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Biomedical subjects

M Chikamori

Publications and source records attributed to M Chikamori.

At least 19 recordsLinked to original sources
PubMed2006

Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation.

The t(2;5) chromosomal translocation occurs in anaplastic large-cell lymphoma arising from activated T lymphocytes. This genomic rearrangement generates the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) oncoprotein that is a chimeric protein consisting of parts of the nuclear protein NPM and ALK receptor protein-tyrosine kinase. We used yeast two-hybrid screening to identify an adaptor protein Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT)-2 as a new partner that interacted with the cytoplasmic domain of ALK. Immunoprecipitation assay revealed that SNT-1 and SNT-2 interacted with NPM-ALK and kinase-negative NPM-ALK mutant. Y156, Y567 and a 19-amino-acid sequence (aa 631-649) of NPM-ALK were essential for this interaction. The interaction through Y156 and Y567 was dependent on phosphorylation of these tyrosines, whereas the interaction through the 19-amino-acid sequence was independent of phosphorylation. NPM-ALK mutant protein mutated at these three binding sites showed significantly reduced transforming activity. This transformation-defective NPM-ALK mutant still interacted with signal transducing proteins such as phospholipase C-gamma and phosphatidylinositol 3-kinase, which were previously reported to be relevant to NPM-ALK-dependent tumorigenesis. These observations indicate that the three SNT-binding sites of NPM-ALK are important for its transforming activity. This raises a possibility that SNT family proteins play significant roles in cellular transformation triggered by NPM-ALK, which though remains to be verified.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Unique role of SNT-2/FRS2beta/FRS3 docking/adaptor protein for negative regulation in EGF receptor tyrosine kinase signaling pathways.

The membrane-linked docking protein SNT-2/FRS2beta/FRS3 becomes tyrosine phosphorylated in response to fibroblast growth factors (FGFs) and neurotrophins and serves as a platform for recruitment of multiple signaling proteins, including Grb2 and Shp2, to FGF receptors or neurotrophin receptors. We previously reported that SNT-2 is not tyrosine phosphorylated significantly in response to epidermal growth factor (EGF) but that it inhibits ERK activation via EGF stimulation by forming a complex with ERK2. In the present report, we show that expression of SNT-2 suppressed EGF-induced cell transformation and proliferation, and expression level of SNT-2 is downregulated in cancer. The activities of the major signaling molecules in EGF receptor (EGFR) signal transduction pathways, including autophosphorylation of EGFR, were attenuated in cells expressing SNT-2 but not in cells expressing SNT-2 mutants lacking the ERK2-binding domain. Furthermore, SNT-2 constitutively bound to EGFR through the phosphotyrosine binding (PTB) domain both with and without EGF stimulation. Treatment of cells with MEK inhibitor U0126 partially restored the phosphorylation levels of MEK and EGFR in cells expressing SNT-2. On the basis of these findings, we propose a novel mechanism of negative control of EGFR tyrosine kinase activity with SNT-2 by recruiting ERK2, which is the site of negative-feedback loop from ERK, ultimately leading to inhibition of EGF-induced cell transformation and proliferation.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Regulation of type II renal Na+-dependent inorganic phosphate transporters by 1,25-dihydroxyvitamin D3. Identification of a vitamin D-responsive element in the human NAPi-3 gene.

Vitamin D is an important regulator of phosphate homeostasis. The effects of vitamin D on the expression of renal Na+-dependent inorganic phosphate (Pi) transporters (types I and II) were investigated. In vitamin D-deficient rats, the amounts of type II Na+-dependent Pi transporter (NaPi-2) protein and mRNA were decreased in the juxtamedullary kidney cortex, but not in the superficial cortex, compared with control rats. The administration of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to vitamin D-deficient rats increased the initial rate of Pi uptake as well as the amounts of NaPi-2 mRNA and protein in the juxtamedullary cortex. The transcriptional activity of a luciferase reporter plasmid containing the promoter region of the human type II Na+-dependent Pi transporter NaPi-3 gene was increased markedly by 1,25-(OH)2D3 in COS-7 cells expressing the human vitamin D receptor. A deletion and mutation analysis of the NaPi-3 gene promoter identified the vitamin D-responsive element as the sequence 5'-GGGGCAGCAAGGGCA-3' nucleotides -1977 to -1963 relative to the transcription start site. This element bound a heterodimer of the vitamin D receptor and retinoid X receptor, and it enhanced the basal transcriptional activity of the promoter of the herpes simplex virus thymidine kinase gene in an orientation-independent manner. Thus, one mechanism by which vitamin D regulates Pi homeostasis is through the modulation of the expression of type II Na+-dependent Pi transporter genes in the juxtamedullary kidney cortex.

Animals↗
PubMed1998

Characterization of the 5' flanking region of the human NPT-1 Na+/phosphate cotransporter gene.

To elucidate the expression and regulation of the human type I Na+/phosphate transporter gene (NPT-1), the 5' flanking region of the NPT-1 gene was cloned, and its nucleotide sequence and function were determined. A genomic clone that contained approximately 14.0 kb of the 5'-flanking region of the NPT-1 gene was isolated. A single transcription start site was located 104 base pairs (bp) upstream of the 3' end of exon 1. In addition to the sequence of the 5'-flanking region contained a sequence weakly homologous to a TATA box at position -41 to -36 and many transcriptional regulatory elements. Transient expression revealed that a 45-bp region of proximal to exon 1, which contained TATA-like sequence, was sufficient for promoting luciferase expression in OK-cells derived from opossum kidney proximal tubule.

Carrier Proteins↗
PubMed1998

Rapid and convenient method of autoradiography for DNA cloning using digital imaging analysis.

Digital image analysis has been used for various biochemical and molecular biological analyses instead of autoradiography with X-ray film. However, in such cases the data manipulated by an imaging analyzer was generally printed out on normal printing paper. With normal paper, it is difficult to align the signal or its position relative to the original sample. Here in, we demonstrate it to be convenient and accurate to align signal obtained by imaging analyzer with OHP film.

Autoradiography↗
PubMed1997

Gene structure and functional analysis of the human Na+/phosphate co-transporter.

Three lambda phage clones encompassing the Na+/phosphate co-transporter (NaPi-3) gene and its 5' flanking region were isolated from a human genomic DNA library. The gene comprises 13 exons and 12 introns and spans approx. 14 kb. All exon-intron junctions conform to the GT/AG rule. The major transcription-initiation site was determined by primer-extension analysis and is an adenosine residue 57 bp upstream of the 3' end of the first exon. There is a typical TATA box 28 bp upstream of the major transcription-initiation site and various cis-acting elements, including a cAMP-responsive element, AP-1, AP-2 and SP-1 sites in the 5' flanking region. This region also contains three direct-repeat-like sequences that resemble the consensus binding sequence for members of the steroid-thyroid hormone receptor superfamily, including vitamin D. Deletion analysis suggests that the region from nt-2409 to nt-1259 in the 5' flanking region may be involved in kidney-specific gene expression. Vitamin D responsiveness of the NaPi-3 promoter was also detected in COS-7 cells co-transfected with a human vitamin D receptor expression vector. The presence of the three vitamin D receptor- responsive elements in the NaPi-3 promoter may be important in mediating the enhanced expression of the gene by 1,25-dihydroxyvitamin D3.

Amino Acid Sequence↗
PubMed1994

[Successful treatment of two patients with advanced gastric cancer by neoadjuvant chemotherapy with EAP regimen].

Two patients with unresectable gastric cancer accompanied with multiple liver metastases were treated with a 3-drug combination consisting of etoposide, adriamycin, and cisplatin (EAP) as neoadjuvant chemotherapy. After confirmation of maximal response to EAP, both patients received surgical resection of the primary tumor and infusion of cisplatin and 5-FU into hepatic artery, and they survived 15.0 and 15.8 months, respectively. These results indicate that neoadjuvant chemotherapy with EAP regimen is useful in the treatment of advanced gastric cancer.

Adenocarcinoma↗
PubMed1993

[Meningeal carcinomatosis in patients with small cell lung cancer].

Six patients (2.7%) developed meningeal carcinomatosis among 207 patients with small cell lung cancer (SCLC) receiving intensive combination chemotherapy. The cumulative probability of developing meningeal carcinomatosis was 2.7% at 3 years and 7.8% at 5 years after diagnosis of SCLC. Pain in legs, gait disturbance, headache, nausea and vomiting were the characteristic symptoms at the onset of meningeal carcinomatosis. Although cytological examination of cerebro-spinal fluid (CSF) was essential for the diagnosis of meningeal carcinomatosis, elevated protein, LDH, CEA and/or NSE concentration and decreased glucose concentration in CSF were also helpful for the diagnosis. For treatment of meningeal carcinomatosis, all patients received intrathecal administration of methotrexate, cytosine arabinoside and/or prednisolone. Additionally, 3 patients received spinal irradiation, and one received cerebro-spinal irradiation. However, only 2 patients responded, and survival was brief ranging from 2 to 38 weeks. Development of meningeal carcinomatosis seems to be a rare event; however, it may be an obstacle to the prolongation of patient survival in the treatment of SCLC.

Adolescent↗
PubMed1990

Effect of water isolation and early finishing on hardness of glass ionomer cements.

Glass ionomer cements have the disadvantage of being vulnerable to moisture. We would like to overcome this problem by clinical procedures. Three glass ionomer cements were tested in vitro with the goal of protecting these materials from moisture during clinical operations. To observe the effectiveness of various surface protective measures, we divided each cement sample into six groups, each of which underwent 24-hour surface treatment. The first group was a control where the cement was covered with a glass slab for 24 hours. The remaining five groups were subjected to no treatment or treatment with varnish, cocoa butter, Teethmate-A, or Ketac-Glaze. Two additional groups were prepared for comparison of early finishing with and without water spray. When the Vickers hardness number (HVN) for each sample was measured at 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, and 40 days, it tended to increase after 24 hours, reaching a maximum value at different times with different cements. Analysis of variance revealed that during the first few days the hardness of the control was significantly different from that without treatment or with treatment by varnish or cocoa butter. However, treatment with Teethmate-A or Ketac-Glaze produced results close to those for the control. Significant differences in hardness during the first few days were noted when early finishing was carried out under wet and dry conditions. These findings indicate that a light-cured unfilled resin should be applied to the surface of glass ionomer cement immediately after the initial set to allow complete setting without interference by oral fluids. Also, water spray should be avoided during contouring of the cements if they have not fully hardened.

Glass Ionomer Cements↗
PubMed1990

[A staged restoration system for the uncooperative children utilizing glass ionomer cements].

The purpose of this study was to investigate a treatment system intended to promote improvement in the cooperation of patients. The subjects of the investigation were 45 uncooperative patients who had difficulty in accepting regular dental treatment. This treatment system consists of A) caries inhibition stage by Ag(NH3)2F, B) first temporary restoration stage with low viscosity glass ionomer cement, C) second temporary restoration stage with restorative glass ionomer cement and D) final restoration with regular restorative material. One treatment stage in the system was carried out according to the grade of the cooperation of the patients, then the advanced treatment stage superseded the former when the cooperation was improved. The period of time required for the improvement of cooperation, and the durability of the glass ionomer cements were examined. The following results were obtained. 1. The durability of the low viscosity glass ionomer cement was 11 months for the anterior teeth, and 12 months for the posterior teeth. 2. The durability of the regular glass ionomer cement was revealed to be 18 months for the anterior teeth and 17 months for the posterior teeth. 3. 7 months were required for the improvement in the cooperation of the patients from stage B to stage C and 14 months for improvement from stage C to stage D. 4. Improvement in cooperation appeared in a shorter time when this treatment system is begun to be applied to the patients at lower age. The staged restoration system is an effective method for the behavior management of uncooperative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1990

[SEM observation for composite resin filler].

The nature and the type of fillers in composite resin are multifarious. The purpose of this study is to determine the methods of distinguishing the fillers. After the treatments stated below, the surface of polymerized composite resins was observed by means of SEM. 1) The air-inhibited layer on the surface of composite resins was removed by acetone. Observations showed inorganic filler and prepolymerized filler protrusions on the resin surface; submicron filler and microfiller were noticeable. 2) Following the treatment in #1, composite resins were soaked in fluoric acid in order to dissolve any inorganic filler substance. Results displayed pores in the area of the dissolved inorganic filler while a microporous surface was observed on the prepolymerized filler. By this process the type of prepolymerized filler can be classified according to the forms of the contained inorganic filler. 3) The surface of the composite resin was polished with #1200 sand paper. This method shows the difference between the fillers and the matrix resin; however, a clear distinction of the type of filler is difficult to determine. 4) After treatment in #3, the specimen was soaked in fluoric acid. Similar results as treatment in #2 were found; however, microstructure of the syntered filler was easily observed. It is possible to distinguish the filler types of the composite resins by the above mentioned treatments.

Composite Resins↗
PubMed1988

A case of vasculitic cholecystitis associated with Schönlein-Henoch purpura in an adult.

A case of Schönlein-Henoch Purpura (SHP) in a 32 year-old female, showing gastrointestinal manifestations including acute vasculitic cholecystitis was reported. In the course of hospitalization urgent laparotomy was performed because of the severe abdominal pain. The gallbladder was inflamed with a brownish-red edematous wall and subserosal hemorrhage, and was resected. Histological examination of the resected gallbladder specimen revealed leucocytoclastic vasculitis. The patient was treated with prednisolone postoperatively, and symptoms abated over two weeks. Acute cholecystitis with SHP is extremely rare, and as far as the authors know this is the second case of this disorder documented by histological examination. Patients with acute abdomen associated with SHP should be managed with consideration of the complications of acute cholecystitis.

Abdomen, Acute↗
PubMed1983

Ontogenesis of hypothalamic immunoreactive ACTH cells in vivo and in vitro: role of Rathke's pouch.

The ontogenesis of immunoreactive (ir) ACTH cells and ir alpha-MSH cells in rat hypothalamus was studied in vivo and in vitro. Ir ACTH cells first appeared in the neuroepithelial cell layer lining the floor of the third ventricle on Day 13.5 of gestation, whereas ir alpha-MSH first appeared in the cytoplasm of several ir ACTH cells in the basal part of the arcuate nucleus of the hypothalamus on Day 19.5. When the medial-basal hypothalamus of 12.5-day embryos was cultured alone, a few ir ACTH cells were found after culture for 10 days, but not 3 days, and no ir alpha-MSH cells were observed in the cultures. When the hypothalamus was cultured with Rathke's pouch (intact or without the intermediate lobe anlage), ir ACTH cells appeared within 3 days. In these cultures on Days 6 and 10, long beaded fibers were seen projecting from cells in the neuronal tissue, and some cells showed immunolabeling for alpha-MSH. When the hypothalamus was cocultured with oral epithelium instead of Rathke's pouch, the appearance of neuronal ir ACTH cells was like that in cultures of hypothalamus alone. These in vitro findings suggest that stimulus from the anterior lobe anlage of the pituitary is necessary for normal development of ir ACTH/alpha-MSH cells in the hypothalamus.

Adrenocorticotropic Hormone↗