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Yoshihiro Nakamura

Publications and source records attributed to Yoshihiro Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

Crystal structure of the human BRD2 bromodomain: insights into dimerization and recognition of acetylated histone H4.

The BET (bromodomains and extra terminal domain) family proteins recognize acetylated chromatin through their bromodomain and act as transcriptional activators. One of the BET proteins, BRD2, associates with the transcription factor E2F, the mediator components CDK8 and TRAP220, and RNA polymerase II, as well as with acetylated chromatin during mitosis. BRD2 contains two bromodomains (BD1 and BD2), which are considered to be responsible for binding to acetylated chromatin. The BRD2 protein specifically recognizes the histone H4 tail acetylated at Lys12. Here, we report the crystal structure of the N-terminal bromodomain (BD1, residues 74-194) of human BRD2. Strikingly, the BRD2 BD1 protein forms an intact dimer in the crystal. This is the first observation of a homodimer among the known bromodomain structures, through the buried hydrophobic core region at the interface. Biochemical studies also demonstrated BRD2 BD1 dimer formation in solution. The two acetyllysine-binding pockets and a negatively charged secondary binding pocket, produced at the dimer interface in BRD2 BD1, may be the unique features that allow BRD2 BD1 to selectively bind to the acetylated H4 tail.

Acetylation↗
PubMed2006

Structure of apo-glyceraldehyde-3-phosphate dehydrogenase from Synechococcus PCC7942.

The crystal structure of NADP-dependent apo-glyceraldehyde-3-phosphate dehydrogenase (apo-GAPDH) from Synechococcus PCC 7942 is reported. The crystal structure was solved by molecular replacement and refined to an R of 21.7% and R(free) of 27.5% at 2.9 angstroms resolution. The structural features of apo-GAPDH are as follows. The S-loop has an extremely flexible conformation and the sulfate ion is only taken into the classical P(i) site. A structural comparison with holo-GAPDHs indicated that the S-loop fixation is essential in the discrimination of NADP and NAD molecules.

Apoenzymes↗
PubMed2006

Structure of NADP-dependent glyceraldehyde-3-phosphate dehydrogenase from Synechococcus PCC7942 complexed with NADP.

The crystal structure of NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (NADP-GAPDH) from Synechococcus PCC 7942 (S. 7942) in complex with NADP was solved by molecular replacement and refined to an R factor of 19.1% and a free R factor of 24.0% at 2.5 A resolution. The overall structure of NADP-GAPDH from S. 7942 was quite similar to those of other bacterial and eukaryotic GAPDHs. The nicotinamide ring of NADP, which is involved in the redox reaction, was oriented toward the catalytic site. The 2'-phosphate O atoms of NADP exhibited hydrogen bonds to the hydroxyl groups of Ser194 belonging to the S-loop and Thr37. These residues are therefore considered to be essential in the discrimination between NADP and NAD molecules. The C-terminal region was estimated to have an extremely flexible conformation and to play an important role in the formation of the supramolecular complex phosphoribulokinase (PRK)-regulatory peptide (CP12)-GAPDH, which regulates enzyme activities.

Bacterial Proteins↗
PubMed2006

Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer.

Nrf2 regulates the cellular oxidative stress response, whereas Keap1 represses Nrf2 through its molecular interaction. To elucidate the molecular mechanism of the Keap1 and Nrf2 interaction, we resolved the six-bladed beta propeller crystal structure of the Kelch/DGR and CTR domains of mouse Keap1 and revealed that extensive inter- and intrablade hydrogen bonds maintain the structural integrity and proper association of Keap1 with Nrf2. A peptide containing the ETGE motif of Nrf2 binds the beta propeller of Keap1 at the entrance of the central cavity on the bottom side via electrostatic interactions with conserved arginine residues. We found a somatic mutation and a gene variation in human lung cancer cells that change glycine to cysteine in the DGR domain, introducing local conformational changes that reduce Keap1's affinity for Nrf2. These results provide a structural basis for the loss of Keap1 function and gain of Nrf2 function.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Null mutants of Drosophila B-type lamin Dm(0) show aberrant tissue differentiation rather than obvious nuclear shape distortion or specific defects during cell proliferation.

To elucidate the function of metazoan B-type lamins during development, new null mutations of the Drosophila B-type lamin gene, lamDm(0), were analyzed in parallel with the misg(sz18) mutation, a lamDm(0) allele reported previously. Although in all these mutants, lamin Dm(0) protein was undetectable in neuroblasts and imaginal disc cells from the second instar larval stage onward, cells continued to proliferate. In contrast to the embryonic lethality of another Drosophila lamDm(0) allele, lam(PM15), reported previously, lethality did not occur until late pupal stages. Chromosomal structure and the overall nuclear shape remained normal even at these late pupal stages, although obviously abnormal nuclear pore complex distribution was observed concomitant with the loss of lamin Dm(0) protein. Compensating expression of lamin C was not induced in the absence of lamin Dm(0). Thus, no lamin-containing nuclear structures were found in proliferating larval neuroblasts. We did find that developmental abnormalities appeared in specific organs during the late pupal stage, preceding lethality. Surprisingly, coordinated size increase (hypertrophy) of the ventriculus was observed accompanied by cell division and muscle layer formation. Hypertrophy of the ventriculus correlated with a decrease in ecdysteroid hormone receptor B1 (EcRB1) protein, and furthermore could be suppressed by a heat-inducible EcRB1 transgene. In contrast, both gonadal and CNS tissues exhibited underdevelopment.

Animals↗
PubMed2004

Purification, crystallization and preliminary X-ray diffraction analysis of the Kelch-like motif region of mouse Keap1.

Keap1 (Kelch-like ECH-associating protein 1) is a negative regulator of the Nrf2 transcription factor in the cytoplasm. The Kelch/DGR (double-glycine repeat) domain of Keap1 associates with Nrf2 as well as with actin filaments. A recombinant protein containing both the Kelch/DGR domain and the C-terminal region of mouse Keap1 was expressed in Escherichia coli, purified to near-homogeneity and crystallized by the sitting-drop vapour-diffusion method. The crystal belongs to space group P6(1) or P6(5), with unit-cell parameters a = b = 102.95, c = 55.21 A, and contains one molecule in the asymmetric unit. A complete diffraction data was collected to 2.25 A resolution using an R-AXIS IV++ imaging plate mounted on an RA-Micro7 Cu Kalpha rotating-anode X-ray generator.

Actins↗
PubMed2004

Tracheal release and thymus wrapping of the tracheoplasty anastomosis through mini-sternotomy.

Despite breakthroughs in general thoracic surgery, tracheoplasty remains a technically difficult procedure. The authors performed tracheoplasty on a 75-year-old woman diagnosed with recurrent thyroid cancer and tracheal invasion. Through an L-shaped unilateral mini-sternotomy added to a collar incision, we performed tracheal mobilization and release followed by resection of six tracheal rings. The tracheoplasty anastomosis was then wrapped with the right lobe of the thymus. Using this procedure, tracheoplasty was successfully performed with no complications related to the tracheal anastomosis. Tracheoplasty performed through mini-sternotomy, with a combination of full tracheal release and wrapping with the right lobe of the thymus, may represent a novel, effective, and less-invasive surgical procedure.

Aged↗
PubMed2004

Newspaper reporting on child raising in Japan.

Study of child-raising issues published in newspapers is lacking. The purpose of this article is to determine the spectrum of issues associated with child raising based on a newspaper. We conducted a cross-sectional study of items related to children (aged <19 years) reported in a Japanese newspaper from July 1, 2001, to June 30, 2002. A total of 1287 child-related items were published. The percentages of reports regarding individual health, health-related issues, topics on two or more issues, and global child issues were 5.9%, 28.8%, 62.9%, and 2.4%, respectively. The most common singly reported issues from 446 items were on child play and recreation, welfare activities, security, child abuse, child death, sports, and parenting. These reports assist parents, families, nurses, pediatricians, and child care workers in providing information on healthy child raising.

Adolescent↗
PubMed2004

Thyroid blockade during a radiation emergency in iodine-rich areas: effect of a stable-iodine dosage.

We examined the effect of stable iodine on thyroid gland blockade in patients with hyperthyroidism in order to make a preliminary evaluation of the appropriate dose of iodine prophylaxis in the event of a radiation emergency in Japan in which radioiodine is released to the environment. Eight patients were orally given single doses of 50 mg or 100 mg of potassium iodide, which contained 38 mg and 76 mg of iodide, respectively. Both doses significantly suppressed a thyroid uptake of (123)I for 24 h (p = 0.03). The protective effects at 24 h were 73.3% and 79.5%, respectively. No side effects were observed during the trial. The present study demonstrates that a single oral administration of 38 mg of iodide produces a thyroid-blocking effect equivalent to that of 76 mg of iodide, suggesting that a reevaluation of the stable iodine dosage during radiation emergencies in iodine-rich areas such as Japan is warranted.

Administration, Oral↗
PubMed2004

A new technique for endobronchial ultrasonography and comparison of two ultrasonic probes: analysis with a plot profile of the image analysis software NIH Image.

STUDY OBJECTIVES: Endobronchial ultrasonography (EBUS) is currently the sole clinical method available for delineating the bronchial wall structure; however, the image resolution is inadequate. Thus, an improved image analysis system is needed for both a more accurate and more readily interpretable endobronchial ultrasonogram. MATERIALS AND METHODS: A total of 10 patients underwent pulmonary resection for lung cancer. EBUS was performed on the bronchi of the resected lungs, which had been immersed in physiologic saline solution. The same bronchial lesion in each specimen was imaged with two probes: 20 MHz and 30 MHz. The images were analyzed using the plot profile derived from freeware image analysis software: NIH Image (National Institutes of Health; Bethesda, MD). The measured echo intensity of the bronchial wall was statistically analyzed. RESULTS: A normal bronchial wall image consists of five layers, and the plot profile shows a W-shaped curve. The mean value of the echo intensity of each peak or trough of the W-shaped curve was calculated and compared for both probes. The differences in the mean echo intensity between both the third and fourth layer and the second and fourth layer were found to be significantly greater with the 30-MHz probe than with the 20-MHz probe. The echo intensity curve of a central-type lung cancer was not W shaped, indicating that the bronchial wall was not composed of the normal five layers. CONCLUSION: We employed image analysis software and drew a plot to obtain a W-shaped curve from the EBUS image data. This enabled us to make an objective assessment of the laminar structure of the bronchial wall. In order to clearly recognize the laminar structure of the bronchial wall, the 30-MHz probe was found to be more useful than the 20-MHz probe.

Bronchi↗
PubMed2004

[Adrenocorticotropic hormone-secreting adrenal pheochromocytoma: a case report].

A 55-year-old woman with transient faintness was referred to our hospital. Laboratory studies showed high levels of plasma catecholamines, cortisol, adrenocorticotropic hormone (ACTH) and urinary vanyl mandelic acid (VMA). Abdominal computed tomography (CT) showed a right adrenal tumor measuring 4.5 cm diameter that was enhanced heterogeneously by contrast medium. Brain CT and chest CT did not detect any other tumors. Under the clinical diagnosis of ectopic ACTH secreting adrenal pheochromocytoma, we performed right adrenalectomy. Pathological findings showed pheochromocytoma, and tumor cells were heterogeneously stained by anti-ACTH antibody.

Adrenal Gland Neoplasms↗
PubMed2003

Stanford type A aortic dissection which ruptured into the left atrium: report of a case.

A Stanford type A aortic dissection ruptures usually into the pericardial space or the mediastinal space. We herein report the rare surgical case of a Stanford type A aortic dissection which ruptured into the left atrium. The patient had a previous history of mitral valve replacement. The time and the cause of the aortic dissection was unclear. At operation, adhesions around the proximal aorta and between the aortic root and the left atrial roof were confirmed to be one of the causes for this rare form. A fistula to the cardiac cavity following an aortic dissection may occur in any patient, especially in those with a history of previous cardiac surgery.

Aged↗
PubMed2003

Endobronchial carcinoid tumor combined with pulmonary non-tuberculous mycobacterial infection: report of two cases.

We report here two cases of endobronchial carcinoid tumor complicated with pulmonary infection with non-tuberculous mycobacteria (NTM). Case 1 was an 81-year-old woman with the left lower lobe atelectasis. Bronchoscopy showed complete obstruction of the left basal bronchus by a tumor and a sleeve lower lobectomy with mediastinal lymph node dissection was performed. Pathological examination showed typical carcinoid located in the left basal bronchus and many caseous granulomas containing mycobacteria in the lung parenchyma distal to the bronchus. Bacterial examinations of sputum and gastric juice after the operation showed a growth of Mycobacterium kansasii. Case 2 was a 50-year-old woman with the atelectasis of the left upper division. Bronchoscopy showed complete obstruction of the left upper division bronchus by a tumor and a left upper lobectomy with mediastinal lymph node dissection was performed. Pathological examination showed typical carcinoid located in the left upper division bronchus and many caseous granulomas in the lung parenchyma distal to the bronchus. The Ziehl-Neelsen stain showed many mycobacteria in these granulomas and they were identified as Mycobacterium avium by PCR analysis. Although NTM are not well recognized as possible pathogens of pulmonary infection related to bronchial obstruction by endobronchial carcinoma, our experiences rouse a caution to consider NTM as potential pathogens. We also discuss the possible mechanisms responsible for the specific relationship between carcinoid tumor and TNM.

Aged↗
PubMed2003

A prospective evaluation of transbronchial ultrasonography for assessment of depth of invasion in early bronchogenic squamous cell carcinoma.

In order to determine the appropriate treatment modality for roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC), it is essential to evaluate the depth of invasion, because ROSCC invading beyond the cartilaginous layer cannot be effectively treated by photodynamic therapy (PDT) due to spread of disease. Transtracheal endoscopic ultrasonography (TUS) was useful for predicting the depth of invasion in some ROSCCs. In order to assess the actual significance of TUS as a diagnostic tool for predicting the depth of carcinoma invasion, we have conducted a prospective trial with 22 lesions of ROSCCs. We ultrasonographically classified the degree of the depth of invasion into two groups; A: "invasion does not reach cartilaginous layer" and B: "invasion involves cartilaginous layer". Then the patients were treated by irradiation, PDT, or surgical resection. Pathological findings were also classified into A or B. In order to calculate the sensitivity for evaluating the depth of invasion by TUS, the cases without any tumor and/or malignant cells after PDT were regarded as pathological A. In the evaluation of the depth of carcinoma invasion staying inside the cartilaginous layer, the sensitivity and the positive predictive value were 85.7%, the specificity was 66.7%, and the accuracy was 80.0%. With TUS, preoperative evaluation of the depth of invasion would be more accurate, and the decision of treatment modality would be more appropriate, compared with the conventional bronchoscopic observation alone.

Aged↗
PubMed2003

Crystal structure of chloroplastic ascorbate peroxidase from tobacco plants and structural insights into its instability.

Ascorbate peroxidase (APX) is a heme-containing protein that plays a central role in scavenging H(2)O(2) in higher plants. The structure of stromal APX (sAPX) was determined at 1.6 A to an R-factor of 19.1% and an R-free-factor of 22.3%. The electrostatic potential of the gamma-channel that connects the molecular surface of sAPX to the gamma-edge of heme was more positive than that of cytosolic APX (cAPX) from pea, so sAPX might bind more easily with ascorbate than cAPX. The overall structure of sAPX was similar to those of cAPX from pea and cytochrome c peroxidase (CCP) from yeast, with a substantial difference in a loop structure located in the vicinity of the heme. The side chain of Arg169 in sAPX corresponding to His169 in cAPX and His181 in CCP extended in the opposite direction from the heme, forming two hydrogen bonds with carbonyl groups in the loop structure. The rapid inactivation of sAPX might be due to the characteristic conformation of Arg169 owing to the loop structure of sAPX.

Ascorbate Peroxidases↗
PubMed2003

Using a vortex mixer for testicular sperm collection.

OBJECTIVE: To evaluate 2 methods of processing testicular tissue for the retrieval of viable sperm from men with nonobstructive azoospermia. STUDY DESIGN: Fresh testicular tissue was obtained from nonobstructive azoospermia patients using a biopsy needle. The specimens were divided into 2 fractions. All specimens were minced and immersed in human tubal fluid (HTF). The first fraction was filtered through a nylon filter and incubated for 3 hours. The supernatant was centrifuged, resuspended in HTF and analyzed. The second fraction was immediately vortexed for 5 minutes and filtered through a nylon filter. The supernatant was centrifuged, resuspended in HTF and analyzed. RESULTS: Spermatozoa were obtained in 13 of 24 cases (54.2%) using the vortex method and in 5 of 24 cases (20.8%) with the nylon filter method. CONCLUSION: The vortex mixing method may be a better option than the conventional method for processing testicular tissue for sperm collection.

Adult↗
PubMed2002

Asymptomatic pelvic Castleman disease in an infertile woman: case report.

Castleman disease is defined as angiofollicular benign lymph node hyperplasia usually found in the mediastinum. Pelvic lymph node involvement is very rare. We now report a case of asymptomatic intrapelvic Castleman disease found by chance in an infertile woman. Transvaginal ultrasonography is very useful in diagnosing the disease. After 7 years of follow-up, the patient is free from recurrence.

Adult↗