PubMed Health⌕ Search

Biomedical subjects

A Ueda

Publications and source records attributed to A Ueda.

At least 73 records · Page 4Linked to original sources
PubMed1999

Administration of an IL-12-encoding DNA plasmid prevents the development of chronic graft-versus-host disease (GVHD).

The transfer of DBA/2 spleen cells into (C57BL/10 x DBA/2)F1 mice induces chronic graft-vs-host disease (GVHD), which is characterized by the production of Th2 cytokines, hypergammaglobulinemia, and immune complex-mediated glomerulonephritis like systemic lupus erythematosus. IL-12 strongly induces the production of Th1 cytokines and reduces Th2 activity in vivo. In this study, the effect of gene therapy on the development of murine chronic GVHD was examined using an IL-12-encoding plasmid (pCAGGSIL-12), with the expectation that it might regulate Th1/Th2 activity and have a beneficial impact on the clinical manifestations of disease. pCAGGSIL-12 or its p40 antagonist plasmid (pCAGGSp40) were injected i.m. every 3 wk in GVHD-induced (C57BL/10 x DBA/2)F1 mice. A total of 100 microg of pCAGGSIL-12 improved the Th1/Th2 balance in vivo, suppressed the production of IgG, and significantly reduced the development of glomerulonephritis. GVHD was exacerbated by injection of the pCAGGSp40 antagonist. Our results demonstrate that GVHD can be treated successfully by the administration of an IL-12-encoding plasmid, and that such therapy does not induce acute GVHD.

Animals↗
PubMed1999

Expression of inducible nitric oxide synthase and enzymes of arginine metabolism in Fusarium kyushuense-exposed mouse lung.

Expression of inducible nitric oxide (NO) synthase (iNOS) and related enzymes of arginine metabolism in the mouse lung exposed to filamentous fungus Fusarium kyushuense was studied by RNA blot, immunoblot, and histological analyses. When mice were exposed intranasally to the fungi only once, no induction of iNOS mRNA was observed. However, when the animals were infected again 6 days after the first exposure, iNOS mRNA was induced, reached a maximum 12-24 h after the exposure, and decreased to an undetectable level at 48 h. mRNAs for cationic amino acid transporter-2 (CAT2) and argininosuccinate synthetase were induced gradually, reached a maximum at 24 h, and decreased at 48 h. Arginase II mRNA increased at 24 h and decreased markedly at 48 h. On the other hand, arginase I mRNA started to increase at 24 h and reached to a much higher level at 48 h. Ornithine decarboxylase and ornithine aminotransferase mRNAs were also induced. Immunoblot analysis showed that iNOS, argininosuccinate synthetase, and arginase I and II proteins were induced with similar kinetics as those of their respective mRNAs. In histological examination, fungal elements were observed in the bronchoalveolar lumen at 3-6 h, decreased at 12 h, and almost disappeared at 48 h. Small granuloma appeared 3 h after the infection and their size increased with time. These results suggest that NO is produced in the mouse lung in response to F. kyushuense exposure and that the NO production is regulated by CAT2, the citrulline-NO cycle, and arginase isoforms. Enhanced synthesis of polyamines and proline (and thus collagen) is also suggested.

Amino Acid Transport Systems, Basic↗
PubMed1999

Up-regulation of ICH-1L protein by thromboxane A2 antagonists enhances cisplatin-induced apoptosis in non-small-cell lung-cancer cell lines.

We evaluated the effect of thromboxane A2 (TXA2) blockade on cisplatin-induced apoptosis in non-small-cell lung cancer (NSCLC) cell lines. Cisplatin induced apoptosis in PC/9 and PC-9/CDDP in a dose-dependent manner. Treatment with specific TXA2 antagonist, calcium 5(Z)-1R,2S,3S,4S-7-[3-phenylsulfonylaminobicyclo[2,2,1]hept-2-yl]- 5-heptonoate hydrate (S-1452) and 5(Z-6-[(1R,2R,3R,4S)-3-(N-4-bromobenzenesulfonyl aminomethyl) bicyclo[2,2,1]heptane-2-yl]-hex-5-enoic acid (ONO-NT-126), enhanced the cisplatin-induced apoptosis in each cell line. Acetyl-L-aspartyl-glutamyl-valyl-aspart-1-aldehyde (Ac-DEVD-CHO) inhibited cisplatin-induced apoptosis and enhancement of the apoptosis by TXA2 blockade, but acetyl-L-tyrosyl-valyl-alanyl-aspart-1-aldehyde (Ac-YVAD-CHO) had no effect on the apoptosis. There was no difference in the interleukin-1beta-converting enzyme (ICE) protease protein expression in either cell line. Cysteine protease p32(CPP32) protein expression was lower in PC-9/CDDP but was not changed by S-1452, cisplatin, or cotreatment with cisplatin and S-1452. Ice and Ced-3 homolog (ICH-1L) expression was significantly lower in PC-9/CDDP and was up-regulated by S-1452 or ONO-NT-126. These data suggest that ICH-1L might play a critical role in cisplatin-induced apoptosis and that TXA2 blockade up-regulates ICH-1L protein expression. Overexpression of ICH-1L and treatment with cisplatin might result in an increase in apoptosis in NSCLC cell lines.

Apoptosis↗
PubMed1999

Hypoxemia is a risk factor for bone mass loss.

Time-dependent changes of bone mass in ambulant chronic respiratory failure patients 60 or more years of age were compared between those on home oxygen therapy (HOT) and those still free of HOT (non-HOT). HOT (n = 31) showed initial PaO2 of slightly greater than 60 Torr and non-HOT (n = 32) had PaO2 moderately greater than 60 Torr (64.4 Torr vs 75.1 Torr). PaCO2 in HOT was significantly higher than that of non-HOT (44.8 Torr vs 40.0 Torr). There was no difference in pulmonary function test results. The whole bone mineral density (BMD) as adjusted by age and sex was significantly lower in the HOT group than that in the non-HOT. At endpoints of the follow-up period over 2 years or more, daily bone losses in the whole BMD, whole bone mineral content, and lumber BMD were significantly more accelerated in HOT compared with non-HOT. When the Wistar rats were pair-fed and their locomotion was limited, the animal group placed for 4 weeks under hypoxic air showed a reduction in BMD as compared with the control. We suggest that hypoxemia contributes to bone mass loss.

Aged↗
PubMed1999

Characterization of the ybdT gene product of Bacillus subtilis: novel fatty acid beta-hydroxylating cytochrome P450.

We have characterized the gene encoding fatty acid alpha-hydroxylase, a cytochrome P450 (P450) enzyme, from Sphingomonas paucimobilis. A database homology search indicated that the deduced amino acid sequence of this gene product was 44% identical to that of the ybdT gene product that is a 48 kDa protein of unknown function from Bacillus subtilis. In this study, we cloned the ybdT gene and characterized this gene product using a recombinant enzyme to clarify function of the ybdT gene product. The carbon monoxide difference spectrum of the recombinant enzyme showed the characteristic one of P450. In the presence of H2O2, the recombinant ybdT gene product hydroxylated myristic acid to produce beta-hydroxymyristic acid and alpha-hydroxymyristic acid which were determined by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry. The amount of these products increased with increasing reaction period and amount of H2O2 in the reaction mixture. The amount of beta-hydroxyl product was slightly higher than that of alpha-hydroxyl product at all times during the reaction. However, no reaction products were detected at any time or at any concentration of H2O2 when heat-inactivated enzyme was used. HPLC analysis with a chiral column showed that the beta-hydroxyl product was nearly enantiomerically pure R-form. These results suggest that this P450 enzyme is involved in a novel biosynthesis of beta-hydroxy fatty acid.

Amino Acid Sequence↗
PubMed1999

Vasodilating effect of benidipine hydrochloride in the renal and hindquarter vascular regions (supplied by terminal aorta) of spontaneously hypertensive rats.

One of two Ca antagonists, benidipine (3-30 microg/kg) or nifedipine (30-600 g/kg), was administered in a bolus injection through the jugular vein, and the changes in mean arterial pressure (MAP), renal flow (RF), and hindquarter flow (HQF) in conscious spontaneously hypertensive rats (SHRs) and normotensive control rats (NCRs). Renal vascular resistance (RR) and hindquarter resistance (HQR) were calculated as MAP divided by RF and HQF, respectively. When a high dose was administered to decrease the blood pressure by about 20%, the RR was significantly lower with benidipine than with nifedipine. The decrease in HQR was not significantly different between benidipine and nifedipine. When a low dose was administered to decrease the blood pressure by about 7%, the decrease in RR was not significantly different between benidipine and nifedipine, but the HQR was significantly lower with benidipine than with nifedipine. In the NCRs, no pharmacological properties were significantly different between these two Ca antagonists.

Animals↗
PubMed1999

c-Rel and p65 trans-activate the monocyte chemoattractant protein-1 gene in interleukin-1 stimulated mesangial cells.

BACKGROUND: The chemokine monocyte chemoattractant protein-1 (MCP-1) is secreted by human glomerular mesangial cells in response to interleukin-1 (IL-1) and has a central role in amplifying the inflammatory response during glomerulonephritis. However, the mechanism by which IL-1 regulates its transcription is not understood. Specific members of the nuclear factor kappaB/rel (NF-kappaB) proteins may regulate MCP-1 expression in a stimulus- and tissue-specific manner. METHODS: Electrophoretic mobility shift assays and Western blot analysis characterized the members of the NF-kappaB family that bound the two NF-kappaB sites of the MCP-1 enhancer (A1 and A2) in vitro. Trans-activation of the MCP-1 gene was investigated by transfer of the MCP-1 enhancer DNA to mesangial cells. RESULTS: Primary human mesangial cells contained in addition to p50 (NF-kappaB1) and p65 (Rel A) NF-kappaB proteins, the oncoprotein c-rel, and Rel B, but not p52 (NF-kappaB2). IL-1 induced c-rel to form a complex with p65, which bound the MCP-1 A2 site but not the A1 or IL-6 NF-kappaB sites in vitro. IL-1 up-regulated transfected MCP-1 enhancer activity. Cotransfer of the MCP-1 enhancer together with individual members of the NF-kappaB family showed that the heterodimer c-relp65 or (p65)2 can selectively trans-activate the MCP-1 gene via its A1 and A2 sites in mesangial cells. CONCLUSIONS: This study demonstrates for the first time that the c-rel oncoprotein can enhance MCP-1 transcription in mesangial cells and suggests that it may have an important role in amplifying gene expression in the inflamed glomerulus.

Animals↗
PubMed1999

Imaging of hydroperoxides in a rat glomerulus stimulated by puromycin aminonucleoside.

BACKGROUND: To determine the locus of the increased oxidation induced by puromycin aminonucleoside (PAN), we imaged hydroperoxides in glomeruli stimulated by PAN in vivo and in vitro. METHODS: Dichlorofluorescein diacetate (DCFH-DA) in cells makes dichlorofluorescein, a substance that fluoresces when reacted with hydroperoxides. Fluorescence was detected using a photon detection video camera connected to a microscope. Two kinds of isolated glomeruli of Wistar rats were examined. One was the glomerulus obtained from rats on the seventh day following the injection of PAN. In this case, glomeruli were incubated in a buffer containing 5 mM DCFH-DA. Another was the glomerulus collected at 30 minutes after a large amount of DCFH-DA was intravenously injected. These glomeruli were incubated with either PAN or phorbol myristate acetate (PMA) in Krebs-Henseleite bicarbonate buffer. RESULTS: The images from the glomeruli treated by PAN in vivo resemble pictures of a galaxy by telescope. When the glomeruli were treated by PAN in vitro, two localized points appeared in each glomerulus after 15 minutes of incubation with PAN, and after 75 minutes of incubation, the fluorescence spread throughout the glomerulus. When glomeruli were incubated with PMA, two points that gave a very strong fluorescence were observed in each glomerulus, but they did not spread throughout the glomeruli. In both experiments, glomeruli without stimulants did not fluoresce. CONCLUSION: Increases in hydroperoxides were observed in the glomeruli from rats made nephrotic by exposure to PAN, and were also observed in glomeruli following 15 minutes of incubation with PAN in vitro.

Animals↗
PubMed1999

[Successful treatment of primary CNS lymphoma diagnosed by 201thallium-single photon emission computed tomography (201Tl-SPECT) with whole-brain radiation therapy in an AIDS patient].

The patient, a 51-year-old male with a two year history of AIDS, was admitted to our hospital because of hemiparalysis and vomiting. The MRI study showed multiple lesions with ring-enhancement in the right basal brain area. Empirical therapy for toxoplasma encephalitis was started. After 64 days, the subsequent brain MRI showed deterioration. A 201Tl-SPECT study was performed and the findings were consistent with those of malignant lymphoma (ML). The patient was treated with 40 Gy of whole brain radiation, MRI showed partial response to this therapy, and clinical improvement was achieved. The definitive diagnosis of primary CNS lymphoma can be made only by brain biopsy, and many cases have been diagnosed at autopsy. The clinical and radiological findings of primary CNS lymphoma resemble toxoplasma encephalitis. An empirical therapy for toxoplasma encephalitis is recommended to avoid brain biopsy in these cases. The use of 201Tl-SPECT for the differential diagnosis of these diseases have been reported. Considering the poor prognosis of primary CNS lymphoma in AIDS, the application of 201Tl-SPECT before empirical therapy for toxoplasma must be important for appropriate treatment.

Brain Neoplasms↗
PubMed1999

Novel dolichyl derivatives in rat spleen.

Novel dolichyl derivatives were found in rat spleen. The compounds were eluted from reverse phase HPLC after eluting dolichyl fatty acid ester. The elution profiles of the unsaponified forms of the unknown compounds were coincident with that of dolichol from spleen on reverse phase HPLC. The compounds were not dolichyl dolichoate, which are present in bovine thyroid. The compounds were not found in young rats (4 months of age) but were found in old rats (above 12 months of age), and they were not detected in other tissues under our conditions.

Age Factors↗
PubMed1999

Immunological alterations in patients with primary tumors in central nervous system.

Natural killer (NK) cells play an important role in immune surveillance against tumors. The present work aimed to study the cytotoxic activity of NK cells and T cell subsets in peripheral blood of 13 patients with primary tumors in central nervous system (CNS). As controls 29 healthy subjects with the age range equivalent to the patients were studied. The methods employed were: a) determination of cytotoxic activity of NK cells towards K562 target cells, evaluated by single cell-assay; b) enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets defined by monoclonal antibodies; c) the identification of tumors were done by histologic and immunochemistry studies. The results indicated that adults and children with tumor in CNS display reduced percentage of total T cells, helper/inducer subset and low helper/suppressor ratio. The cytotoxic activity of NK cells was decreased in patients with CNS tumors due mainly to a decrease in the proportion of target-binding lymphocytes. These results suggest that cytotoxic activity of NK cells may be affected by the immunoregulatory disturbances observed in patients with primary tumors in CNS.

Adolescent↗
PubMed1999

[Chlamydia-induced reactive arthritis--HLA-B 27 negative two patients].

Two cases with HLA-B 27 negative, Chlamydia-induced reactive arthritis (ReA) were described. Case 1: A 30 y.o. male developed balanitis, urethritis, arthritis of both knees, elbows, shoulders and hip joints on May in 1997. Laboratory findings revealed CRP 2.7 mg/dl (normal range < 0.3), ESR 33 mm/h and negative rheumatoid factor (RF) test. Anti-Chlamydia trachomatis antibodies, IgG 2.22, IgA 3.33 were positive. HLA-typing revealed A 2, A 24 (9), B 39 (16), B 52 (5). He was diagnosed as ReA and arthritis subsided with treatment of minocycline and nonsteroidal antiinflammatory drugs (NSAIDs). Case 2: A 40 y.o. Iranian American male developed balanitis, urethritis, lumbago, arthritis of both elbows, knees and foot joints, iridocyclitis on August in 1995. Chlamydia trachomatis was detected in the urethral swab culture. He was diagnosed as ReA and treated with minocycline and NSAIDs. He was referred to our hospital on June in 1996. Arthritis at both knees and feet was detected. Laboratory findings revealed CRP 0.8 mg/dl, negative RF test was revealed. Antibodies to Chlamydia were positive (IgG 1.49, IgA 1.53) positive. HLA typing revealed A 1, A 2, B 37, B 55 (22). He was again treated with minocycline and NSAIDs and ReA ameliorated. Since HLA-B 22, B 37 and B 39 have been reported to cross-react or to have homology with B 27, B 22, B 37 and B 39 are likely to related to inducing ReA.

Adult↗
PubMed1998

Positive regulation of the human macrophage stimulating protein gene transcription. Identification of a new hepatocyte nuclear factor-4 (HNF-4) binding element and evidence that indicates direct association between NF-Y and HNF-4.

We previously reported that the transcription of the human macrophage stimulating protein (MSP) gene was positively regulated by the binding of NF-Y to the CAATT sequence in the promoter region of this gene. Here we confirmed our previous results and further characterized the MSP promoter. Luciferase assay with deletion constructs showed the importance of the region, +32 to +39, for the promoter activity in Hep3B cells. Two nuclear protein-DNA probe (+15 to +40) complexes, C1 and C2, were detected by electrophoretic mobility shift assay. C2 was specific to hepatoma cells and contained hepatocyte nuclear factor-4 (HNF-4). DNase I footprinting with recombinant HNF-4 located another HNF-4-binding site in the distal region, -89 to -54. Mutations in the CAATT or the proximal HNF-4-binding site significantly reduced the promoter activity in Hep3B cells and HNF-4-transfected HeLa cells, whereas mutations in the distal HNF-4-binding site had no effect. The close proximity between the CAATT and the proximal HNF-4-binding site suggested that a direct contact between NF-Y and HNF-4 might be important. Protein-protein interaction between the A-subunit of NF-Y and HNF-4 was detected by a yeast two-hybrid system. The binding of in vitro translated HNF-4 to immobilized NF-YA and in vitro translated NF-YA to immobilized HNF-4 was also detected. These results suggest the binding of HNF-4 to the proximal HNF-4-binding site directs the basal transcription of the MSP gene, and the maximal promoter activity may depend on the direct association between HNF-4 and NF-Y.

Base Sequence↗
PubMed1998

Reconstruction for the brilliance-upgrading project of the Photon Factory storage ring.

Reconstruction of the Photon Factory storage ring (PF ring; 2.5 GeV) is now in progress to provide very brilliant synchrotron radiation to users, i.e. the emittance is being reduced by a factor of five. Components, such as the quadrupole and sextupole magnets, vacuum chambers, beamlines and beam-position monitors, are being replaced by new ones in 16 normal-cell sections of the PF ring. The accelerating cavities, injection systems and control systems are also being replaced. Operation will commence when the improvements are completed on 1 October 1997.

Journal Article↗
PubMed1998

Single-pass BPM system of the Photon Factory storage ring.

At the 2.5 GeV ring of the Photon Factory, a single-pass beam-position monitor (BPM) system is being prepared for the storage ring and the beam transport line. In the storage ring, the injected beam position during the first several turns can be measured with a single injection pulse. The BPM system has an adequate performance, useful for the commissioning of the new low-emittance lattice. Several stripline BPMs are being installed in the beam transport line. The continuous monitoring of the orbit in the beam transport line will be useful for the stabilization of the injection energy as well as the injection beam orbit.

Journal Article↗
PubMed1998

Distinct requirements for evoked and spontaneous release of neurotransmitter are revealed by mutations in the Drosophila gene neuronal-synaptobrevin.

Two modes of vesicular release of transmitter occur at a synapse: spontaneous release in the absence of a stimulus and evoked release that is triggered by Ca2+ influx. These modes often have been presumed to represent the same exocytotic apparatus functioning at different rates in different Ca2+ concentrations. To investigate the mechanism of transmitter release, we have examined the role of synaptobrevin/VAMP, a protein involved in vesicular docking and/or fusion. We generated a series of mutations, including null mutations, in neuronal-synaptobrevin (n-syb), the neuronally expressed synaptobrevin gene in Drosophila. Mutant embryos completely lacking n-syb form morphologically normal neuromuscular junctions. Electrophysiological recordings from the neuromuscular junction of these mutants reveal that the excitatory synaptic current evoked by stimulation of the motor neuron is abolished entirely. However, spontaneous release of quanta from these terminals persists, although its rate is reduced by 75%. Thus, at least a portion of the spontaneous "minis" that are seen at the synapse can be generated by a protein complex that is distinct from that required for an evoked synaptic response.

Animals↗
PubMed1998

The effect of HLA alleles on response to interferon therapy in patients with chronic hepatitis C.

OBJECTIVE: To compare HLA alleles in the patients with chronic hepatitis C treated with interferon-alpha (IFN-alpha) between patients with response to IFN treatment and nonresponse. METHOD: Sixty-seven Japanese patients with chronic hepatitis C were treated with daily intramuscular administration of IFN-alpha (6 million units) for 2 weeks followed by three times per week for 22 weeks. Viral loads of hepatitis virus C (HCV), HCV genotypes and HLA antigens were determined just before IFN-alpha treatment. Responders to IFN-alpha were defined as normalization of alanine aminotransferase at the end of treatment and during a follow-up period at least longer than 6 months. The patients who could not reach the above response criteria were defined as nonresponders. RESULTS: There were 20 responders and 47 nonresponders to IFN treatment. The low viral load with less than 1 x 10(6) copy/ml (P< 0.05), and type 2a genotype (P< 0.05) were significantly increased in responders. Other clinical and biochemical parameters were not significant. There was no difference in HLA-A and C antigens between responders and nonresponders. In contrast, HLA-B54,DR4 and A24-B54-DR4 haplotype of nonresponders increased compared with responders or controls (Pc < 0.0001, Pc < 0.001, Pc < 0.0001, respectively). At multivariate analysis, viral loads, HLA-B54 and HLA-A24-B54-DR4 haplotype were significant (P=0.0002, P=0.0258, P=0.0378, respectively). CONCLUSION: The low viral load is a good predictor. HLA-B54 and HLA-A24-B54-DR4 haplotype should be predictors for poor response to IFN therapy in patients with chronic hepatitis C.

Alanine Transaminase↗