Biomedical subjects

M Tatsumi

Publications and source records attributed to M Tatsumi.

At least 19 recordsLinked to original sources

PubMed2006

Possible association between nonsynonymous polymorphisms of the anaplastic lymphoma kinase (ALK) gene and schizophrenia in a Japanese population.

We examined, for the first time, the possible association between schizophrenia and the anaplastic lymphoma kinase (ALK) gene which plays an important role in neurodevelopment. When two nonsynonymous polymorphisms (Arg1491Lys and Glu1529Asp) were examined, there were significant differences in genotype and allele distributions between patients and controls. Individuals homozygous for the minor allele (1491Lys-1529Asp) were more common in patients than in controls (p = 0.0064, odds ratio 2.4, 95% CI 1.3-4.6). These results suggest that genetic variations of the ALK gene might confer susceptibility to schizophrenia.

Alleles↗

PubMed2006

A complex polymorphic region in the brain-derived neurotrophic factor (BDNF) gene confers susceptibility to bipolar disorder and affects transcriptional activity.

Previous studies have suggested that genetic variations in the brain-derived neurotrophic factor (BDNF) gene may be associated with several neuropsychiatric diseases including bipolar disorder. The present study examined a microsatellite polymorphism located approximately 1.0 kb upstream of the translation initiation site of the BDNF gene for novel sequence variations, association with bipolar disorder, and effects on transcriptional activity. Detailed sequencing analysis revealed that this polymorphism is not a simple dinucleotide repeat, but it is highly polymorphic with a complex structure containing three types of dinucleotide repeats, insertion/deletion, and nucleotide substitutions that gives rise to a total of 23 novel allelic variants. We obtained evidence supporting the association between this polymorphic region (designated as BDNF-linked complex polymorphic region (BDNF-LCPR)) and bipolar disorder. One of the major alleles ('A1' allele) was significantly more common in patients than in controls (odds ratio 2.8, 95% confidential interval 1.5-5.3, P=0.001). Furthermore, a luciferase reporter gene assay in rat primary cultured neurons suggests that this risk allele (A1) has a lower-transcription activity, compared to the other alleles. Our results suggest that the BDNF-LCPR is a functional variation that confers susceptibility to bipolar disorder and affects transcriptional activity of the BDNF gene.

Adult↗

PubMed2005

Association study of the frizzled-3 (FZD3) gene with schizophrenia and mood disorders.

Two research groups have recently reported a significant association between schizophrenia and genetic variants of Frizzled-3 (FZD3) gene. We examined a possible association in a Japanese sample of schizophrenia, bipolar disorder, unipolar depression and controls with four single nucleotide polymorphisms (SNPs), tested in previous reports. We failed to find significant association in the four SNPs or haplotype analysis. The FZD3 gene might not play a role in conferring susceptibility to major psychosis in our sample.

Adult↗

PubMed2004

Association analysis of the -308G>A promoter polymorphism of the tumor necrosis factor alpha (TNF-alpha) gene in Japanese patients with schizophrenia.

Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (-308G > A) of the gene encoding tumor necrosis factor alpha (TNF-alpha), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the -308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the -308G > A polymorphism of the TNF-alpha gene.

Adenine↗

PubMed2004

Radionuclide imaging metabolic activity of brown adipose tissue in a patient with pheochromocytoma.

We describe a patient with extra-adrenal pheochromocytoma and high plasma norepinephrine levels. Radionuclide images of this patient obtained using (18)F-fluorodeoxyglucose and (123)I-metaiodobenzylguanidine revealed bilateral tracer accumulation in the shoulder and lower neck. The regions of radiotracer uptake corresponded to the location of human brown adipose tissue (BAT). Excessive sympathetic stimulation by high circulating catecholamine concentrations augmented the metabolic activity and tracer uptake in the BAT. This study showed that radionuclide imaging can noninvasively visualize human BAT in terms of metabolic and functional activity.

Adipose Tissue, Brown↗

PubMed2004

Analysis of enhancer activity of a dinucleotide repeat polymorphism in the neurotrophin-3 gene and its association with bipolar disorder.

Growing evidence has implicated the possible involvement of neurotrophins in the pathogenesis of functional psychoses such as schizophrenia and bipolar disorder. Previous studies reported a significant association of a dinucleotide repeat polymorphism of the neurotrophin-3 (NTF3) gene with schizophrenia. The aims of the present study were to examine whether this polymorphism is associated with bipolar disorder and whether the polymorphic region has an enhancer/silencer effect on transcriptional activity in an allele-dependent manner. In an association analysis between the polymorphism and bipolar disorder in a Japanese sample of 88 patients and 98 controls matched for age, sex, and ethnicity, the distribution of alleles did not differ significantly between the two groups. pGL3-promoter luciferase reporter vectors containing the polymorphic region increased luciferase activity relative to empty pGL3-promoter vector in HeLa, IMR-32 (neuroblastoma) and Hs683 (glioma) cell lines; however, no significant difference was detected between alleles for either cell line. Our results suggest that the examined polymorphism has no major role in giving susceptibility to bipolar disorder. Although the polymorphic region may have an enhancer-like effect on transcriptional activity, we obtained no evidence for allele-dependent differential effects.

Alleles↗

PubMed2003

Gamma camera coincidence imaging with [18F]fluorodeoxyglucose in the pretreatment evaluation of patients with oesophageal cancer.

This study investigated the role of [18F]fluorodeoxyglucose (FDG) dual-head gamma camera coincidence imaging (GCI) in the pretreatment evaluation of patients with oesophageal cancer. Twenty-two patients (20 men; mean age, 64 years) with untreated, biopsy proven squamous cell carcinoma of the oesophagus underwent positron emission tomography (PET) and GCI 1 and 3 h after a single injection of FDG, respectively. Computed tomography (CT) was performed within 2 weeks of the FDG imaging. The sensitivity of lesion detection was compared between GCI and PET. Regional (N) and distant (M) metastases detected by GCI were evaluated with reference to PET and CT. The staging obtained by each modality was also compared with pathological staging in nine patients who underwent surgery. FDG PET detected 22 primary tumours, 34 metastatic lymph nodes and four organ metastases. Of them, GCI detected all primary tumours, 24 (71%) metastatic lymph nodes, and none of the organ metastases. Lymph nodes missed by GCI were smaller in size and the majority of them were located in the thoracic region. GCI provided N and M staging identical to CT and PET in eight patients and improved staging over CT in four patients. On the other hand, GCI missed metastases detected by both PET and CT in five patients. The addition of GCI to CT could improve detection of patients with metastasis to 82% (18/22) compared with 64% (14/22) detected by CT alone. In patients with pathological staging (n = 9), GCI could influence management changes in two patients (22%). In conclusion, FDG GCI has a role that is complementary to CT in the initial staging of patients with oesophageal cancer, and due to the additional detection of nodal metastasis, GCI can provide staging information, which may influence changes in management.

Aged↗

PubMed2003

Perceptibility curves for the Digora system.

OBJECTIVES: To construct perceptibility curves (PCs) for given calibration settings in order to define psychophysical properties of the Digora storage phosphor system and to evaluate the effects of automatic exposure correction (AEC) on the PCs. METHODS: The Digora system was calibrated at two exposures, 80 microC kg(-1) (high calibration) and 40 microC kg(-1) (low calibration). Since the grey levels displayed in the radiographs are adjusted by AEC, dose-response functions at high calibration were obtained using AEC on and off modes. The dose-response function at low calibration was obtained with AEC off. The PC at each experimental setting was calculated using known physical parameters of the system and the performance of the average observer used in a previous study. In addition, PCs were also constructed using transmitted radiation flux behind the test object calculated from the attenuation coefficient in order to study observer and system performance. PCs obtained under these conditions were compared. RESULTS: The PC using calculated transmitted radiation flux behind the test object showed a wide plateau at the peak owing to AEC, while the PC obtained by a modified approach showed a higher but narrower peak. There were no differences between the two PCs using AEC on and off modes when the PCs were constructed using a modified approach. There were no differences between the two PCs obtained at high and low calibration settings or between the three PCs obtained with AEC on except for the position along the exposure axis. CONCLUSIONS: Psychophysical properties of the Digora system may be determined if we employ registered exposures from a dose-response function with AEC off under a given calibration setting. Under these circumstances the shape and height of the PCs will be unchanged irrespective of the AEC mode.

Algorithms↗

PubMed2002

Association study of C825T polymorphism of the G-protein b3 subunit gene with schizophrenia and mood disorders.

Alterations of G proteins have been implicated in major psychiatric illnesses. A C825T polymorphism of a gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3) was reported to be associated with several pathological conditions, such as hypertension and depressive disorder. We examined whether this polymorphism is associated with functional psychoses in a Japanese sample of 370 schizophrenics, 164 bipolars, 68 depressive patients, and 198 controls. We obtained no evidence for an association of the polymorphism with any diagnostic group.

Adult↗

PubMed2002

Effects of iterative reconstruction on image contrast and lesion detection in gamma camera coincidence imaging in lung and breast cancers.

To investigate the effects of iterative reconstruction in 18F-fluorodeoxyglucose (FDG) gamma camera coincidence imaging (GCI), image contrast and visual detection obtained by using the iterative ordered-subsets expectation maximization (OSEM) reconstruction, in a phantom and in patients with lung cancer and breast cancer, were compared with those obtained by using the conventional filtered backprojection (FBP) reconstruction. Images of a cylindrical phantom containing hot spheres of various sizes (10-38 mm) were acquired by positron emission tomography (PET) and GCI at various sphere-to-background activity ratios. Forty-one consecutive patients with biopsy-proven cancer of lung (n = 20) and breast (n = 21) underwent PET and GCI on the same day after intravenous injection of 370 MBq of FDG. GCI images reconstructed by the OSEM and the FBP were compared. FDG PET was considered as the standard of reference. In GCI phantom images, OSEM yielded better contrast and signal-to-noise ratio (SNR) than FBP over the range of sphere sizes. Attenuation correction improved both the image measures and sphere detection obtained by the OSEM in GCI. In the study involving patients, FDG PET depicted 41 primary tumours and 25 metastatic lymph nodes. All of the tumours >2 cm in diameter (n = 25), six of the nine tumours 1.5-2.0 cm in diameter (67%), two of seven tumours <1.5 cm in diameter (29%), and 20 metastatic lymph nodes (80%) were detected in attenuation uncorrected GCI reconstructed by the OSEM as well as the FBP. The undetected lesions in GCI were identical between the OSEM and the FBP reconstructions. OSEM yielded significantly greater tumour-to-background (T/B) ratios and lower noise than FBP in GCI (T/B ratios, 4.1+/-3.2 vs 3.7+/-2.7, P = 0.02; noise, 0.09+/-0.04 vs 0.14+/-0.05, P<0.0001). In conclusion, OSEM yielded better image contrast and less noise than the FBP in GCI, but the lesion detection obtained by the OSEM and the FBP in attenuation uncorrected GCI in patients with lung cancer and breast cancer were similar. Phantom data suggest the potential of OSEM for improving lesion detection in GCI after attenuation correction.

Breast Neoplasms↗

PubMed2001

Infectious DNA clone of HIV type 1 A/G recombinant (CRF02_AG) replicable in peripheral blood mononuclear cells.

We constructed an infectious DNA clone of the HIV-1 A/G recombinant 97GH-AG2, which was isolated in Ghana in 1997 and was classified originally as subtype A. By phylogenetic and recombination breakpoint analyses, p97GH-AG2 was grouped in the circulating form of A/G recombinants (CRF02_AG) and was found to contain the least amount of subtype G-derived region among the known CRF02_AG HIV-1 DNAs. This result suggests that CRF02_AG may be a predominant form in Ghana. Virions produced by transfection of p97GH-AG2 into 293T cells grew in phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs). 97GH-AG2 also replicated efficiently in CCR5-expressing HeLa cells, MAGIC5, but only weakly in the parent MAGI cells, indicating that 97GH-AG2 uses mostly CCR5 as a coreceptor. Isolation of the first HIV-1 (CRF02_AG) DNA clone that replicates in PBMCs will accelerate the molecular analysis of this subtype.

Adult↗

PubMed2001

Isolation and characterization of a full-length molecular DNA clone of Ghanaian HIV type 1 intersubtype A/G recombinant CRF02_AG, which is replication competent in a restricted host range.

We have isolated a replication-competent, full-length molecular clone of HIV-1 CRF02_AG, designated p97GH-AG1, by reconstituting two separately amplified genomic regions of an HIV-1 provirus of a 1997 Ghanaian isolate. The phylogenetic and recombination breakpoint analyses revealed that 97GH-AG1 had an A/G recombinant structure similar to that of prototype Nigerian isolate IbNG. The 17-nucleotide insertion downstream of the primer-binding site appeared to be a common sequence signature specific to most CRF02_AG strains, including 97GH-AG1. 97GH-AG1 showed an R5 phenotype and exerted productive infection in both HOS and NP2 cell infectivity assays, whereas it failed to show a detectable level of progeny production in peripheral blood mononuclear cells (PBMCs). The data may suggest the presence of unknown determinant(s) that dictate efficient replication in PBMCs, but that are not required for replication in immortalized cell lines.

Amino Acid Sequence↗

PubMed2001

Sensitive detection and differentiation of Sapporo virus, a member of the family Caliciviridae, by standard and booster nested polymerase chain reaction.

Norwalk virus and Sapporo virus (SV) were approved as type species of the genus Norwalk-like viruses and the genus Sapporo-like viruses, respectively, in the family Caliciviridae. Nested polymerase chain reaction (PCR), using newly designed primers in the RNA-dependent RNA polymerase region, was developed to detect and differentiate viruses in the three genetic groups of SV based on the relative size of the PCR products obtained. In addition, a booster nested PCR that performs nested PCR in a single tube was introduced to reduce the chance of contamination during the procedure of standard nested PCR. The specificity of the newly developed PCR was confirmed by testing 77 stool specimens and 16 tissue culture fluids derived from growth of unrelated viruses. The sensitivity of the nested PCR was compared with the conventional PCR using Sapp35/Sapp36 primer pair by testing the three cDNA clones obtained from viruses in the SV/SV82, the SV/London92, and the SV/Parkville virus, respectively. This assay can detect SV in a more sensitive way than the conventional PCR and Southern hybridization. Sensitive and suitable methods to detect and differentiate SV are required to obtain accurate epidemiological data on these viruses and the standard and booster nested PCR should be a very useful tool for this purpose.

Caliciviridae↗

PubMed2001

A novel missense mutation in human lactate dehydrogenase B-subunit gene.

Reduced activity of serum lactate dehydrogenase (LDH; EC 1.1.1.27) was found in a male medical student during practical examinations of his own blood. Serum LDH isoenzyme pattern showed reductions in activities of the isoenzymes with lower subunit A/B ratios such as LDH1 and LDH2. These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting. Polymerase chain reaction (PCR)-based DNA sequence analysis of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B subunit gene that resulted in a glycine to glutamic acid substitution (G69E). The mutation was confirmed by PCR-restriction fragment length polymorphism (RFLP) analysis using a mismatched primer to introduce a new NcoI restriction site. The same heterozygous mutation was found in his mother but not in other family members. This mutation involves a residue belonging to alphaC helix in LDH-B subunit protein molecule that functions as an interface for other subunits.

Adult↗

PubMed2001

Feasibility of a short acquisition protocol for whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose.

The conventional protocol for whole-body positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) requires a total acquisition time of 40-60 min, which is inconvenient for many oncological patients owing to fatigue and discomfort. This study examined the feasibility of a short protocol for whole-body PET. A phantom containing six "hot" spheres of gradually increasing diameter (10-38 mm) was imaged using a dedicated PET scanner for 20, 40, 60, 80, 120 and 600 s at various count rates. Thirty-four patients with various neoplasms underwent whole-body emission scans for 1 min per bed position 1 h after intravenous injection of 370 MBq of FDG (short protocol). A standard simultaneous transmission-emission acquisition for 10 min per bed position was performed thereafter. The images were reconstructed using an iterative algorithm. At a count rate of 40 kcps, which is close to the average count rate obtained in a whole-body FDG PET study, the 60-s image visualised five spheres, of which the smallest was 13 mm in size. Despite the better image quality, lesion detection was not improved in images acquired for more than 60 s (80-600 s). Only three of the six spheres could be detected in images acquired for less than 60 s. In the patient study, the standard protocol visualised 120 tumour lesions, of which 93 (78%) could be detected using the short protocol. Among the non-visualised lesions, 22 (82%) were < or =1.5 cm in size and 17 (63%) were lymph nodes. It is concluded that the proposed short protocol for whole-body FDG PET has a reasonably high detection rate and may be suitable for patients who are unable to undergo scanning for a prolonged period. It may also be useful as a pre-scan guide before a standard whole-body acquisition.

Adult↗

PubMed2001

Requirement of nef for HIV-1 infectivity is biased by the expression levels of Env in the virus-producing cells and CD4 in the target cells.

The nef gene of human immunodeficiency virus type 1 (HIV-1) encodes a 27 to 34 kDa myristoylated protein, which enhances viral infectivity in a single-round infection assay. The level of Nef enhancement of HIV-1 infectivity depends on the viral strains, on the target cells, and on the cells used for propagating the viruses. In this study, we aimed at clarifying the molecular basis of these differences in the requirement for Nef. We found that the requirement for Nef was increased when we decreased the quantity of Env protein in the virus-producing cells or the quantity of CD4 in the target cells. Both the wild-type and Nef-defective HIV-1 viruses were propagated in 293T cells, which did not express any CD4; therefore, Nef-induced CD4 down-regulation did not explain this phenomenon. Moreover, we did not observe any increase in the viral entry or fusion activity of gp120env in the wild-type HIV-1 compared to that in the Nef-defective HIV-1. Thus, we propose that Env on the virion and CD4 on the target cells have inhibitory effects on the post-entry step of the HIV-1 replication cycle, and that Nef functions to counteract this negative effect.

CD4 Antigens↗

PubMed2001

Establishment of a MAGI-derived indicator cell line that detects the Nef enhancement of HIV-1 infectivity with high sensitivity.

The Nef protein of the simian and human immunodeficiency viruses (SIV and HIV) is regarded as one of the critical determinants of the pathogenicity of HIV-1 in vivo. The positive effect of Nef on viral replication is examined most easily in vitro by the use of indicator cells such as HeLa-CD4-LTR-beta-gal cells (MAGI) or MAGIC5 cells, which are MAGI-derived, CCR5-expressing cells. However, Nef increases the infectivity of many HIV-1 strains no more than 10-fold in these indicator cells. It was noted that MAGI cells expressing a lower level of CD4 enabled us to discriminate more clearly between wild-type and Nef-defective virions. A MAGIC5-derived cell line, MAGNEF, which stably expressed a low level of CD4, was established. The infectivity of the Nef-defective HIV-1 NL4-3 strain was consistently less than one-twentieth of that of the wild type in MAGNEF cells. By using MAGNEF cells, it was shown that Nef enhanced the infectivity of a subtype C HIV-1, Indie-C1 strain, although the effect of Nef on Indie-C1 was significantly less than that on the subtype B strains NL4-3 and SF2. These results validate the versatility of MAGNEF cells for use in the simple and sensitive assay for the level of Nef dependence of various HIV-1 isolates.

CD4 Antigens↗

PubMed2001

Conventional and predicted perceptibility curves for contrast-enhanced direct digital intraoral radiographs.

OBJECTIVES: To construct Perceptibility Curves (PCs) for contrast-enhanced digital intraoral radiographs. METHODS: Radiographs of a test object having holes of increasing depths were exposed using three digital systems, the CDR (Schick Technologies, Long Island, NY, USA), the Dixel (J Morita MFG, Kyoto, Japan) and the Sens-A-Ray (Regam Medical Systems, Sundsvall, Sweden). The radiographs were contrast-enhanced and PCs constructed in the conventional way using 10 observers. Predicted PCs were calculated and compared with observer data. RESULTS: The PCs showed that contrast enhancement is effective for the perception of small contrast details, especially in the low exposure range. Predicted PCs demonstrated excellent agreement with observer data. CONCLUSIONS: Contrast enhancement should be advantageous in digital radiography. The effects of contrast enhancement on PCs may be predicted without previous knowledge of observer performance.

Algorithms↗