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Biomedical subjects

Y Kurata

Publications and source records attributed to Y Kurata.

At least 91 records · Page 5Linked to original sources
PubMed1996

[Analysis of immunoglobulin classes of five anti-phospholipid antibodies in sera from patients with SLE, ITP and recurrent fetal abortion by enzyme linked immunosorbent assay].

Using a panel of phospholipid(PL) antigens, we have established an enzyme linked immunosorbent assay (ELISA) for measuring both IgG and IgM type anti-phospholipid antibodies (APA) in sera from patients with systemic lupus erythematosus (SLE), idiopathic thrombocytopenic purpura (ITP) and recurrent fetal abortion (RFA). The percentage of anticardiolipin antibody (aCL) positive patients was increased in SLE (73% for IgG, 74% for IgM), ITP (24% for IgG, 8% for IgM) and RFA (20% for IgG, 52% for IgM) as compared with normal controls. The percentage of other APAs in each disease was significantly different from one another, suggesting the existence of disease-specific APA in these autoimmune disorders. We consider that it is important to analyze these APAs for the investigation of pathogenesis of autoimmune disorders.

Abortion, Habitual↗
PubMed1995

Somatostatin receptor on the afferent nerve terminals in the rat hepatoportal area.

To determine whether somatostatin receptor (SSR) actually exists on the nerve terminals in the rat hepatoportal area, the area was immunostained by the labeled streptoavidin-biotin complex method using a monoclonal antibody against rat brain SSR. The SSR staining revealed many fiber arborizations with terminal nodular swellings like the afferent nerve endings in the neural body, which was located beneath the endothelium of the large branches of the intrahepatic portal vein. The results indicate that SSR is expressed on the characteristic structure, adding further evidence for our previous observation which showed the hepatic vagal reception for intraportal somatostatin and the somatostatin-binding neural body as a relevant structure.

Afferent Pathways↗
PubMed1995

Monoclonal anticardiolipin autoantibodies established from the (New Zealand white x BXSB)F1 mouse model of antiphospholipid syndrome cross-react with oxidized low-density lipoprotein.

OBJECTIVE: Autoimmunity-prone (New Zealand white x BXSB)F1 ([NZW x BXSB]F1) mice have been shown to be useful as a model of antiphospholipid syndrome with myocardial infarction. The aim of this study was to examine the cross-reactivity of anticardiolipin antibody (aCL) derived from (NZW x BXSB)F1 mice with oxidized low-density lipoprotein (ox-LDL), which is closely associated with atherosclerosis. METHODS: Six monoclonal antibodies (MAb) against CL were established from (NZW x BXSB)F1 mice, and reactivity of aCL with ox-LDL was examined by micro-enzyme-linked immunosorbent assay. RESULTS: Higher titers of anti-ox-LDL autoantibodies were found in adult (NZW x BXSB)F1 mice compared with other autoimmunity-prone mouse strains (P < 0.01) or a control strain (P < 0.005). There was a significant positive correlation between titers of aCL and those of anti-ox-LDL in (NZW x BXSB)F1 mice (r = 0.79, P < 0.001). Of the 6 MAb against CL, 2 clones that showed beta 2-glycoprotein 1-dependent reactivity also cross-reacted with ox-LDL. Binding of monoclonal aCL to solid-phase cardiolipin was inhibited by ox-LDL, but not by native LDL. CONCLUSION: We confirmed that aCL derived from (NZW x BXSB)F1 mice can cross-react with ox-LDL. This result suggests that aCL, which is closely associated with lupus-associated thrombosis, may also play an important role in atherosclerotic complications in patients with systemic lupus erythematosus.

Animals↗
PubMed1995

Effect of ingestion of 20 pesticides in combination at acceptable daily intake levels on rat liver carcinogenesis.

Exposure of agricultural workers and the general population to pesticides is a major concern, and possible summation or synergistic effects deserves particular attention. In this study, however, combined dietary administration of 19 organophosphorus compounds and one organochlorine pesticide, each at acceptable daily intake (ADI) levels, did not enhance rat liver preneoplastic lesion development initiated by diethylnitrosamine. In contrast, a mixture of 100 times ADI significantly increased the number and area of lesions. The results thus provide direct support for the present safety factor approach to the quantitative hazard evaluation of pesticides.

Administration, Oral↗
PubMed1995

Molecular basis of CD36 deficiency. Evidence that a 478C-->T substitution (proline90-->serine) in CD36 cDNA accounts for CD36 deficiency.

CD36 deficiency is divided into two subgroups: neither platelets nor monocytes express CD36 (type I deficiency), and monocytes express CD36 in spite of the lack of platelet CD36 (type II deficiency). We have already demonstrated that a 478C-->T substitution (proline90-->serine) in platelet CD36 cDNA predominates in type II deficiency (Kashiwagi, H., S. Honda, Y. Tomiyama, H. Mizutani, H. Take, Y. Honda, S. Kosugi, Y. Kanayama, Y. Kurata, and Y. Matsuzawa. 1993. Thromb. Haemostasis. 69:481-484). In this study, we revealed that monocyte CD36 cDNA from two type II deficient subjects was heterozygous for C478 and T478 form, while platelet CD36 cDNA of these subjects consisted of only T478 form. In a type I deficient subject, both platelet and monocyte CD36 cDNA showed only T478 form. Expression assay using C478 or T478 form of CD36 cDNA transfected cells revealed that there was an 81-kD precursor form of CD36, and that the maturation of the 81-kD precursor form to the 88-kD mature form of CD36 was markedly impaired by the substitution. The mutated precursor form of CD36 was subsequently degraded in the cytoplasm. These results indicate that the 478C-->T substitution directly leads to CD36 deficiency via defects in posttranslational modification, and that this substitution is the major defects underlying CD36 deficiency.

Amino Acid Sequence↗
PubMed1995

Disposition of DN-2327, a new anxiolytic, in rats, dogs, and monkeys.

The disposition of DN-2327 after oral dosing of 14C-labeled DN-2327 ([14C]DN-2327) to rats, dogs and monkeys was studied. DN-2327 was absorbed from the small intestine after oral administration. In the plasma of these animals, a small amount of unchanged compound and M-I were detected, with M-II (a pharmacologically active metabolite) as a major component. The concentration of the unchanged compound in rat plasma attained a peak (Cmax 0.002 microgram/ml), then declined, with a half-life (t1/2) of 3 h. Tmax, Cmax and t1/2 of DN-2327 in dogs and monkeys were 0.6 h, 0.332 microgram/ml and 1.5 h, and 2.3 h, 0.036 microgram/ml and 6.2 h, respectively. About 60, 75 and 48% of the radioactivity dosed was absorbed in rats, dogs and monkeys, respectively, whereas the bioavailability in rats, dogs and monkeys was less than 1, 34 and 10%, respectively, indicating that DN-2327 had been subjected to the first pass effect. In rats given [14C]DN-2327 orally, the radioactivity was distributed widely in various tissues, including the brain. In the brain regions, DN-2327 and M-II were distributed and M-II was major component, indicating that the pharmacological effects of DN-2327 may depend largely on M-II. In these animals, [14C]DN-2327 was excreted in feces via bile mostly as metabolites. During repeated oral administration, DN-2327 and its metabolites did not accumulate in rat tissues, except in the kidney.

Administration, Oral↗
PubMed1995

Abnormal processing of the glycoprotein IIb transcript due to a nonsense mutation in exon 17 associated with Glanzmann's thrombasthenia.

We analyzed the molecular genetic defect responsible for type I Glanzmann's thrombasthenia in a Japanese patient. In an immunoblot assay using polyclonal anti-GpIIb-IIIa antibodies, some GPIIIa (15% of normal amount) could be detected in the patient's platelets, whereas GPIIb could not (< 2% of normal amount). Nucleotide sequence analysis of platelet GPIIb mRNA-derived polymerase chain reaction (PCR) products revealed that patient's GPIIb cDNA had a 75-bp deletion in the 3' boundary of exon 17 resulting in an in-frame deletion of 25 amino acids. DNA analysis and family study revealed that the patient was a compound heterozygote of two GPIIb gene defects. One allele derived from her father was not expressed in platelets, and the other allele derived from her mother had a 9644C--> T mutation which was located at the position -3 of the splice donor junction of exon 17 and resulted in a termination codon (TGA). Moreover, quantitative analysis demonstrated that the amount of the abnormal GPIIb transcript in the patient's platelets was markedly reduced. Thus, the C --> T mutation resulting in the abnormal splicing of GPIIb transcript and the reduction in its amount is responsible for Glanzmann's thrombasthenia.

Adult↗
PubMed1995

Family studies of type II CD36 deficient subjects: linkage of a CD36 allele to a platelet-specific mRNA expression defect(s) causing type II CD36 deficiency.

We performed family studies with type II CD36 deficiency. In the Mi. Y family, the proband (YII.1) and his brother (YII.2) displayed a type II deficient phenotype. In the mother (YI.2), binding of the anti-CD36 monoclonal antibody, OKM5, to both platelets and monocytes was reduced as compared to CD36 positive control cells. In the father (YI.1), while OKM5 binding to his platelets was reduced, that of his monocytes was almost the same as normal control monocytes. Analysis of genomic DNA showed that YI.2, YII.1 and YII.2 were heterozygous for a proline90-->serine mutation, and showed that both alleles of YI.1 did not have the mutation. Analysis of CD36 cDNA showed that the Pro90 form of CD36 cDNA could be detected in monocytes, but not in platelets from YII.1 and YII.2. These data indicated that YII.1 and YII.2 could be compound heterozygotes; an allele having a platelet-specific mRNA expression defect(s), which was responsible for the different CD36 expression between their platelets and monocytes, and the Ser90 allele. YI.1 was suggested to be a carrier of the platelet-specific silent allele. The platelet-specific silent allele was linked to a specific genotype of a polymorphic microsatellite sequence in the CD36 gene, supporting our hypothesis that mRNA expression defect(s) occurred at or near the CD36 gene. In a second type II CD36 deficient family, we also obtained results consistent with this hypothesis.

Alleles↗
PubMed1994

Identification of molecular defects in a subject with type I CD36 deficiency.

We performed a molecular analysis of a subject whose platelets and monocytes did not express any cell surface CD36 (designated as a type I CD36 deficiency). Amplification of the 5' half of platelet and monocyte CD36cDNA (corresponding to nucleotide [nt] 191-1009 of the published CD36 cDNA sequence [Oquendo et al, Cell, 58:95, 1989]) showed that two different-sized CD36 cDNAs existed. One cDNA was of predicted normal size, whereas the other was about 150 bp smaller than that predicted for normal CD36 cDNA. Amplification of the 3' region of CD36 cDNA (nt 962-1714) in this subject showed only normal-sized CD36 cDNA. Cloning and nt sequence analysis of the cDNAs showed that the smaller sized CD36 cDNA had 161-bp deletion (from nt 331 to 491), and a dinucleotide deletion starting at nt position 539. The same dinucleotide deletion was also detected in the normal sized CD36 cDNA. Both deletions caused a frameshift leading to the appearance of a translation stop codon. RNA blot analysis and quantitative assay using the reverse transcription-polymerase chain reaction (RT-PCR) showed that the CD36 transcripts in both platelets and monocytes were greatly reduced. Comparison of the determined cDNA sequences with the genomic DNA sequence for the human CD36 gene showed that the dinucleotide deletion was located in exon 5, and that the 161-bp deletion corresponded to a loss of exon 4. PCR-based analysis using genomic DNA showed that this subject was homozygous for the dinucleotide deletion in exon 5. Except for the dinucleotide deletion, we could not find any abnormalities around exon 3, 4, and 5 including the splice junctions. These results suggested that the deletions in CD36 mRNA were likely to be responsible for instability of the transcripts, and the dinucleotide deletion in exon 5 might affect the splicing of exon 4.

Antigens, CD↗
PubMed1994

Calorie restriction prevents the occlusive coronary vascular disease of autoimmune (NZW x BXSB)F1 mice.

Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, thrombocytopenia, lupus nephritis, and coronary vascular disease (CVD) with myocardial infarction. To determine whether this murine lupus-associated CVD can be prevented by the reduction of dietary calories, male W/BF1 mice were separated into five experimental groups and fed either ad libitum (designated group A, n = 50), fed 32% fewer calories of an otherwise comparable diet (designated group B6, n = 20), or initially fed ad libitum and then switched to reduced calorie intake (RCI) feeding at ages 14, 17, or 22 weeks (designated B14, n = 10; B17, n = 20; or B22, n = 20). Occlusive CVD was prevented by RCI. Life-span was significantly extended among the early onset RCI cohorts, B6 and B14 (P = 0.0001 and P = 0.005), compared to group A mice. Mean anti-cardiolipin autoantibody titers and mean levels of circulating immune complexes were also lowered in RCI mice when all RCI mice were compared to ad libitum fed group A mice. Histological grades of both coronary vascular and glomerular lesions were significantly less than those of group A mice (P < 0.001). Immunoprecipitates indicative of immunoglobulin deposition within coronary or glomerular vascular walls were also substantially less than those of group A mice. These findings indicate a possible causal role for anti-cardiolipin autoantibody in development of autoimmune CVD in W/BF1 mice and suggest that regulating dietary calories can influence the mechanism involved in pathogenesis of autoimmune-associated CVD development.

Animals↗
PubMed1994

Comparative hyaline droplet nephropathy in male F344/NCr rats induced by sodium barbital and diethylacetylurea, a breakdown product of sodium barbital.

Hyaline droplet nephropathy in male rats due to alpha 2u-globulin accumulation in proximal tubules is caused by chemicals from several chemical classes. We have previously shown that the well-known sedative/hypnotic barbiturate, sodium barbital, and its breakdown product, diethylacetylurea, are renal toxins and renal tumor promoters. To determine comparative induction of hyaline droplets in renal tubules by sodium barbital and diethylacetylurea, male F344/NCr rats, 6 weeks of age, were given diets containing 0, 170, 341, 500, or 1000 ppm of diethylacetylurea or containing 500, 1000, or 4000 ppm of sodium barbital for periods of 2 or 10 weeks. Rats were terminated at 2 or 10 weeks and the histology of the kidney was evaluated using light microscopy with hematoxylin and eosin staining and staining by the Heidenhain method. Quantitative analysis showed dose responses for the degree of droplet accumulation in the P2 and P3 segments of the proximal tubules. Diethylacetylurea was more potent. Immunohistochemistry and ultrastructural evaluation revealed the nature of the droplets. Western blotting confirmed the presence of alpha 2u-globulin. Renal tubular necrosis, regeneration, and increased levels of cell proliferation using proliferating cell nuclear antigen immunohistochemistry were also found. Female rats similarly exposed to each chemical did not show tubule droplet accumulations nor renal lesions. We confirm for the first time that these two chemicals can be added to the enlarging list of nephrotoxic chemicals inducing alpha 2u-globulin nephropathy and possessing tumor promoting and renal carcinogenic properties.

Animals↗
PubMed1994

Thirteen-week oral toxicity study of magnesium chloride in B6C3F1 mice.

Magnesium chloride (MgCl2.6H2O) was administered at dietary levels of 0 (control), 0.3, 0.6, 1.25, 2.5 or 5% to groups of 10 male and 10 female B6C3F1 mice for 13 weeks. In both sexes of the 5% treatment group a decrease in body weight was observed. While clinical signs and hematological or blood biochemistry parameters showed no treatment-related effects, histopathologically, vacuolation of kidney tubular cells was apparent in males of the 2.5 and 5% concentration groups. Thus, the study demonstrated that diet containing over 2.5% MgCl2.6H2O exerts toxic effects in B6C3F1 mice. We therefore conclude that a 2.5% level of MgCl2.6H2O in the diet is the minimal toxic dose.

Animals↗
PubMed1994

Energy restriction prevents and reverses immune thrombocytopenic purpura (ITP) and increases life span of ITP-prone (NZW x BXSB) F1 mice.

Male (NZW x BXSB)F1 (W/BF1) mice develop immune thrombocytopenic purpura (ITP), which involves antiplatelet autoantibodies and shortened platelet life span. To determine whether reduction of dietary energy can prevent the development or reverse the progression of ITP, male W/BF1 mice were separated into five experimental groups and either given free access to semipurified diet (designated Group A, n = 50) or consumed 32% less energy from an otherwise comparable diet (Group B6, n = 20), or were initially allowed free access to diet then switched to energy restriction at ages 14, 17 or 22 wk (Groups B14, n = 10; B17, n = 20; B22, n = 20). Thrombocytopenia was prevented by energy restriction in Group B6 mice. Platelet-associated IgG (PAIgG) autoantibody levels and the number of splenic antiplatelet antibody-forming cells were low (P < 0.01) and the survival of injected IgG-coated RBC was extended in energy-restricted Group B6 mice (P < 0.01) compared with mice in Group A. Group A mice became progressively thrombocytopenic, with platelet counts as low as 34 x 10(10)/L. Progression of thrombocytopenia was reversed when energy restriction was initiated in Groups B14, B17 and B22, with platelet counts > or = 88 x 10(10)/L and reduction of PAIgG. Life span was extended among early onset energy-restricted Group B6 and Group B14 mice (P = 0.0001 and P = 0.005) but not among late onset energy-restricted Group B17 and Group B22 mice (P = 0.06 and P = 0.35) compared with Group A mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Demonstration of a marked reduction in the amount of GPIIb in most type II patients with Glanzmann's thrombasthenia.

In this study employing a sensitive immunoblot assay, we have characterized GPIIb and GPIIIa in thrombasthenic platelets from seven type II and four type I patients from 10 unrelated families. The amounts of GPIIb and GPIIIa were both markedly reduced in all these patients, and abnormal molecular weight GPIIb or GPIIIa was not detected. In all of four type I patients the amount of GPIIb was much lower than that of GPIIIa. In this study, however, we found that the amount of GPIIb was also lower even in six out of seven type II patients. Immunodepletion of patients' platelets with AP2 (a monoclonal antibody specific for the GPIIb-IIIa complex), AP3 (specific for GPIIIa) or AMF7 (specific for alpha v) further confirmed that GPIIIa existed in excess, and demonstrated that excess GPIIIa were mostly in free form and not associated with GPIIb or alpha v. The reduction of GPIIb may represent an abnormality in GPIIb processing in these type II and type I thrombasthenic platelets. It remains unclear whether these two subgroups represent distinct categories.

Blood Platelets↗
PubMed1994

Cyclic thrombocytopenia associated with IgM anti-GPIIb-IIIa autoantibodies.

We studied a female patient with cyclic fluctuation in platelet count following splenectomy for autoimmune thrombocytopenia. The cyclical fluctuation appeared to be in phase with her menstrual cycle and her platelet count was low during menses. Bone marrow examinations performed at the peak as well as the bottom of the platelet count showed normal or increased numbers of megakaryocytes. The patient's platelet count increased rapidly after intravenous gamma-globulin (IVIgG) therapy, suggesting that a failure of platelet production is unlikely to account for the cycle. Platelet-associated IgM (PAIgM) was markedly elevated, whereas PAIgG was normal at any stage of the cycle. MACE assay demonstrated that PAIgM contained IgM anti-glycoprotein (GP) IIb-IIIa autoantibodies. Comparison between MACE assay using untreated and EDTA-treated platelets at 37 degrees C demonstrated that the platelet-associated IgM autoantibodies mainly recognized divalent cation-dependent conformation(s) of GPIIb-IIIa. No antibodies were, however, detected in her serum. The levels of IgM anti-GPIIb-IIIa showed an inverse relationship with the platelet count. In spite of the marked increase in platelet count after IVIgG, however, the levels of IgM anti-GPIIb-IIIa remained elevated. These findings suggest that platelet-associated IgM anti-GPIIb-IIIa autoantibodies are of pathogenic significance in this patient.

Autoantibodies↗