Biomedical subjects

T Uehara

Publications and source records attributed to T Uehara.

At least 37 records · Page 2Linked to original sources

PubMed2001

Real-time measurement of low-energy-range neutron spectra on board the space shuttle STS-89 (S/MM-8).

We have developed a real-time, Bonner Ball-type (neutron energy range is from thermal to 15 MeV) neutron spectral measurement system (Bonner Ball Neutron Detector (BBND)) for use on board the International Space Station (ISS). From measurements taken inside STS-89 (S/MM-8), we successfully distinguished neutrons from protons and other particles in a mixed radiation field; a task hitherto considered difficult. Although the experimental period was short, only 3.5 days (January 24-27, 1998), we were able to obtain energy spectral data and the Earth's neutron dose-equivalent map for the ISS orbital conditions (altitude 400 km, orbit inclination angle 51.6 degrees). A method for calculating the neutron energy spectrum and compensating for the particle interaction with the sensors is also described in detail.

Aluminum↗

PubMed2001

HscA is involved in the dynamics of FtsZ-ring formation in Escherichia coli K12.

BACKGROUND: FtsZ, a homologue of eukaryotic tubulin, localizes throughout the cytoplasm in non-dividing Escherichia coli. However, it assembles in cytokinetic rings at the early stages of septation. Factors controlling the dynamics of FtsZ ring formation are unknown, and the molecular mechanism governing these dynamics is yet to be determined. RESULTS: At 42 degrees C, JE10715 mutant bacteria formed multinucleated filaments with a highly reduced number of FtsZ-rings at potential division sites. The JE10715 phenotype resulted from a mis-sense mutation in the hscA gene which encodes a heat shock Hsp70 family protein, with a single alanine-to-valine substitution at position 192 within the ATPase domain. Both JE10715 and the hscA knockout strain of JE10715 were completely complemented by a plasmid-born, wild-type hscA gene, but not by a mutant-type hscA715 gene. An hscA conditional knockout of the wild-type strain under non-permissive conditions exhibited longer rod cells with an abnormal localization of FtsZ. The over-expression of dnaK partially complemented the JE10715 mutation. In vitro, the ATPase activity of the mutant protein HscA715 was reduced to 63% of wild-type HscA activity. HscA co-sedimented with FtsZ-polymers in the presence of GTP. CONCLUSION: HscA is involved in FtsZ-ring formation, through a chaperon-like interaction with FtsZ. Defects in hscA, however, can partially be compensated for by redundant genes, including the wild-type dnaK.

Adenosine Triphosphatases↗

PubMed2001

Referral and care for acute ischemic stroke in a Japanese tertiary emergency hospital.

To examine the current emergency referral and care for acute stroke at a Japanese tertiary emergency hospital with a 24-h stroke team and care unit, we surveyed the presentations of patients with acute ischemic stroke or transient ischemic attack (TIA) seen within 7 days of onset. Delay from symptom onset to arrival at our hospital, from arrival to initial diagnostic brain computed tomography (CT), and the type of anti-thrombotic treatments were evaluated. During the 18-month period, there were 254 ischemic events in 244 patients; 239 (94%) had an ischemic stroke and 15 (6%) TIA. Eighty-two (32%) events presented within 3 h of onset, and 102 (40%) and 179 (70%) within the first 6 and 24 h, respectively. The median delay from hospital arrival to CT was 32 min, ranging 10 min to 22 h. Two hundred (79%) events underwent CT within 1 h of arrival (n=172) or at the referral hospitals before transfer (n=28). Direct ambulance transportation and more severe neurological deficits were independent predictors both for early arrival and short in-hospital delay to CT. Anti-thrombotic therapies including anticoagulant and/or antiplatelet medications were given in 237 (93%) episodes. Two (1%) patients received thrombolysis, although 18 (7%) patients fulfilled the National Institute of Neurological Disorders and Stroke guidelines for intravenous thrombolysis with tissue plasminogen activator. As in western communities, our pre-hospital emergency referral systems for acute stroke require substantial improvements including the wider use of ambulance calling. Although our in-hospital stroke management is functioning relatively well, further efforts are necessary in reducing the diagnostic delay.

Acute Disease↗

PubMed2001

MR angiographic evaluation of carotid and intracranial arteries in Japanese patients scheduled for coronary artery bypass grafting.

BACKGROUND AND PURPOSE: Stroke is a serious complication of coronary artery bypass grafting (CABG). Preoperative evaluation of the cerebral arteries to identify patients at increased risk of stroke after CABG is important. In a prospective study, we evaluated cerebral artery occlusive lesions with MR angiography in Japanese patients scheduled to undergo CABG to determine the prevalence of occlusive diseases in the extracranial carotid and intracranial arteries in this population and to identify preoperative risk factors for these patients. METHODS: The subjects were 151 consecutive patients (115 men and 36 women ranging in age from 41 to 82 years) who were scheduled for CABG under nonemergency conditions between October 1995 and February 1998. Carotid and intracranial arteries were examined for occlusive lesions with MR angiography. Patient demographics and risk factors including age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking habit, history of stroke, peripheral vascular disease and preoperative thromboembolic infarcts revealed by MR imaging were recorded and analyzed. RESULTS: Cervical carotid artery stenoses of more than 50% narrowing were detected in 16.6% of the subjects, and intracranial artery stenoses of more than 50% narrowing were detected in 21.2% of the subjects. Multiple logistic regression analyses identified peripheral vascular disease and lacunar infarcts in the basal ganglia as significant and independent predictors of cervical carotid arterial stenoses. No significant predictor for intracranial arterial stenoses was identified. CONCLUSIONS: The prevalence of extracranial carotid and intracranial artery stenosis in Japanese patients scheduled for CABG is considerably high. MR angiography is of value of identifying these patients. Preoperative evaluation of cranial arteries is recommended, particularly in patients with peripheral vascular disease and infarcts in the basal ganglia.

Adult↗

PubMed2001

Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B.

The potential of the paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) types for modifying an IgE antibody-mediated allergic response was evaluated in mouse bone marrow-derived mast cells. Although mast cells produced both PIR-A and PIR-B, PIR-B was found to be preferentially expressed on the cell surface, where it was constitutively tyrosine phosphorylated and associated with intracellular SHP-1 protein tyrosine phosphatase. PIR-B coligation with the IgE receptor (FcepsilonRI) inhibited IgE-mediated mast cell activation and release of serotonin. Surprisingly, the inhibitory activity of PIR-B was unimpaired in SHP-1-deficient mast cells. A third functional tyrosine-based inhibitory motif, one that fails to bind the SHP-1, SHP-2, and SHIP phosphatases, was identified in parallel studies of FcepsilonRI-bearing rat basophilic leukemia (RBL) cells transfected with constructs having mutations in the PIR-B cytoplasmic region. These results define the preferential expression of the PIR-B molecules on mast cells and an inhibitory potential that can be mediated via a SHP-1-independent pathway.

Animals↗

PubMed2001

Cell lineage specificity of newly raised monoclonal antibodies against gastric mucins in normal, metaplastic, and neoplastic human tissues and their application to pathology diagnosis.

The specificity of monoclonal antibodies against gastric mucins (designated as HIK1083, PGM 36, and PGM 37) was studied immunohistochemically in normal, metaplastic, and neoplastic human tissues. These antibodies labeled class III mucin-producing cells identified by paradoxical concanavalin A staining in normal stomach, duodenum (Brunner gland), biliary tract, and main pancreatic duct; in mucinous metaplasia of pancreas and gallbladder; and in adenocarcinomas of stomach (90%), bile duct (80%), gallbladder (100%), pancreas (80%), lung (100% of goblet cell type adenocarcinomas), ovary (67% of mucinous carcinomas), and uterine cervix (100% of adenoma malignum tumors). Normal and neoplastic cells of esophagus, colon, salivary gland, kidney, endometrium, breast, prostate, and liver, as well as normal small intestine, lung, and uterine cervix, were all negative. The antibodies used should be valuable for the detection of class III mucin and class III mucin-producing cells in normal, metaplastic, and neoplastic tissues.

Antibodies, Monoclonal↗

PubMed2001

Hybrids of two closely related tropical sea urchins (genus Echinometra): evidence against postzygotic isolating mechanisms.

A series of cross-fertilization experiments were conducted with two unnamed, sympatric species of sea urchins in the Echinometra mathaei species complex, Echinometra sp. A (Ea) and Echinometra sp. C (Ec). Heterogametic fertilization success was high when eggs of Ec and sperm of Ea were involved, and low with eggs of Ea and sperm of Ec. Hybrids produced from crosses in either direction developed normally to sexually mature adults; Ea x Ea were largest in test size, followed by Ec (ova) x Ea (sperm), Ea (ova) x Ec (sperm), and Ec x Ec, respectively. Color patterns of the hybrids were closer to the maternal coloration, whereas other characters such as relative test dimensions and spine lengths, morphology of tubefoot and gonad spicules, and gamete sizes were intermediate. Fertilization rates in F1 backcrosses were high, minimizing the possibility that hybrid infertility is a postzygotic mechanism of reproductive isolation. On the other hand, intensive surveys failed to find individuals with hybrid characteristics in the field, suggesting that natural hybridization between the two species is rare. Prezygotic isolating mechanisms, such as microhabitat separation and gamete incompatibility, at least between Ea eggs and Ec sperm, most likely maintain the genetic integrity of these two closely related species.

Animals↗

PubMed2001

[Two elderly patients with sarcoidosis and Sjögren's syndrome].

Two elderly patients with sarcoidosis complicated with Sjögren's syndrome are described. Case 1: A 70-year-old woman was admitted due to dry eyes. Histological examination of a minor salivary gland specimen revealed lymphocytic infiltration, which was compatible with Sjögren's syndrome. Because uveitis was demonstrated, transbronchial lung biopsy (TBLB) was performed, to confirm a diagnosis of lung sarcoidosis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis. Case 2: A 70-year-old woman was admitted due to dyspnea on exercise and blurred vision. Two years previously, Sjögren's syndrome was diagnosed because of a positive Shirmer test and positive SS-A antibody. Result of ophthalmic examination were compatible with uveitis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis. Certain similarities between sarcoidosis and Sjögren's syndrome in terms of immunological aspects have attracted attention. In the present manuscript, a possible relationship between the two diseases as well as the characteristics of elderly sarcoidosis are discussed.

Aged↗

PubMed2001

Clinical analysis of myocardial perfusion and metabolism in patients with hypertrophic cardiomyopathy by single photon emission tomography and positron emission tomography.

BACKGROUND AND OBJECTIVES: Changes in myocardial energy metabolism and their relation to coronary flow reserve in hypertrophic cardiomyopathy were assessed by myocardial fatty acid imaging with iodine-123 beta-methyliodophenyl pentadecanoic acid single photon emission tomography (123I-BMIPP SPECT) (fasting), glucose imaging with fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) (fasting), and perfusion imaging with nitrogen-13 (13N)-ammonia PET (dipyridamole-stress and at rest) in adult patients with hypertrophic cardiomyopathy and with asymmetric septal hypertrophy. RESULTS: 123I-BMIPP defects mismatched with thallium-201 (201Tl) uptake were often observed in the hypertrophic septal regions indicating reduced fatty acid utilization incidence of 59% (22/37). 18F-FDG images showed diffusely increased uptake in most of the patients (73%, 27/37), but showed regionally increased 18F-FDG uptake at the septal regions in only two patients. Study of 18 hypertrophic cardiomyopathy patients with the mismatched 123I-BMIPP defects found that the severity of the defects correlated with reduced coronary flow reserve determined by the 13N-ammonia PET study. On the other hand, changes in 18F-FDG images were not related to those in coronary flow reserve. CONCLUSIONS: These results suggest that the mismatched 123I-BMIPP defects, which indicate abnormality in myocardial fatty acid metabolism, occur under reduced coronary flow reserve, and may contribute to the prediction of progressive myocardial failure in patients with hypertrophic cardiomyopathy. The significance of 18F-FDG in patients with hypertrophic cardiomyopathy is still uncertain.

Adult↗

PubMed2001

A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression.

A novel single-nucleotide polymorphism (SNP), 829C-->T in the 3'-untranslated region of the human dihydrofolate reductase (DHFR) gene transcript, was identified in the study population of 37 patients with childhood leukemias/lymphomas and 83 healthy Japanese children. Frequencies of the DHFR 829C/C, 829C/T, and 829T/T genotypes were 83.8, 10.8, and 5.4%, respectively, in the cases and 74.7, 19.3, and 6.0% in the controls, showing no significant difference in genotype frequencies between the cases and controls. When determined by real-time quantitative reverse transcription-PCR analysis, the highest expression of the DHFR transcript was demonstrated in the samples with a DHFR 829T/T polymorphism (P < 0.001). Direct association of the presence of the SNP with methotrexate-related adverse events in each patient was not demonstrated in this limited analysis. These data suggest that the novel DHFR 829 polymorphism is associated with a positive role in gene expression and provide evidence of a functional SNP in the 3' regulatory region of the gene.

3' Untranslated Regions↗

PubMed2001

Cardiac reoperation in a patient with osteogenesis imperfecta: a case report.

A case of a 40-year-old man with dehiscence of the prosthetic aortic valve and recurrence of mycotic aneurysm of the left ventricular outflow tract with osteogenesis imperfecta is presented. He had an operation of aortic valve replacement and direct closure of the mycotic aneurysm for infective endocarditis twenty-one months ago. We performed reoperation of prosthetic aortic valve, patch closure of the mycotic aneurysm and graft replacement of the ascending aorta. He was complicated with multiple fractures of bilateral scapla and dislocation of left shoulder one postoperative day. Fortunately, cardiac reoperation was performed successfully in this patient despite anticipated difficulties with tissue friability with osteogenesis imperfecta.

Adult↗

PubMed2000

Changes in expressions of proinflammatory cytokines IL-1beta, TNF-alpha and IL-6 in the brain of senescence accelerated mouse (SAM) P8.

The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. The SAMP8 strain shows age-related deterioration of learning and memory at an earlier age than control mice (SAMR1). In the present study, we investigated the changes in expressions of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the brain of SAMP8. In the hippocampus of 10 months old SAMP8, the expression of IL-1 mRNA was significantly elevated in comparison with that of SAMR1. In both strains of SAMs, increases in IL-1beta protein in the brain were observed at 10 months of age compared with 2 and 5 months. The only differences found between the strain in protein levels were at 10 months and were elevations in IL-1beta in the hippocampus and hypothalamus, and in TNF-alpha and IL-6 in the cerebral cortex and the hippocampus in SAMP8 as compared with SAMR1. However, lipopolysaccharide-induced increases in the expression of these cytokines in brain did not differ between SAMP8 and SAMR1. Increases in expression of proinflammatory cytokines in the brain may be involved in the age-related neural dysfunction and/or learning deficiency in SAMP8.

Aging↗

PubMed2000

Mechanism of nitric oxide-induced apoptosis in human neuroblastoma SH-SY5Y cells.

We have attempted to elucidate the precise mechanism of nitric oxide (NO)-induced apoptotic neuronal cell death. Enzymatic cleavages of DEVD-AFC, VDVAD-AFC, and LEHD-AFC (specific substrates for caspase-3-like protease (caspase-3 and -7), caspase-2, and caspase-9, respectively) were observed by treatment with NO. Western blot analysis showed that pro-forms of caspase-2, -3, -6, and -7 are decreased during apoptosis. Interestingly, Ac-DEVD-CHO, a caspase-3-like protease inhibitor, blocked not only the decreases in caspase-2 and -7, but also the formation of p17 from p20 in caspase-3 induced by NO, suggesting that caspase-3 exists upstream of caspase-2 and -7. Bongkrekic acid, a potent inhibitor of mitochondrial permeability transition, specifically blocked both the loss of mitochondrial membrane potential and subsequent DNA fragmentation in response to NO. Thus, NO results in neuronal apoptosis through the sequential loss of mitochondrial membrane potential, caspase activation, and degradation of inhibitor of caspase-activated DNase (CAD) (CAD activation).

Apoptosis↗

PubMed2000

Involvement of nuclear factor-kappaB (NF-kappaB) signaling in the expression of inducible nitric oxide synthase (iNOS) gene in rat C6 glioma cells.

It has been demonstrated from studies using NF-kappaB inhibitors that NF-kappaB may be involved in the iNOS induction stimulated by cytokines and/or lipopolysaccharide (LPS) in various cell types and tissues. However, the actions of the inhibitors are less selective and highly cytotoxic. We constructed stable clones of C6 cells transfected with two types of IkappaBalpha mutant genes (IkappaBalpha(SS --> AA); Ser-32/36 to Ala-32/36, IkappaBalpha(KK --> RR); Lys-21/22 to Arg-21/22). IkappaBalpha(SS --> AA) strongly inhibited (1) LPS-, IL-1beta-, and TNF-alpha-induced nuclear translocation and DNA binding of NF-kappaB to the kappaB site; and (2) iNOS induction stimulated by LPS or IL-1beta plus IFN-gamma. These results indicate that NF-kappaB plays a critical role in cytokines and/or LPS-induced iNOS induction. Surprisingly, similar to the endogenous IkappaBalpha, IkappaBalpha(KK --> RR) was degraded by various stimuli, and proteasome inhibitors blocked this event. These results suggest that another Lys residue(s), other than Lys-21/22, may be required for the ligand-induced IkappaBalpha degradation by the ubiquitin-proteasome pathway.

Animals↗

PubMed2000

Up-regulation of protein-disulfide isomerase in response to hypoxia/brain ischemia and its protective effect against apoptotic cell death.

We isolated and identified a stress protein that is up-regulated in response to hypoxia in primary-cultured glial cells. Protein-disulfide isomerase (PDI) was up-regulated not only by hypoxia in glia in vitro, but also by transient forebrain ischemia in rats in vivo. To determine whether newly synthesized PDI is involved in tolerance to ischemic stress, we carried out two procedures to induce PDI gene expression in human neuroblastoma SK-N-MC cells, as well as intrahippocampal injection following electroporation of an expression vector capable of overexpressing PDI in rats. Overexpression of this gene resulted in attenuation of the loss of cell viability induced by hypoxia in neuroblastoma SK-N-MC cells and a reduction in the number of DNA-fragmented cells in the CA1 area of the hippocampus in brain ischemic rats, respectively. These findings suggest that up-regulated PDI may play a critical role in resistance to ischemic damage, and that the elevation of levels of this protein in the brain may have beneficial effects against brain stroke.

Amino Acid Sequence↗

PubMed2000

Neonatal lesions of the left entorhinal cortex affect dopamine metabolism in the rat brain.

The present study was performed to determine the effects of neonatal excitotoxic lesions of the left entorhinal cortex on dopamine (DA) metabolism and release in limbic regions of the rat brain. Quinolinic acid or phosphate buffered saline was infused into the left entorhinal cortex of rat pups on postnatal day 7 (PD7). Concentrations of DA,3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the lateral amygdala, nucleus accumbens, caudate-putamen, and medial prefrontal cortex were determined in the postmortem brains of lesioned and sham-operated rats on PD35 and PD56. On PD35, concentrations of DA in the bilateral lateral amygdala and HVA in the left lateral amygdala were significantly increased in lesioned rats compared with sham-operated animals, while no significant change was observed in the other three brain areas. On PD56, in addition to the increased concentration of DA in the left lateral amygdala, those of DA, DOPAC and HVA in the caudate-putamen, and DA in the nucleus accumbens were found to be increased, but DA concentrations in the right medial prefrontal cortex were decreased. The DOPAC/DA concentration ratio was, however, decreased in the amygdala and nucleus accumbens of the lesioned rats. In an in vivo microdialysis study, methamphetamine (MAP: 2 mg/kg, i.p.)-induced DA release in the amygdala of lesioned rats was significantly enhanced compared with sham-operated rats on both PD35 and PD56. There were no significant differences in MAP-induced DA release in the caudate-putamen between the sham-operated and lesioned rats at any time point. These findings provide evidence that neonatally induced structural abnormalities in the entorhinal cortex affect DA transmission in the limbic regions at the adolescent stage.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Isolation of Ich-1S (caspase-2S)-binding protein that partially inhibits caspase activity.

Members of the caspase family are essential executors of apoptosis. Caspase-2 has two messenger RNAs generated by alternative splicing, which encode caspase-2L and caspase-2S. Although caspase-2L induces apoptosis, caspase-2S also has the ability to antagonize cell death. Experiments in caspase-2-deficient mice showed that caspase-2 functions to delay cell death in some neuronal populations, suggesting that caspase-2S dominantly acts for cell survival in the brain. However, the mechanism of caspase-2S-mediated anti-apoptotic effect is still unclear. Here, we isolated a protein that interacts with caspase-2S, designated as Ich-1S (caspase-2S)-binding protein (ISBP), by yeast two-hybrid screening using full-length caspase-2S cDNA as a bait. ISBP is identical to the recently isolated calcium and integrin-binding protein, and a small molecule calcium-binding protein with two EF-hand motifs of its C-terminus. In vitro transcribed and translated ISBP interacts specifically with glutathione-S-transferase-fused caspase-2S. Moreover, the interaction between ISBP and caspase-2S was observed in cultured cells. Northern blot analysis indicated that ISBP may be a ubiquitous protein. Interestingly, ISBP can partially inhibit the processing of pro-caspase-2L induced by anti-Fas antibody-treated Jurkat cytosolic lysates. These results suggested that ISBP may be the mediator for the survival function of caspase-2S.

3T3 Cells↗

PubMed2000

Plasma homovanillic acid in the prodromal phase of schizophrenia.

BACKGROUND: Plasma levels of homovanillic acid (pHVA) have been used as a peripheral measure of central dopaminergic activity. Despite a large body of studies investigating pHVA in schizophrenia, little is known about pHVA in patients in the prodromal phase of the illness. METHODS: Plasma HVA levels of 12 male outpatients meeting DSM-III-R criteria for the prodromal phase of schizophrenia at the time of blood sampling (who later developed psychotic symptoms) were compared with those of 12 normal male healthy volunteers. Task amounts in the Kraepelin arithmetic test at the time of blood sampling were compared between the prodromal patients and normal controls and were correlated with pHVA levels. RESULTS: The prodromal patients had significantly higher pHVA levels compared with normal control subjects. The mean amount of the arithmetic task for the prodromal patients was significantly less than that for controls. In the patient group, a significant negative correlation was observed between pHVA levels and the task amounts. CONCLUSIONS: Data from the present study indicate the presence of dopaminergic dysfunction in the prodromal stage of schizophrenia that is associated with neuropsychological impairment. Increased pHVA levels in the prodromal patients may have implications for early detection of schizophrenia.

Acute Disease↗