density. Type 2 diabetic patients also suffer from increased fracture rate, but bone mineral density is almost the same as those without diabetes, or even increase. Thus, the etiologies of fractures seem to be different between type 1 and type 2 diabetic patients. Increased fracture rate in type 2 diabetic patients may be partly explained by poor bone quality as well as the extra-skeletal factors like falling. Further studies are needed to clarify bone quality and the etiology of fractures in type 2 diabetes.

Bone Density↗
PubMed2006

[Anabolic treatment for osteoporosis: PTH treatment].

There are several lines of evidence about the effectiveness of parathyroid hormone (PTH) as a bone anabolic reagent for the treatment of osteoporosis, and the large-scale randomized controlled trial revealed that PTH increases and reduces lumbar spine bone mineral density and fracture risk, respectively, more potently than other inhibitors for bone resorption. Moreover, alendronate was useful for the further increase in bone mineral density after the withdrawal of PTH treatment, and the combined treatment of PTH and raloxifene was additive. On the other hand, strontium ranelate significantly inhibited osteoporotic fractures in randomized placebo controlled trial, which is expected as a new bone anabolic reagent for osteoporosis.

Anabolic Agents↗
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

Multiple vertebral fractures are associated with refractory reflux esophagitis in postmenopausal women.

We examined the frequency of multiple vertebral fractures (MVFs) and esophageal hiatal hernia (HH) in 18 Japanese postmenopausal women (74.1 +/- 9.9 years, mean +/- SD), with refractory reflux esophagitis (RRE) that had needed a proton pump inhibitor for more than 6 months to suppress symptoms such as heartburn and acid regurgitation, as well as in 57 control subjects without RE (71.4 +/- 5.9 years). MVFs (two or more VFs), HH, and both features were found in 11 (61%), 16 (89%), and 11 (61%) subjects, respectively, in the RRE group. All 11 patients with MVFs also had HH, suggesting their strong association. On the other hand, MVFs, HH, and both were found in 15 (26%), 23 (40%), and 8 (14%) subjects, respectively, in those without RE. The differences in frequencies of MVFs, HH, and both between the two groups were significant (chi2 = 7.3, 12.9, and 16.0; P = 0.015, 0.0009, and 0.0002, respectively). When univariate logistic regression analysis was performed with the presence of RRE as a dependent variable and the presence of MVFs, HH, and both as independent variables, MVFs, HH, and both were selected as indices affecting the presence of RRE (age-adjusted odds ratios: 4.34, 11.07, and 10.30; 95% confidential intervals: 1.40-13.45, 2.30-53.22, and 2.96-35.86; P = 0.0109, 0.0027, and 0.0002, respectively). These results show that the presence of MVFs is associated with the presence of RRE in Japanese postmenopausal women, and this association becomes more significant when HH is present. Thus, a kyphotic lumbar spine with MVFs may cause HH and RE by raising the intraabdominal pressure. As recent therapeutic agents for osteoporosis, alendronate and risedronate, are known to be very effective for suppressing the occurrence of new VFs, these agents may also prevent gastrointestinal disorders such as HH and RRE in osteoporotic women when administered to subjects without VFs.

Aged↗
PubMed2005

Low-dose parathyroid hormone and estrogen reverse alkaline phosphatase activity suppressed by dexamethasone in mouse osteoblastic cells.

Glucocorticoid (GC)-induced osteoporosis (GIO) is frequently seen in patients with excessive GC. Numerous questions remain to be clarified about the pathogenesis and treatment of GIO, and the mechanism of GC-inhibited bone formation is not well known. Several studies suggest that parathyroid hormone (PTH) and hormone replacement therapy are effective for GIO. We therefore investigated whether PTH and estrogen would affect cell proliferation and alkaline phosphatase (ALP) activity inhibited by dexamethasone (Dex) in mouse osteoblastic cell-line MC3T3-E1 cells. Low-dose (10(-11) M) PTH as well as 10(-8) M 17-beta-estradiol (17beta-E2) significantly attenuated Dex-inhibited ALP activity, although 10(-8) M PTH did not affect it. ICI 182780 (10(-8) M) antagonized the effects of 17beta-E(2) on Dex-suppressed ALP activity. Neutralizing anti-IGF-I antibody (3 microg/ml) blocked the reverse effects of 17beta-E2 on ALP activity suppressed by Dex. PTH (10(-11) M), but not 17beta-E2, significantly attenuated [3H]thymidine incorporation inhibited by Dex. On the other hand, PTH and estrogen did not affect the level of 11-beta-hydrosteroid dehydrogenase type I mRNA increased by Dex. In conclusion, the present study demonstrated that low-dose PTH and estrogen reversed Dex-inhibited ALP activity in the mouse osteoblastic cell-line.

11-beta-Hydroxysteroid Dehydrogenases↗