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Yasato Komatsu

Publications and source records attributed to Yasato Komatsu.

At least 19 recordsLinked to original sources
PubMed2006

Interferon-alpha improves bone resorption and osteopenia in patients with chronic hepatitis C.

BACKGROUND: Interferon (IFN)-beta is known to be involved in the regulation of bone homeostasis. As IFN-alpha and -beta share the same receptor complex and signaling pathway, we speculated that treatment with IFN-alpha for chronic hepatitis C (CHC) may provide a beneficial effect on bone loss. METHODS: Urinary deoxypyridinoline (uDPD) of 41 patients with CHC who had been receiving IFN-alpha for 24 weeks was examined during the period of observation. Among them, eight patients showed a bone mineral density (BMD) of less than 0.850g/cm(2) before IFN therapy and they were examined a BMD again after completion of IFN administration. Relationships between the percentage difference of uDPD after discontinuation of IFN and various factors related to CHC were also examined. RESULTS: A mean uDPD of 7.1+/-3.4nM/mM creatinine before IFN therapy decreased to 4.5+/-2.4 in the 4th week and 4.2+/-2.7 in the 24th week of IFN therapy, respectively (p<0.0001). The reduction in uDPD was more prominent in cases with a lower viral load (p=0.0266). The BMD of the eight patients, which was less than 0.850g/cm(2) before IFN therapy, showed significant increase after the end of therapy (p=0.0172). CONCLUSION: IFN-alpha can improve bone resorption in CHC patients, especially in those with a lower viral load, and increased BMD. These effects are thought to be a result of direct action of IFN on bone homeostasis.

Journal Article↗
PubMed2006

Clinical significance of risedronate for osteoporosis in the initial treatment of male patients with Graves' disease.

It has been well established that hyperthyroidism leads to diminished bone mineral density (BMD), and that a previous history of hyperthyroidism remains a risk factor for fractures. However, little is known about how to manage the reduction in BMD caused by hyperthyroidism. The purpose of this study was to evaluate the efficacy of risedronate for the treatment of osteoporosis/osteopenia in patients with Graves' disease (GD). Of 34 Japanese male patients with newly diagnosed GD, 27 with osteoporosis/osteopenia were included in this study. They were randomly divided into two groups by therapeutic regimen. Group A consisted of 14 patients treated with an antithyroid drug and risedronate. Group B consisted of 13 patients treated with the same antithyroid drug only. We used dual-energy X-ray absorptiometry to measure BMD at the lumber spine, femoral neck, and distal radius at baseline, and at 6 and 12 months after the trial. Bone-specific alkaline phosphatase and urinary N-terminal telopeptide of type I collagen normalized by creatinine were significantly more reduced in group A than in group B after both 6 and 12 months. The percentage increases in BMD at the lumbar spine and distal radius were significantly greater in group A than in group B. These beneficial effects of risedronate for patients with osteoporosis/osteopenia caused by GD may lead to a reduced risk of future fractures. We thus conclude that risedronate should be considered for the treatment of decreased bone mass associated with GD.

Adult↗
PubMed2005

Expression of the adrenomedullin gene in adipose tissue.

Adrenomedullin (AM) is a potent vasodilating peptide originally isolated from human pheochromocytoma cells. This report concerns the expression and secretion of AM from adipose tissue. Northern blot analysis demonstrated marked expression of AM mRNA in mouse adipose tissue. Expression levels in adipose tissues were 2.5-3.2 times higher than in the kidney. AM mRNA level in mature adipocytes was 7.3 times higher than in the stroma-vascular fraction of adipose tissue. In mature adipocyte culture, time-dependent increase of AM peptide concentration in the culture medium was detected. AM expression was also detected in human subcutaneous adipose tissue. Adipose AM expression significantly increased in obesity mouse model, high-fat diet fed mice and ob/ob mice. These results suggest that adipose tissue, especially mature adipocytes, is major source of AM in the body, and that adipocyte-derived AM plays a pathophysiological role in obesity.

Adipocytes↗
PubMed2005

Complementary antagonistic actions between C-type natriuretic peptide and the MAPK pathway through FGFR-3 in ATDC5 cells.

We previously reported that C-type natriuretic peptide (CNP) stimulates endochondral ossification and corrects the reduction in body length of achondroplasia model mouse with constitutive active fibroblast growth factor receptor 3 (FGFR-3). In order to examine the interaction between CNP and FGFR-3, we studied intracellular signaling by using ATDC5 cells, a mouse chondrogenic cell line, and found that FGF2 and FGF18 markedly reduced CNP-dependent intracellular cGMP production, and that these effects were attenuated by MAPK inhibitors. Western blot analysis demonstrated that the level of GC-B, a particulate guanylyl cyclase specific for CNP, was not changed by treatment with FGFs. Conversely, CNP and 8-bromo-cGMP strongly and dose-dependently inhibited the induction of ERK phosphorylation by FGF2 and FGF18 without changing the level of FGFR-3, although they did not affect the phosphorylation of STAT-1. In the organ-cultured fetal mouse tibias, CNP and FGF18 counteracted on the longitudinal bone growth, and both the size and number of hypertrophic chondrocytes. The FGF/FGFR-3 pathway is known as the negative regulator of endochondral ossification. We found that FGFs inhibited CNP-stimulated cGMP production by disrupting the signaling pathway through GC-B while CNP antagonized the activation of the MAPK cascade by FGFs. These results suggest that the CNP/GC-B pathway plays an important role in growth plate chondrocytes and constitutes the negative cross talk between FGFs and the activity of MAPK. Our results may explain one of the molecular mechanisms of the growth stimulating action of CNP and suggest that activation of the CNP/GC-B pathway may be effective as a novel therapeutic strategy for achondroplasia.

Animals↗
PubMed2005

Papillary thyroid carcinoma without metastases manifesting as an autonomously functioning thyroid nodule.

A 59-year-old woman with papillary thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this report. The patient was referred to our clinic because of rapid weight loss and swelling on the left side of the neck. Ultrasonography of the thyroid demonstrated a nonhomogeneous nodule in the lower part of an enlarged left lobe. Both 99mTc and 123I thyroid scintigraphic imaging showed a hot area corresponding to the nodule with lower uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed papillary adenocarcinoma, and the immunohistochemistry proved weak but positive staining for triiodothyronine and thyroxine. Based on these findings, the nodule was diagnosed as a functioning papillary adenocarcinoma. Although thyroid carcinoma manifesting as a hot nodule on the radionuclide isotope scan is an extremely rare occurrence, the current case is clinically important because it suggests that the diagnosis of a hot nodule cannot always rule out thyroid carcinoma in the nodule, and that even a hot nodule requires careful management so that the malignancy is not overlooked.

Adenocarcinoma, Papillary↗
PubMed2005

Anaplastic thyroid carcinoma associated with Graves' disease.

This report concerns a 79-year-old woman with coexisting anaplastic thyroid carcinoma (ATC) and Graves' disease (GD). The patient was referred to our clinic because of palpitation and a palpable mass on the left side of her neck. Thyroid function tests showed hyperthyroidism with elevated thyroid-stimulating antibodies. Ultrasonography of the thyroid demonstrated an adenomatous nodule-like marcated nodule (27.6 x 26.5 x 36.4 mm) with cystic degeneration inside the left lobe. (123)I thyroid scintigraphic imaging showed a cold area corresponding to the nodule with continuous uptake in the remaining thyroid tissue despite suppressed TSH levels. These findings led to a diagnosis of GD. On the other hand, the thyroid nodule could not be definitely diagnosed even after fine needle aspiration biopsy (FNAB) which produced findings suggestive of both papillary thyroid carcinoma and ATC. Open biopsy of the nodule showed an ATC. Regional lymph node metastases as well as multiple lung metastases, which could not be found at the initial visit, had been already developed by that time. Our case is pathophysiologically interesting because it suggests that GD or thyroid-stimulating antibodies (TSAb) may stimulate malignant transformation of differentiated carcinoma. It is also clinically important because it indicates that all thyroid nodules, particularly palpable cold nodules, associated with GD require careful management to detect malignancy because they are at higher risk of harboring malignancy.

Aged↗
PubMed2005

Primary hyperparathyroidism presumably caused by chronic parathyroiditis manifesting from hypocalcemia to severe hypercalcemia.

A 67-year-old woman who presented with hypocalcemia compatible with idiopathic hypoparathyroidism gradually changed into a state of primary hyperparathyroidism. The left upper parathyroid gland, which was larger and harder than other glands, was resected. Despite the operation, hypercalcemia and high levels of intact PTH persisted. Six weeks later total parathyroidectomy was done to induce remission. The resected gland in the first operation had clusters of lymphoid follicles with germinal centers indicating a chronic autoimmune inflammation. This case suggests a transition from hypoparathyroidim to hyperparathyroidism associated with chronic parathyroiditis, possibly by a mechanism analogous to that observed in chronic thyroiditis.

Aged↗
PubMed2003

Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.

Achondroplasia is the most common genetic form of human dwarfism, for which there is presently no effective therapy. C-type natriuretic peptide (CNP) is a newly identified molecule that regulates endochondral bone growth through GC-B, a subtype of particulate guanylyl cyclase. Here we show that targeted overexpression of CNP in chondrocytes counteracts dwarfism in a mouse model of achondroplasia with activated fibroblast growth factor receptor 3 (FGFR-3) in the cartilage. CNP prevented the shortening of achondroplastic bones by correcting the decreased extracellular matrix synthesis in the growth plate through inhibition of the MAPK pathway of FGF signaling. CNP had no effect on the STAT-1 pathway of FGF signaling that mediates the decreased proliferation and the delayed differentiation of achondroplastic chondrocytes. These results demonstrate that activation of the CNP-GC-B system in endochondral bone formation constitutes a new therapeutic strategy for human achondroplasia.

Achondroplasia↗
PubMed2003

Over expression of bone morphogenetic protein-3b (BMP-3b) using an adenoviral vector promote the osteoblastic differentiation in C2C12 cells and augment the bone formation induced by bone morphogenetic protein-2 (BMP-2) in rats.

BMP-3b is a novel BMP-3-related protein and its biological functions are unknown. In order to investigate the biological actions of BMP-3b, we constructed a BMP-3b-expressing recombinant adenoviral vector (AxCAKBMP-3b). We show that over expression of BMP-3b stimulated the induction of differentiation and the osteoinduction activity of a human BMP-2-expressing recombinant adenoviral vector (AxCAOBMP-2). C2C12 cells were infected in vitro with AxCAKBMP-3b, AxCAOBMP-2 and a control vector containing no foreign genes (AxCAwt). Cells infected with AxCAOBMP-2 and AxCAKBMP-3b produced more alkaline phosphatase and secreted more osteocalcin into the culture medium than cells infected with AxCAOBMP-2 and AxCAwt. When AxCAOBMP-2, AxCAKBMP-3b, and AxCAwt were injected into the calf muscles of nude rats (F 344/N Jcl-rnu), the osteoinduction seen with AxCAOBMP-2 and AxCAKBMP-3b was greater than that seen with AxCAOBMP-2 and AxCAwt.

Adenoviridae↗
PubMed2003

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Journal Article↗
PubMed2003

[The possible novel treatment of achondroplasia, C-type natriuretic peptide (CNP)].

C-type natiruetic peptide (CNP) showed a potent effect on the elongation of the tibial organ culture system. CNP also corrected the dwarfing phenotype of the CNP knockout mice. These results suggest that CNP is the novel promoter of the endochondral ossification, and that CNP/GC-B activation is possible target of the treatment of the achondroplasia.

English Abstract↗
PubMed2002

A novel interaction between thyroid hormones and 1,25(OH)(2)D(3) in osteoclast formation.

Thyroid hormones enhance osteoclast formation and their excess is an important cause of secondary osteoporosis. 3,5,3' -Triiodo-L-thyronine (T3) induced the mRNA expression of receptor activator of nuclear factor-kappa B ligand (RANKL), which is a key molecule in osteoclast formation, in primary osteoblastic cells (POB). This effect was amplified in the copresence of 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Although T3 alone did not induce octeoclasts in coculture of bone marrow cells with POB, T3 enhanced 1,25(OH)(2)D(3)-induced osteoclast formation. Thyroxine (T4) also enhanced 1,25(OH)(2)D(3)-induced osteoclast formation. These data suggested that T4 was locally metabolized to T3 for its action, since T4 is a prohormone with little hormonal activity. The mRNA expression of type-2 iodothyronine deiodinase (D2), which is responsible for maintaining local T3 concentration, was induced by 1,25(OH)(2)D(3) dose- and time-dependently. Our data would facilitate our understanding of the mechanism of osteoclast formation by thyroid hormones and suggest a novel interaction between thyroid hormones and 1,25(OH)(2)D(3).

Animals↗
PubMed2002

C-type natriuretic peptide/guanylate cyclase B system in ATDC5 cells, a chondrogenic cell line.

Natriuretic peptides constitute a family of three structurally related peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Particulate guanylate cyclases, GC-A, and GC-B, are the receptors for these peptides to mediate their action. ANP and BNP possess high affinities for GC-A, and CNP is the preferred ligand for GC-B. In this article, we report our study of the expression and possible role(s) of natriuretic peptides in ATDC5 cells, which represent a chondrogenic cell line. ATDC5 cells produced cyclic guanosine monophosphate (cGMP) in response to natriuretic peptides. CNP was far more potent than ANP in terms of cGMP production. The messages for GC-A and GC-B were demonstrated by means of Northern blot analysis, and the presence of CNP was shown by Southern blotting coupled with reverse transcription-polymerase chain reaction (RT-PCR). These results suggest that the CNP/GC-B system is preferentially expressed in ATDC5 cells. GC-B mRNA expression was higher at 14 days after confluency than that at confluency. CNP or 8-bromo cGMP reduced [3H] thymidine uptake and slightly increased the message for collagen type X, which is a marker of hypertrophic chondrocytes. These data suggest that the CNP/GC-B system is likely to be an autocrine/paracrine regulator of ATDC5 cells, thus affecting both their growth and differentiation.

Animals↗