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Biomedical subjects

Tatsuya Nakamura

Publications and source records attributed to Tatsuya Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth.

ALR (MLL2) is a member of the human MLL family, which belongs to a larger SET1 family of histone methyltransferases. We found that ALR is present within a stable multiprotein complex containing a cohort of proteins shared with other SET1 family complexes and several unique components, such as PTIP and the jumonji family member UTX. Like other complexes formed by SET1 family members, the ALR complex exhibited strong H3K4 methyltransferase activity, conferred by the ALR SET domain. By generating ALR knockdown cell lines and comparing their expression profiles to that of control cells, we identified a set of genes whose expression is activated by ALR. Some of these genes were identified by chromatin immunoprecipitation as direct ALR targets. The ALR complex was found to associate in an ALR-dependent fashion with promoters and transcription initiation sites of target genes and to induce H3K4 trimethylation. The most characteristic features of the ALR knockdown cells were changes in the dynamics and mode of cell spreading/polarization, reduced migration capacity, impaired anchorage-dependent and -independent growth, and decreased tumorigenicity in mice. Taken together, our results suggest that ALR is a transcriptional activator that induces the transcription of target genes by covalent histone modification. ALR appears to be involved in the regulation of adhesion-related cytoskeletal events, which might affect cell growth and survival.

Animals↗
PubMed2006

Mll partial tandem duplication induces aberrant Hox expression in vivo via specific epigenetic alterations.

We previously identified a rearrangement of mixed-lineage leukemia (MLL) gene (also known as ALL-1, HRX, and HTRX1), consisting of an in-frame partial tandem duplication (PTD) of exons 5 through 11 in the absence of a partner gene, occurring in approximately 4%-7% of patients with acute myeloid leukemia (AML) and normal cytogenetics, and associated with a poor prognosis. The mechanism by which the MLL PTD contributes to aberrant hematopoiesis and/or leukemia is unknown. To examine this, we generated a mouse knockin model in which exons 5 through 11 of the murine Mll gene were targeted to intron 4 of the endogenous Mll locus. Mll(PTD/WT) mice exhibit an alteration in the boundaries of normal homeobox (Hox) gene expression during embryogenesis, resulting in axial skeletal defects and increased numbers of hematopoietic progenitor cells. Mll(PTD/WT) mice overexpress Hoxa7, Hoxa9, and Hoxa10 in spleen, BM, and blood. An increase in histone H3/H4 acetylation and histone H3 lysine 4 (Lys4) methylation within the Hoxa7 and Hoxa9 promoters provides an epigenetic mechanism by which this overexpression occurs in vivo and an etiologic role for MLL PTD gain of function in the genesis of AML.

Animals↗
PubMed2006

Room-temperature miscibility gap in LixFePO4.

The rechargeable lithium-ion cell is an advanced energy-storage system. However, high cost, safety hazards, and chemical instability prohibit its use in large-scale applications. An alternative cathode material, LiFePO(4), solves these problems, but has a kinetic problem involving strong electron/hole localization. One reason for this is believed to be the limited carrier density in the fixed monovalent Fe(3+)PO(4)/LiFe(2+)PO(4) two-phase electrode reaction in LixFePO4. Here, we provide experimental evidence that LixFePO4, at room temperature, can be described as a mixture of the Fe(3+)/Fe(2+) mixed-valent intermediate LialphaFePO4 and Li1-betaFePO4 phases. Using powder neutron diffraction, the site occupancy numbers for lithium in each phase were refined to be alpha=0.05 and 1-beta=0.89. The corresponding solid solution ranges outside the miscibility gap (0<x<alpha,1-beta<x<1) were detected by the anomaly in the configurational entropy, and also by the deviation of the open-circuit voltage from the constant equilibrium potential. These findings encourage further improvement of this important class of compounds at ambient temperatures.

Journal Article↗
PubMed2006

Epidemiological study of Candida infections in blood: susceptibilities of Candida spp. to antifungal agents, and clinical features associated with the candidemia.

The purpose of this study was to evaluate the susceptibility to antifungal agents of Candida spp. isolated from blood samples from patients in our hospital, located in Osaka, Japan. We also examined the clinical background of these patients. We analyzed fungi isolated from clinical blood samples obtained in our hospital over a period of 10 years (1993 to 2002). Antifungal susceptibility testing was carried out for six agents, using the National Committee of Clinical Laboratory Standards (NCCLS) M-27-A2 method. The clinical backgrounds were reviewed using the medical records of 125 patients who were diagnosed as having candidemia. The major fungi isolated were Candida parapsilosis (39.2%) and C. albicans (30.1%), and both were sensitive to fluconazole. One strain of C. glabrata and six strains of C. krusei were resistant to fluconazole, and they constituted 4.4% of all Candida spp. isolated. With the exception of C. parapsilosis, most fungi were susceptible to micafungin, although there is no universally agreed breakpoint for this drug. Analysis of the patients' clinical backgrounds revealed that the major underlying disease was cancer (46.4% excluding hematological malignancies). C. krusei was detected almost exclusively in patients with hematological malignancies. Indwelling venous catheters had been responsible for infection in 93.6% of the infected patients. The clinical outcomes of the 125 patients were favorable in 52% and poor in 48%, and subsequent removal of the indwelling catheters was effective in about half of the patients in whom this was done, with good prognosis. To prevent mycosis and its complications, indwelling catheters should be avoided as much as possible. Attention must be paid to the possibility that resistant isolates of Candida spp. can be selected as a result of the use of antifungal agents.

Adolescent↗
PubMed2006

[Extended-spectrum-beta-lactamase-producing Proteus mirabilis: laboratory-based surveillance in cooperation with 12 clinical laboratories in the Kinki Region of Japan].

We studied 247 strains of Proteus mirabilis collected during the 6 months from November 2003 to April 2004 from 12 clinical laboratories in the Kinki region of Japan for the production of extended-spectrum beta-lactamase (ESBL). Eighteen strains (7.3%) showed MICs for cefpodoxime of > or = 2 microg/mL and 13 strains (5.2%) were positive for the double-disk synergy test. Susceptibility depended on genotype. MICs for cefepime, cefozopran, and cefpirome were high (> or = 8 microg/mL), and that for ceftazidime was low (0.12-0.5 microg/mL). Meropenem showed the lowest MIC (< or = 0.03-0.25 microg/mL) of the calbapenems, while other calbapenems showed somewhat higher values (0.5-2 microg/mL). The MIC of tazobactam/piperacillin was also relatively low (< or = 0.25-1 microg/mL). Analysis of the ESBL genotype by the polymerase chain reaction showed that 12 of 13 strains were CTX-M2 types. CTX-M9 was detected in a single laboratory. The clinical background showed 5 strains in urine samples. Twelve of 13 strains were detected in patients with minimal devices use. No symptoms were found in most cases of established syndrome. Analysis of PCR fingerprint profiles of random amplified polymorphic DNA patterns showed that 6 of 7 strains from hospital 1 showed the same pattern, and 5 of 5 strains from hospital 13 showed the same pattern, suggesting the nosocomial spread of P. mirabilis in each hospital.

Drug Resistance, Bacterial↗
PubMed2005

Computer-aided diagnosis: a shape classification of pulmonary nodules imaged by high-resolution CT.

We investigated the possibility of using computer analysis of high-resolution CT images to radiologically classify the shape of pulmonary nodules. Using a combination of circularity and second moment as quantitative measures we were able to classify pulmonary nodules in each shape group as effectively as could a radiologist. We found that pulmonary nodules with circularity < or =0.75 and second moment < or =0.18 were very likely to reveal lung cancer.

Aged↗
PubMed2005

Global and Hox-specific roles for the MLL1 methyltransferase.

The mixed-lineage leukemia (MLL1/ALL-1/HRX) histone methyltransferase is involved in the epigenetic maintenance of transcriptional memory and the pathogenesis of human leukemias. To understand its role in cell type specification, we determined the human genomic binding sites of MLL1. We found that MLL1 functions as a human equivalent of yeast Set1. Like Set1, MLL1 localizes with RNA polymerase II (Pol II) to the 5' end of actively transcribed genes, where histone H3 lysine 4 trimethylation occurs. Consistent with this global role in transcription, MLL1 also localizes to microRNA (miRNA) loci that are involved in leukemia and hematopoiesis. In contrast to the 5' proximal binding behavior at most protein-coding genes, MLL1 occupies an extensive domain within a transcriptionally active region of the HoxA cluster. The ability of MLL1 to serve as a start site-specific global transcriptional regulator and to participate in larger chromatin domains at the Hox genes reveals dual roles for MLL1 in maintenance of cellular identity.

Chromatin Immunoprecipitation↗
PubMed2005

Differentiation of noncancerous tissue and cancer lesions by apparent diffusion coefficient values in transition and peripheral zones of the prostate.

PURPOSE: To compare the apparent diffusion coefficient (ADC) values of prostate cancer in both the peripheral zone (PZ) and the transition zone (TZ) with those of benign tissue in the same zone using echo-planar diffusion weighted imaging with a parallel imaging technique. MATERIALS AND METHODS: A total of 29 consecutive male patients (mean age 61.3 years, age range 53-88 years) with suspected prostate cancer were referred for MR imaging. All patients underwent transrectal ultrasound (TRUS)-guided biopsy of the prostate after MR imaging at 1.5 T, including ADC. For each patient, seven to 10 specimens were obtained from the prostate, and regions of interest (ROIs) were drawn on the ADC map by referring to the urologist's illustration of TRUS-guided biopsy sites. ADC values of cancerous tissue in both the PZ and TZ were compared to those of noncancerous tissue in the same zone. RESULTS: Out of 29 patients, 23 had cancer tissue. In the 23 patients with cancer, the mean ADC value of all cancer ROIs and that of all noncancer ROIs, respectively, were 1.11 +/- 0.41 x 10(-3) and 1.68 +/- 0.40 x 10(-3) mm(2)/second (values are mean +/- SD) (P < 0.01). The mean ADC value of TZ cancer ROIs and that of TZ noncancer ROIs, respectively, were 1.13 +/- 0.42 x 10(-3) and 1.58 +/- 0.37 x 10(-3) mm(2)/second (P < 0.01). CONCLUSIONS: ADC measurement with a parallel imaging technique showed that ADC values of prostate cancer in both the PZ and TZ were significantly lower than those of benign tissue in the PZ and TZ, respectively.

Adenocarcinoma↗
PubMed2005

Diffusion-weighted images of the liver: comparison of tumor detection before and after contrast enhancement with superparamagnetic iron oxide.

PURPOSE: To study the recognition of malignant lesions of the liver on diffusion-weighted images (DWI) can be improved by the administration of superparamagnetic iron oxide (SPIO). MATERIALS AND METHODS: Pre- and post-SPIO mediated DWI of the liver was compared in six patients with suspected malignant liver lesions at 1.5 Tesla using a parallel imaging technique. RESULTS: Post-SPIO DWI showed improved contrast-to-noise ratio between malignant lesions and liver. Furthermore, the spleen signal was decreased on post-SPIO DWI, thus avoiding the overlap of the spleen and left lobe of the liver on maximum intensity projections (MIP). CONCLUSION: Recognition of malignant lesions of the liver was improved by SPIO on DWI. On MIP images of DWI, SPIO helped to decrease the overlap of spleen signal on the liver in some projection angles.

Adult↗
PubMed2005

Screening of antibiotics resistance to Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii by an advanced expert system.

The VITEK2 advanced expert system (AES) gives information about the antibiotics-resistance mechanisms based on the biological validation derived from the VITEK2 susceptibility result. In this study, we investigated whether or not this system correctly categorized the beta-lactamase resistance mechanism data derived from the VITEK2 susceptibility result using the testing card, AST-N025, with Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We used 131 strains, and their phenotypes were determined according to the biological and genetic screening. The AES analysis result matched the phenotype testing in 120 (91.6%) of the 131 strains. Incorrect findings were found in six strains, including three strains of Serratia marcescens. The resistance mechanism could not be determined in five strains, including three strains of Providencia rettgeri. The analysis of those phenotypes agreed in 34 (97.1%) among 35 strains with extended spectrum beta-lactamase (ESBL), and in 27 (96.4%) among 28 strains with high-level cephalosporinase. The agreement ratio in the phenotype was very high as we expected. The incorrect and nondeterminable samples were strains with relatively high cephalosporinase that has variation of outer membrane protein. The AES was able to detect the phenotype for carbapenemase. The AES is a clinically useful system that allows taking prompt measures to treat patients because it can provide information about the resistance mechanism in less than half a day after starting the analysis.

Acinetobacter baumannii↗
PubMed2005

A motif within SET-domain proteins binds single-stranded nucleic acids and transcribed and supercoiled DNAs and can interfere with assembly of nucleosomes.

The evolutionary conserved SET domain is present in many eukaryotic chromatin-associated proteins, including some members of the trithorax (TrxG) group and the polycomb (PcG) group of epigenetic transcriptional regulators and modifiers of position effect variegation. All SET domains examined exhibited histone lysine methyltransferase activity, implicating these proteins in the generation of epigenetic marks. However, the mode of the initial recruitment of SET proteins to target genes and the way that their association with the genes is maintained after replication are not known. We found that SET-containing proteins of the SET1 and SET2 families contain motifs in the pre-SET region or at the pre-SET-SET and SET-post-SET boundaries which very tightly bind single-stranded DNA (ssDNA) and RNA. These motifs also bind stretches of ssDNA generated by superhelical tension or during the in vitro transcription of duplex DNA. Importantly, such binding withstands nucleosome assembly, interfering with the formation of regular nucleosomal arrays. Two representatives of the SUV39 SET family, SU(VAR)3-9 and G9a, did not bind ssDNA. The trxZ11 homeotic point mutation, which is located within TRX SET and disrupts embryonic development, impairs the ssDNA binding capacity of the protein. We suggest that the motifs described here may be directly involved in the biological function(s) of SET-containing proteins. The binding of single-stranded nucleic acids might play a role in the initial recruitment of the proteins to target genes, in the maintenance of their association after DNA replication, or in sustaining DNA stretches in a single-stranded configuration to allow for continuous transcription.

Amino Acid Motifs↗
PubMed2005

[Susceptibility of ESBL-producing Escherichia coli and Klebsiella pneumoniae to various antibacterial agents].

With the increasing use of broad-spectrum antibacterial agents, the increase in various drug-resistant bacterial strains has become a concern in recent years. Especially, the development of drug-resistance by Enterobacteriaceae which significantly affects therapy and prognosis in sepsis and lower gastrointestinal post-operative infection. The extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae strains isolated in the Surveillance Program of Bacterial Resistance in Kinki region of Japan (SBRK) were supplied between November 2000 and March 2003. The susceptibilities of them to 16 kinds of antimicrobial agents were investigated. The number of them was 48 strains consisting of 36 Escherichia coli strains (75%) and 12 Klebsiella pneumoniae strains (25%). Our focus was on carbapenem and the new quinolone antibacterial agents. Among the 16 major antibacterial agents examined, carbapenem had low MIC50/90 values. Meropenem had a MIC50/90 of 0.03/0.06microg/ml, followed by biapenem (0.12/0.5), imipenem (0.25/0.5) and panipenem (0.25/0.5). Among cephem, ceftazidime had the lowest MIC50 at 4 microg/ml. All four of the cephem agents had a MIC90 of greater than 128microg/ml. Among beta-lactamase inhibitors, tazobactam/piperacillin had the lowest MIC50 at 4 microg/ml, and sulbactam/cefoperazone had a MIC50 of 32 microg/ml. Among the new quinolones, prulifloxacin had the lowest MIC50 at 1 microg/ml, and the other drugs had a MIC50 of 2 microg/ml. The resistance rate of ciprofloxacin was 61.1% in E. coli and 16.6% in K. pneumoniae. Comparison of drug-sensitivity to cephem by ESBL-gene type revealed that cefpirome, cefepime and cefozopran had higher MIC50/90 values against the CTX-M group with a MIC50 of greater than 128microg/ml. Ceftazidime and aztreonam had higher MIC50/90 values against the TEM/SHV group than those against the CTX-M group. In the CTX-M group, the MIC50 was 4 and 16microg/ml, respectively.

Anti-Bacterial Agents↗
PubMed2005

[Surveillance of antimicrobial resistance of Streptococcus pneumoniae isolates from the Kinki Region of Japan during 2003/2004. The Surveillance Program of Bacterial Resistance in the Kinki Region of Japan; SBRK].

Three hundred seventy five isolates of Streptococcus pneumoniae were collected from 14 medical institutions in the Kinki region of Japan between November 2003 and February 2004. We determined the minimum inhibitory concentration (MIC) of penicillin G (PCG) and 25 of other antimicrobial agents against these isolates according to the National Committee for Clinical Laboratory Standards (NCCLS). Overall, 71.5% of all isolates were resistant to PCG (intermediate and resistant categories were 51.7% and 19.8%, respectively). For the carbapenems and penem, the rank order of activity was PAPM (MIC90, 0.12 microg/ml) > IPM (0.25 microg/ml) > MEPM (0.5 microg/ml) = FRPM (0.5 microg/ml). For the cephems, the overall rank order of activity was CPR (MIC90, 0.5 microg/ml) = CDTR (0.5 microg/ml) > CTRX (1 microg/ml) = CTX (1 microg/ml) = CZOP (1 microg/ml) = CFPN (1 microg/ml). Rank order activity for six of fluoroquinolones was TFLX = MFLX (MIC90, 0.25 microg/ml) > GFLX (0.5 microg/ ml) = SPFX (0.5 microg/ml) > LVFX (1 microg/ml) > PZFX (4 microg/ml). The rate of resistance to fluoroquinolones per the NCCLS criteria were very low, ranging from 0.7% to 2.6%. Rate of resistance to other antimicrobiotics were CAM, 77.0%; CLDM, 41.7%; TEL, 0%; VCM, 0%; ST, 32.7%, and CP, 21.4%.

Drug Resistance, Bacterial↗
PubMed2004

Contralateral and ipsilateral responses in primary somatosensory cortex following electrical median nerve stimulation--an fMRI study.

OBJECTIVE: Ten healthy adult subjects were examined using functional magnetic resonance imaging (fMRI) to investigate responses in the contralateral and ipsilateral primary somatosensory cortex (SI) following electrical stimulation of the median nerve. METHODS: The right and left median nerves were stimulated alternately at the wrist in the different sessions. First, the location of the response in contralateral SI was identified following median nerve stimulation, and then, a spherical search volume with a 10mm radius centered on the region of the contralateral response was determined. Whether or not fMRI activation occurred within this sphere following ipsilateral stimulation was examined using a 3T MR imager. RESULTS: A response in contralateral SI was observed in 8 of the 10 subjects in right and left hemisphere. Responses in ipsilateral SI were observed in 6 of 8 subjects in right hemisphere, and the region of the response tended to be posterior to the contralateral region. On the other hand, in left hemisphere, the ipsilateral responses were found in three. CONCLUSIONS: In the present study, not only contralateral SI but also ipsilateral SI was activated following median nerve. The location of the ipsilateral activation was significantly more posterior than the contralateral one in right hemisphere. SIGNIFICANCE: The region of activation in ipsilateral SI was located in the posterior portion of post central gyrus, corresponding to around BA2 and 5 in human.

Adult↗
PubMed2004

Expression of leukemic MLL fusion proteins in Drosophila affects cell cycle control and chromosome morphology.

The Mixed Lineage Leukemia (MLL) gene is involved in lymphoblastic and myeloid leukemia through chromosome translocations leading to fusion of MLL to partner genes, or through internal MLL rearrangements. MLL is the mammalian counterpart of the Drosophila trithorax (trx) gene, involved in maintaining active gene expression states. We have used transgenic Drosophila to assess the molecular targets and cellular processes affected by MLL and two of its leukemic fusion proteins. We find that whereas expression of normal human MLL in flies does not result in phenotypic alterations, overexpressing the human MLL-AF9 and MLL-AF4 proteins causes larval to pupal lethality, which interestingly resembles the phenotypes displayed by certain Drosophila trx mutant alleles. MLL-AF9 and MLL-AF4 transgenic flies exhibit antagonistic alterations in cell cycle progression. Additionally, flies expressing MLL-AF9 display impairment in higher order chromatin integrity, evidenced in decondensation of mitotic figures. The effects of MLL fusion proteins in Drosophila suggest that alteration of chromatin structure by MLL fusion proteins may contribute to the lethal phenotype. Our results indicate that the mode(s) of action of MLL-AF9 in Drosophila varies from that of MLL-AF4. Taken together, the expression of MLL fusion proteins in Drosophila provides a new and powerful system to reveal and characterize biological activities associated with MLL fusion proteins.

Animals↗
PubMed2004

Comparison of flow artifacts between 2D-FLAIR and 3D-FLAIR sequences at 3 T.

It has been reported that 3D-FLAIR can reduce the flow artifact resulting from cerebrospinal fluid (CSF) at 1.5 T compared to 2D-FLAIR. Flow-related artifacts tend to be worse at 3 T than at 1.5 T. The purpose of this study was to compare the CSF flow artifacts of 2D-FLAIR and 3D-FLAIR sequences at 3 T in eight healthy volunteers. The grade of CSF-related artifacts were scored through observing the perimedullary cistern, cerebellopontine angle cisterns, fourth ventricule, prepontine cistern, suprasellar cistern, ambient cisterns, sylvian fissures, third ventricle and lateral ventricles. Grading was performed on either axial or sagittal images. The CSF in-flow artifact scores were significantly higher on axial 2D-FLAIR than on axial 3D-FLAIR MPR images in all areas except the bilateral sylvian fissures, and higher on sagittal 2D-FLAIR than on sagittal 3D-FLAIR MPR images in perimedullary, bilateral CP angle and suprasellar cisterns. The CSF-related flow artifacts were significantly reduced by 3D-FLAIR, while structures in the cistern were depicted more clearly, even at 3 T. Further study is necessary to compare the clinical efficacy between 2D-FLAIR and 3D-FLAIR in depicting subtle abnormalities.

Adult↗
PubMed2004

Long-term result of high dose-rate afterloading brachytherapy in squamous cell carcinoma of the cervix: relationship between facility structure and outcome.

OBJECTIVE: To compare outcome results for squamous cell carcinoma of the uterine cervix between patients treated in a single facility [single facility therapy: (SFT)] and others combined with external beam irradiation (EBRT) in a small facility and intracavitary brachytherapy in a central facility (combined facilities therapy: CFT). METHODS: This is a retrospective analysis of 155 patients with histologically proven squamous cell carcinoma of the cervix radically treated by EBRT and high dose-rate (HDR) intracavitary brachytherapy from August 1995 to May 2000. The overall survival and cause-specific survival rates were calculated by using the Kaplan-Meier method. The endpoint was defined as death due to cervical cancer for the cause-specific survival. The log-rank test and the generalized Wilcoxon test were used to compare the survival curves between the two treatment groups. RESULTS: Nine patients were lost, so 146 patients were retrospectively analyzed. There were 22 patients (15%) in stage I, 21 (14%) stage IIA, 51 (35%) stage IIB, 41 (28%) stage III, 11 (8%) stage IVA. The median age was 72 years (range, 30-89 years). The median follow-up time was 58 months. The proportion of patients treated with SFT was 23% (33/146) and CFT 77% (113/146). The overall survival rate was 62.3% and the cause-specific survival rate was 71.3%. The cause-specific survival rates for SFT and CFT were 87.9% and 66.4%, respectively; the difference between these two treatments was statistically significant (P = 0.024). The difference in the survival rate between these two treatments for stage III and IVA patients was also statistically significant (P = 0.021). However, no significant difference between these treatments was seen in the cause-specific survival rate for each stage. There was a significant difference between SFT and CFT in the incidence rate of severe late complications (grade 3-5) (P = 0.038). There was no significant difference in overall treatment times and total dose between the two groups; the applied photon beam energy showed a significant difference. CONCLUSION: Our results suggest that the survival outcome will be aggravated by CFT. If the treatment process of using a lower photon beam energy were to be improved by the installation of a high-energy linear accelerator, CFT can be applied to patients with cervical cancer.

Adult↗