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Biomedical subjects

K Hirata

Publications and source records attributed to K Hirata.

At least 253 records · Page 14Linked to original sources
PubMed2000

[A case of Gerstmann-Sträussler-Scheinker disease with severe muscular atrophy and vertical gaze palsy].

Here we report a case of 56-year-old man with Gerstmann-Sträussler-Scheinker disease (GSS). He had gait disturbance, limb and truncal ataxia, dysarthria and dysphagia at the age of 53. When he developed vertical gaze palsy and dystonic posture of the neck, subcortical dementia, progressive supuranuclear palsy was suspected. Thereafter dementia rapidly progessed, and CT scan showed severe atrophy of the brain. Since severe muscular atrophy and fasciculation also appeared, and abnormality in the codon 102 of prion protein gene was found, he was diagnosed to have the classical type of GSS. GSS with vertical gaze palsy has never been reported, and involvement of the lower motor neuron is also very rare. Therefore, the present case is an atypical type of GSS.

Codon↗
PubMed2000

[Complications with plasma exchange].

The value of plasma exchange in the treatment of Guillain-Barré syndrome is well established, but in Japan patients often receive double-filtration plasmapheresis or immunoadsorption therapy. In this study, we examined the frequency of complications with plasma exchange. The complications occurred in 55 of 197 sessions (28%) during plasma exchange. The most frequent complication was transient symptomatic hypotension (16%). There were fever (10%), nausea or vomiting (7%), chill (5%), headache (5%), tachycardia (2%) and thromboembolism (2%). No significant bleeding was seen in any of the patients. In this study, we clarified that the frequency of the complications tended to increase with the aging.

Adolescent↗
PubMed1999

Interleukin-10 reduces natural killer (NK) sensitivity of tumor cells by downregulating NK target structure expression.

We examined the effect of exogenous IL-10 on the sensitivity of rat W14 and W31 tumor cells to natural killer (NK) cell-mediated cytotoxicity in relation to previously identified NK target structure (NKTS) expressed on these cells. We also examined the effect of endogenous interleukin-10 (IL-10) on rat IL-10 cDNA-introduced W31 cells (W31T-H, a high-IL-10-producer clone; W31T-L, a low-IL-10-producer clone). Both exogenous and endogenous IL-10 had no effect on the proliferative activity of these cells, but incubation of cells with recombinant human (rh) IL-10 resulted in a dose-dependent decrease in the expression of NKTS recognized by mAb 109. The expression level of NKTS on W31T-H cells was dramatically decreased compared with that on W31T-L cells and parental W31 cells. In addition, treatment of W31 cells with the culture supernatants of W31T-H cells could downregulate the expression of the NKTS. Moreover, NK sensitivity of W31T-H was suppressed down to a level equivalent to that of W31 cells pretreated with exogenous rhIL-10, and cytolysis could no longer be inhibited by mAb 109. We previously demonstrated that IL-10 downregulated MHC class I expression in this model. Nevertheless, NK susceptibility was also decreased. Taken together, these results suggest that the IL-10-mediated decrease in NKTS expression has a larger effect than decreased MHC class I expression on NK sensitivity. Thus, our data reveal a novel mechanism for an IL-10-mediated escape of tumor cells from host immune surveillance by downregulation of NKTS expression.

Animals↗
PubMed1999

Reduced facilitation and vesicular uptake in crustacean and mammalian neuromuscular junction by T-588, a neuroprotective compound.

Bath application of compound T-588, a neuroprotective agent, reduced paired-pulse and repetitive-pulse facilitation at mammalian and crustacean neuromuscular junctions. In addition, it reduced voltage-gated sodium and potassium currents in a use-dependent fashion, but had only a small effect on the presynaptic Ca(2+) conductance. By contrast, it blocked FM 1-43 vesicular uptake but not its release, in both species. Postsynaptically, T-588 reduced acetylcholine currents at the mammalian junction in a voltage-independent manner, but had no effect on the crayfish glutamate junction. All of these effects were rapidly reversible and were observed at concentrations close to the compound's acute protective level. We propose that this set of mechanisms, which reduces high-frequency synaptic transmission, is an important contributory factor in the neuroprotective action of T-588.

Action Potentials↗
PubMed1999

Acute motor axonal neuropathy and acute motor-sensory axonal neuropathy share a common immunological profile.

Griffin and colleagues (Griffin JW, Li CY, Ho TW, Tian M, Gao CY, Xue P, Mishu B, Cornblath DR, Macko C, McKhann GM, Asbury AK. Pathology of motor-sensory axonal Guillain-Barré syndrome. Ann Neurol 1996;39:17-28 [4]) proposed that acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) are part of the spectrum of a single type of immune attack on the axon. In contrast, IgG anti-GM1 antibody is associated closely with AMAN, but whether other IgG anti-ganglioside antibodies are associated with this neuropathy is not clear. We investigated whether IgG anti-ganglioside antibodies can be used as immunological markers to differentiate AMAN from acute inflammatory demyelinating polyneuropathy (AIDP) and whether these autoantibodies are present in AMSAN. The frequencies of anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies in 21 AMAN patients were significantly higher than in 19 AIDP patients. Anti-GM1b and anti-GD1a IgG, as well as anti-GM1 IgG antibodies, therefore are immunological markers for AMAN. The patients with AMSAN had anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies, indicative that AMAN and AMSAN share a common immunological profile.

Adolescent↗
PubMed1999

Beneficial effects of inducible nitric oxide synthase inhibitor on reperfusion injury in the pig liver.

BACKGROUND: Although inhibition of endothelial nitric oxide synthase (eNOS) has been reported to aggravate hepatic ischemia-reperfusion (I/R) injury, the role of inducible nitric oxide synthase (iNOS) has been still unknown. We investigated the role of NO produced by iNOS, and evaluated the effect of an iNOS inhibitor on prolonged warm I/R injury in the pig liver. METHODS: Pigs were subjected to 120 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in serum and hepatic microdialysate NO2- + NO3- (NOx) and the cellular distribution of eNOS and iNOS by immunohistochemistry, including a double-immunofluorescence technique in combination with confocal laser scanning microscopy. The effect of iNOS inhibitor was also investigated. RESULTS: Hepatic I/R induced new nitric oxide production in serum and hepatic microdialysate NOx after reperfusion and severe hepatic damage in the centrilobular region where nitrotyrosine was strongly expressed. Diffuse eNOS expression in sinusoidal endothelium did not differ before and after reperfusion. In contrast, strong iNOS expression in Kupffer cells and neutrophils appeared strongly in the centrilobular region after reperfusion. Pigs with intraportal administration of N(G)-nitro-L-arginine (10 mg/kg) died during the period of ischemia or early in the period of reperfusion with a high mortality rate (80.0%). Intraportal administration of aminoguanidine hemisulfate (10 mg/kg) significantly suppressed nitric oxide production and serum aspartate aminotransferase after reperfusion, inhibited nitrotyrosine expression, and attenuated hepatic damage. CONCLUSIONS: These results indicate that hepatic I/R injury is triggered by centrilobular iNOS expression; and attenuated by inhibition of iNOS.

Animals↗
PubMed1999

Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoxic T lymphocytes.

Peptides of human melanomas recognized by CD8+ CTLs have been identified, but the nature of those of nonmelanoma tumors remains to be elucidated. Previously, we established a gastric signet ring cell carcinoma HST-2 and HLA-A31 (A*31012)-restricted autologous CTL clone, TcHST-2. In the present study, we determined the natural antigenic peptides of HST-2 cells. The purified preparation of acid-extracted Ags was submitted to the peptide sequencer, and one peptide, designated F4.2 (Tyr-Ser-Trp-Met-Asp-Ile-Ser-Cys-Trp-Ile), appeared to be immunogenic. To confirm the antigenicity of F4.2 further, we constructed an expression minigene vector (pF4.2ss) coding adenovirus E3, a 19-kDa protein signal sequence plus F4.2. An introduction of pF4.2ss minigene to HST-2 and HLA-A31(+) allogeneic tumor cells clearly enhanced and induced the TcHST-2 reactivity, respectively. Furthermore, when synthetic peptides of F4.2 C-terminal-deleted peptides were pulsed to HST-2 cells, F4.2-9 (nonamers), but not F4.2-8 or F4.2-7 (octamer or heptamer, respectively), enhanced the reactivity of TcHST-2, suggesting that the N-terminal ninth Trp might be a T cell epitope. This was confirmed by lack of antigenicity when using synthetic substituted peptides as well as minigenes coding F4.2 variant peptides with Ala or Arg at the ninth position of F4.2. Meanwhile, it was indicated that the sixth position Ile was critically important for the binding to HLA-A31 molecules. Thus, our data indicate that F4.2 may work as an HLA-A31-restricted natural antigenic peptide recognized by CTLs.

Amino Acid Sequence↗
PubMed1999

Selective coupling of mouse brain metabotropic sigma receptor with recombinant Gi1.

Various sigma (sigma) ligands including (+)-pentazocine stimulated [35S]GTPgammaS binding in synaptic membranes from the mouse cerebellum. The (+)-pentazocine-stimulated [35S]GTPgammaS binding was blocked by the treatment of membranes with pertussis toxin (PTX), but completely recovered by the reconstitution of PTX-treated membranes with recombinant Gi1, but not with GoA. These findings suggest that metabotropic sigma receptors are selectively coupled to Gi1 protein.

Animals↗
PubMed1999

Antibodies to GD1alpha and to GQ1beta in Guillain-Barré syndrome and the related disorders.

Certain species of anti-ganglioside antibodies are associated with specific clinical features in various neurologic diseases. Serum autoantibodies to these minor gangliosides were investigated in a number of neurological diseases in order to examine the biological functions of GD1alpha and GQ1beta. Eleven patients with Guillain-Barré syndrome had remarkably high IgG anti-GD1alpha antibody titers, but no GD1alpha was detected in human peripheral nerve. An absorption study showed that IgG anti-GD1alpha antibodies from eight of the 11 patients were significantly absorbed by GD1a and GM1b, indicative that the IgG anti-GD1alpha antibodies cross-react with GD1a and GM1b. Both GD1a and GM1b have been reported to be target molecules for serum antibodies in certain patients with Guillain-Barré syndrome. GD1alpha may induce the production of IgG anti-GD1alpha antibody which cross-reacts with GD1a or GM1b, and subsequently functions in the development of Guillain-Barré syndrome. The IgGs from six patients with Fisher's syndrome who had the anti-GQ1beta antibody had anti-GQ1b activity as well. All the patients had external ophthalmoplegia, but no GQ1beta was detected in the human oculomotor nerve, further evidence that GQ1b, not GQ1beta, is the molecule targeted by the autoantibody in Fisher's syndrome.

Antibody Specificity↗
PubMed1999

Cloning of a unique lipase from endothelial cells extends the lipase gene family.

A new lipoprotein lipase-like gene has been cloned from endothelial cells through a subtraction methodology aimed at characterizing genes that are expressed with in vitro differentiation of this cell type. The conceptual endothelial cell-derived lipase protein contains 500 amino acids, including an 18-amino acid hydrophobic signal sequence, and is 44% identical to lipoprotein lipase and 41% identical to hepatic lipase. Comparison of primary sequence to that of lipoprotein and hepatic lipase reveals conservation of the serine, aspartic acid, and histidine catalytic residues as well as the 10 cysteine residues involved in disulfide bond formation. Expression was identified in cultured human umbilical vein endothelial cells, human coronary artery endothelial cells, and murine endothelial-like yolk sac cells by Northern blot. In addition, Northern blot and in situ hybridization analysis revealed expression of the endothelial-derived lipase in placenta, liver, lung, ovary, thyroid gland, and testis. A c-Myc-tagged protein secreted from transfected COS7 cells had phospholipase A1 activity but no triglyceride lipase activity. Its tissue-restricted pattern of expression and its ability to be expressed by endothelial cells, suggests that endothelial cell-derived lipase may have unique functions in lipoprotein metabolism and in vascular disease.

Amino Acid Sequence↗
PubMed1999

Subclass distribution and the secretory component of serum IgA anti-ganglioside antibodies in Guillain-Barré syndrome after Campylobacter jejuni enteritis.

Previously, we reported that IgA anti-GM1 antibody is more closely associated with preceding Campylobacter jejuni enteritis in Guillain-Barré syndrome (GBS) than are IgG and IgM antibodies. However, the mechanism of the induction of IgA anti-ganglioside antibodies is not clear. In this study, serum IgA antibodies against GM1, GM1b, and GD1a, and GalNAc-GD1a were examined in 152 GBS patients. In GBS, antecedent C. jejuni infection is closely associated with IgA antibodies, other than GM1, against GM1b. The IgA subclass distribution is completely restricted to IgA1, no secretory IgA anti-ganglioside antibody being detected. This result does not support the hypothesis that the serum IgA antibodies present in GBS after C. jejuni enteritis originate at mucosal sites, such as the gut mucosal immune system. Seventeen (85%) of 20 patients with IgA anti-ganglioside antibodies had serological evidence of C. jejuni infection and/or a history of antecedent diarrhea. Moreover, a motor nerve conduction study showed that patients with IgA antibodies frequently had axonal neuropathy, whereas none had demyelinating neuropathy. This may support the previous report that IgA isotype anti-GM1 antibodies are more closely associated with poor outcome than are the IgG or IgM isotypes. The induction mechanism of IgA anti-ganglioside antibodies must be clarified by determining whether concentrations of cytokines, which increase the IgA class switch, are elevated in patients with GBS after C. jejuni enteritis.

Antibodies↗
PubMed1999

Pantropic retroviral vectors mediate gene transfer and expression in Entamoeba histolytica.

Transformation of Entamoeba histolytica has been previously reported, but the foreign genes have all been replicated episomally. Pantropic retroviral vectors based on the Moloney murine leukemia virus with the envelope glycoprotein of vesicular stomatitis virus (VSV-G) have an extremely broad host range and can be concentrated to high titer. To investigate whether these pseudotyped, pantropic vectors can mediate gene transfer and expression in E. histolytica, we constructed a retroviral vector, in which a hygromycin phosphotransferase is expressed from the E. histolytica actin promoter. Data confirm the infection, integration, and expression of a foreign gene mediated by the provirus. To our knowledge, this is the most evolutionarily distant example of successful integration and expression of a mammalian retrovirus. Pantropic retroviral vectors may thus facilitate genetic analysis in species lacking transformation systems.

Animals↗
PubMed1999

Autoantibodies to GM1b and GalNAc-GD1a: relationship to Campylobacter jejuni infection and acute motor axonal neuropathy in China.

IgG antibodies to the minor gangliosides GM1b and GalNAc-GD1a frequently are present in sera of Japanese patients with Guillain-Barré syndrome. The relationship between these autoantibodies and Campylobacter jejuni infection, the type of disease (acute motor axonal neuropathy [AMAN], or acute inflammatory demyelinating polyneuropathy [AIDP]) has yet to be established. Sera samples were obtained from 55 Chinese patients with clinically defined Guillain-Barré syndrome. An electrophysiology study showed nine AIDP, 28 had AMAN, and 18 unclassified. C. jejuni serology was positively correlated with anti-GM1b and anti-GalNAc-GD1a IgG antibodies (respective P values, 0.007 and 0.02). The frequencies of positive anti-GM1b and anti-GalNAc-GD1a serology were greater in AMAN (32 and 21%) than in AIDP (11 and 0%), but the differences were not significant. Infection by C. jejuni may induce IgG anti-GM1b antibody in some patients and IgG anti-GalNAc-GD1a antibody in others. A larger population of patients must be studied to show whether there is a definite correlation.

Acute Disease↗
PubMed1999

Antibodies to GD3, GT3, and O-acetylated species in Guillain-Barré and Fisher's syndromes: their association with cranial nerve dysfunction.

We examined serum antibodies to the four fetal antigens GD3, O-acetyl GD3, GT3, and O-acetyl GT3 ganglioside in patients with Guillain-Barré syndrome (GBS) or its variant Fisher's syndrome (FS). The patients with FS more often had significant IgG antibodies against GD3, GT3, and O-acetyl GT3 than did the healthy controls. Furthermore, anti-GD3 and anti-GT3 IgG antibodies were more often significantly present in the patients with FS than in those with GBS. IgG antibody to GD3, GT3, and O-acetyl GT3 had a significant association with the presence of ophthalmoparesis. These antibodies, however, cross-reacted with GQ1b and we detected no antibodies which specifically reacted with fetal gangliosides. In addition, oculomotor involvement was more closely related to IgG antibodies to GQ1b than to those to fetal gangliosides. No evidence was obtained that the serum antibodies to these fetal gangliosides are associated with specific neurologic signs of cranial nerves.

Cranial Nerve Diseases↗
PubMed1999

CTLA4IgG treatment induces long-term acceptance of rat small bowel allografts.

BACKGROUND: CTLA4 immunoglobulin (Ig)G that binds to B7 effectively inhibits the signaling of CD28/CTLA4-B7 pathway and induces antigen specific T cell unresponsiveness in vitro and in vivo. Using CTLA4IgG, we examined induction of long-term graft survival and the mechanism of maintenance of tolerance in rat allogeneic small bowel transplantation. METHODS: Small bowels of Brown-Norway rats (RT1n) were heterotopically transplanted into Lewis rats (RT1l). Recipients were treated with an i.p. injection of either CTLA4IgG or control IgG for 7 days. RESULTS: Long-term survival was observed in rats treated with CTLA4IgG, whereas control rats died within 16 days after transplantation. To examine whether a tolerant state was established in long-term survival rats, secondary transplantation was performed using small bowels of Brown-Norway rats or ACI (RT1b) rats. It was demonstrated that small bowels of Brown-Norway rats were accepted; however, those of ACI rats were rejected within 10 days. Serum concentrations of interleukin (IL)-4 were maintained at >50 microg/ml for 7 days after transplantation in rats treated with CTLA4IgG but <15 microg/ml in control rats. IL-2 concentration was reduced to half in CTLA4IgG-treated rats compared with that in control recipients. Serum IFN-gamma in CTLA4IgG-treated recipients increased after transplantation and was not distinguishable from that of control recipients during the first 7 days after transplantation. Conclusion. We demonstrated that CTLA4IgG treatment alone for 7 days induced a long-term donor specific tolerance in rat allogeneic small bowel transplantation. The induction of long-term acceptance of small bowel allografts by CTLA4IgG is not caused by simply the shift of anti-alloimmune responses from Thl to Th2 cytokine production.

Abatacept↗
PubMed1999

Are Campylobacter curvus and Campylobacter upsaliensis antecedent infectious agents in Guillain-Barré and Fisher's syndromes?

Campylobacter curvus and Campylobacter upsaliensis were isolated from stools of patients with Guillain-Barré (GBS) or Fisher's (FS) syndromes. Whether these microorganisms are pathogens of antecedent diarrhea in GBS and FS is not clear, therefore, we made a serological examination. There were no differences in antibody titer to these organisms among the patients with GBS, FS, and the controls. Some patients had elevated antibodies to the bacteria, but most also had serological evidence of C. jejuni infection. Moreover, the patients from whom C. curvus had been isolated did not have antibodies to the bacterium, indicative that they were healthy carriers of C. curvus or that the isolates were the product of contamination. We conclude that neither C. curvus nor C. upsaliensis is the major agent of antecedent diarrhea in GBS and FS.

Antibodies, Bacterial↗