[Development of rapid and sensitive screening methods for natural products using specific monoclonal antibodies].
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Animals↗
Biomedical subjects
Hiroyuki Tanaka
Publications and source records attributed to Hiroyuki Tanaka.
[Bone mass measurement in pediatrics].
The methodology of the bone mineral measurement from childhood through adolescence contains a few problems. Continuously growing child shows continuous enlargement of the bone and the difference in bone size exerts ineligible effects on the DXA value. Therefore, we should be careful to evaluate the value from the point of this view. This manuscript overviewed normal bone growth and problems in bone mineral assessment during childhood and adolescence.
Absorptiometry, Photon↗
Synthesis of optically active oligonaphthalenes via second-order asymmetric transformation.
Synthesis of numerous optically active rod-shaped oligo(2,3-dioxyfunctionalized)naphthalenes connected at their 1,4-positions was achieved using oxidative coupling under CuCl2/alpha-methylbenzylamine conditions by second-order asymmetric transformation. We believe this method is practical and should contribute to the field of material science.
Journal Article↗
The negative-feedback regulation of the IL-13 signal by the IL-13 receptor alpha2 chain in bronchial epithelial cells.
Bronchial asthma is a complex disease characterized by airway inflammation involving Th2 cytokines. Among Th2 cytokines, the significance of IL-13 in the pathogenesis of bronchial asthma has recently emerged. Particularly, the direct action of IL-13 on bronchial epithelial cells (BECs) is critical for generation of airway hyperresponsiveness. IL-13 has two binding units; the IL-13 receptor alpha1 chain transduces the IL-13 signal comprising a heterodimer with the IL-4R alpha chain, whereas the IL-13 receptor alpha2 chain (IL-13Ralpha2) is thought to act as a decoy receptor. However, it remains obscure how expression of these molecules is regulated in each cell. In this article, we analyzed the expression of these components in BECs. Either IL-4 or IL-13 induced intracellular expression of IL-13Ralpha2 in BECs, which was STAT6-dependent and required de novo protein synthesis. IL-13Ralpha2 expressed on the cell surface as a monomer inhibited the STAT6-dependent IL-13 signal. Furthermore, expression of IL-13Ralpha2 was induced in lung tissues of ovalbumin-induced asthma model mice. Taken together, our results suggested the possibility that IL-13Ralpha2 induced by its ligand is transferred to the cell surface by an unknown mechanism, and it down-regulates the IL-13 signal in BECs, which functions as a unique negative-feedback system for the cytokine signal.
Animals↗
Immunoquantitative analysis for berberine and its related compounds using monoclonal antibodies in herbal medicines.
The monoclonal antibody (MAb) against berberine, a bioactive constituent of Coptis japonica M., Phellodendron amurense R. and Hydrastis canadensis L., was produced and characterized. As immunogen, the derivative of berberine, 9-O-carboxymethyl berberrubine was synthesized and conjugated to carrier protein, bovine serum albumin (BSA). In order to confirm its immunogenicity, the ratio of hapten in berberine-BSA conjugate was determined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). After immunization, hybridomas secreting MAbs against berberine were produced by fusing splenocytes with mouse myeloma cell line, P3-X63-Ag8-653. After the screening, anti-berberine MAb 1D5-3B-7 was obtained. Subsequently, a quantitative ELISA system for berberine and its related compounds using the MAb was established and evaluated comparing with HPLC method. The ELISA method described in this study can be available as an analytical tool for quality control and standardization of medicinal plants and its prescriptions containing berberine and its related compounds.
Animals↗
Requirement of intracellular free thiols for hydrogen peroxide-induced hypertrophy in cardiomyocytes.
Reactive oxygen species (ROS) are by-products of aerobic metabolism and are implicated in the pathogenesis of several diseases. H(2)O(2) produces oxidative stress and acts as a second messenger in several cell types. We tested whether the effect of H(2)O(2) on cellular events could be altered by changes in the intracellular redox status in a cardiomyocyte cell line. Using flow cytometric measurements, we found that adding H(2)O(2) induced hypertrophy in control cells in a time-dependent manner. Pre-incubation of the cells with buthionine sulfoximine (BSO), an inhibitor of de novo GSH synthesis, induced increase in the number of cells of small sizes by the addition of H(2)O(2) as compared to non-BSO pre-incubated control cells, and exacerbated the decrease in viability. Total thiol and GSH levels in H9c2 cells pre-incubated with BSO were about 75 and 30% of control, respectively, and GSH levels fell to below the limitation of detection after the addition of H(2)O(2), although total thiol levels were not markedly decreased. In the cells pre-incubated with BSO, hypertrophy was not observed by the addition of H(2)O(2) at any level of concentration. N-acetyl-L-cysteine and cysteine not only prevented increase in the number of cells of small sizes caused by H(2)O(2) but also induced hypertrophy in cells pre-incubated with BSO. These results suggest that the intracellular free thiol levels determine whether cell death or hypertrophy occurs in cardiomyocytes in the presence of H(2)O(2). On the other hand, the hypertrophied cells did not become larger by adding H(2)O(2), but had high levels of cellular GSH, suggesting the possibility that the hypertrophied cells have tolerance to oxidative stress.
Animals↗
Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity.
Physical interaction of T cells and dendritic cells (DCs) is essential for T cell proliferation and differentiation, but it has been unclear how this interaction is regulated physiologically. Here we show that DCs produce thromboxane A2 (TXA2), whereas naive T cells express the thromboxane receptor (TP). In vitro, a TP agonist enhances random cell movement (chemokinesis) of naive but not memory T cells, impairs DC-T cell adhesion, and inhibits DC-dependent proliferation of T cells. In vivo, immune responses to foreign antigens are enhanced in TP-deficient mice, which also develop marked lymphadenopathy with age. Similar immune responses were seen in wild-type mice treated with a TP antagonist during the sensitization period. Thus, TXA2-TP signaling modulates acquired immunity by negatively regulating DC-T cell interactions.
Animals↗
Role of prostaglandin I2 in airway remodeling induced by repeated allergen challenge in mice.
Recently, we demonstrated that prostaglandin (PG)I2 has a regulatory role in allergic responses through the receptor, IP; however, the role of PGI2 in airway remodeling associated with chronic airway inflammation has not been elucidated. In the present study, we examined the role of PGI2 in allergen-induced airway remodeling using IP gene-deficient mice. Mice were sensitized to ovalbumin (OVA) with alum, and exposed daily for 3 wk to aerosolized OVA. Twenty-four hours after the final antigen inhalation, bronchoalveolar lavage, biochemical, and histopathologic examinations were performed. In wild-type mice, prolonged allergen exposure in sensitized animals induced the increases in the numbers of inflammatory leukocytes (including eosinophils and lymphocytes), levels of T helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13), levels of OVA-specific immunoglobulin (Ig)E and IgG1 in serum, and amount of hydroxyproline in the right lungs associated with transforming growth factor-beta1 levels in bronchoalveolar lavage fluid. Moreover, goblet cell hyperplasia and subepithelial fibrosis were also appreciated after repeated allergen challenge. In contrast, the disruption of IP gene significantly augmented all these parameters. These findings suggest that PGI2 has a regulatory role in allergen-induced airway remodeling as well as airway eosinophilic inflammation, Th2 cytokine production and IgE production, and that a PGI2 agonist is a therapeutic approach for the treatment of airway remodeling in allergic asthma.
Allergens↗
The primary varicella infection near term: a case report.
A 33-year-old pregnant woman developed skin rash at the 40 weeks' gestation. She was diagnosed as primary varicella zoster infection. Upon hospitalization, she was administered acyclovir and also a tocolytic agent (ritodorine hydrochloride) to postpone labor. The patient delivered a female baby 7 days after she developed skin lesions. Serological tests conducted after delivery showed that the mother was positive for IgG and IgM against varicella zoster. The baby was observed in a neonatal intensive care unit and found to be free of varicella zoster symptoms.
Acyclovir↗
Prostaglandin E2 attenuates SR141716A-precipitated withdrawal in tetrahydrocannabinol-dependent mice.
The present study aimed to clarify the role of the arachidonic acid cascade in mediating the expression of withdrawal signs in cannabinoid-dependent mice. Mice were injected with Delta(8)-tetrahydrocannabinol (THC) at 20 mg/kg (i.p.) every 12 h, 11 times. When SR141716A, a specific cannabinoid CB1 receptor antagonist, at 10 mg/kg (i.p.) was given 4 h after the last THC injection, withdrawal signs such as forepaw licking, facial preening, grooming, forepaw tremor, head shakes and weight loss were clearly observed. PGE(2) at 0.1, 1.0 and 3.2 microg (per animal; i.c.v.) given prior to SR141716A (10 mg/kg, i.p.) dose-dependently decreased the number of forepaw licking, facial preening, grooming and forepaw tremor episodes. Instead of SR141716A, a cyclooxygenase inhibitor diclofenac at 10 mg/kg (i.p.) also precipitated these withdrawal signs. The results suggest that the expression of THC withdrawal is due to a decrease in prostaglandin levels through inactivation of the arachidonic acid cascade in the brain.
Animals↗
Characterization of transcripts generated from mouse hepatocyte growth factor activator inhibitor type 2 (HAI-2) and HAI-2-related small peptide (H2RSP) genes: chimeric mRNA transcribed from both HAI-2 and H2RSP genes is detected in human but not in mouse.
We previously reported a novel small gene, designated hepatocyte growth factor activator inhibitor type 2 (HAI-2) related small peptide (H2RSP), in the process of the search for splicing variant forms of HAI-2 by 3(')-rapid amplification of cDNA ends method [Biochem. Biophys. Res. Commun. 288 (2001) 390]. Human H2RSP gene consisted of four exons spanning approximately 1kbp and was located in 11kbp downstream of HAI-2 gene. In this study, we cloned and characterized the mouse counterpart of H2RSP gene, which was located in 6.6kbp downstream of mouse HAI-2 gene, and analyzed the transcripts generated from both genes. Similar to human, mouse H2RSP mRNA (0.5kb) was detected abundantly in various tissues including the gastrointestinal tract, and has nuclear localization signal (NLS) in the lysine-rich region (exon 4), which was well-conserved between human and mouse genes. However, chimeric mRNA transcribed from both HAI-2 (exons 1-7) and H2RSP (exons 2-4) genes, which was found in the kidney, prostate, and placenta of human by Northern blot analysis, was not detected in mouse tissue even by a reverse transcription-polymerase chain reaction (RT-PCR). Instead of the chimeric mRNA, a novel splicing variant lacking putative transmembrane domain of HAI-2 was found in mouse but not in human as a putative secrete form of HAI-2. These results suggest that the organization of H2RSP and HAI-2 gene complex is well-conserved, but the usage of these genes was quite different between human and mouse.
Alternative Splicing↗
Characterization of a novel diol column for high-performance liquid chromatography.
For the investigation of a diol phase (Inertsil Diol column) in hydrophilic interaction chromatography, urea, sucrose and glycine were used as test compounds. The chromatographic conditions were investigated for optimal column efficiency. The column temperature used in common reversed-phase liquid chromatography could also be used for the separation and the flow-rate should be adjusted to 0.3-0.5 ml/min to optimize column efficiency. It is suggested that the velocity of the hydrophilic interaction is slower than the hydrophobic interaction in RPLC. The addition of trifluoroacetic acid is effective for the retention of glycine, but ineffective for urea and sucrose. The diol phase exhibited sufficient chemical stability even if exposed to water in high percentage, and could be applied with isocratic elution for the separation/analysis of amino acids and glucose.
Chromatography, High Pressure Liquid↗
A pseudoaneurysm after repair of thoraco-abdominal aortic aneurysm.
We report a 63-year-old female patient developing a pseudoaneurysm three years after patch-plasty of an aneurysm located at the distal thoracic aorta. Redo-operation was performed including total replacement of the descending thoracic aorta with reimplantation of distal intercostal arteries using small-caliber interposition grafts. This case presentation underlines the ineffectiveness of patch repair for the treatment of aortic aneurysms. Furthermore, the surgical technique of reimplantation of intercostal arteries using a separate graft is discussed.
Aneurysm, False↗
Transient increase in wall thickness of the left ventricular apex during recovery from "ampulla" cardiomyopathy.
"Ampulla" cardiomyopathy is a syndrome characterized by transient abnormal left ventricular wall motion with hypokinesia around the apical area and hyperkinesia at the basal area, without any detectable coronary lesion. Two cases of transient wall thickening of the left ventricular apex during recovery from "ampulla" cardiomyopathy are described. Apical wall thickening was documented by left ventriculography, echocardiography, and thallium (201Tl) single-photon emission computed tomography (SPECT) during the recovery phase. The thickness of the apical wall subsequently returned to normal. Both patients underwent provocation tests. Coronary spasms were positive. This transient increase in left ventricular apical volume may have been caused by myocardial inflammation secondary to "ampulla" cardiomyopathy.
Aged↗
Significance of serum atrial and brain natriuretic peptide release after coronary artery bypass grafting.
PURPOSE: The aim of this study was to examine whether serial changes in endogenous levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were associated with clinical status after coronary artery bypass grafting (CABG). METHODS: Serial blood samples were collected from 14 patients preoperatively, 2, 5 and 8 h after cardiopulmonary bypass, then up to 7 days postoperatively. Follow-up was done 2 years later. RESULTS: We found a significant increase from the preoperative values in ANP and BNP concentrations on postoperative days 1 and 3 (P < 0.001). The elevated BNP concentration correlated with the preoperative values (r2 = 0.824, P = 0.0005). Retrospectively, the BNP concentrations after surgery in the patients who suffered cardiac events within 2 years were significantly higher than those in the patients free of cardiac events (P = 0.0023). CONCLUSION: The BNP concentration after CABG was found to be corrected with interim clinical status after surgery. Thus, it may be necessary for patients with a high postoperative BNP concentration to be closely monitored for coronary events.
Atrial Natriuretic Factor↗
Efficacy of growth hormone therapy for patients with skeletal dysplasia.
Most patients with skeletal dysplasia show severe short stature. Surgical therapy has been attempted to correct bone deformities, but therapy for improving their severe short stature has been rarely attempted. We undertook a clinical trial of growth hormone (GH) therapy for patients with skeletal dysplasia accompanying severe short stature caused by achondroplasia (ACH), hypochondroplasia (HCH), pseudoachondroplasia (PSACH), spondyloepiphyseal dysplasia congenita (SED), or Schmid type metaphyseal dysplasia (MD). This study examined the efficacy of GH therapy on height increase and change of height SD score over a 1-year period in patients with skeletal dysplasia and showed a short-term efficacy for skeletal dysplasia. In ACH, HCH, and MD, GH had a significant effect on height gain. However, PSACH and SED showed no height gain efficacy; in cases of PSACH, height SD score was worse after therapy. Severe adverse events were not observed except in one SED case, in which scoliosis worsened and height did not increase. For patients with skeletal dysplasia, GH therapy is moderately effective for height gain. It is ineffective in cases with severe spinal deformities, however; although bone growth was promoted, the ligaments and matrix were too weak to support muscle tonus and the effects of gravity, resulting in worsened kyphosis and lordosis. These results clarify why GH therapy is ineffective for height gain. The pathogenic genes of skeletal dysplasia have recently been detected and consequently changes in bone formation have been investigated in detail. Careful consideration of indications for therapy and cautious observation during therapy are crucial when attempting to treat advanced bone deformities.
Achondroplasia↗
Analysis of linear growth in survivors of childhood acute lymphoblastic leukemia.
Therapy for childhood acute lymphoblastic leukemia (ALL) is entering a new era in terms of quality-of-life. In the current study, 21 patients with childhood-onset ALL were assessed for linear growth, bone mineral density (BMD), and endocrinological status, focusing especially on longitudinal analysis of the growth of each patient. Linear growth was uniformly attenuated during therapy in all patients. In contrast, after the cessation of therapy, the growth of each patient varied widely from attenuated to dramatic catch-up growth. In pubertal survivors who had received chemotherapy and cranial irradiation during prepuberty, the degree of growth after the cessation of therapy was negatively correlated with changes in height Z scores during therapy ( r = -0.76, P= 0.004). One of the factors involved in catch-up growth, urinary N-telopeptide/creatinine (U-NTx/Cr), was significantly higher in patients whose Z scores decreased after cessation of therapy ( P = 0.01), despite normal pubertal development and normal endocrinological assessments. The present study revealed individual differences in linear growth after the cessation of therapy and suggests the importance of catch-up growth during puberty.
Adolescent↗
Clinical study of biocompatibility between open and closed heparin-coated cardiopulmonary bypass circuits.
The objective of this study was to investigate the difference between the closed circuit system and the open circuit system in clinical heparin-coated cardiopulmonary bypass (CPB) circuits with a centrifugal pump. We evaluated the coagulation, fibrinolysis, and inflammatory response in valvular heart surgery. Nineteen patients were assigned at random to a group for the closed circuit system or the open circuit system. This is the first report on the effect of a closed circuit in valvular surgery. We measured the platelet count, white blood cell count, plasma fibrinogen concentration, thrombin-antithrombin III complex, plasmin-Alpha2 plasmin inhibitor complex, D-dimer, interleukin-6, polymorphic neutrophil-elastase, and the plasma free hemoglobin. Blood samples were collected before the start of perfusion, 15 and 60 min after the start of perfusion, 60 min after the administration of protamine, and 1 day after the operation. During the perfusion, coagulation, fibrinolysis, and inflammatory responses were activated; however, no significant differences between the two groups were noted. In this clinical investigation with suction and the cell saving system, the closed circuit was not found to be superior to the open circuit with regard to biocompatibility.
Aged↗