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Biomedical subjects

A Yoshioka

Publications and source records attributed to A Yoshioka.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Successful induction of immune tolerance and novel hemostatic effects in a hemophilia A with high-responder inhibitor by regular infusions of factor VIII].

A hemophilia A patient with high responder inhibitor had been treated by (activated) prothrombin complex concentrates (A) PCC and activated factor VII until the occurrence of intracranial bleeding at the age of 6 years. Since the inhibitor titer was decreased less than 1 Bethesda Units/ml, high dose of factor VIII was given followed by the infusions of factor VIII concentrates (100 units/kg) three times a week. In spite of previous episodes of anamnestic responses by factor VIII products before, the inhibitor titer did not increase and disappeared completely 6 months after the FVIII infusion therapy. The specific anti-factor VIII IgG subclasses of the inhibitor were IgG2 and IgG4. The inhibitor recognized both light and heavy chains. He have no bleeding episode for 6 months since the beginning of the prophylactic with factor VIII concentrates.

Blood Coagulation Factors↗
PubMed1996

[Neutrophil elastase and elastin-derived peptides in BAL fluid and emphysematous changes on CT scans].

We examined the relationship between neutrophil elastase, elastin-derived peptides in bronchoalveolar lavage (BAL) fluid, and the development of pulmonary emphysema. The level of neutrophil elastase was higher in asymptomatic current smokers with emphysematous changes on computed tomographic scans than in current smokers without emphysematous changes, and was found to be correlated with the level of elastin-derived peptides in BAL fluid. Subjects with high levels of neutrophil elastase in BAL fluid had faster annual declines in FEV1. We conclude that the level of neutrophil elastase in BAL fluid can be used to differentiate asymptomatic cigarette smokers who are at risk for pulmonary emphysema from those who are not.

Aged↗
PubMed1995

cDNA cloning, molecular characterization, and chromosomal localization of NET(EPHT2), a human EPH-related receptor protein-tyrosine kinase gene preferentially expressed in brain.

By screening a human fetal brain cDNA expression library using a monoclonal anti-phosphotyrosine antibody, we have isolated a cDNA clone encoding a receptor type protein-tyrosine kinase belonging to the EPH family, NET (neuronally expressed EPH-related tyrosine kinase). NET shows 87% homology in nucleotide sequence and 99% homology in the deduced amino acid sequence to rat elk, suggesting that NET is the human homologue of elk. The NET gene is mapped to human chromosome 3q21-q23 by PCR screening of a human-rodent somatic cell hybrid panel and by fluorescence in situ hybridization. Examination of NET mRNA expression in several human tissues has shown that the NET gene is expressed preferentially in brain as a 5-kb transcript. Steady-state levels of NET mRNA in human brain are greater in the midterm fetus than in the adult. Lower levels of NET mRNA are found in fetal kidney and adult skeletal muscle. The expression pattern of NET mRNA thus differs from that of elk, suggesting that these two gene products may perform distinct roles in human and rat. NET transcripts are detected in human NTera-2 teratocarcinoma cells after retinoic acid-induced neuronal differentiation. Several human tumor cell lines derived from neuroectoderm including primitive neuroectodermal tumor, small cell lung carcinoma, and neuroblastoma also express NET transcripts. Since the NET mRNA expression in human brain is developmentally regulated and is induced during neuronal differentiation, NET potentially plays important roles in human neurogenesis.

Adult↗
PubMed1995

Measurement of anti-factor VIII IgG, IgG4 and IgM alloantibodies in previously untreated hemophilia A patients treated with recombinant factor VIII. Kogenate Japanese Clinical Study Group.

Using enzyme-linked immunosorbent assay (ELISA), we measured anti-factor VIII immunoglobulin G (IgG), IgG4 and IgM in serum samples obtained from hemophilia A patients treated with a recombinant factor VIII (rFVIII) preparation (Kogenate). Twelve pre- and post-treatment serum samples from 3 previously untreated patients who developed an inhibitor (alloantibody) were evaluated. Both rFVIII and plasma-derived factor VIII (pdFVIII) were used as antigen. Serum samples were diluted 37.5-fold. For the measurement of IgM antibody, protein A Sephadex suspension was added to the patients' serum samples and the supernatant was assayed. Anti-human IgG, IgG4, and IgM monoclonal antibodies labelled with peroxidase were added and absorbance at 450nm was determined. The reactivity of the IgG antibody with rFVIII and pdFVIII was extremely low. Samples containing the IgG4 inhibitor with a neutralizing activity of approximately 7.5 Bethesda units (BU)/ml resulted in absorbance values of 0.451-0.551, thus demonstrating a considerably high degree of sensitivity. The correlation between the neutralizing activity and reactions of the IgG4 antibody with rFVIII and pdFVIII antigens was high, with correlation coefficients of 0.912 and 0.966, respectively. Furthermore, the correlation coefficient between the measured absorbance values for the antibody reacted with pdFVIII and rFVIII was 0.961. No correlation was found between the reactivity of IgM to rFVIII and pdFVIII.

Adult↗
PubMed1995

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage.

We demonstrate by reverse transcriptase-polymerase chain reaction and Southern blotting that an immortalized rat oligodendroglial cell line (CG-4) expresses the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor (GluR) genes GluR2-7, KA-1, and KA-2 and that nonimmortalized cells of the rat oligodendroglial lineage express the GluR1-3, GluR5-7, KA-1, and KA-2 genes. Lactic dehydrogenase release assays show that both immortalized and nonimmortalized cells of the oligodendroglial lineage are damaged by a 24-h exposure to 500 microM kainate or 5 mM L-glutamate, but not by a 24-h exposure to up to 10 mM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NMDA GluR channel inhibitor 6-cyano-7-nitroquinoxaline-2,3-dione and is also averted if Ca2+ is removed from the culture medium. Cyclothiazide, which blocks desensitization of AMPA-preferring GluRs, increases cytotoxicity of kainate as well as inducing toxicity of AMPA. We conclude that cells of the oligodendroglial lineage express a population of AMPA-preferring and possibly also kainate-preferring GluR channels that are capable of mediating Ca(2+)-dependent excitotoxicity and that AMPA-induced cytotoxicity is blocked by desensitization of AMPA-preferring GluRs.

Animals↗
PubMed1995

Molecular characterization and chromosomal localization of DRT (EPHT3): a developmentally regulated human protein-tyrosine kinase gene of the EPH family.

By screening a human fetal brain cDNA expression library using a monoclonal antiphosphotyrosine antibody and by 5' RACE procedures, we have isolated overlapping cDNAs encoding a receptor-type tyrosine kinase belonging to the EPH family, DRT (Developmentally Regulated EPH-related Tyrosine kinase gene). The DRT gene is expressed in three different size transcripts (i.e. 4, 5 and 11 kb). DRT transcripts are expressed in human brain and several other tissues, including heart, lung, kidney, placenta, pancreas, liver and skeletal muscle, but the 11 kb DRT transcript is preferentially expressed in fetal brain. Steady-state levels of DRT mRNA in several tissues, including brain, heart, lung and kidney, are greater in the midterm fetus than those in the adult. DRT transcripts are detectable at low levels in a human teratocarcinoma cell line (NTera-2), but its expression is greatly increased after the NTera-2 cells are induced to become postmitotic neurons (NTera-2N) by retinoic acid treatment. These data suggest that DRT plays a part in human neurogenesis. A large number of tumor cell lines derived from neuroectoderm express DRT transcripts, including 12 neuroblastomas, two medulloblastomas, one primitive neuroectodermal tumor and six small cell lung carcinomas (SCLC). Interestingly, several neuroblastoma cell lines with 1p deletion and one SCLC cell line express DRT transcripts of aberrant size (i.e. 3, 6 and 8 kb) in addition to those found in normal tissues. We mapped the DRT gene to human chromosome 1p35-1p36.1 by PCR screening of human-rodent somatic cell hybrid panels and by fluorescence in situ hybridization. As the distal end of chromosome 1p is often deleted in neuroblastomas and altered in some cases in SCLCs, these chromosomal abnormalities may have resulted in the generation of aberrant size transcripts. Thus, the DRT gene may play a part in neuroblastoma and SCLC tumorigenesis.

Amino Acid Sequence↗
PubMed1995

Anti-Ro/SSA-associated annular erythema in childhood.

We report four children with anti-Ro/SSA positive who presented with an annular erythema as a manifestation of Sjögren's syndrome. One patient had an aseptic meningoencephalitis as well as cutaneous lesions. Children with annular erythema should be carefully followed for features of Sjögren's syndrome, which is believed to be a rare condition in children.

Adolescent↗
PubMed1995

Common inhibitory effects of human anti-C2 domain inhibitor alloantibodies on factor VIII binding to von Willebrand factor.

Factor VIII (FVIII) inhibitor alloantibodies obtained from seven severe haemophilia A patients were examined for their binding regions and their effects on FVIII binding to von Willebrand factor (vWF). Immunoblotting analysis with a panel of recombinant fragments demonstrated that the binding regions of antibodies in cases 1-5 were contained in the C2 domain of the light chain. Antibodies from cases 1 and 2, which recognized an epitope within residues 2248-2312, completely inhibited FVIII/vWF binding in an ELISA (IC50: 5.0 and 9.0 micrograms/ml, respectively). Antibodies from case 3 recognizing 2170-2312 and case 5 recognizing 2170-2327 also inhibited FVIII/vWF binding (IC50: 110 and 400 micrograms/ml, respectively). Case 4 antibodies recognizing 2218-2307 showed barely detectable inhibition and cases 6 and 7 antibodies recognizing the 44 kD heavy chain, did not inhibit. Our results demonstrate that all anti-C2 alloantibodies with epitopes that extend to the residue 2312 inhibit vWF binding and that an overlap of the inhibitor epitope with residues 2308-2312 is critical for maximal inhibition of vWF binding. Prevention of FVIII/vWF binding appears to be a common property of anti-C2 domain inhibitor alloantibodies.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

ABO blood group genotype and plasma von Willebrand factor in normal individuals.

von Willebrand factor (vWF) is a multimeric plasma protein with ABO (H) blood group sugar chains. We investigated a total of 330 plasmas from normal individuals having various ABO genotypes, with special reference to vWF antigen and its platelet glycoprotein-Ib-related biological activities, termed ristocetin cofactor (RCof) and botrocetin cofactor (BCof). RCof reflects the biological activity of higher vWF multimers, while BCof reflects that of vWF of multimers of all sizes. Plasmas from normal individuals carrying one O gene (genotypes AO and BO) had slightly, but proportionally lower levels of vWF antigen, RCof, and BCof than those carrying no O gene (genotypes AA, AB, and BB). Normal plasmas from individuals carrying two O genes (genotype OO) showed much lower values for these parameters than the other plasmas, as previously reported. However, multimeric analysis of plasma vWF antigen revealed no differences among the different genotypes.

ABO Blood-Group System↗
PubMed1995

Partial clinical improvement in Upshaw-Schulman syndrome following prostacyclin infusion.

We report on a Japanese girl with Upshaw-Schulman syndrome, a congenital disorder characterized by recurrent thrombocytopenia, microangiopathic hemolytic anemia, proteinuria and hematuria that can be transiently improved by the transfusion of plasma or various plasma components. Unusually Large von Willebrand Factor (ULvWF) multimers were found during both relapse and remission phases. Serial plasma levels of 6-keto-prostaglandin F1 alpha (PGF1 alpha), the stable metabolite of prostacyclin (PGI2), were low at relapse. When the patient was treated with continuous PGI2 infusion, the microangiopathic hemolytic process gradually subsided within 10 days. These results suggest that PGI2 may be partly involved in the pathogenesis of this congenital disorder.

Anemia, Hemolytic, Congenital↗
PubMed1995

Neutrophil elastase associated with alveolar macrophages from older volunteers.

We focused on the role of neutrophil elastase (NE) in alveolar macrophages (AMs), and evaluated the esterolytic activity using an NE-sensitive substrate, methoxysuccinyl-alanyl-alanyl-prolyl-valyl paranitroanilide (MEOSAAPVNA) in AMs from 36 older healthy volunteers (61 +/- 2 yr mean age +/- standard error) and examined the relationship to chronic effects of cigarette smoking and also to the presence of low attenuation areas (LAAs) on the computed tomographic (CT) scans. The AMs from the subjects with LAAs showed significantly higher activity than those from the current smokers without LAA (1.16 +/- 0.40 versus 0.34 +/- 0.07 nM, respectively, p < 0.05). Although the study of inhibitory profile revealed that the esterolytic activity could not be attributed to NE alone, the NE activity seemed to dominate in AMs at least from some who had higher esterolytic activity. We then examined the releasability of NE from cultured AMs in 10 subjects. The immunologic NE complex with alpha 1-protease inhibitor (alpha 1-PI) was released significantly higher in the LAA(+) group than in the LAA(-) group (17.4 +/- 6.5 versus 1.8 +/- 0.6 micrograms/L, respectively, p < 0.05). These data suggest that NE in AMs may play a role in the development of emphysematous changes in susceptible smokers.

Adult↗
PubMed1995

Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema.

In an attempt to further evaluate the role of neutrophil elastase (NE) in the development of emphysema, we examined the immunologic quantity of NE bound to alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF) supernatant from 36 community-based older volunteers. They were classified into three groups: 10 current smokers with low attenuation areas (LAAs) on the lung computed tomography (CT) scans who were considered to have subclinical emphysema, 13 current smokers who had a comparable smoking history but no LAA, and 13 noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was significantly increased in the subjects with subclinical emphysema when compared not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52 +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory activity measured by a spectrophotometric method using methoxysuccinyl-alanyl-alanyl-prolyl-valyl-paranitroanilide did not show any significant difference between the two groups of current smokers. There was no difference in the pattern or density of native and proteolysed alpha 1-PI bands between the three groups by Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that may differentiate smokers who are potentially developing emphysema from those who are not.

Aged↗
PubMed1995

Maternal autoimmune response to recombinant Ro/SSA and La/SSB proteins in Japanese neonatal lupus erythem atosus.

BACKGROUND: Neonatal lupus erythematosus (NLE) is a syndrome characterized by dermatitis and congenital heart block (CHB). The disease is mostly associated with transplacental passage of maternal anti-Ro/SSA and/or La/SSB antibodies. OBJECTIVE: To examine maternal autoimmune response to recombinant Ro/SSA and La/SSB proteins in NLE with a single ethnic background. METHODS: This study examined 12 NLE infants and their mothers. Serum samples were tested by enzyme-linked immunosorbent assay for reactivity with full-length recombinant human 60-kd Ro/SSA, 52-kd Ro/SSA, and 48-kd La/SSB proteins. RESULTS: All 10 infants with skin lesions and/or CHB had maternal antibodies reactive to both the 60- and 52-kd Ro/SSA polypeptide components of the Ro/SSA particle. Anti-60-kd Ro/SSA without anti-52-kd Ro/SSA, or vice versa, was found in mothers of infants who had only hepatic manifestation of NLE. Nine of 12 NLE infants had anti-48-kd La/SSB. CONCLUSION: In the majority of Japanese infants with NLE, maternal anti-Ro/SSA autoimmune response was directed against both of 60-kd and 52-kd recombinant Ro/SSA proteins. There was no profile of anti-Ro/SSA and La/SSB response unique to mothers of children with CHB or cutaneous manifestations of NLE.

Adenosine Triphosphatases↗
PubMed1995

[An enzyme-linked immunosorbent assay determining anti-principal neutralizing determinant antibodies using synthetic peptides deduced from cDNA sequences of HIV-1 V3 loop domain].

The V3 domain, one of the hypervariable regions of gp 120 in HIV-1 possesses principal type-specific neutralizing determinant (PND). The V3 domain has the epitopes for class I major histocompatibility antigens of cytotoxic-T lymphocyte and helper-T-lymphocyte recognition sites, and also has major determinants for cell tropism towards macrophage, microglia, and human brain-derived fibroblast. Therefore, establishment for the assay of anti-PND antibodies in patients with HIV-1 infection appears to be important for the estimation on developing AIDS in these patients. We here describe a simple enzyme-linked immunosorbent assay (ELISA) for the measurement of anti-PND antibodies found in Japanese hemophiliacs. ELISA was performed using synthetic peptides, each 15 amino acid residues deduced from cDNA sequences of seven HIV-1 V3 domain mutants, which include 5 North-American and European strains (IIIB, MN, RF, SC, and WMJ-2) and 2 African strains (Af1. Con and Af2, Con). The specific antibody binding to each peptide was determined after subtraction of the non-specific binding from the total. In 49 control sera from healthy individuals with HIV-1 antibody negative, the absorbance (M +/- 1SD) at 405 nm was -0.002 +/- 0.064. Then, the cut off value was determined to be M + 4SD. In 48 hemophiliac sera with HIV-1 antibody negative, the absorbance was uniformly less than the cut off value. However, among 44 hemophiliac sera with HIV-1 antibody positive, the anti-PND antibodies were detected in the following frequencies; 2 for IIIB, 20 for MN, 1 for RF, 1 for Af1. Con, and 5 for Af2. Con.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗
PubMed1995

[Spinal canal bleeding in hemophilia A].

Case 1: Sensory and motor paralysis below the L3 level developed in a moderate hemophilia A due to spinal epidural bleeding following lumbar anesthesia for the resection of retro-peritoneal hematoma. By the treatment with cryoprecipitates, the patient recovered to walk with sticks after laminectomy. Case 2: the patient had severe hemophilia A with 220 Bethesda units/ml of inhibitor. The patient suffered from epidural and intramedullary spinal bleeding from C3 to C7 and developed tetraplegia. Since the inhibitor titer was high, infusion therapy with FEIBA was performed. Paralysis gradually reduced to the T5 level, but the patient had both sensory and motor paralysis of the extremities. It is required that an effective hemostastic treatment for spinal canal bleeding in hemophilia A with high-responder inhibitor is established.

Adolescent↗
PubMed1995

[Shear-induced platelet aggregation (SIPA) monitoring of hemostatic effect during platelet transfusion in a patient with Glanzmann's thrombasthenia: a comparison between SIPA and conventional platelet aggregation].

Shear-induced platelet aggregation (SIPA) in a patient with Glanzmann's thrombasthenia was examined during platelet infusion therapy. Prior to platelet infusion, SIPA measured with the modified cone-and-plate type viscometer, as well as ADP-and collagen-induced platelet aggregation measured with the conventional platelet aggregometer, were absent. The patient's SIPA after multiple infusions of platelet, in parallel with the bleeding time and the clinical hemostatic effect, improved to the normal level, while ADP-and collagen-induced platelet aggregation remained abnormal. These observations imply that SIPA is physiologically more relevant than the conventional agonist-induced platelet aggregometry in this type of the disease.

Adenosine Diphosphate↗
PubMed1994

Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene, second edition.

A large number of different mutations in the factor VIII (F8) gene have been identified as a cause of haemophilia A. This compilation lists known single base-pair substitutions, deletions and insertions in the F8 gene and reviews the status of the inversional events which account for a substantial proportion of mutations causing severe haemophilia A.

Base Sequence↗