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K Chihara

Publications and source records attributed to K Chihara.

At least 37 records · Page 2Linked to original sources
PubMed2001

Steroid myopathy: pathogenesis and effects of growth hormone and insulin-like growth factor-I administration.

Glucocorticoids have been widely used in the treatment of autoimmune and other diseases. Chronic steroid use, however, could cause proximal muscle weakness and atrophy, termed steroid myopathy. The onset of steroid myopathy is usually insidious and there are no specific laboratory findings except for elevated urinary creatine excretion. Muscle biopsy reveals non-specific type II fiber atrophy. There are many reports showing preventive effects of either growth hormone (GH) or insulin-like growth factor (IGF)-I on steroid myopathy. The pathogenesis of steroid myopathy is not fully understood. Recently, glutamine synthetase has been reported to play a key role in steroid myopathy. GH as well as IGF-I decreased the steroid-induced glutamine synthetase activity in skeletal muscle.

Animals↗
PubMed2001

Interleukin-1beta stimulates transendothelial mobilization of human peripheral blood mononuclear cells with a potential to differentiate into osteoclasts in the presence of osteoblasts.

There is accumulating evidence that interleukin-1 (IL-1) levels are increased locally at the site of active bone resorption in a variety of diseases including osteoporosis, periodontal disease and rheumatoid arthritis. However, the pathogenic role of IL-1 in bone loss remains to be fully elucidated. We present here additional evidence that IL-1beta enhances endothelial activation and thereby stimulates mobilization of peripheral blood mononuclear cells (PBMCs) from luminal to abluminal spaces across the endothelium. Furthermore, IL-1beta stimulates the differentiation of PBMCs into osteoclast-like cells with bone-resorbing activity in the presence of human osteoblastic SaOS-2 cells without systemic hormones. These findings provide circumstantial evidence for the hypothesis that IL-1beta generated in the bone microenviroment plays a stimulatory role in PBMC mobilization from the peripheral circulation and their subsequent differentiation into osteoclast-like cells in the bone tissue. In addition, the present study supports the notion that osteoclast progenitor cells might be derived from the peripheral circulating blood mononuclear cells in human.

Acid Phosphatase↗
PubMed2001

Skeletal responsiveness to parathyroid hormone in pseudohypoparathyroidism.

BACKGROUND: Although there have been some case reports suggesting that bone in patients with pseudohypoparathyroidism (PHP) might respond to parathyroid hormone (PTH), no information is available as to whether serum PTH concentration is related to bone metabolic markers or to bone mineral density (BMD) in PHP. OBJECTIVE: To address these relationships, by comparing intact serum PTH, bone metabolic markers and BMD in patients with PHP with those in patients with idiopathic hypoparathyroidism (IHP) and postoperative hypoparathyroidism (OHP). METHODS: Intact serum PTH, bone metabolic markers (osteocalcin, tartrate-resistant acid phosphatase, pyridinoline, deoxypyridinoline) and BMD by dual-energy X-ray absorptiometry or single-photon absorptiometry were measured in patients with PHP Ia (n=2) and PHP Ib (n=8). The results were compared with those in patients with IHP (n=5) and OHP (n=14). RESULTS: All bone metabolic markers measured were present in significantly greater amounts in patients with PHP Ib than in those with IHP+OHP. The Z score (standard deviation of average BMD at each age) of the BMD of femoral neck was significantly lower in patients with PHP Ib than in those with IHP+OHP. The Z scores of BMD of lumbar spine and radius were also lower in patients with PHP Ib than in those with IHP+OHP, but the difference was not significant. Moreover, the intact serum PTH concentrations were significantly and positively related to bone metabolic marker levels in all patients, and the intact serum PTH concentrations were significantly and negatively related to BMD of lumbar spine in PHP patients. CONCLUSIONS: These results suggest that PTH stimulates bone turnover in PHP Ib patients, resulting in a relatively lower BMD in PHP Ib patients than in IHP+OHP patients. The present study indicates that bones of most cases of PHP could respond to PTH.

Acid Phosphatase↗
PubMed2001

[March gangrene].

Explore the source record for details and available documents.

Anterior Compartment Syndrome↗
PubMed2001

Measurement of in-vivo local shear modulus by combining multiple phase offsets mr elastography.

To provide realistic surgical simulation, haptic feedback is important. In the existing surgical simulators, the fidelity of the deformation and haptic feedback is limited because they are based on the subjective evaluation of the expert-user and not on an objective model-based evaluation. To obtain elastic modulus of in-vivo human tissues, magnetic resonance elastography (MRE) was developed. MRE is a phase-contrast- based method that can visualize propagating strain waves in materials. The quantitative values of shear modulus can be calculated by estimating the local wavelength of the wave pattern. Low frequency mechanical motion must be used for soft tissue-like materials, because strain waves rapidly attenuate at higher frequency. Therefore, wavelength in MRE is long. It is difficult to estimate local wavelength with high spatial resolution especially from noisy MRE. In the MRE sequence, motion-sensitizing gradient (MSG) are synchronized with the mechanical cyclic motion. MRE with multiple initial phase offsets can be generated with increasing delays between the MSG and mechanical excitation. In this paper, we describe a method of measuring local wavelength with high spatial resolution by combining multiple phase offsets MRE. To confirm the reliability of this method, a computer simulation and phantom study were performed. The shear modulus measured with various elastic objects was well consistent with the value obtained by MRE and the mechanical method. The shear moduli of excised porcine liver and in-vivo human calf muscle were also analyzed by this method. on the subjective evaluation of an expert-user and not on objective model-based methods.

Acoustic Stimulation↗
PubMed2001

[Anterior chest wall reconstruction with myocutaneous flap after open drainage for infectious bulla and empyema following T4 lung cancer resection via anterior approach].

A 48-year-old man with T4 lung cancer underwent resection of the right upper lobe, chest wall, and superior vena cava, and reconstruction of the last 2 tissues via anterior approach after induction chemo-radiotherapy. However, a bulla in the apical segment of the lower lobe divided by stapling was infected after the operation, and open drainage through the anterior chest wall was mandatory due to massive air leak and spread of infection to the pleural space. As the incision were fortunately restricted in the anterior chest, he could undergo successful reconstruction of a full-thickness defect of the anterior chest wall using a serratus anterior muscle flap and a myocutaneous flap of lattissimus dorsi with minimum rib resection after 2 months. He has in regular work with a small limitation of raising the right upper extremitus these 7 years.

Carcinoma, Large Cell↗
PubMed2000

Cloning and characterization of the 5'-flanking region of the human prolactin-releasing peptide receptor gene.

Recently a novel peptide which specifically stimulates the secretion of prolactin (PRL) was found and named PRL-releasing peptide (PrRP). To evaluate the regulation of human (h) PrRP-receptor (PrRP-R) gene expression, we cloned the 5'-flanking region of the hPrRP-R gene and determined the nucleotide sequence of 4.0 kilobase pairs (kb) upstream from the translation start site. Analysis of the hPrRP-R transcripts by means of 5'-rapid amplification of cDNA ends suggested that the hPrRP-R gene had multiple transcription start sites between -429 and -365 from the translation start site. There is no typical TATA or CAAT but a GC box and putative binding sites for several transcription factors including Pit-1 and pituitary homeobox 1 (Ptx1). However, transient transfection studies using a luciferase reporter gene demonstrated that 5'-flanking region exerts promoter activity in several non-pituitary cell lines as well as in GH(3) cells. The GC box located from -467 to -457 was identified as an important region for the basal expression of the hPrRP-R gene. Knowledge of the promoter region of the hPrRP-R gene, which was obtained in the present study, will facilitate the clarification of its transcriptional regulation.

Animals↗
PubMed2000

Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse.

We previously identified Rho-associated protein kinase (Rho-kinase) as a specific effector of Rho. In this study, we identified collapsin response mediator protein-2 (CRMP-2), as a novel Rho-kinase substrate in the brain. CRMP-2 is a neuronal protein whose expression is up-regulated during development. Rho-kinase phosphorylated CRMP-2 at Thr-555 in vitro. We produced an antibody that specifically recognizes CRMP-2 phosphorylated at Thr-555. Using this antibody, we found that Rho-kinase phosphorylated CRMP-2 downstream of Rho in COS7 cells. Phosphorylation of CRMP-2 was observed in chick dorsal root ganglion neurons during lysophosphatidic acid (LPA)-induced growth cone collapse, whereas the phosphorylation was not detected during semaphorin-3A-induced growth cone collapse. Both LPA-induced CRMP-2 phosphorylation and LPA-induced growth cone collapse were inhibited by Rho-kinase inhibitor HA1077 or Y-32885. LPA-induced growth cone collapse was also blocked by a dominant negative form of Rho-kinase. On the other hand, semaphorin-3A-induced growth cone collapse was not inhibited by a dominant negative form of Rho-kinase. Furthermore, overexpression of a mutant CRMP-2 in which Thr-555 was replaced by Ala significantly inhibited LPA-induced growth cone collapse. These results demonstrate the existence of Rho-kinase-dependent and -independent pathways for growth cone collapse and suggest that CRMP-2 phosphorylation by Rho-kinase is involved in the former pathway.

Amino Acid Sequence↗
PubMed2000

Stimulation by eicosapentaenoic acids of leptin mRNA expression and its secretion in mouse 3T3-L1 adipocytes in vitro.

Recent evidence indicates that both leptin and eicosapentaenoic acids (EPA) improve insulin sensitivity. In the present study, we examined the effect of EPA on endogenous leptin expression in 3T3-L1 adipocytes to clarify whether the EPA's effect is exerted through leptin expression. EPA caused a time- and dose-dependent increase of leptin mRNA levels in 3T3-L1 adipocytes. Leptin mRNA expression was significantly increased up to 309.4 +/- 17.0% of the control by 24 h (P < 0.01; n = 6). Leptin secretion was also significantly increased up to 193.3 +/- 12.1% of the control by 24 h (P < 0.01; n = 6). EPA is a ligand for peroxisome proliferator-activated receptors (PPARs) with the highest affinity to PPARalpha. We examined the effect on leptin expression of clofibrate, a ligand for PPARalpha, bezafibrate, for PPARbeta, or troglitazone, for PPARgamma, to clarify whether these ligands for PPARs could mimic EPA-induced stimulation of leptin expression. Neither clofibrate nor bezafibrate affected leptin mRNA expression, whereas troglitazone significantly suppressed leptin mRNA expression. On the other hand, inhibition by 6-diazo-5-oxo-l-norleucine of the rate-limiting enzyme in hexosamine biosynthesis blunted EPA-induced stimulation of leptin mRNA expression and its secretion. These data suggest that EPA up-regulates leptin gene expression and its secretion probably through a hexosamine biosynthetic pathway.

3T3 Cells↗
PubMed2000

Parathyroid hormone-activated volume-sensitive calcium influx pathways in mechanically loaded osteocytes.

This paper documents for the first time a volume-sensitive Ca(2+) influx pathway in osteocytes, which transmits loading-induced signals into bone formation. Stretch loading by swelling rat and chicken osteocytes in hypo-osmotic solution induced a rapid and progressive increase of cytosolic calcium concentration, [Ca(2+)](i). The influx of extracellular Ca(2+) explains the increased [Ca(2+)](i) that paralleled the increase in the mean cell volume. Gadolinium chloride (Gd(3+)), an inhibitor of stretch- activated cation channels, blocked the [Ca(2+)](i) increase caused by hypotonic solutions. Also, the expression of alpha1C subunit of voltage-operated L-type Ca(2+) channels (alpha1C) is required for the hypotonicity-induced [Ca(2+)](i) increase judging from the effect of alpha1C antisense oligodeoxynucleotides. Parathyroid hormone (PTH) specifically potentiated the hypotonicity-induced [Ca(2+)](i) increase in a dose-dependent manner through the activation of adenyl cyclase. The increases induced by both PTH and hypotonicity were observed primarily in the processes of the osteocytes. In cyclically stretched osteocytes on flexible-bottomed plates, PTH also synergistically elevated the insulin-like growth factor-1 mRNA level. Furthermore, Gd(3+) and alpha1C antisense significantly inhibited the stretch-induced insulin-like growth factor-1 mRNA elevation. The volume-sensitive calcium influx pathways of osteocytes represent a mechanism by which PTH potentiates mechanical responsiveness, an important aspect of bone formation.

Animals↗
PubMed2000

Treatment of osteopenia secondary to primary hyperparathyroidism.

A major challenge in the management of primary hyperparathyroidism (pHPT) is the decision regarding which patients should undergo parathyroidectomy (PTX). although the Consensus Development Conference of the National Institutes of Health (NIH) has proposed guidelines for the indication of surgery. We found that PTX brings about increases in radial and lumbar BMD values as high as 10% in virtually all pHPT patients including postmenopausal women and those without an indication for surgery based on NIH criteria. Serum alkaline phosphatase (ALP) level and the severity of cortical bone mass reduction are clinically useful for predicting the changes in lumbar BMD after PTX. The present findings provide a useful clue for the indication of surgery in pHPT, and seem to warrant a more extended indication than that of the NIH. We also described the recent progress in studies on calcium-sensing receptor (CaR), and discussed the possibility of bone mass recovery by medical treatment of pHPT with a newly introduced CaR agonist ('calcimimetics').

Absorptiometry, Photon↗
PubMed2000

Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene polymorphism and the extent of bone mass reduction in primary hyperparathyroidism.

Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analyzed the relationship between polymorphism of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene existing in exon M7 and the clinical characteristics of primary hyperparathyroidism (pHPT). PTH/PTHrP receptor genotypes were analyzed in 92 pHPT patients by direct sequence to determine whether nucleotide 1417 of the cDNA was C or T. BMD levels at the lumbar spine and at the radius before and one year after parathyroidectomy, as well as serum levels of calcium, phosphorus, alkaline phosphatase (ALP) and intact PTH were measured. Although there were no significant differences in serum levels of calcium, phosphorus and intact PTH, ALP was significantly lower in the CT genotype compared with the TT genotype. BMD level at the radius was significantly higher in the CT genotype than in the CC genotype. Moreover, an increase in radial BMD one year after parathyroidectomy was significantly less in CT genotype than two other genotypes (CC, TT). The present study is the first to indicate that the polymorphism of PTH/PTHrP receptor gene is closely related to the extent of bone mass reduction in pHPT and that this polymorphism would be one of the genetic factors responsible for the severity of the pathological state of pHPT.

Alkaline Phosphatase↗
PubMed2000

Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism.

BACKGROUND: The down-regulation of both calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) in parathyroid (PT) glands of secondary hyperparathyroidism (HPT) caused by chronic renal failure has been associated with PT hormone hypersecretion as well as PT hypergrowth. To clarify the predominance of decreased expression of CaSR and VDR in the high proliferative activity of PT glands, we examined the relationship between the expression of both receptors and proliferative activity in human PT glands. METHODS: Serial sections of 56 PT glands, including 52 glands from secondary HPT and 4 normal PT glands resected together with thyroid carcinoma, were examined immunohistochemically with specific antibodies against CaSR, VDR, and Ki67. The Ki67-positive cell number was counted and expressed as the Ki67 score. The CaSR and VDR expressions were semiquantitatively analyzed. RESULTS: The expressions of both CaSR and VDR were markedly decreased in PT glands of secondary HPT, while the Ki67 score was significantly higher than it was in normal controls. When hyperplastic glands were classified into two subgroups, with [N(+)] or without [N(-)] nodular formation, CaSR expression was significantly decreased in N(+), while VDR expression was not different. Multiple regression analyses revealed that the decreased expression of CaSR could contribute significantly to the high proliferative activity, even if VDR expression was taken into account. CONCLUSION: The decrease in CaSR expression is associated with the high proliferative activity of PT glands in secondary HPT, independently of the decreased VDR expression. These findings provide a new insight into the pathogenesis of PT hyperplasia, which is refractory to vitamin D therapy in patients with severe secondary HPT.

Cell Division↗
PubMed2000

Spontaneous and cytokine regulated c-fos gene expression in rheumatoid synovial cells: resistance to cytokine stimulation when the c-fos gene is overexpressed.

OBJECTIVE: To study the effect of cytokines on the transactivation of the c-fos gene in relation to the contribution of overexpression of c-fos/AP-1 in rheumatoid joint destruction. METHODS: The promoter region (-447 to +109) of the human c-fos gene was integrated upstream of the chloramphenicol acetyltransferase (CAT) reporter gene, and the effect of cytokines on the expression of the c-fos gene was studied in the rheumatoid synovial cells of early (3-4) or late (14-18) passages, in the presence or absence of cytokines, by the transient transfection assay. RESULTS: Expression of c-fos gene was enhanced by tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) in the synovial cells of early passage, whereas it was not enhanced in the synovial cells of late passage. The c-fos gene expression was also enhanced by 13-O-tetradecanoyl phorbol-13-acetate (TPA) in early passage but was somewhat suppressed in the late passage. It was found that the c-fos gene and c-Fos protein were both increased in the synovial cells of late passage. Similarly, c-fos gene expression was also not increased by TPA or cytokine stimulation in the stable c-fos transformants (fos-pH8) or H-ras transformed NIH3T3 cells (NIH H-ras cells) that constitutively expressed c-fos genes. CONCLUSIONS: Although TNF alpha and IL6 augmented c-fos gene expression of rheumatoid synovial cells, transactivation of c-fos gene became resistant against cytokine stimulation under prolonged expression of c-fos gene, which may impart a tumour-like characteristic to rheumatoid synovial cells.

Arthritis, Rheumatoid↗
PubMed2000

Association of polymorphic alleles of the calcium-sensing receptor gene with parathyroid hormone secretion in hemodialysis patients.

The present study was performed to investigate the association of calcium-sensing receptor (CaSR) genotypes with parathyroid hormone (PTH) secretion in hemodialysis patients. Subjects were 122 Japanese hemodialysis patients, including 39 patients with diabetes mellitus (DM). The CaSR polymorphisms tested were codon 990 in intracellular domain (A/A, A/G, and G/G groups) as well as T to C base change of intron 4 (T/T, T/C, and C/C groups). Statistical analysis of these polymorphisms revealed that the serum PTH level was significantly higher in the A/A group than in the G/G group in the former. In addition, the serum PTH level was also significantly higher in patients displaying C allele, as compared with the T/T group in the latter. This association of two polymorphisms with the serum PTH level was observed only in non-DM patients. Although two polymorphisms affected the PTH level independently, patients who possessed both genotypes (AAC+) had a markedly high level of PTH not only in the non-DM group but also in the DM group. The present findings indicate the possibility of the prediction for the extensive progression of secondary hyperparathyroidism through analyzing the CaSR polymorphisms in chronic hemodialysis patients.

Adult↗
PubMed2000

Prediction of bone mass change after parathyroidectomy in patients with primary hyperparathyroidism.

A major challenge in the management of primary hyperparathyroidism (pHPT) is the decision regarding which patients should undergo parathyroidectomy (PTX), although the Consensus Development Conference of the NIH has proposed guidelines for the indication of surgery. In the present study, changes in bone mineral density (BMD) after PTX were compared between pHPT patients who did and did not meet the NIH criteria, and we further tried to predict the BMD change after PTX from preoperative parameters. The subjects were 44 pHPT patients (30 women and 14 men) who had had successful PTX. Lumbar and radial BMD were measured before and 1 yr after PTX by dual energy x-ray absorptiometry and single photon absorptiometry, respectively. Average annual percent increases in lumbar and radial BMD after PTX were 12.2 +/- 1.4% and 11.6 +/- 1.6% (mean +/- SEM), respectively, and those net increases were 0.0803 +/- 0.0008 and 0.0484 +/- 0.0006 g/cm2, respectively. There were no significant differences in percent or net changes in either radial or lumbar BMD after PTX between the groups divided according to each of the NIH criteria, such as age (> or =50 and <50 yr), serum calcium level (> or =12 and <12 mg/dL) or the existence of urinary stones (presence and absence). On the other hand, when the subjects were divided on the basis of radial BMD (above and below a z-score of -2), the annual percent and net increases in lumbar BMD and percent increase in radial BMD after PTX were significantly higher in the group with the lower z-score. Next, patients were divided into two groups with and without the indication of PTX based on NIH guidelines. Twenty-nine patients had the surgical indication by meeting one or more of these criteria and 15 patients had no indication without meeting any of the criteria. There were no significant differences between the two groups in annual percent or net changes in radial or lumbar BMD after PTX. A stepwise multiple regression analysis revealed that serum alkaline phosphatase level and the severity of cortical bone mass reduction were the best predictors of both percentage and net changes in lumbar BMD, with high determination coefficients (r2 > 0.7). In conclusion, a considerable increase in BMD could be obtained after PTX even in patients without surgical indication from the NIH. Alkaline phosphatase and the severity of cortical bone mass reduction are clinically useful for predicting the changes in lumbar BMD after PTX. The present findings provide a useful clue for the indication of surgery in pHPT.

Alkaline Phosphatase↗