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D Inoue

Publications and source records attributed to D Inoue.

At least 19 recordsLinked to original sources
PubMed2006

Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.

The aim of the study was to examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in the airways. Human tracheal epithelial cells were infected with a major-group RV, RV14. RV14 infection increased virus titres and the cytokine content of supernatants. Carbocisteine reduced supernatant virus titres, the amount of RV14 RNA in cells, cell susceptibility to RV infection and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the expression of mRNA encoding intercellular adhesion molecule (ICAM)-1, the receptor for the major group of RVs. It also reduced the supernatant concentration of a soluble form of ICAM-1, the number and fluorescence intensity of acidic endosomes in the cells before RV infection, and nuclear factor-kappaB activation by RV14. Carbocisteine also reduced the supernatant virus titres of the minor group RV, RV2, although carbocisteine did not reduce the expression of mRNA encoding a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits rhinovirus 2 infection by blocking rhinovirus RNA entry into the endosomes, and inhibits rhinovirus 14 infection by the same mechanism as well as by reducing intercellular adhesion molecule-1 levels. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.

Aged↗
PubMed2001

Clinical significance of the atrial fibrillation threshold in patients with paroxysmal atrial fibrillation.

AF threshold and the other electrophysiological parameters were measured to quantify atrial vulnerability in patients with paroxysmal atrial fibrillation (PAF, n = 47), and those without AF (non-PAF, n = 25). Stimulations were delivered at the right atrial appendage with a basic cycle length of 500 ms. The PAF group had a significantly larger percentage of maximum atrial fragmentation (%MAF, non-PAF: mean +/- SD = 149 +/- 19%, PAF: 166 +/- 26%, P = 0.009), fragmented atrial activity zone (FAZ, non-PAF: median 0 ms, interquartile range 0-20 ms, PAF: 20 ms, 10-40 ms, P = 0.008). Atrial fibrillation threshold (AF threshold, non-PAF: median 11 mA, interquartile range 6-21 mA, PAF: 5 mA, 3-6 mA, P < 0.001) was smaller in the PAF group than in the non-PAF group. Sensitivity, specificity, and positive predictive value of electrophysiological parameters were as follows, respectively: %MAF (cut off at 150%, 78%, 52%, 76%), FAZ (cut off at 20 ms, 47%, 84%, 85%), AF threshold (cut off at 10 mA, 94%, 60%, 81%). There were no statistically significant differences between the non-PAF and PAF groups in the other parameters (effective refractory period, interatrial conduction time, maximum conduction delay, conduction delay zone, repetitive atrial firing zone, wavelength index), that were not specific for PAF. In conclusion, the AF threshold could be a useful indicator to evaluate atrial vulnerability in patients with AF.

Adult↗
PubMed2001

17beta-estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-alpha.

Osteoprotegerin (OPG) is a recently identified member of the tumor necrosis factor (TNF) receptor superfamily that regulates bone mass through an inhibitory action on osteoclast differentiation and function. To determine its potential roles of OPG in pathological changes in bone metabolism caused by estrogen deficiency, we investigated effects of estrogen on OPG expression by a mouse stromal cell line, ST-2, in vitro. Treatment of ST-2 cells with 17beta-E(2) resulted in up-regulation of OPG expression at both the messenger RNA and protein levels. The effect was time and dose dependent and steroid specific. The stimulatory action of 17beta-E(2) on OPG expression appeared to be mediated by the estrogen receptor-alpha (ERalpha) subtype because stable overexpression of ERalpha, but not of ERbeta, enhanced the OPG induction by 17beta-E(2). Moreover, estrogen withdrawal after 5-day pretreatment, mimicking the event occurring in vivo at menopause, dramatically diminished the expression of OPG. These findings suggest that down-regulation of OPG after estrogen withdrawal contributes to the enhanced osteoclastic bone resorption and bone loss after menopause by enhancing RANK ligand-RANK system that lies downstream of a large number of bone-resorbing cytokines.

Animals↗
PubMed2001

[Clinical application of metabolic bone markers in hematologic malignancies].

Hematologic malignancies such as multiple myeloma, adult T cell leukemia and malignant lymphoma are often complicated with bone lesions and/or hypercalcemia. The abnormal bone metabolism in these diseases are modified by co-existing cachexia, malnutrition, sex hormone deficiency and abnormal parathyroid function or by chemotherapy in a complex manner. Metabolic bone markers are not only clinically useful for evaluation and diagnosis of such bone abnormalities but may also be used to monitor the disease activity itself, particularly in multiple myeloma which almost inevitably involves bone destructive lesions.

English Abstract↗
PubMed2001

[Not Available].

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Journal Article↗
PubMed2000

Parathyroid hormone-related peptide and bone: pathological and physiological aspects.

Parathyroid hormone-related peptide (PTHrP) was initially discovered as a tumor-derived systemic factor which causes humoral hypercalcemia of malignancy. When overproduced and secreted by tumor cells, PTHrP acts on target organs such as bone and kidney to cause hypercalcemia through its 'PTH-like effects'. The hypercalcemic effects of PTHrP are attributed to its N-terminal portion (1-36) which shows a limited homology with PTH and is able to bind to the common PTH/PTHrP receptor. In contrast to such pathological effects as a humoral factor, PTHrP is now recognized as a locally active cytokine produced by a variety of tissues and cell types. Gene knockout experiments have revealed critical roles for PTHrP in a wide spectrum of physiological processes including chondrogenesis. It also significantly contributes to various pathological processes such as tumor metastasis to bone and bone destruction in arthropathies, acting as a bone-resorbing cytokine. Consistent with its divergent roles, regulation of PTHrP expression as well as its mode of action seems to be much more complex than its hormonal counterpart, PTH. In this article, we will briefly review the recent progress in our understanding of both physiological and pathological aspects of PTHrP biology, with a particular focus on its roles as a bone cytokine.

Bone Diseases↗
PubMed2000

Transient complete atrioventricular block during catheter ablation of left free wall bypass tract.

Radiofrequency catheter ablation of accessory bypass tracts associated with the Wolff-Parkinson-White (WPW) syndrome has become an accepted and widespread therapy. When bypass tracts are located in the free wall of the left ventricle, complete atrioventricular (AV) block is an unusual complication. Two cases of symptomatic WPW syndrome with transient complete atrioventricular block during catheter ablation are described. The first case was a 14-year-old female with an accessory pathway located in the left posterior wall, and the second was a 72-year-old female with an accessory pathway located in the left lateral wall. Radiofrequency energy application resulted in transient complete AV block with escape rhythm. In the first case, AV conduction with left bundle branch block resumed the next day, whereas in the second case, AV conduction soon resumed with prolongation of atrio-His (AH) interval and no evidence of pre-excitation. This phenomenon could have been due to either trauma to the AV node during catheter entry into the left ventricle or compression of the AV node with a catheter shaft during ablation because both patients' hearts were comparatively small.

Adolescent↗
PubMed2000

Successful catheter ablation against ventricular tachycardia associated with myotonic dystrophy.

Myotonic dystrophy (MD) is characterized by myotonia and muscular dystrophy and cardiac involvement with tachy-arrhythmia is rarely encountered. We report a case of MD complicated with severe left ventricular hypofunction and incessant ventricular tachycardia (VT) with varying heart rates. The morphology of VT suggested that it originated from the right ventricular outflow tract, and electrophysiological study disclosed that the mechanism of VT was abnormal automaticity. Catheter ablation was performed to treat this VT. The patient had a cardiomyopathy with normal coronary arteries. The specimen of RV biopsy showed moderate hypertrophy, mild fat infiltration and slight fibrosis. These findings are histologically consistent with myotonic dystrophy.

Bradycardia↗
PubMed1999

Protein kinase C antagonizes pertussis-toxin-sensitive coupling of the calcitonin receptor to adenylyl cyclase.

The calcitonin receptor is known to couple to Gs and Gq, activating adenylyl cyclase and phospholipase C, respectively. The observation of pertussis-toxin-sensitive responses to calcitonin suggests that the receptor is capable of coupling to Gi/o as well. However, the calcitonin-dependent activation of adenylyl cyclase in HEK-293 cells that stably express the cloned rabbit calcitonin receptor, as in many other cells that express calcitonin receptors, shows little pertussis toxin sensitivity. Calcitonin treatment of these cells stimulates protein kinase C, which is reported to antagonize the receptor-dependent activation of Gi. The possibility that protein kinase C could be antagonizing Galphai-adenylyl cyclase coupling was tested by examining the effects of protein kinase C inhibitors (chelerythrine chloride and sphingosine) or of chronic treatment with phorbol ester to deplete protein kinase C. All three treatments led to a reduction of calcitonin-induced adenylyl cyclase activity that was reversed by pertussis toxin. Inhibiting or depleting protein kinase C had no effect on the activation of adenylyl cyclase by cholera toxin, indicating that Gs and adenylyl cyclase were not affected by these treatments. Calcitonin treatment of HEK-293 cells, that stably express a myc-tagged rabbit calcitonin receptor, induced the formation of complexes of the receptor and Galphai subunits, confirming that the calcitonin receptor interacts with Gi. Thus, the calcitonin receptor can couple to Gi, but the inhibition of adenylyl cyclase by Galphai is negatively regulated by protein kinase C.

Adenylate Cyclase Toxin↗
PubMed1999

Calcitonin-dependent down-regulation of the mouse C1a calcitonin receptor in cells of the osteoclast lineage involves a transcriptional mechanism.

Although expression of the calcitonin (CT) receptor (CTR) decreases after CT binding, there has been no evidence that it occurs at the transcriptional level. In the present study we investigated the mechanism of CTR messenger RNA (mRNA) down-regulation by CT in mouse cocultures of bone marrow and osteoblasts. Ribonuclease protection analysis revealed that osteoclast-like cells purified from cocultures predominantly express the C1a isoform and do not express an appreciable amount of the brain-specific C1b mRNA (< 1% of C1a). Treatment of day 5 cocultures with CT caused a dose- and time-dependent decrease in the steady state level of C1a mRNA. This CT effect was mimicked by the cAMP agonists forskolin and (Bu)2cAMP. Prolonged suppression of C1a mRNA was observed after short treatment with CT, but not with (Bu)2cAMP, suggesting that persistent intracellular cAMP elevation is necessary for the prolonged CT effect. The half-life of the C1a mRNA in cocultures was 4-6 h and was not altered by CT or (Bu)2cAMP. Moreover, competitive RT-PCR analysis revealed that 1-h treatment with CT reduced the level of CTR heterogeneous nuclear RNA to 10% in a cycloheximide-independent manner. These results suggest that CT down-regulates C1a-CTR mRNA expression at least in part by a transcriptional mechanism, thereby contributing to the ligand-induced desensitization in cells of the osteoclast lineage.

Animals↗
PubMed1999

A case of ectopic thyroid in lateral neck associated with Graves' disease.

Thyroid follicles in the lateral position of the neck are usually thought to represent the metastasis of thyroid carcinoma. Here we present a case of a 28-year-old woman with accessory ectopic thyroid associated with Graves' disease. Despite a history of Graves' disease poorly controlled with large dose propylthiouracil she was found to be pregnant and artificial abortion was planned. Thyroid scintigraphy was carried out, which indicated an uptake into the region above the left lobe as well as into both lobes of the thyroid gland. In order to control hyperthyroidism and to exclude the possibility of metastasis, total thyroidectomy with tumor resection was performed before the artificial abortion. Pathological examinations of the thyroid gland indicated findings compatible with Graves' disease. The lateral neck mass was revealed to be composed of nonneoplastic thyroid tissue, showing similar histological findings to those of the goiter, which were consistent with Graves' disease. Taken together with several previous reports, it appears that there are some cases with lateral ectopic thyroid tissue, whose pathogenetic mechanism remains to be elucidated.

Abortion, Induced↗
PubMed1998

The calcitonin receptor stimulates Shc tyrosine phosphorylation and Erk1/2 activation. Involvement of Gi, protein kinase C, and calcium.

While it is well established that adenylyl cyclase and phospholipase C-beta are two proximal signal effectors for the calcitonin receptor, the more distal signaling pathways are less well characterized. G protein-coupled receptors can activate Erk1/2 by Gs-, Gi-, or Gq-dependent signaling pathways, depending on the specific receptor and cell type examined. Since the calcitonin receptor can couple to all three of these G proteins, the ability of calcitonin to activate Erk1/2 was investigated. Calcitonin induced time- and concentration-dependent increases in Shc tyrosine phosphorylation, Shc-Grb2 association and Erk1/2 phosphorylation and activation in a HEK 293 cell line that stably expresses the rabbit calcitonin receptor C1a isoform. Pertussis toxin, which inactivates Gi, and calphostin C, a protein kinase C inhibitor, each partially inhibited calcitonin-induced Shc tyrosine phosphorylation, Shc-Grb2 association, and Erk1/2 phosphorylation. In contrast, neither forskolin nor H89, a protein kinase A inhibitor, had a significant effect on basal or calcitonin-stimulated Erk1/2 phosphorylation. Our results suggest that the calcitonin receptor induces Shc phosphorylation and Erk1/2 activation in HEK293 cells by parallel Gi- and PKC-dependent mechanisms. The calcitonin-induced elevation of cytosolic free Ca2+ was required for Erk1/2 phosphorylation, since preventing any change in cytosolic free Ca2+ by chelating both cytosolic and extracellular Ca2+ abolished the response. However, the change in Ca2+ that is induced by calcitonin is not sufficient to account for the calcitonin-induced Erk1/2 phosphorylation, since treatment with 100 nM ionomycin or 10 microM thapsigargin, each of which induced elevations of Ca2+ comparable to those induced by calcitonin, induced significantly less Erk1/2 phosphorylation than that induced by calcitonin. Erk1/2 may have important roles as downstream effectors mediating cellular responses to calcitonin stimulation.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Cloning and initial characterization of mouse meltrin beta and analysis of the expression of four metalloprotease-disintegrins in bone cells.

Here we report the cloning and initial biochemical characterization of the mouse metalloprotease/disintegrin/cysteine-rich (MDC) protein meltrin beta and the analysis of the mRNA expression of four MDC genes (meltrin alpha, meltrin beta, mdc9, and mdc15) in bone cells, including osteoclasts and osteoblasts. Like most other MDC proteins, the predicted meltrin beta protein consists of a signal sequence, prodomain, metalloprotease domain with a predicted catalytic site, disintegrin domain, cysteine-rich region, epidermal growth factor repeat, transmembrane domain, and cytoplasmic domain with putative signaling motifs, such as potential SH3 ligand domains. Northern blot analysis indicates that meltrin beta is widely expressed, with the highest expression in bone, heart, and lung. RNase protection studies revealed expression of all four MDC genes analyzed here in osteoblasts, whereas only mdc9 and mdc15 mRNAs were detectable in osteoclast-like cells generated in vitro. Treatment of primary osteoblasts with 10 nM calcitriol increased meltrin beta expression more than 3-fold, and both meltrin alpha and meltrin beta expression is apparently regulated in a differentiation-associated manner in a mouse osteoblastic cell line, MC3T3E1. Collectively, these results suggest that meltrin alpha and meltrin beta may play a role in osteoblast differentiation and/or function but are not likely to be involved in osteoclast fusion.

ADAM Proteins↗
PubMed1998

Clonal analysis helps to differentiate aberrant thyroid tissue from thyroid carcinoma.

A rare case of multiple aberrant of thyroid tissues in the tongue and lymph nodes of the bilateral neck was studied by immunohistochemistry and molecular clonal analysis to determine whether these tissues represent aberrant ectopic thyroid or metastases of a thyroid carcinoma. The thyroid tissues in the tongue and lymph nodes were all of polyclonal origins, consistent with ectopic thyroid in the tongue and bilateral cervical lymph nodes, rather than malignant thyroid tissues. This case shows that molecular clonal analysis can be used to distinguish aberrant thyroid from metastases of thyroid carcinoma.

Adult↗
PubMed1998

Oligonephronia, not exuberant apoptosis, accounts for the development of glomerulosclerosis in the bcl-2 knockout mouse.

BACKGROUND: A main function attributed to B cell leukaemia/lymphoma 2 gene (bcL-2) is its ability to confer resistance against apoptosis. In bcl-2 deficient mice, extensive apoptosis occurs during abnormal nephrogenesis, and renal failure is found very quickly after birth. However, the underlying mechanisms remain poorly understood. The aim of the present study was to clarify whether the degenerative process in the kidneys seen after birth is based either on increased apoptosis of glomerular cells or on mechanisms independent from the genetic defect. MATERIALS AND METHODS: Kidneys from 7-56-day-old bcl-2 knockout mice and wild-type litter mates were studied. Glomerular number, glomerular tuft volume, cell counts in 'non-sclerotic' glomeruli as well as the glomerular damage score were determined by histomorphometrical studies. Apoptosis was evaluated by morphological criteria and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL)-technique. RESULTS: The number of nephrons at birth was severely decreased in bcl-2 knockout mice compared to controls (<20%; P < 0.001). These nephrons undergo dramatic hypertrophy with an approximately 4-fold increase in volume (P < 0.001). In hypertrophic, but 'non-sclerotic' glomeruli, the number density of glomerular cells progressively declined with time (P<0.001). Starting with day 20, enlarged glomeruli developed sclerosis beginning with a segmental distribution, but quickly progressing to global sclerosis. Apoptosis was neither detected in non-sclerotic glomeruli nor in stages prior to fully established sclerosis. As shown by the glomerular damage score, post-natal degeneration of kidneys from bcl-2 knockout animals proceeded rapidly. CONCLUSIONS: Bcl-2 knockout mice exhibit deficient nephrogenesis resulting in severe oligonephronia at birth. Post-partum development of glomerulosclerosis does not seem to be due to augmented apoptosis. The degenerative process appears to be based on a glomerular overload with increased mechanical stress to the filtration barrier, leading via glomerular hypertrophy, podocyte damage and formation of tuft adhesions to glomerulosclerosis.

Animals↗