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Biomedical subjects

S Ueno

Publications and source records attributed to S Ueno.

At least 109 records · Page 6Linked to original sources
PubMed1999

The alkaline single cell gel electrophoresis assay with mouse multiple organs: results with 30 aromatic amines evaluated by the IARC and U.S. NTP.

The genotoxicity of 30 aromatic amines selected from IARC (International Agency for Research on Cancer) groups 1, 2A, 2B and 3 and from the U.S. NTP (National Toxicology Program) carcinogenicity database were evaluated using the alkaline single cell gel electrophoresis (SCG) (Comet) assay in mouse organs. We treated groups of four mice once orally at the maximum tolerated dose (MTD) and sampled stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow 3, 8 and 24 h after treatment. For the 20 aromatic amines that are rodent carcinogens, the assay was positive in at least one organ, suggesting a high predictive ability for the assay. For most of the SCG-positive aromatic amines, the organs exhibiting increased levels of DNA damage were not necessarily the target organs for carcinogenicity. It was rare, in contrast, for the target organs not to show DNA damage. Organ-specific genotoxicity, therefore, is necessary but not sufficient for the prediction of organ-specific carcinogenicity. For the 10 non-carcinogenic aromatic amines (eight were Ames test-positive and two were Ames test-negative), the assay was negative in all organs studied. In the safety evaluation of chemicals, it is important to demonstrate that Ames test-positive agents are not genotoxic in vivo. Chemical carcinogens can be classified as genotoxic (Ames test-positive) and putative non-genotoxic (Ames test-negative) carcinogens. The alkaline SCG assay, which detects DNA lesions, is not suitable for identifying non-genotoxic carcinogens. The present SCG study revealed a high positive response ratio for rodent genotoxic carcinogens and a high negative response ratio for rodent genotoxic non-carcinogens. These results suggest that the alkaline SCG assay can be usefully used to evaluate the in vivo genotoxicity of chemicals in multiple organs, providing for a good assessment of potential carcinogenicity.

Amines↗
PubMed1999

A novel missense mutant inactivates GTP cyclohydrolase I in dopa-responsive dystonia.

Dopa-responsive dystonia (DRD) due to mutant GTP cyclohydrolase I (GCH) shows the considerable heterogeneity of clinical phenotypic expression. To explain the clinical diversity, we studied a Japanese family with a novel mutant GCH (GCH-G90V), where an affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote. Coexpression experiments using the mutant with wild-type GCH showed that GCH-G90V inactivated the normal enzyme in a dose-dependent manner, suggesting that the dominant negative effect of a mutant GCH on the normal enzyme might be one of the molecular mechanisms for the clinical heterogeneity of DRD.

Adult↗
PubMed1999

Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive hyperphenylalaninemia.

Guanosine 5'-triphosphate cyclohydrolase I (GCH) mutants (H144P and T186K) associated with dominant dopa-responsive dystonia were enzymatically inactive and inhibited the normal enzyme, suggesting that GCH activity in a heterozygote was <50% of control. The M211I mutant associated with recessive hyperphenylalaninemia was slightly active and had no inhibitory effects, so GCH activity in a heterozygote would be <50% of normal; therefore hyperphenylalaninemia would be evident only in homozygotes.

Animals↗
PubMed1999

Treatment for accidental occlusion of the hepatic artery after hepatic resection: report of two cases.

Two patients in whom accidental hepatic artery occlusion (HAO) occurred after hepatic resection (Hx) were reported. A 59-year-old female who underwent Hx for hepatocellular carcinoma with underlying liver cirrhosis developed HAO on postoperative day (POD) 14 and died of hepatic failure on POD 23. The autopsy findings showed multiple necrosis in the remnant liver and an extraluminal hematoma of the hepatic artery, suggesting an injury caused by Pringle's maneuver. The second case was a 53-year-old male who underwent Hx for cholangiocarcinoma without any underlying liver disease. He developed HAO on POD 6, and radiological studies indicated a pseudoaneurysma formation and severe stenosis of the hepatic artery. It was speculated that the cause of the HAO was intraluminal injury of the hepatic artery during an angiographic study conducted prior to Hx. Partial arterialization of the portal vein was performed, following which his liver function test results improved. In both cases, measuring the serum hepatocyte growth factor level and the hepatic vein oxygen saturation proved useful, not only for determining the degree of liver injury, but also for predicting the outcome after treatments for HAO. Furthermore, the partial arterialization of the portal vein for HAO after Hx may rescue the normal remnant liver.

Aneurysm, False↗
PubMed1999

Syringobulbia caused by delayed postoperative tethering of the cervical spinal cord - delayed complication of foramen magnum decompression for Chiari malformation.

Postoperative tethering of the high cervical spinal cord is a rare cause of neurological deterioration after foramen magnum decompression (FMD) with duraplasty for Chiari type I malformation. A review of the literature revealed that only 5 cases have been reported. This entity is not widely known to occur as a complication of the common surgical procedure for Chiari type I malformation. A 17-year-old boy experienced rapidly progressive neurological deterioration over a 3-month period. FMD and duraplasty with lyophilized cadaver dura had been performed 8 years previously. Follow-up MR images showed that the cerebrospinal fluid (CSF) space dorsal to the cord was gradually disappearing and that syringobulbia had developed. Opening the dura mater of the posterior fossa revealed dense fibrous scarring, arachnoid thickening over the cervicomedullary area, and tethering the cord to the dura from the medulla to C2. The adhesions were dissected free, and the tethering was released. A syringosubarachnoid (SS) shunt was inserted and duraplasty was performed with an expended polytetrafluoroethylene sheet (Gore-Tex). Postoperative MR images demonstrated that the syringobulbia had completely collapsed and that a dorsal CSF space was present. Follow-up MR images provided significant information on the cervical spinal cord tethering after FMD with duraplasty for Chiari malformation. We encourage sharp surgical detethering and duraplasty with Gore-Tex to avoid retethering. Early recognition and treatment of this unusual but important complication are emphasized.

Adolescent↗
PubMed1999

Molecular interactions and kinetic properties of fats.

This article has reviewed the recent work on the molecular interactions and kinetic properties of the polymorphic transformations of the TAGs in the single and mixed states. Progress has recently been made in the molecular-level understanding of the polymorphic transformations of the TAGs. Particularly, the use of the time-resolved X-ray diffraction with Synchrotron radiation (SR-XRD) has provided precise information of the structural changes of the fat crystals at a time scale of 10 sec. Therefore, fruitful information was obtained on the kinetic and molecular aspects of crystallization and mixing processes of the various types of mixed-acid TAGs, which were not obtained with the traditional thermal and structural techniques because of their complicated structural properties. One may anticipate that, although the experimental sites and machine times are limited, the SR-XRD techniques will be more applied to the fat systems involving the following materials and systems; (a) multicomponent natural fats with and without additives of emulsifiers, proteins and carbohydrates, (b) fats in dispersed phases such as oil-in-water (O/W) and water-in-oil (W/O) emulsions, (c) crystallization and transformation processes under external influences of hydrostatic pressure and shear stress [68].

Fats↗
PubMed1999

Oral administration of hot water extracts of Chlorella vulgaris reduces IgE production against milk casein in mice.

Hot water extract of Chlorella vulgaris (CVE) is a biological response modifier (BRM) which enhances resistance to Listeria monocytogenes through augmentation of helper T cell type 1 (Thl) responses producing gamma-interferon (gammaIFN). We show here that oral administration of CVE in mice suppressed the production of immunoglobulin (Ig)E against casein antigen accompanied by increased gammaIFN and IL-12 mRNA expression. Oral administration of CVE enhanced Thl response to casein in the spleen of casein immunized mice. CVE may be useful for prevention of allergic diseases with a predominant Th2 response.

Administration, Oral↗
PubMed1999

Antibiotic-induced endotoxemia in a patient with endogenous endophthalmitis.

PURPOSE: The aim of the study is to describe a case of suspected endotoxin-induced uveitis associated with septic endogenous endophthalmitis followed by antibiotic-induced endotoxemia. METHODS: The human leukocyte antigen (HLA) typing of peripheral leukocytes was studied by lymphocytotoxicity technique. Histological and immunohistochemical studies of paraffin embedded specimen were conducted. RESULTS: Findings of HLA typing revealed positive reaction for B 51, Cw 3, DR 8, DR 11, DQ 3. The vitreous body of an eviscerated eye was occupied by the non-specific granulomatous tissue, composed of fibroblast, plasma cells, and Sudan black staining positive foamy cells, including melaniferous phagocytes, identified as CD 68 positive macrophage. CONCLUSION: It is suggested that antibiotic-induced endotoxemia of a patient with septic endogenous endophthalmitis produced endotoxin-induced uveitis under an upregulation of HLA and endotoxin activated macrophages may release cytokines, followed by fibrin formation and subsequent granuloma.

Aged↗
PubMed1999

Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons.

1. The aim of our study is to clarify the relationship between expression pattern of P2X receptors and the cell type of male adult rat (Wistar) dorsal root ganglion (DRG) neurons. We identified the nociceptive cells of acutely dissociated DRG neurons from adult rats type using capsaicin sensitivity. 2. Two types of ATP-activated currents, one with fast, the other with slow desensitization, were found under voltage-clamp conditions. In addition, cells with fast but not slow desensitization responded to capsaicin, indicating that there was a relationship between current kinetics and capsaicin-sensitivity. 3. Both types of neurons were responsive to ATP and alpha, beta methylene-ATP (alpha,betameATP). The concentration of alpha,(beta)meATP producing half-maximal activation (EC50) of neurons with fast desensitization was less (11 microM) than that of neurons with slow desensitization (63 microM), while the Hill coefficients were similar. Suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS) antagonized alpha,betameATP-induced currents in both types of neurons. 4. In situ hybridization revealed that small cells of the DRG predominantly expressed mRNAs of P2X3 and medium-sized cells expressed mRNAs of P2X2 and P2X3. In contrast, both of mRNAs were not detected in large cells of the DRG. 5. These results suggest that capsaicin-sensitive, small-sized DRG neurons expressed mainly the homomeric P2X3 subunit and that capsaicin-insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor with P2X2 and P2X3.

Adenosine Triphosphate↗
PubMed1999

Subunit mutations affect ethanol actions on GABA(A) receptors expressed in Xenopus oocytes.

1. Mutations of specific amino acids were introduced in transmembrane domains (TM) of GABA(A) receptor alpha2, beta1 and gamma2L subunits. The effects of these mutations on the action of ethanol were studied using the Xenopus oocyte expression system and two-electrode voltage-clamp recording techniques. 2. Mutant alpha2 subunits containing S270I (TM2) or A291W (TM3) made the receptor more sensitive to GABA, as compared to wild-type alpha2beta1gamma2L receptor. The mutation S265I (TM2) of beta1 and S280I (TM2) or S30IW (TM3) in gamma2L subunits did not alter apparent affinity of the receptor for GABA. M286W (TM3) in the beta1 subunit resulted in a receptor that was tonically open. 3. Using an EC5 concentration of GABA, the function of the wild-type receptor with alpha2beta1gamma2L subunits was potentiated by ethanol (50-200 mM). The mutations in TM2 or TM3 of the alpha2 subunit diminished the potentiation by ethanol. The action of ethanol was also eliminated with a mutation in the TM2 site of the beta1 subunit. Ethanol produced significant inhibition of GABA responses in receptors containing the combination of alpha2 and beta1 TM2 mutants with a wild-type gamma2L subunit. A small but significant reduction in the potentiation by ethanol was observed with gamma2L TM2 and/or TM3 mutants. 4. From these results, we suggest that in heteromeric GABA(A) receptors composed of the alpha, beta and gamma subunits, ethanol may bind in a cavity formed by TM2 and TM3, and that binding to the alpha or beta subunit may be more critical than the gamma subunit.

Amino Acid Sequence↗
PubMed1999

In vivo pathway of thermal hyperalgesia by intrathecal administration of alpha,beta-methylene ATP in mouse spinal cord: involvement of the glutamate-NMDA receptor system.

1. The aim of the present study is to characterize the role of the P2X receptor in spinal nociceptive processing in vivo. We investigated the mechanisms of the P2X receptor agonist alpha,beta-methylene ATP (alpha,betameATP)-induced modulation of acute nociceptive signalling in mouse spinal cord. 2. Intrathecal administration of alpha,betameATP produced a significant and dose-dependent thermal hyperalgesic response. This response was completely blocked by intrathecal pretreatment with the non-selective P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonate (PPADS) and the selective P2X1, P2X3 and P2X2-3 receptor antagonist, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP). Pretreatment with alpha,betameATP 15, 30 and 60 min prior to administration of a second dose of alpha,betameATP diminished the alpha,betameATP-induced thermal hyperalgesia. 3. A potent agonist for the P2X1 receptor, beta,gamma-methylene-L-ATP, did not show the hyperalgesic response, indicating that the P2X1 receptor is not involved in the spinal nociceptive pathway. 4. In fura-2 experiments using mouse dorsal root ganglion (DRG) neurons, alpha,betameATP (100 microM) increased intracellular Ca2+ ([Ca2+]i). This was not produced by a second application of alpha,betameATP. The same DRG neurons also showed a marked [Ca2+]i increase in response to capsaicin (3 microM). 5. Intrathecal pretreatment with the Ca2+-dependent exocytosis inhibitor, botulinum neurotoxin B, abolished the thermal hyperalgesia by alpha,betameATP. Furthermore, thermal hyperalgesia was significantly inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonists, 2-amino-5-phosphonopentanoate (APV), dizocilpine and ifenprodil. 6. These findings suggest that alpha,betameATP-induced thermal hyperalgesia may be mediated by the spinal P2X3 receptor subtype that causes unresponsiveness by repetitive agonist applications, and that alpha,betameATP (perhaps through P2X3 receptors) may evoke spinal glutamate release which, in turn, leads to the generation of thermal hyperalgesia via activation of NMDA receptors.

Adenosine Triphosphate↗
PubMed1999

Evidence for the involvement of spinal endogenous ATP and P2X receptors in nociceptive responses caused by formalin and capsaicin in mice.

1. The aim of the present study is to characterize the role of spinal endogenous ATP and P2X receptors in the generation of neurogenic and inflammatory pain. We examined the effects of intrathecal treatment with P2X receptor antagonists on the formalin- and capsaicin-induced nociceptive behaviours in mice. 2. Intrathecal pretreatment with the general P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS), significantly suppressed both the first and second phases of the formalin-induced nociceptive behaviour. The second phase of the nociceptive response was also suppressed by intrathecal treatment with PPADS after the first phase. Furthermore, pretreatment with the selective antagonist for the P2X1, P2X3 and P2X2+3 receptors, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP), significantly reduced the first phase, but not the second phase. The second phase was also not suppressed by intrathecal TNP-ATP after the first phase. 3. Capsaicin-induced nociceptive behaviour that has been shown to be a model for neurogenic pain, was also significantly suppressed by intrathecal pretreatment with PPADS or TNP-ATP. 4. Nociceptive behaviour in the first phase of the formalin test and in the capsaicin test were significantly inhibited by intrathecal pretreatment with alpha, beta-methylene ATP (alpha,betameATP: 5 microg mouse-1) 15 min prior to injection of formalin or capsaicin. This treatment has been previously shown to desensitize spinal P2X3 receptor subtypes in vivo. 5. These findings suggest that spinal endogenous ATP may play a role in (1) the formalin- and capsaicin-induced neurogenic pain via the PPADS- and TNP-ATP-sensitive P2X receptors which are also desensitized by alpha,betameATP (perhaps the P2X3 receptor subtype) and (2) formalin-induced inflammatory pain via PPADS-sensitive, TNP-ATP- and alpha,betameATP-insensitive P2X (and/or P2Y) receptors.

Adenosine Triphosphate↗
PubMed1999

Polymorphisms of the human homologue of the Drosophila white gene are associated with mood and panic disorders.

The Drosophila white gene is a member of the ATP-binding cassette (ABC) transporter superfamily and is involved in the cellular uptake of tryptophan. Its human homologue gene (hW) has been mapped to chromosome 21q22.3. Tryptophan is the precursor for the neurotransmitter serotonin, which has been implicated in the regulation of mood and anxiety. The locus 21q22.3 has also been reported to be associated with mood disorders. The 3'-untranslated region (3'-UTR) in the hW gene has been shown to contain a polymorphic poly(T) region. We have identified a new polymorphism G2457A in the 3'-UTR in the present study. We examined the relationship between these polymorphisms and mood and panic disorders, and a significant association between the poly(T) polymorphisms and mood disorders was detected (P=0.039 (allele frequency)). Associations were found between the polymorphisms and mood (poly(T) polymorphism: P=0.047 (allele frequency), G2457A: P=0.040 (allele frequency), P=0.044 (genotype frequency)) and panic disorders (G2457A: P=0.026 (allele frequency), P=0.011 (genotype frequency)) in males, but not in females. These findings suggest that the hW gene may be an important gene in the control of mood and anxiety as well as one of the genetic factors related to mood disorders and panic disorder in males. The statistical significance of the association remains relatively low and larger materials facilitating further dissection of the clinical phenotype will be needed to confirm and independently validate this finding and to evaluate its significance.

3' Untranslated Regions↗
PubMed1999

Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism.

Human dopamine transporter gene (DAT1) has a variable number of tandem repeats (VNTR) in its 3'-untranslated region (UTR). The association between the VNTR polymorphism and neuropsychiatric disorders has been studied, but their relationship is still unclear. Here we identified a novel polymorphism in the 3'-UTR of the DAT1 gene, G2319A, and a significant association between the polymorphism and alcoholism was observed in both genotypic and allelic frequencies (P = 0.040 and 0.019, extended Fisher's exact test, respectively). There was a significant gene dose effect on the risk for alcoholism associated with the 2319-A allele (chi2 = 6.16, df = 2, P = 0.046, linearity tendency test: Cochranq-Armitage analysis). Moreover, in the haplotype analysis with G2319A- and VNTR-polymorphisms, a positive gene dose efffect on the risk with the A10 allele (P = 0.044, linearity tendency test) and a negative gene dose effect with the G10 allele (P = 0.010, linearity tendency test) for alcoholism were significantly detected. Odds ratio for alcoholism with the A10 and G10 alleles were 1.76 (1.12-2.76) and 0.53 (0.32-0.79), respectively. These results indicate that the DAT1 gene may confer vulnerability to alcoholism.

3' Untranslated Regions↗
PubMed1999

Localization of a gene for benign adult familial myoclonic epilepsy to chromosome 8q23.3-q24.1.

Benign adult familial myoclonic epilepsy is an autosomal dominant idiopathic epileptic syndrome characterized by adult-onset tremulous finger movement, myoclonus, epileptic seizures, and nonprogressive course. It was recently recognized in Japanese families. In this study, we report that the gene locus is assigned to the distal long arm of chromosome 8, by linkage analysis in a large Japanese kindred with a maximum two-point LOD score of 4.31 for D8S555 at recombination fraction of 0 (maximum multipoint LOD score of 5.42 for the interval between D8S555 and D8S1779). Analyses of recombinations place the locus within an 8-cM interval, between D8S1784 and D8S1694, in which three markers, D8S1830, D8S555, and D8S1779, show no recombination with the phenotypes. Although three other epilepsy-related loci on chromosome 8q have been recognized-one on chromosome 8q13-21 (familial febrile convulsion) and two others on chromosome 8q24 (KCNQ3 and childhood absence epilepsy)-the locus assigned here is distinct from these three epilepsy-related loci. This study establishes the presence of a new epilepsy-related locus on 8q23.3-q24.11.

Adolescent↗
PubMed1999

Actions of fluorinated alkanols on GABA(A) receptors: relevance to theories of narcosis.

UNLABELLED: Previous work demonstrates that various anesthetics enhance the effect of gamma-aminobutyric acid (GABA), and this enhancement has been proposed as an explanation for how anesthetics cause anesthesia. This explanation extends to both fluorinated and unfluorinated alkanols. In the present study, we tested the capacity of fluorinated alkanols to enhance the function of the GABA(A) receptors expressed in Xenopus oocytes. CF3CH2OH, CF3(CF2)2CH2OH and CF3(CF2)4CH2OH potentiated GABA(A) receptor function, but CF3(CF2)5CH2OH did not. The degree of potentiation decreased in proportion to the chain length of the alkanols. These findings were not specific for receptors expressed in oocytes, as similar results were obtained with muscimol-stimulated 36Cl- uptake using mouse brain membrane vesicles. Although CF3(CF2)5CH2OH has been reported to enhance the capacity of desflurane to produce immobility in vivo, in our in vitro studies, this compound reduced potentiation of GABA-gated response by anesthetics such as isoflurane, enflurane, and pentobarbital. CHF2(CF2)5CH2OH, which has in vivo anesthetic effects, also failed to potentiate GABA(A) receptor function. These results indicate that the GABA(A) receptor is not the only receptor affected by fluorinated alkanols and that other receptors contribute to the capacity of alkanols to produce immobility. In particular, CF3(CF2)5CH2OH and CF3CH2OH inhibited N-methyl-D-aspartate receptor-mediated responses, which raises the possibility that this receptor is important for actions of fluorinated alkanols. IMPLICATIONS: We find a consistent parallel between the immobilization produced by fluorinated alkanols and their actions on N-methyl-D-aspartate receptors but do not find a consistent parallel between immobilization and effects on gamma-aminobutyric acid type A receptors. Thus, we suggest that N-methyl-D-aspartate, but not gamma-aminobutyric acid type A, receptors may mediate the capacity of anesthetics to produce immobilization.

Alcohols↗