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Biomedical subjects

Y Nakatani

Publications and source records attributed to Y Nakatani.

At least 19 recordsLinked to original sources
PubMed2006

Ca channel currents inhibited by serum from select patients with Guillain-Barré syndrome.

We performed an electrophysiological study demonstrating inhibition of spontaneous muscle action potentials within a coculture of rat muscle and spinal cord by exposure to serum, as well as purified IgG, from patients with the acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome (GBS). However, exposure to serum from two patients with the acute inflammatory demyelinating polyneuropathy (AIDP) form of GBS had no effect. Using a whole-cell recording technique, we then investigated the effects of serum and purified IgG from patients with GBS on voltage-dependent calcium channel (VDCC) currents in nerve growth factor-differentiated PC12 cells. Serum from patients with GBS (AMAN) inhibited VDCC currents in PC12 cells, which was fully reversible by washing with the bath solution. Similarly, purified IgG from the serum of two patients with GBS (AMAN) also inhibited VDCC currents in PC12 cells. In contrast, sera from patients with AIDP and healthy volunteers did not affect VDCC currents in PC12 cells. These results suggest that muscle weakness in some patients with GBS might be induced by inhibition of Ca2+ channel currents within motor nerve terminals.

Action Potentials↗
PubMed2006

How is epigenetic information on chromatin inherited after DNA replication?

Although most somatic cells have identical genetic information, gene expression profiles are quite distinct in each cell type. The gene expression profiles are considered to be determined mainly by chromatin-encoded epigenetic information that includes histone modifications, histone variants, and factors such as HP1 and polycomb group proteins that organize higher-ordered chromatin structures. To gain insights into how such epigenetic information on chromatin is inherited on daughter DNA strands after DNA replication, we have purified the preassembled form of histone H3 by immunoaffinity purification. The histone H3 complex contains the two histone H3-H4 chaperones CAF1 and ASF1. Surprisingly, the H3 complex also contains a pair of H3-H4 dimers. This observation is striking because histones H3-H4 are known to exist as tetramers in solution. Since histones H3-H4 in the predeposition complex exist as a dimer, this raises the possibility that the H3-H4 dimer in the complex pairs with a parental H3-H4 dimer, assembling the de novo-synthesized and parental H3-H4 dimers in the same nucleosome. Based on these results, we propose a semi-conservative model of nucleosome duplication, which allows for segregation of parental H3-H4 dimers with encoded epigenetic information evenly to daughter DNA strands.

Animals↗
PubMed2006

Transbronchial fine needle aspiration cytological examination: a useful tool for diagnosing primary lung cancer.

BACKGROUND: Obtaining a definitive preoperative diagnosis plays a critical role in deciding upon the treatment approach for lung carcinoma. However, success in making definitive diagnoses of small primary lung cancers will require new approaches because these cancers are difficult to detect using standard biopsy procedures. METHODS: We evaluated the results of morphologic definitive diagnosis together with various clinical factors in 1003 primary lung cancers resected surgically. Patients underwent transbronchial brushing, fine needle aspiration cytology, forceps biopsy, and/or forceps biopsy-stamp cytology for preoperative diagnoses, in conjunction with the use of Diff-Quik to confirm that hits had been made on the radiographic shadows before terminating the examinations. RESULTS: Sensitivities of the diagnostic procedures for primary lung cancers were as follows: 64.8% for brushing, 56.1% for transbronchial forceps biopsy, 72.0% for transbronchial forceps biopsy-stamp cytology, and 86.4% for transbronchial fine needle aspiration. The four transbronchial biopsy procedures had a combined overall sensitivity of 92.7%. In patients with peripheral lung cancers of 2 cm or less in diameter, transbronchial fine needle aspiration had a sensitivity of 75.9%, which was the highest sensitivity for all transbronchial examinations. In the subset of 296 patients who underwent all four transbronchial biopsy examinations, transbronchial fine needle aspiration had the highest sensitivity of preoperative diagnosis of all the transbronchial examination methods. CONCLUSIONS: The sensitivity of preoperative cytological diagnosis for primary lung cancers, especially transbronchial aspiration cytology, is high. Transbronchial fine needle aspiration cytology is useful for the preoperative diagnosis of primary lung cancer.

Adolescent↗
PubMed2006

Increased stress protein ORP150 autoantibody production in Type 1 diabetic patients.

AIMS: Various genetic and environmental stresses interfere with protein folding in the endoplasmic reticulum (ER), which leads to the induction of ER stress. It has recently been reported that ER stress is involved in the development of diabetes in diabetic animal models. The aim of this study is to estimate ER stress levels in Type 1 diabetic patients. METHODS: We recruited Type 1 diabetic patients undergoing periodic follow-up examinations (n = 91) and healthy non-diabetic individuals (n = 37), and measured their serum anti-oxygen-related protein (ORP)150 autoantibody levels. RESULTS: Anti-ORP150 autoantibody levels in Type 1 diabetic patients were significantly higher compared with those in healthy non-diabetic subjects. Furthermore, the serum autoantibody levels in Type 1 diabetic patients correlated with HbA(1c) (F > 3.0, P = 0.079), indicating that hyperglycaemia itself induces ER stress in diabetes. CONCLUSIONS: Anti-ORP150 autoantibody levels in Type 1 diabetic patients are higher compared with non-diabetic subjects, suggesting that ER stress is increased in Type 1 diabetes.

Adult↗
PubMed2005

Blue-dye technique complements four-node sampling for early breast cancer.

AIMS: To examine four-node axillary sampling assisted by a blue dye (4NAS/dye) technique as a sentinel node biopsy (SNB) for breast cancer. METHODS: Lymphatic mapping was performed by injection of patent blue for 33 consecutive cases with breast cancer. Axillary sampling was performed until four nodes were obtained. This was followed by back-up axillary lymph node dissection to examine the feasibility of 4NAS/dye. The same study with 30 cases was conducted at an independent hospital to confirm the feasibility of this method. This method was then applied to 101 consecutive clinically node-negative patients to avoid axillary-node dissection, with intraoperative diagnosis made by frozen section examination. RESULTS: The median numbers of blue-stained nodes and nodes excised by 4NAS/dye were 1.7 and 3.4, respectively. The identification rate of sentinel lymph nodes (SNs) was 81.8% using the dye alone and 97.0% when the combination was used. Pathological examination revealed that the nodal status was correctly predicted by the dye alone in 62.5% of cases with metastasis, whereas in 100% by 4NAS/dye. The dye alone was not sufficient to identify SNs, especially in cases with prior excisional biopsy. The identification rate of SNs and the accuracy rate in another feasibility study were 100% and 92.5% in 30 consecutive cases, respectively. 4NAS/dye successfully detected SNs in 100 of 101 cases of the subsequent observational study with an acceptable post-operative axillary morbidity and thus succeeded as an SNB. CONCLUSIONS: The 4NAS/dye method is reliable for the detection of SNs. This method could be applied to observational studies without radio-isotope.

Adult↗
PubMed2005

The metabolism of hyaluronan in cultured rabbit growth plate chondrocytes during differentiation.

Hyaluronan (HA) is one of the major extracellular matrix components in cartilage. In addition to the biomechanical functions, HA has various important roles in the differentiation of chondrocytes. The purpose of this study was to clarify the nature of HA synthesis during chondrocyte differentiation. Growth plate chondrocytes were isolated from rabbit ribs and cultured in chondrocyte differentiation medium. The amount of HA and HA synthase (HAS) mRNA levels were analyzed for each stage of chondrocyte differentiation by means of high-performance liquid chromatography (HPLC) and real-time PCR, respectively. The distribution of HA in cultured chondrocytes was observed by histochemical staining. The amount of HA, ranging widely in size, was increased substantially during the hypertrophic stage. The expression levels of HAS2 and HAS3 mRNAs were low during the matrix-forming stage. HAS2 mRNA level was substantially enhanced at the pre-hypertrophic stage, whereas HAS3 mRNA level exhibited a slight increase. HAS1 mRNA was not detected. The intensity of HA staining was high around the hypertrophic chondrocytes. These results suggest that HA metabolism in chondrocyte differentiation is regulated by the selective expression of HASs, and HAS2 and the related large size-HA may have a certain association with the hypertrophic changes of chondrocytes.

Animals↗
PubMed2004

Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the synovial membrane of the rabbit temporomandibular joint.

Hyaluronan (HA) synthesis in the synovial membrane is affected by various chemical mediators. It is hypothesized that transforming growth factor-beta 1 (TGF-beta 1) would be a mediator to modulate HA synthesis in cultured synovial membrane fibroblasts of the temporomandibular joint (TMJ). Fibroblasts were extracted from the TMJ synovial membrane of four-week-old Japanese white rabbits. The amount of HA and expression levels of HA synthase (HAS) mRNAs induced by TGF-beta 1 treatment were analyzed by means of high-performance liquid chromatography and real-time polymerase chain-reaction, respectively. Both medium and large amounts of HA were enhanced by the stimulation of TGF-beta 1. HAS2 mRNA expression was enhanced 13-fold after six-hour stimulation with TGF-beta 1 (10 ng/mL), whereas HAS3 mRNA expression was not changed significantly. These results suggest that TGF-beta 1 enhances the expression of HAS2 mRNA in the TMJ synovial membrane fibroblasts and may contribute to the production of high-molecular-weight HA in the joint fluid.

Animals↗
PubMed2003

Mechanical stimuli enhances the expression of RGD-CAP/betaig-h3 in the periodontal ligament.

RGD-CAP, a member of the fasciclin family, is expressed in the periodontal ligament (PDL). Since the PDL is continually subjected to mechanical forces from such orofacial functions as mastication, biting, speech and swallowing, the mechanical stimuli is thought to be associated with the expression of RGD-CAP. Furthermore, the adhesive functions of RGD-CAP may contribute to the maintenance or regeneration of PDL architecture. The objective of this study was to examine whether mechanical stimuli modulate the expression of RGD-CAP in the human PDL, and to examine the effects of recombinant RGD-CAP on the adhesion of PDL cells. During experimental tooth movement, the expression of RGD-CAP was significantly enhanced in the PDL. In vitro experiments with cultured PDL cells showed that the expression of RGD-CAP mRNA was significantly enhanced by mechanical tensile force of 15.4kPa for 48h. The induction of RGD-CAP mRNA, meanwhile, was completely inhibited by cycloheximide which is an inhibitor of protein synthesis. Furthermore, neutralising antibody against TGF-beta also suppressed the mechanical induction of RGD-CAP. The adhesion of cultured PDL cells onto plates coated with recombinant RGD-CAP increased significantly compared with the controls. These findings suggest that RGD-CAP, induced by TGF-beta expressed in response to mechanical stimuli, plays an important role in modulating the homeostasis of PDL.

Blotting, Western↗
PubMed2003

Proliferative activity in primary ovarian carcinoid tumors.

The proliferative potential of six primary ovarian carcinoids with different clinical outcome and histogenetic origin was examined immunohistochemically. The results showed that two cases with extremely high level of proliferative activity were associated with metastatic spread. In the remaining tumors, the examined factor was found to be at low level comparable with excellent prognosis of typical carcinoids in other locations. The preliminary results showed a possibility of a prognosis prediction according to typing of the ovarian carcinoids into two categories, i.e., tumors of low and intermediate malignancy. Topoisomerase II-alpha and Ki-67 are suitable markers giving valuable information about this phenomenon.

Aged↗
PubMed2001

Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm.

Significance of Wnt signaling with beta-catenin mutations on solid-pseudopapillary neoplasm (SPN) of the pancreas was studied by immunohistochemistry and molecular analysis. On immunohistochemistry, all 18 SPNs tested showed diffuse cytoplasmic/nuclear positivity for beta-catenin. Upon direct DNA sequencing of exon 3 of the beta-catenin gene, 15 (83%) of the 18 SPNs showed 1-bp missense mutation in codons 32 (5 cases), 33 (3 cases), 34 (3 cases), 37 (3 cases), and 41 (1 case). Immunoreactivity for cyclin D1, one of the intranuclear targets of beta-catenin complexes, was found in tumor cells of more than half the tumor cells of all of the 18 SPNs. The present study strongly suggested a significant role of Wnt signaling, mostly associated with beta-catenin mutations in the tumorigenesis of SPN.

Adolescent↗
PubMed2001

Catecholamines and opioid peptides increase in plasma in humans during possession trances.

Naturally induced possession trances have been observed in healthy people of many societies. The neurophysiological basis of this phenomenon remains unknown, however, because of the difficulty in accessing subjects in trances due to their sacred context. In the present study, we measured the plasma levels of several neuroactive substances from subjects exhibiting or lacking possession trance characteristics during Balinese dedicatory dramas under natural conditions. The trance group exhibited significant increases in plasma concentrations of noradrenaline, dopamine and beta-endorphin, compared with controls who performed the same actions as the trance group. The present finding suggests that catecholamines and opioid peptides are involved in possession trances.

Adult↗
PubMed2001

The p400 complex is an essential E1A transformation target.

Here, we report the identification of a new E1A binding protein complex that is essential for E1A-mediated transformation. Its core component is a SWI2/SNF2-related, 400 kDa protein (p400). Other components include the myc- and p/CAF-associated cofactor, TRRAP/PAF400, the DNA helicases TAP54alpha/beta, actin-like proteins, and the human homolog of the Drosophila Enhancer of Polycomb protein. An E1A mutant, defective in p400 binding, is also defective in transformation. Certain p400 fragments partially rescued this phenotype, underscoring the role of E1A-p400 complex formation in the E1A transforming process. Furthermore, E1A and c-myc each alter the subunit composition of p400 complexes, implying that physiological p400 complex formation contributes to transformation suppression.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Transcriptional coactivator protein p300. Kinetic characterization of its histone acetyltransferase activity.

The p300/cAMP response element-binding protein-binding protein (CBP) family members include human p300 and cAMP response element-binding protein-binding protein, which are both important transcriptional coactivators and histone acetyltransferases. Although the role of these enzymes in transcriptional regulation has been extensively documented, the molecular mechanisms of p300 and CBP histone acetyltransferase catalysis are poorly understood. Herein, we describe the first detailed kinetic characterization of p300 using full-length purified recombinant enzyme. These studies have employed peptide substrates to systematically examine the substrate specificity requirements and the kinetic mechanism of this enzyme. The importance of nearby positively charged residues in lysine targeting was demonstrated. The strict structural requirement of the lysine side chain was shown. The catalytic mechanism of p300 was shown to follow a ping-pong kinetic pathway and viscosity experiments revealed that product release and/or a conformational change were likely rate-limiting in catalysis. Detailed analysis of the p300 selective inhibitor Lys-CoA showed that it exhibited slow, tight-binding kinetics.

Acetyltransferases↗