[X-linked hypophosphatemic vitamin D resistant rickets: Pathogenesis, pathophysiology, and therapy].
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Animals↗
Biomedical subjects
Hiroyuki Tanaka
Publications and source records attributed to Hiroyuki Tanaka.
[Prognostic value of C-reactive protein and troponin T level in patients with unstable angina pectoris].
OBJECTIVES: The prognosis of unstable angina pectoris may be more accurately predicted by the combination of C-reactive protein (CRP), which is a known inflammation marker, and troponin T (TnT), which is used for risk assessment for the prognosis of acute coronary syndrome. The present study investigated the correlations between pathophysiology and prognosis of severe unstable angina pectoris and CRP and TnT levels. METHODS: The correlation between CRP at admission and the prognosis was studied in 367 patients with severe unstable angina pectoris (Braunwald type II and III) who were admitted to our hospital between January 1998 and December 2000. The in-hospital and long-term prognosis was investigated in TnT-positive patients. In-hospital cardiac events were defined as death, myocardial infarction, heart failure and angina attacks during hospitalization. Long-term cardiac events were defined as death, myocardial infarction, heart failure and recurrence of angina. RESULTS: The incidence of in-hospital cardiac events in all patients was 30.2%. The CRP levels were higher in patients with cardiac events (0.97 +/- 2.67 vs 0.53 +/- 1.29 mg/d/, p = 0.057), but there was no significant difference between the two groups. The incidence of long-term cardiac events was 26.8%. The mean CRP level was significantly higher in patients with cardiac events than in patients without cardiac events (1.17 +/- 1.86 vs 0.43 +/- 1.14 mg/dl, p = 0.098). In TnT-positive patients (TnT > 0.1 ng/ml, 23% of all patients), the incidence of in-hospital cardiac events was 47.6% (p < 0.0001), significantly higher than that in all patients. TnT-positive patients with CRP levels of 0.5 mg/dl or higher (8% of all patients) had a markedly higher incidence of in-hospital cardiac events of 56.7% (p = 0.001) and long-term cardiac events of 46.7% (p = 0.01). CONCLUSIONS: CRP levels were useful in prediction of the long-term prognosis. TnT levels were useful in prediction of in-hospital prognosis. The present study suggested the possibility that the combined use of these biological markers could predict the prognosis of patients with unstable angina at early stage and more accurately.
Angina, Unstable↗
Clinical significance of decreased serum concentration of cartilage oligomeric matrix protein in systemic juvenile idiopathic arthritis.
OBJECTIVE: Serum cartilage oligomeric matrix protein (COMP) concentration is elevated in patients with early osteoarthritis and early rheumatoid arthritis, and may be a biomarker of cartilage turnover. We investigated whether serum COMP concentration could be a clinically significant marker of arthritis and/or growth impairment in juvenile idiopathic arthritis (JIA). METHODS: Specimens were collected from 82 healthy blood donors under 22 years of age with no growth impairment who served as healthy controls, and from 24 patients with JIA (6 with oligoarthritis, 10 with polyarthritis, 8 with systemic JIA) presenting with active arthritis. Serum COMP concentration was determined using a human COMP assay kit. RESULTS: Serum COMP concentrations were significantly higher in all controls less than 16 years of age than in all controls aged 16 years or older. There was a significant negative correlation between serum COMP concentration and serum C-reactive protein in patients with JIA. Serum COMP concentrations in patients with systemic JIA were significantly lower than those in controls. CONCLUSION: Serum COMP concentrations in healthy children reflected increased cartilage turnover in the growth phase. Because the serum COMP concentration was decreased in cases of systemic JIA in which growth impairment was pronounced, the systemic inflammation occurring in systemic JIA may have an effect on cartilage turnover, which plays an important role in growth. Serum COMP concentration may prove to be a marker that indicates growth impairment in systemic JIA.
Adolescent↗
[Management of glucocorticoid-induced osteoporosis in childhood].
Bone turnover rate during growth is extremely rapid. Bone growth is under the control of various hormonal environments. Long term administration of glucocorticoid in childhood induced not only osteoporosis but also growth failure via direct action on bone and cartilage and indirectly via hormonal derangements. Sex steroid is one of the important hormones for the bone mineral accrual and for cartilage maturation. Thus glucocorticoid usage during puberty resulted in irreversible effect on bone health including bone growth and peak bone mass accrual. Recently bisphosphonates have been widely used in the treatment of these steroid induced bone disorders in adult with large amount of evidences. But in pediatrics, we are far from the firm evidences. Large scale randomized controlled study (RCT) is necessary.
Adult↗
[Fibroblast growth factor receptor and achondroplasia].
Fibroblast growth factor receptor 3 (FGFR3) has been establishing its position in growth plate cartilage after the identification as a responsible gene for achondroplasia. The major pathway of the pathogenesis in achondroplasia is the suppression of parathyroid hormone-related protein (PTHrP)-parathyroid hormone receptor (PTHR) system, which is mainly mediated by extracellular signal regulated kinase (ERK) activation induced by constitutive active FGFR3. However, intracellular signaling system in FGFR3 is complex and the molecular pathogenesis of achondroplasia and related disorders has not been fully clarified. In this review, I summarized recent consensus in the pathogenesis of FGFR3 related chondrodysplasia.
Achondroplasia↗
Regulation of dendritic cell maturation and function by Bruton's tyrosine kinase via IL-10 and Stat3.
Btk plays crucial roles in the differentiation and activation of B and myeloid cells. Despite drastic reductions of other Ig isotypes, paradoxically high IgE responses have been known in btk mutant mice. Here we show that btk(-/-) dendritic cells exhibit a more mature phenotype and a stronger in vitro and in vivo T cell-stimulatory ability than wild-type cells. Increased IgE responses were induced by adoptive transfer of btk(-/-) dendritic cells into mice. Consistent with the stronger T cell-stimulatory ability of btk(-/-) dendritic cells, btk(-/-) mice exhibited enhanced inflammation in Th2-driven asthma and Th1-driven contact sensitivity experiments. These negative regulatory functions of Btk in dendritic cells appear to be mediated mainly through autocrine secretion of IL-10 and subsequent activation of Stat3.
Adoptive Transfer↗
Decrease in prostaglandin level is a prerequisite for the expression of cannabinoid withdrawal: a quasi abstinence approach.
Cannabinoid withdrawal has been indicated in both human and animal subjects. One of pathways proposed to facilitate cannabinoid action is the arachidonic acid cascade. Previously, we have shown that prostaglandin attenuated the expression of withdrawal signs in tetrahydrocannabinol-dependent mice. It follows that the cascade might participate in the expression of cannabinoid withdrawal. We utilized a quasi abstinence approach (the induction of a state of cannabinoid withdrawal without giving any cannabinoid substances in a naïve animal) to describe the relationship between the change in prostaglandin level, an end product of the arachidonic acid cascade, and the expression of cannabinoid withdrawal. Administration of 10 mg/kg diclofenac, a prostaglandin synthesis inhibitor, i.p. 30 min before SR 141716A induced cannabinoid withdrawal signs in naïve mice, which were comparable to the true abstinence in cannabinoid-tolerant mice. In turn, 10 mg/kg Delta(8)-THC i.p., given 15 min prior to SR 141716A, blocked the expression of these signs. These results suggested that the decrease in prostaglandin level is a prerequisite for the expression of cannabinoid withdrawal.
Animals↗
Detection and quantification of ginsenoside Re in ginseng samples by a chromatographic immunostaining method using monoclonal antibody against ginsenoside Re.
A chromatographic immunostaining method has been developed for the determination of ginsenoside Re (G-Re) in ginseng samples on a polyethersulphone (PES) membrane. G-Re standard and the extracts of ginseng roots were applied to a PES membrane and developed by methanol-water-acetic acid (45:55:1, by volume). G-Re was clearly detected by an immunostaining method using a monoclonal antibody against G-Re. The coloring spots of G-Re were analyzed quantitatively using NIH Image software indicating at least 0.125 microg of G-Re was detectable. G-Re can be analyzed quantitatively between 0.25 and 4.0 microg.
Animals↗
Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy.
Six missense mutations in human cardiac troponin I (cTnI) were recently found to cause restrictive cardiomyopathy (RCM). We have bacterially expressed and purified these human cTnI mutants and examined their functional and structural consequences. Inserting the human cTnI into skinned cardiac muscle fibers showed that these mutations had much greater Ca2+-sensitizing effects on force generation than the cTnI mutations in hypertrophic cardiomyopathy (HCM). The mutation K178E in the second actin-tropomyosin (Tm) binding region showed a particularly potent Ca2+-sensitizing effect among the six RCM-causing mutations. Circular dichroism and nuclear magnetic resonance spectroscopy revealed that this mutation does not extensively affect the structure of the whole cTnI molecule, but induces an unexpectedly subtle change in the structure of a region around the mutated residue. The results indicate that the K178E mutation has a localized effect on a structure that is critical to the regulatory function of the second actin-Tm binding region of cTnI. The present study also suggests that both HCM and RCM involving cTnI mutations share a common feature of increased Ca2+ sensitivity of cardiac myofilament, but more severe change in Ca2+ sensitivity is associated with the clinical phenotype of RCM.
Actin Cytoskeleton↗
Wnt4-transformed mouse embryonic stem cells differentiate into renal tubular cells.
Embryonic stem (ES) cells have the potential to differentiate into various progenitor cells. Here we investigated the capacity of mouse ES cells to differentiate into renal tubular cells both in vitro and in vivo. After stably transfecting Wnt4 cDNA to mouse ES cells (Wnt4-ES cells), undifferentiated ES cells were incubated by the hanging drop culture method to induce differentiation to embryoid bodies (EBs). During culturing of the EBs derived from the Wnt4-ES cells, aquaporin-2 (AQP2) mRNA and protein were expressed within 15-20 days. The expression of AQP2 in Wnt4-EBs was enhanced in the presence of hepatocyte growth factor (HGF) and activin A. We next performed in vivo experiments by transplanting the Wnt4-EBs into the mouse renal cortex. Four weeks after transplantation, some portions of the EB-derived cells expressing AQP2 in the kidney assembled into tubular-like formations. In conclusion, our in vitro and in vivo experiments revealed two new findings: first, that cultured Wnt4-EBs have an ability to differentiate into renal tubular cells; and second, that Wnt4, HGF, and activin A may promote the differentiation of ES cells to renal tubular cells.
Activins↗
An on-membrane quantitative analysis system for glycyrrhizin in licorice roots and traditional Chinese medicines.
An on-membrane quantitative analysis system has been developed for determining glycyrrhizin (GC) in licorice roots and traditional Chinese medicines. A GC standard and the extracts of licorice roots and traditional Chinese medicines were applied to a polyethersulfone (PES) membrane and were developed by acetonitrile/water/formic acid (45:55:2, by volume), then treated with a NaIO4 solution followed by bovine serum albumin (BSA), resulting in a GC-BSA conjugate on a PES membrane. Anti-GC monoclonal antibody was bound and then a second antibody labeled with peroxidase directed against the first antibody. Finally a substrate reacted with the enzyme and gave staining. The stained membrane was scanned and coloring spots were analyzed quantitatively using graphic analysis by NIH Image software, indicating at least 0.5 microg of GC was clearly detectable. GC can be analyzed quantitatively between 1.0 and 8.0 microg.
Chromatography, High Pressure Liquid↗
Nuclear translocation of H2RSP is impaired in regenerating intestinal epithelial cells of murine colitis model.
Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a recently identified nuclear peptide that is abundantly expressed in the gastrointestinal tract. In this study, we analyzed the expression of H2RSP in normal and injured intestinal mucosa in a murine experimental colitis induced by oral administration of 2.5% dextran sodium sulfate. Results of immunohistochemistry and in situ hybridization showed that H2RSP was expressed predominantly in the epithelium of normal intestine. Whereas H2RSP was localized in the cytoplasm of cells in the crypt, it was translocated into the nuclei of the surface epithelial cells. In injured intestine, H2RSP was detected in the cytoplasm of regenerating epithelial cells, and the nuclear translocation was impaired even in the surface epithelium. However, the mRNA level was not significantly altered in these cells by real-time reverse transcription-polymerase chain reaction using total RNAs obtained from the fractionated mucosal tissue samples prepared by laser-captured microdissection technique. On the other hand, H2RSP mRNA was significantly upregulated in the stromal cells of injured intestinal mucosa compared with those in normal mucosa, which shows cytoplasmic localization of H2RSP. These circumstantial evidences suggest that the nuclear translocation of H2RSP may be related to a signaling involved in the transition from cellular proliferation to differentiation.
Animals↗
Single-turnover kinetics of 2,3-dihydroxybiphenyl 1,2-dioxygenase reacting with 3-formylcatechol.
2,3-Dihydroxybiphenyl 1,2-dioxygenase (EC 1.13.11.39) from Pseudomonas sp. strain KKS102 (BphC) catalyzes the proximal extradiol cleavage of the catechol ring of 2,3-dihydroxybiphenyl (DHB), a key step in the biodegradation of polychlorinated biphenyl. Because the active site Fe(II) ion of the extradiol dioxygenase is colorless, it has been difficult to monitor the reaction cycle kinetics. Here, we have found that BphC binds strongly the chromophoric substrate 3-formylcatechol (3FC) as a monoanion (Kd=0.8 microM) and cleaves it two orders of magnitude slower compared to DHB under air-saturation conditions. By utilizing 3FC as a probe, the reaction cycle kinetics of BphC was monitored for the first time. The binding of 3FC occurred in a three-step process involving rapid deprotonation of 3FC. The bound monoanionic 3FC reacted slowly with O2 in three steps, occurring in sequence, the ring opening step being the slowest one.
Catechols↗
A novel EID family member, EID-3, inhibits differentiation and forms a homodimer or heterodimer with EID-2.
The EID family members, i.e., E1A-like inhibitor of differentiation-1 (EID-1) and EID-1-like inhibitor of differentiation-2 (EID-2), were identified as negative regulators of cellular differentiation. EID-1 seems to inhibit differentiation by blocking histone acetyltransferase activity and EID-2 possibly inhibits differentiation through binding to class I histone deacetylases (HDACs). Here, we report a novel inhibitor of differentiation exhibiting homology with EID-2 termed EID-3 (EID-2-like inhibitor of differentiation-3). Like EID-2, EID-3 inhibited MyoD- and GRalpha-dependent transcription and blocked muscle differentiation in cultured cells by binding to class I HDACs. Unlike that of EID-2, the C-terminus, but not the N-terminus, of EID-3 was required for nuclear localization. EID-3 formed a homodimer or heterodimer with EID-2. These results suggest that EID-3 inhibits differentiation by blocking transcription as a complex in cells.
Acetyltransferases↗
Role of the E2F1-p19-p53 pathway in ischemic acute renal failure.
BACKGROUND: Cell cycle progression and arrest of renal tubular cells after acute injury is a reactive process of renal regeneration. The p16(INK4a)/p19(ARF) (alternative reading frame) locus encodes two proteins involved in cell cycle regulation. We investigated the transcriptional regulation and tissue distribution of p19(ARF) in ischemic acute renal failure (ARF). METHODS: We examined the time course and immunohistochemistry of p19(ARF) in rat kidneys following the induction of ischemic ARF. We also examined the effect of p19(ARF) overexpression on p53 levels and cell cycle progression in MDCK cells. RESULTS: The protein expression of p19(ARF) strongly increased 72 h after the ischemia. Immunohistochemical studies showed that the renal tubular cells in the outer medulla expressed p19(ARF) protein 72 h after ischemic injury. The time course of E2F1 induction was observed at 6-24 h, and it was found to precede p19(ARF) expression. In MDCK cells, the overexpression of E2F1 increased promoter activity and the protein level of p19(ARF) and induced apoptosis. Transfection of the p19(ARF) expression vector caused an increase in p53 protein, cell cycle arrest and apoptosis. CONCLUSIONS: These data support the hypothesis that the E2F1-p19(ARF)-p53 pathway forms a negative feedback loop to regulate the cell cycle of renal tubular cells in the ischemic ARF.
Acute Kidney Injury↗
Aldosterone stimulates proliferation of mesangial cells by activating mitogen-activated protein kinase 1/2, cyclin D1, and cyclin A.
Recently, attention has been focused on the role of aldosterone in the pathophysiology of hypertension and cardiovascular disease. Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. However, the molecular mechanisms of the effects of aldosterone in signal transduction and the cell-cycle progression of mesangial cells are not well known. For determining the signaling pathway of aldosterone in cultured mesangial cells, the effects of aldosterone on the mitogen-activated protein kinase 1/2 (MAPK1/2) pathway and the promoter activities of cyclin D1, cyclin A, and cyclin E were investigated. First, it was shown that the mineralocorticoid receptor (MR) was expressed in rat mesangial cells and glomeruli and that aldosterone stimulated the proliferation of mesangial cells via the MR and MAPK1/2 pathway. Next, it was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells. Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities. The presence of CYP11B2 and 11beta-HSD2 mRNA in rat mesangial cells also was shown. In conclusion, aldosterone seems to exert mainly MR-induced effects that stimulate c-Raf, MEK1/2, MAPK1/2, the activities of CDK2 and CDK4, and the cell-cycle progression in mesangial cells. MR antagonists may serve as a potential therapeutic approach to mesangial proliferative disease.
11-beta-Hydroxysteroid Dehydrogenase Type 2↗
Single molecule visualization of coordination-assembled porphyrin macrocycles reinforced with covalent linkings.
Coordination-assembled porphyrin macrocycles reinforced with covalent bondings were deposited on a metal surface by a pulse injection method, and their scanning tunneling microscopy (STM) images were recorded under ultrahigh vacuum conditions at liquid nitrogen temperature. The decamer ring consisting of 30 porphyrins gave clear circular STM images with hollow structure, whereas that without covalent linking did not give clear circular images, showing that covalent linking of the coordination pairs by ring-closing metathesis reaction was effective to reinforce the supramolecular structure on a metal surface. This strategy will be applicable to a variety of supramolecular assemblies.
Journal Article↗
Chromatographic resolution of glucosidic compounds, ginsenosides on polyethersulphone membrane, and its application to the quantitative immunoassay for ginseng saponins.
A method has been devised for the chromatographic resolution of glucosidic compounds, ginseng saponins, on polyethersulphone (PES) membrane. The method results in good resolution and quantitative immunoassay for ginsenoside Rb1 (G-Rb1), G-Rc, and G-Rd in crude extracts of various ginsengs. The newly established method is simpler and applies for quantitative analysis. Ginsenosides developed by acetonitrile-water-acetic acid solvent system on a PES membrane were directly treated with a NaIO4 solution followed by bovine serum albumin (BSA), resulting in a ginsenoside-BSA conjugate on a PES membrane. Anti-G-Rb1 monoclonal antibody (MAb) was bound, and then a second antibody labeled with peroxidase directed against the first antibody. Finally a substrate reacted to the enzyme and gave staining. The stained membrane was scanned, and spots were analyzed quantitatively using NIH Image software. At least 62.5 ng of G-Rb1, G-Rc, and G-Rd were clearly detectable individually. Three ginsenosides can be analyzed quantitatively between 0.125 and 2.0 microg.
Antibodies, Monoclonal↗