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  • 1
    Electronic Resource
    Electronic Resource
    Midkine, a new neurotrophic factor, is present in glial cytoplasmic inclusions of multiple system atrophy brains (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 481-489 
    Details
    ISSN: 1432-0533
    Keywords: Key words Glial cytoplasmic inclusion ; Granule-coated fibril ; Midkine ; Multiple system ; atrophy ; Oligodendrocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The glial cytoplasmic inclusion (GCI) is a histological hallmark for multiple system atrophy (MSA): these inclusions are found in oligodendrocytes and consist of abnormal granule-coated fibrils of approximately 24- to 40-nm diameter. To clarify the significance of the presence of midkine (MK) in these GCIs, we carried out immunohistochemical, electron and immunoelectron microscopical, and Western blot analyses of MSA brains using a monoclonal antibody against the C-terminal region of human MK. Immunohistochemically, most of the GCIs were intensely stained by the antibody to MK. Electron and immunoelectron microscopy showed that the GCIs were composed of MK-positive granule-coated fibrils that were essential constituents of these inclusions. No significant MK immunoreactivity was observed in oligodendrocytes, astrocytes and neurons of the normal control subjects. The presence of MK in MSA brain but not in normal brain was confirmed by Western blotting. Together with the fact that MK is associated with fetal morphogenesis during the midgestation period, the presence of MK immunoreactivity in oligodendroglial GCIs may suggest the existence of a repair mechanism on the basis of morphogenesis in the degenerated oligodendrocytes themselves as well as the affected neurons and their axons through the oligodendrocyte-axon-neuron relationship.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000214
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  • 2
    Electronic Resource
    Electronic Resource
    Advanced glycation endproduct-modified superoxide dismutase-1 (SOD1)-positive inclusions are common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutations and transgenic mice expressing human SOD1 with a G85R mutation (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 490-505 
    Details
    ISSN: 1432-0533
    Keywords: Key words Advanced glycation endproducts ; Familial amyotrophic lateral sclerosis ; G85R transgenic mice ; Granule-coated fibrils ; Superoxide dismutase-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To clarify the biological significance of the neuronal Lewy body-like hyaline inclusions and astrocytic hyaline inclusions characteristically found in patients with familial amyotrophic lateral sclerosis with superoxide dismutase-1 (SOD1) gene mutations and in transgenic mice expressing human SOD1 with G85R mutation, the detailed protein composition in both types of inclusions was immunohistochemically analyzed using 45 different antibodies. Both types of inclusions had very strong immunoreactivity for SOD1. The SOD1-positive inclusions in both cell types were also immunoreactive for the insoluble advanced glycation endproducts (AGEs) such as N ɛ-(carboxymethyl)lysine (CML), pyrraline and pentosidine: both inclusions in both conditions were ultrastructurally composed of the granule-coated fibrils that had immunoreactivities to CML and pyrraline. Both types of inclusions were negative for stress-response proteins (SRPs), 4-hydroxy-2-nonenal (HNE), acrolein, nitric oxide synthases (NOSs) and nitrotyrosine as representative markers of oxidative stress. The neurons and astrocytes of the normal individuals and non-transgenic mice showed no significant immunoreactivity for SOD1, AGEs, SRPs, HNE, acrolein, NOSs or nitrotyrosine. Our results suggest that a portion of the SOD1 composing both type of inclusions, probably toxic mutant SOD1, is modified by the AGEs, and that the formation of the AGE-modified SOD1 is one of the mechanisms responsible for the aggregation involving no significant oxidative mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000226
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  • 3
    Electronic Resource
    Electronic Resource
    Nonoxidative protein glycation is implicated in familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 275-284 
    Details
    ISSN: 1432-0533
    Keywords: Key words Amyotrophic lateral sclerosis ; Imidazolone ; Nɛ-carboxymethyl-lysine ; Pyrraline ; Superoxide dismutase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess a role for oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS), we analyzed the immunohistochemical localization of 8-hydroxy-2′-deoxyguanosine (OHdG) as a nucleic acid oxidation product, acrolein-protein adduct and 4-hydroxy-2-nonenal (HNE)-protein adduct as lipid peroxidation products, N ɛ-carboxymethyl-lysine (CML) as a lipid peroxidation or protein glycoxidation product, pentosidine as a protein glycoxidation product, and imidazolone and pyrraline as nonoxidative protein glycation products in the spinal cord of three familial ALS patients with superoxide dismutase-1 (SOD1) A4V mutation, six sporadic ALS patients, and six age-matched control individuals. The spinal cord sections of the control cases did not show any distinct immunoreactivities for these examined products. In the familial ALS cases, intense immunoreactivities for pyrraline and CML were confined to the characteristic Lewy body-like hyaline inclusions, and imidazolone immunoreactivity was located in the cytoplasm of the residual motor neurons. No significant immunoreactivities for other examined products were detected in the familial ALS spinal cords. In the sporadic ALS cases, intense immunoreactivities for pentosidine, CML and HNE-protein adduct were seen in the cytoplasm of the degenerated motor neurons, and OHdG immunoreactivity was located in the cell nuclei of the residual neurons and glial cells. The present results indicate that oxidative reactions are involved in the disease processes of sporadic ALS, while there is no evidence for increased oxidative damage except for CML deposition in the familial ALS spinal cords. Furthermore, it is likely that the accumulation of pyrraline and imidazolone supports a nonoxidative mechanism in SOD1-related motor neuron degeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004019900173
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  • 4
    Electronic Resource
    Electronic Resource
    Na,K-ATPase α3 subunit in the goldfish retina during optic nerve regeneration (2002)
    Oxford, UK : Blackwell Science, Ltd
    Journal of neurochemistry 80 (2002), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The goldfish optic nerve can regenerate after injury. To understand the molecular mechanism of optic nerve regrowth, we identified genes whose expression is specifically up-regulated during the early stage of optic nerve regeneration. A cDNA library constructed from goldfish retina 5 days after transection was screened by differential hybridization with cDNA probes derived from axotomized or normal retina. Of six cDNA clones isolated, one clone was identified as the␣Na,K-ATPase catalytic subunit α3 isoform by high- sequence homology. In northern hybridization, the expression level of the mRNA was significantly increased at 2 days and peaked at 5–10 days, and then gradually decreased and returned to control level by 45 days after optic nerve transection. Both in situ hybridization and immunohistochemical staining have revealed the location of this transient retinal change after optic nerve transection. The increased expression was observed only in the ganglion cell layer and optic nerve fiber layer at 5–20 days after optic nerve transection. In an explant culture system, neurite outgrowth from the retina 7 days after optic nerve transection was spontaneously promoted. A low concentration of ouabain (50–100 nm) completely blocked the spontaneous neurite outgrowth from the lesioned retina. Together, these data indicate that up-regulation of the Na,K-ATPase α3 subunit is involved in the regrowth of ganglion cell axons after axotomy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0022-3042.2002.00771.x
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  • 5
    Electronic Resource
    Electronic Resource
    Control of hole carrier density of polycrystalline Cu2O thin films by Si doping (2002)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 80 (2002), S. 950-952 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The effects on the electrical properties of Si doping into Cu2O thin films deposited by reactive sputtering were studied. The hole density increased from 1×1015 to 1×1017 cm−3 with increasing Si content and the minimum resistivity obtained was 12 Ω cm. It was suggested that the electrically active acceptor with an activation energy of 0.19 eV was generated by Si doping. Infrared absorption measurements indicated the formation of silicate in Si-doped Cu2O. The mechanism for Si acting as an acceptor in Cu2O is discussed and modeled based on the silicate formation in Cu2O. © 2002 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1448398
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  • 6
    Electronic Resource
    Electronic Resource
    Effect of taurine on ulcerogenic response and impaired ulcer healing induced by monochloramine in rat stomachs (2002)
    Oxford UK : Blackwell Science Ltd.
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It is well known that neutrophil-derived hypochlorous acid interacts with ammonia (NH4OH) to generate monochloramine (NH2Cl) and that NH2Cl irritates the gastric mucosa and impairs ulcer healing.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To examine the effect of taurine, a hypochlorous acid scavenger, on the mucosal ulcerogenic and the impaired healing response induced by NH2Cl in rat stomachs, in comparison with those of methionine and glycine.〈section xml:id="abs1-3"〉〈title type="main"〉Methods and results:Under anaesthesia, oral administration of NH2Cl (120 mmol/L) produced severe lesions in male Sprague–Dawley rat stomachs. Taurine (10–100 mg/kg) given p.o. 30 min prior to NH2Cl dose-dependently prevented these lesions in response to NH2Cl. This action was mimicked by methionine (3–30 mg/kg) but not by glycine (10–100 mg/kg). Under urethane anaesthesia, mucosal exposure to NH4OH (120 mmol/L) caused a marked reduction of potential difference (PD) in the ex vivo chambered stomachs after induction of ischaemia, resulting in severe lesions. These ulcerogenic and PD responses by NH4OH plus ischaemia were also mitigated by taurine and methionine, but not glycine, applied to the chamber 20 min before the onset of NH4OH plus ischaemia. Moreover, oral administration of 100% ethanol produced severe haemorrhagic lesions in rat stomachs, all of which rapidly healed within 7 days after lesion induction. Daily administration of NH2Cl (20 mmol/L) significantly delayed the healing of these lesions, but recovery of this impaired healing response was obtained by concurrent administration of taurine. Both taurine and methionine showed a potent scavenging effect against NH2Cl in vitro.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:(1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa and impairs the healing response; (2) taurine exerts a prophylactic effect against the deleterious effects of NH2Cl, mainly due to its scavenging action against NH2Cl; and (3) this effect of taurine may be useful for treatment of gastritis associated with Helicobacter pylori infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.16.s2.12.x
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  • 7
    Electronic Resource
    Electronic Resource
    The roles of nitric oxide and prostaglandins in alterations of ulcerogenic and healing responses in adjuvant-induced arthritic rat stomachs (2000)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 14 (2000), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim: To examine alterations of gastric ulcerogenic and healing responses in adjuvant-induced arthritic rats. Methods: Arthritis was induced in male Dark Agouti rats by injection of Freund's complete adjuvant into the right hind paw. Results: The gastric ulcerogenic response to indomethacin was markedly increased in AA rats, depending on the degree of arthritic change. By contrast, HCl/ethanol-induced gastric lesions were significantly suppressed in arthritic rats when compared with normal rats. The increased ulcerogenic response to indomethacin was significantly prevented by L-NAME and antineutrophil serum but not by FR167653, while the reduced ulcerogenic response to HCl/ethanol was significantly prevented by L-NAME and partly by indomethacin or NS-398. On the other hand, the healing of chronic gastric ulcers induced by thermal cauterization was also significantly delayed in arthritic rats when compared with normal rats. This delayed healing of gastric ulcers was affected by neither L-NAME, indomethacin nor FR167653. The gastric mucosa of arthritic rats showed a significant increase in both inducible nitric oxide synthase (iNOS) activity and prostaglandin (PG) E2 contents. Conclusions: Gastric ulcerogenic and healing responses were altered in arthritic rats. The ulcerogenic response to indomethacin was increased while that to HCl/ethanol was decreased. These changes in ulcerogenic responses may both be accounted for by increased production of NO/iNOS, with the latter also being partially related to elevated production of PGs/COX-2. Moreover, the healing of gastric ulcers was also delayed in arthritic rats, but the mechanism was related to neither NO nor PGs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2000.014s1018.x
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  • 8
    Electronic Resource
    Electronic Resource
    Role of inducible nitric oxide synthase in dextran sulphate sodium-induced colitis (2000)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 14 (2000), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Different authors have postulated both toxic and protective effects for nitric oxide (NO) in the pathophysiology of active inflammation. Aim: To examine the role of NO, especially that produced by the inducible form of nitric oxide synthase (iNOS), by investigating the effects of NOS inhibitors and NO donors on inflammation in experimental acute colitis. Methods: Acute colitis was induced in rats by dextran sulphate sodium (DSS). White blood cell counts and levels of thiobarbituric acid reactants in the portal blood were determined, as were histological changes in the colonic mucosa. We then evaluated the effects of NG-nitro- l-arginine methyl ester ( l-NAME), aminoguanidine (AG) and an NO donor on DSS-induced changes in these inflammatory parameters. Results and Conclusions: Inhibition of NO production by either l-NAME or AG worsened DSS-induced inflammation, suggesting a protective role for NO in acute colitis. On the other hand, a NO donor also exaggerated DSS-induced inflammatory parameters, suggesting that acute colitis may be aggravated by either too much or too little NO. These results suggest that medical treatment of ulcerative colitis must aim for maintenance of appropriate NO levels in the intestinal mucosa.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2000.014s1026.x
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  • 9
    Electronic Resource
    Electronic Resource
    Diversity of vacA and cagA genes of Helicobacter pylori in Japanese children (2004)
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Helicobacter pylori infection is generally acquired in childhood and persists as an asymptomatic infection for decades in most infected individuals. Only a minority develops a clinical outcome even in childhood, such as peptic ulcer. It has been reported that H. pylori infection with the type I strain, which expresses the VacA and CagA antigen, is associated with peptic ulcer.Aim : We examined the diversity of vacA and cagA genes in isolates obtained from Japanese paediatric patients with peptic ulcer or chronic gastritis to investigate the relationship between genetic diversity and clinical outcome.Methods : The diversity of vacA and cagA genes was investigated by PCR and sequence analysis in 30 isolates obtained from Japanese paediatric patients with peptic ulcer (eight strains) or chronic gastritis (22 strains).Results : All isolates from Japanese children were cagA-positive strains. Twenty-six strains (86.7%) had East Asian type CagA, and 4 (13.3%) had Western type CagA. The predominant vacA genotype was s1c/m1b (22/30, 73.3%). There was no significant association between the diversity of cagA and vacA genes and clinical outcome. All four children infected with Western CagA strain had a history of overseas travel or residence.Conclusion : The predominant genotype of H. pylori in Japanese children is East Asian CagA and vacA s1c/m1b genotype, regardless of clinical outcome. Japanese H. pylori strains are homogeneously of the East Asian type; however, Western strains can be introduced into Japan concomitant with host movement from foreign countries in childhood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2004.01980.x
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  • 10
    Electronic Resource
    Electronic Resource
    Sex differences in mucosal response to Helicobacter pylori infection in the stomach and variations in interleukin-8, COX-2 and trefoil factor family 1 gene expression (2004)
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Gastric cancer incidence in men is almost double that in women. We investigated mucosal responses in the stomach against Helicobacter pylori (H. pylori) infections to elucidate the interindividual or sex-related differences, which may in turn be associated with gastric cancer incidence, mucosal changes of stomach as measured by the Sydney System, and interleukin-8, cyclooxygenase-2 and trefoil factor family 1 (TFF1) gene expression.Methods : An age-, sex-, H. pylori status- and disease-matched case−control study was performed in 574 H. pylori-positive and 225 H. pylori-negative patients selected from 4125 patients with a diagnosis of benign disease of the stomach. Levels of acute and chronic inflammations, atrophy and intestinal metaplasia scored according to the Sydney System were compared by stomach site and by sex. Two biopsy specimens (antral and corpus gastric mucosa) from patients with benign gastric diseases (142 patients; 72 men, 70 women) were analysed for interleukin-8, cyclooxygenase-2 and TFF1 mRNA expression as measured by real-time PCR.Results : Inflammation and activity scores in antrum with H. pylori infection were higher in men, but scores declined according to age. Atrophy and intestinal metaplasia scores in corpus with H. pylori infection appeared more severe in men than in women, especially in older patients. In women, atrophy score increased with increasing age, particularly in postmenopausal H. pylori-negative patients. Interleukin-8 mRNA induction was detected in both antrum and corpus mucosa in H. pylori infection, but sex differences were not found. Response of cyclooxygenase-2 mRNA expression against H. pylori infection in the mucosa was higher in men than women. In H. pylori-negative patients, TFF1 mRNA levels in women were significantly higher than in men, and TFF1 mRNA was significantly lower in positive than negative women.Conclusions : Sex differences in mucosal responses to H. pylori infection in the stomach may be correlated with sex differences in the incidence of stomach cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2004.01985.x
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