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Biomedical subjects

M Tatsumi

Publications and source records attributed to M Tatsumi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Clinical severity of Norwalk virus and Sapporo virus gastroenteritis in children in Hokkaido, Japan.

OBJECTIVE: To clarify the clinical significance and etiologic impact of Norwalk virus (NV) and Sapporo virus (SV) in viral gastroenteritis in Japanese children. STUDY DESIGN: Two outbreaks each of NV gastroenteritis and SV gastroenteritis occurring in an infant home in Sapporo, Japan, as well as 95 hospitalized children with acute gastroenteritis were retrospectively evaluated using a 0- to 20-point clinical severity scoring system. RESULTS: The mean severity scores for NV and SV gastroenteritis outbreaks were 7.9 and 5.2, respectively, as compared with 8.4 for rotavirus A gastroenteritis that occurred in the same infant home. Among 95 hospitalized children with acute gastroenteritis, rotavirus A was detected in 47% followed by NV in 18%. SV was not found. CONCLUSION: Our data indicate that NV can cause severe gastroenteritis and is an important etiologic agent in hospitalized cases, whereas SV causes mild gastroenteritis in Japanese children.

Acute Disease↗
PubMed2001

Rapid and simple phenotypic assay for drug susceptibility of human immunodeficiency virus type 1 using CCR5-expressing HeLa/CD4(+) cell clone 1-10 (MAGIC-5).

We describe a rapid and simple novel phenotypic assay for drug susceptibility of human immunodeficiency virus type-1 (HIV-1) using a CCR5-expressing HeLa/CD4(+) cell clone 1-10 (MAGIC-5). MAGIC-5 cells produced large amounts of HIV-1 in culture supernatants, which enabled us to perform the phenotypic resistance assay. Determination of HIV-1 susceptibility to various protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors was completed within 15 days in T-cell-tropic (X4) and macrophage-tropic (R5) viruses using fresh plasma samples containing at least 10(4) copies/ml. The nucleotide sequence of the envelope V3 region of HIV-1 in plasma was almost identical to that of the virus isolated by MAGIC-5 cells, suggesting a lack of selection bias in our assay. The assay variability was confined to within five-fold in all drugs examined. Accordingly, we used a 10-fold increase in the 50% inhibitory concentration as the cutoff value for viral resistance in the present assay. HIV-1 resistant to lamivudine, which was not detected by conventional genotypic assays, was isolated. In HIV-1 with PI-associated primary amino acid substitutions, our assay showed that drug resistance profiles correlated well with previously reported genotypic-assay data. Furthermore, our assay provided comprehensive results regarding PI resistance in the presence of multiple mutations. The novel assay successfully quantified the level of resistance of clinical HIV-1 isolates to a battery of anti-HIV drugs, indicating its clinical usefulness, particularly in patients who failed to respond to antiretroviral chemotherapy.

Amino Acid Sequence↗
PubMed2001

Augmentation of human immunodeficiency virus type 1 subtype E (CRF01_AE) multiple-drug resistance by insertion of a foreign 11-amino-acid fragment into the reverse transcriptase.

A human immunodeficiency virus type 1 (HIV-1) subtype E (CRF01_AE) variant (99JP-NH3-II) possessing an in-frame 33-nucleotide insertion mutation in the beta3-beta4 loop coding region of the reverse transcriptase (RT) gene was isolated from a patient who had not responded to nucleoside analogue RT inhibitors. This virus exhibited an extremely high level of multiple nucleoside analog resistance (MNR). Neighbor-joining tree analysis of the pol sequences indicated that the 99JP-NH3-II variant had originated from the swarm of drug-sensitive predecessors in the patient. Population-based sequence analyses of 82 independently cloned RT segments from the patient suggested that the variants with the insertion, three or four 3'-azido-3'-deoxythymidine resistance mutations, and a T69I mutation in combination had strong selective advantages during chemotherapy. Consistently, in vitro mutagenesis of a drug-sensitive predecessor virus clone demonstrated that this mutation set functions cooperatively to confer a high level of MNR without deleterious effects on viral replication capability. Homology modeling of the parental RT and its MNR mutant showed that extension of the beta3-beta4 loop by an insertion caused reductions in the distances between the loop and the other subdomains, narrowing the template-primer binding cleft and deoxynucleoside triphosphate-binding pocket in a highly flexible manner. The origin of the insert is elusive, as every effort to find a homologue has been unsuccessful. Taken together, these data suggest that (i) HIV-1 tolerates in vivo insertions as long as 33 nucleotides into the highly conserved enzyme gene to survive multiple anti-HIV-1 inhibitors and (ii) the insertion mutation augments multiple-drug resistance, possibly by reducing the biochemical inaccuracy of substrate-enzyme interactions in the active center.

Adult↗
PubMed2001

Whole-body hybrid PET with 18F-FDG in the staging of non-Hodgkin's lymphoma.

UNLABELLED: PET with a double-head gamma camera (hybrid PET) is a new approach to tumor imaging with 18F-FDG. This study was conducted to clarify the feasibility of whole-body FDG hybrid PET in the staging of non-Hodgkin's lymphoma (NHL) in comparison with PET with a dedicated camera (dedicated PET) and to compare the results of both FDG studies with those of CT and 67Ga scanning as conventional imaging studies (CIS). METHODS: Thirty patients with NHL were prospectively evaluated. The results of the imaging studies regarding detection of the sites involved and staging were compared with each other and with those of the reference standard based on the final overall clinical evaluation. RESULTS: Of the total of 206 sites, whole-body FDG hybrid PET and dedicated PET detected 159 sites (77.2%) and 179 sites (86.9%), respectively. Eighteen of the 20 sites missed by hybrid PET alone consisted of lesions < 1.5 cm. Both FDG studies provided concordant staging results in all but 2 patients. CIS, on the other hand, detected 164 (79.6%) of the 206 sites, 137 of which were also detected by hybrid PET. Hybrid PET detected an additional 22 sites not found by CIS, whereas CIS detected 27 additional sites. Hybrid PET and CIS provided concordant staging results in 19 patients. Hybrid PET correctly staged NHL in 5 additional patients, whereas CIS correctly staged NHL in only 1 additional patient. CONCLUSION: Whole-body FDG hybrid PET appeared to be an accurate method of staging NHL. Despite its poorer image quality compared with dedicated PET, hybrid PET provided NHL staging results comparable with those of dedicated PET. Hybrid PET also yielded results comparable with those of CIS. However, whole-body FDG hybrid PET is currently inadequate as a single modality for staging NHL and is complementary to CT.

Adolescent↗
PubMed2000

Changes in local cerebral blood flow in photochemically induced thrombotic occlusion model in rats.

We demonstrated earlier that in a photochemically induced thrombotic occlusion model, a reperfusion-like phenomenon may be involved in the progress of brain damage. Therefore, we now investigated changes in local cerebral blood flow in a photochemical model compared with changes in a thermocoagulated occlusion model, using autoradiography. At 5 min, and 3, 6 and 24 h after middle cerebral artery occlusion, local cerebral blood flow was measured by intravenous injection of 4-iodo[N-methyl-14C]antipyrine (20 mu Ci). In the ischemic core zone, the reduction in blood flow was similar in the two models. However, blood flow in the ischemic border zone in the photochemical model decreased transiently in the third hour after ischemia and then increased again, while the blood flow in a thermocoagulated model continued to decrease. Time courses of brain damage formation in both models were no different up to 24 h. These findings suggest that the transient reduction in cerebral blood flow in the third hour following ischemia may contribute to a reperfusion-like phenomenon in a photochemical model.

Animals↗
PubMed2000

Transforming growth factor-beta(1) restores antiplatelet function of endothelial cells exposed to anoxia-reoxygenation injury.

Transforming growth factor-beta(1) released from platelet alpha-granules may preserve endothelial functions in injured vessels. However, direct evidence is lacking regarding how this cytokine modifies the antithrombotic function of injured endothelial cells. We performed an in vitro study to investigate the effects of transforming growth factor-beta(1) on platelet functions in the presence of cultured endothelial cells exposed to anoxia-reoxygenation injury. Cultured bovine aorta endothelial cells were placed in an anoxic chamber (0.5% O(2), 5% CO(2)) for 60 minutes followed by a 90-minute reoxygenation. Collagen (2 microg/mL)-induced platelet aggregation (10(8) platelets/mL), as determined by impedance aggregometry, was potently inhibited in the presence of control endothelial cells (17.4+/-3.3 Omega) at a concentration of 5x10(4) cells/mL, as compared to their absence (68. 2+/-2.2 Omega). Inhibition of platelet aggregation was attenuated in endothelial cells exposed to anoxia-reoxygenation (54.6+/-2.5 Omega). However, preincubation of endothelial cells with transforming growth factor-beta(1) (1.0 ng/mL) for 16 hours partially recovered the inhibitory capability of platelet aggregation by injured endothelial cells (40.6+/-3.8 Omega). Cell viability, confirmed by a trypan blue dye exclusion test, was similar (93-96%), including control, 1.0 ng/mL transforming growth factor-beta(1)- and/or anoxia-reoxygenation-pretreated cells. The capability of platelet inhibition was restored when the endothelial cells were preincubated for 4 hours or more. Restoration of antiplatelet capacity in endothelial cells by transforming growth factor-beta(1) was suggested to be due to several mechanisms, including an increase in nitric oxide synthase activity, up-regulation of prostacyclin release, and restoration of adenosine triphosphate diphosphohydrolase activity, which was attenuated by anoxia-reoxygenation pretreatment. In summary, transforming growth factor-beta(1) released from activated platelets may play a compensatory role in the preservation of endothelial functions to inhibit platelet activation.

Animals↗
PubMed2000

Ibudilast modulates platelet-endothelium interaction mainly through cyclic GMP-dependent mechanism.

3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast) has been widely used in Japanese clinics for its antiasthmatic and antithrombotic effects. We investigated the mechanisms involved in the antiplatelet effects of the agent, specifically focusing on platelet-endothelium interaction. Ibudilast inhibits both phosphodiesterase (PDE) 3 and 5, the two major PDE isoforms of human platelets, with an IC50 of 31 and 2.2 microM, respectively. Cyclic guanosine monophosphate (GMP) accumulation in washed human platelets exposed to ibudilast alone increased significantly only at high concentrations of the agent (100 microM), whereas > or = 1 microM ibudilast enhanced cyclic GMP levels in the platelets cocultured with bovine aorta endothelial cells (ECs). In contrast, ibudilast enhanced cyclic AMP accumulation only at 100 microM, either with or without ECs. The synergistic effect of ibudilast and EC on cyclic nucleotide accumulation also was demonstrated by the inhibitory capability of the drug and the cells on platelet aggregation. The synergism between ibudilast and aspirin-pretreated ECs was more pronounced than that between ibudilast and N(omega)-nitro-L-arginine (L-NNA)-pretreated ECs. Ibudilast affected neither ATP diphosphohydrolase activity nor NO release from EC up to a concentration of 10 microM. We conclude that ibudilast exhibits antiplatelet properties mainly by inhibiting PDE5 to potentiate antiplatelet function of endothelium-derived NO.

Animals↗
PubMed1999

An infectious DNA clone of HIV type 1 subtype C.

Among the 10 subtypes of the M group of human immunodeficiency virus type 1, subtype C is the most prevalent in India and may dominate worldwide in the near future; however, there has been no report on the infectious DNA clone of this subtype. We have isolated an infectious DNA clone of the 93IN101 strain of HIV-1 subtype C, which was isolated in India in 1993. MAGIC5 cells, which are derived from HeLa-CD4-LTR-beta-gal (MAGI) cells and express CCR5, were inoculated with the 93IN101 strain of HIV-1 subtype C. The genomic DNA of the infected cells was used as a template for amplification of the HIV-1 genome. The genome DNA obtained was subcloned into pBR322, and the resulting plasmid was designated as pIndie-C1. The insert of pIndie-C1 was 9680 bp in length and had an intact genomic organization with open reading frames of all structural, regulatory, and accessory proteins. Phylogenetic analysis confirmed that the nucleotide sequence of pIndie-C1 is closely related to those of HIV-1 subtype C isolated in India. Transfection of pIndie-C1 into 293T cells yielded as much virus as did pNL432, one of the most widely used HIV DNA clones. The recovered Indie-C1 virus infected MAGIC5 but not the parent MAGI cells, indicating that Indie-C1 is CCR5 tropic. Expressed Env protein was reacted efficiently with the sera of HIV-1-infected patients of India, but not of Japan. Expression of Nef and Vpr was also confirmed by immunoblotting.

Gene Products, env↗
PubMed1999

The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas.

BACKGROUND: The c-met and the c-erb B-2 protooncogenes belong to a family of tyrosine kinase growth factor receptors. Abnormalities of these oncogenes and protein products have been reported in several cancers. The authors investigated the correlation between clinical factors and amplification or overexpression of the c-met and/or c-erb B-2 gene in Japanese patients with gastric carcinoma patients, with a focus on prognostic significance. METHODS: Amplification and overexpression of c-met and c-erb B-2 were investigated retrospectively in 128 gastric carcinoma patients by using immunohistochemistry and Southern blot hybridization. Survival analysis was performed with the Kaplan-Meier test, and the log rank test was used for statistical analysis. RESULTS: Overexpression of c-met and c-erb B-2 was observed in 46.1% and 16.4% of gastric carcinoma cases, respectively. Gene amplification of c-met and c-erb B-2 was detected in 10.2% and 11.7% of gastric carcinoma cases, respectively. Amplification and overexpression of c-met were correlated significantly with depth of tumor invasion and lymph node metastasis, whereas amplification and overexpression of c-erb B-2 were correlated significantly with histologic type. The survival rate of patients with amplification and/or overexpression of c-met or c-erb B-2 was significantly poorer than that of patients with no amplification or overexpression. Multivariate analysis revealed that c-met overexpression and lymph node metastasis were independent prognostic factors. CONCLUSIONS: These data suggest that overexpression and/or gene amplification of c-met and c-erb B-2 may be prognostic factors in gastric carcinoma.

Adult↗
PubMed1999

Pharmacological profile of neuroleptics at human monoamine transporters.

Using radioligand binding techniques, we determined the equilibrium dissociation constants (K(D)) for 37 neuroleptics and one metabolite of a neuroleptic (haloperidol metabolite) for the human serotonin, norepinephrine, and dopamine transporters with [3H]imipramine, [3H]nisoxetine, and [3H]WIN35428, respectively. Among neuroleptics, the four most potent compounds at the human serotonin transporter were triflupromazine, fluperlapine, chlorpromazine, and ziprasidone (K(D) 24-39 nM); and at the norepinephrine transporter, chlorpromazine, zotepine, chlorprothixene, and promazine (K(D) 19-25 nM). At the human dopamine transporter, only pimozide (K(D) = 69+/-3) ziprasidone (K(D) = 76+/-5) had notable potency. These data may be useful in predicting therapeutic and adverse effects, including drug interactions of neuroleptics.

Antipsychotic Agents↗
PubMed1999

Technetium-99m HL91 uptake as a tumour hypoxia marker: relationship to tumour blood flow.

Technetium-99m HL91 (HL91) is a potential agent for imaging hypoxic tissue in vivo. To elucidate the relationship between hypoxia and blood flow in a tumour, dual-tracer autoradiography with HL91 and carbon-14 iodoantipyrine (IAP) was performed in a tumour-bearing rat model. The distribution of each tracer was analysed visually and semiquantitatively. In the tumours with central necrotic areas, HL91 uptake was marked around the necrotic areas whereas IAP uptake was marked at the periphery of the tumours, around the areas of marked HL91 uptake. Normalized HL91 uptake (%HL91) was highest in the low normalized IAP uptake (%IAP) fraction in the non-necrotic areas. There was a weak negative correlation between %HL91 and %IAP in the non-necrotic areas (r = -0.322, P<0.0001). In tumours with few or no necrotic areas, HL91 uptake was heterogeneous throughout the tumours, while IAP uptake predominantly occurred at the periphery of the tumours. %HL91 was higher in the inner two-thirds of the tumour than in the outer third. There was again a weak negative correlation between %HL91 and %IAP (r = -0.354, P<0.0001). This study confirmed that high HL91 uptake is related to low blood flow. The marked HL91 uptake around the necrotic region suggests the presence of chronic hypoxia in a tumour.

Animals↗
PubMed1999

Assessment of image quality in dental radiography, part 1: phantom validity.

OBJECTIVE: The purpose of this study was to describe and validate an image-quality phantom to be used in dental radiography for comparison of film and digitally acquired images. STUDY DESIGN: An aluminum block of 12 steps, with 7 holes in each step, was covered by acrylic blocks. This phantom was radiographed with Kodak Ultra-speed and Ektaspeed Plus films at 70, 65, and 60 kVp with the whole exposure range available. All together, 50 dental films were randomly sequenced and presented to 7 observers. The average number of perceptible holes from all steps was plotted against exposure for each tube voltage and film type, generating a modified perceptibility curve. The tentative optimum exposure level was determined from perceptibility curves in each experimental condition and compared with that determined by means of the standard aluminum stepwedge and the preset time of the x-ray machine. The density range of this phantom at the optimum exposure was compared with that of clinical dental radiographs. Validity of the phantom was evaluated according to the optimum exposure level from the modified perceptibility curves and the overall density range. Finally, the average maximum numbers of perceptible holes at the tentative optimum exposure level were compared for each tube voltage and film type. The statistical test used was a 2-way factorial analysis of variance. RESULTS: The exposure at the perceptibility curve peak approximated that obtained by means of the standard aluminum step-wedge and the time preset by the manufacturer. The overall density range at the perceptibility curve peak covered the clinical density range for each tube voltage and film type. There were no statistically significant differences between film types or among tube voltages. CONCLUSIONS: The x-ray attenuation range for this phantom seemed to approximate clinical conditions. In addition, differences in image quality could be quantitatively evaluated by means of the number of the holes seen in the phantom.

Absorptiometry, Photon↗
PubMed1999

Assessment of image quality in dental radiography, part 2: optimum exposure conditions for detection of small mass changes in 6 intraoral radiography systems.

OBJECTIVE: The purpose of this study was to compare 2 film systems and several digital intraoral systems with regard to visual image quality through use of a test phantom developed for this purpose. STUDY DESIGN: The detectors used for digital imaging were as follows: Computed Dental Radiography (CDR), Digora, Dixel, and Sens-A-Ray without scintillator layer. Two types of digital images were prepared for the observer performance test: one with original gray scales and another with contrast enhancement. Images with and without enhancement from the 4 systems were displayed to 7 observers. The change in the average number of perceptible holes was plotted against exposure, and modified perceptibility curves were created and compared with curves for the film systems. The exposure level at which the maximum number of holes was perceived was defined to be optimum. The optimum exposure levels were determined for each digital system and compared with that of the film systems. At the optimum exposure, the average maximum numbers of perceptible holes in each digital system with and without contrast enhancement were compared with the maximum numbers for the film systems. The minimum exposure levels were determined to be those at which the number of perceptible holes exceeded the number for film, and the possibility of exposure reduction was evaluated. RESULTS: All digital systems except the Digora system showed lower optimum exposures than E-speed film. In all digital images without enhancement, however, the maximum number of perceptible holes was significantly lower than that for the film systems at that exposure. With contrast enhancement, all digital systems except the Sens-A-Ray system showed visibility superior to that of the film systems. With the CDR, Digora, and Dixel systems, exposures could be further reduced by a considerable amount, with greater retention of information than was associated with film. CONCLUSIONS: Our results strongly suggest that digital systems, if properly used, can exceed film systems in the detection of small mass changes.

Contrast Media↗
PubMed1999

A functional polymorphism in the promoter region of monoamine oxidase-A gene and mood disorders.

A polymorphism of a variable number tandem repeat (VNTR), that was recently found in the promoter region of the monoamine oxidase-A (MAOA) gene, was shown to be associated with its transcriptional activity. This study examined whether this functional polymorphism of the MAOA gene is associated with the risk of developing mood disorders in a Japanese sample of 161 patients with bipolar disorder, 98 with unipolar depression, and 258 controls. There was no significant genotypic or allelic association, suggesting that the functional VNTR polymorphism in the MAOA gene is unlikely to play a major role in the pathogenesis of bipolar disorder or unipolar depression. Furthermore, we found no association between the polymorphism and a history of suicide attempt.

Analysis of Variance↗
PubMed1999

Physical evaluation of a system for direct digital intra-oral radiography based on a charge-coupled device.

OBJECTIVES: To determine technical properties of a direct digital intra-oral radiographic system, the Dixel(R) (J Morita Corporation, Kyoto, Japan). METHODS: A dose response function and the dark current were calculated from two series of exposures to a homogeneous radiation field. The line spread function (LSF) and the modulation transfer function (MTF) were determined from radiographs of an edge. The noise power spectrum (NPS) was determined at three exposures from radiographs exposed to homogeneous radiation fields. Noise equivalent quanta (NEQ) were calculated from the one-dimensional NPS and the MTF. The detective quantum efficiency (DQE) was determined from the NEQ and a representative value of the photon fluence. Signal-to-noise ratios (SNR) were calculated from the NEQs and different signal contrasts. RESULTS: The dose response function demonstrated a slight curvature. There was no effect of the dark current. NPS ranged from 10-5 - 10-7 mm2 depending on exposure and frequency. At a peak of about 2 cycles/mm the DQE is on an average about 30 per cent. SNRs are favorable. CONCLUSION: The technical properties found in this study indicate that the Dixel(R) system is suitable for intra-oral dental radiography.

Artifacts↗
PubMed1999

No evidence for an association of polymorphisms of the tryptophan hydroxylase gene with affective disorders or attempted suicide among Japanese patients.

OBJECTIVE: Tryptophan hydroxylase is the rate-limiting enzyme in the biosynthesis of serotonin. The authors examined whether polymorphisms A218C and A779C in intron 7 of the tryptophan hydroxylase gene are associated with a risk for affective disorders or suicidal behavior. METHOD: Subjects were 141 patients with bipolar disorder and 73 patients with unipolar affective disorder, 46 of whom had a history of attempted suicide, and 208 healthy volunteers. All subjects were unrelated to each other, and all were Japanese. Genotyping was performed by polymerase chain reaction amplification followed by digestion by a restriction enzyme and single-strand conformational polymorphism analysis. RESULTS: There was no significant genotypic or allelic association of the A218C polymorphism with bipolar disorder, unipolar depression, or history of attempted suicide. In nearly 100% of the subjects, genotypes for the A779C were identical to those for the A218C. CONCLUSIONS: The authors conclude that the examined polymorphisms are unlikely to have major relevance to the pathogenesis of affective disorders or suicidal behavior.

Adult↗