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Biomedical subjects

Y Sakiyama

Publications and source records attributed to Y Sakiyama.

At least 73 records · Page 4Linked to original sources
PubMed1996

Detection of a novel splice-site mutation that results in skipping exon 3 of the WASP gene in a patient with Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is one of the primary immunodeficiency diseases, that is inherited as an X-linked recessive trait. Since the responsible gene, the WASP gene, has been identified, various mutations for patients with WAS have been reported. We found a novel splice-site mutation in a patient with clinically diagnosed WAS. The mutation was a replacement of ag by aa in an acceptor site of intron 2 of the WASP gene. Sequencing studies of the WASP cDNA of the patient revealed that exon 3 of the WASP gene was abnormally missing due to a splicing defect.

Exons↗
PubMed1996

Complications of childhood Sjögren syndrome.

UNLABELLED: Sjögren syndrome (SS) is a common disorder in adults and involves both glandular and extraglandular systems. We report here four cases of childhood SS complicated by chronic thyroiditis, interstitial nephritis or sweat gland inflammation. Additionally, in one of these cases, the central nervous system was involved. All of these complications are common in adult cases. CONCLUSION: Childhood SS is a systemic "ductilitis" or "exocrinopathy" with complications which are commonly observed in adult cases.

Acidosis, Renal Tubular↗
PubMed1996

Evaluation of the brain uptake properties of [1-11C]labeled hexanoate in anesthetized cats by means of positron emission tomography.

Positron emission tomography (PET) was performed on the cat brain to characterize [1-11C]hexanoate and other [1-11C]labeled short and medium-chain fatty acids as a tracer of fatty acid oxidative metabolism. After an intravenous injection the brain uptake of [1-11C]hexanoate reached a peak followed by rapid washout until 2 min (first phase). Subsequently the total brain uptake was again increased and reached to a peak 7-10 min after tracer injection (second phase). The blood radioactivity of unmetabolized [1-11C]hexanoate was rapidly decreased and almost eliminated within the first 2 min, whereas the blood radioactivity of [11C]CO2/HCO3- was gradually increased and reached a peak approximately 5 min after tracer injection. As the effect of circulating [11C]CO2/HCO3- was examined by a bolus intravenous injection of [11C]CO2/HCO3-, the brain uptake of [11C]CO2/HCO3- was rapidly increased right after the injection and changed parallel to the blood level of [11C]CO2/HCO3-. These results suggest that, in contrast to the previous mouse data, the time-activity curve in the cat brain following intravenous injection of [1-11C]hexanoate has a biphasic pattern, the second phase being determined by peripherally originating [11C]CO2/HCO3-, and therefore does not reflect the metabolism of 11C-labeled fatty acid in the brain.

Animals↗
PubMed1996

IgE and IgG4 antibodies from patients with mite allergy recognize different epitopes of Dermatophagoides pteronyssinus group II antigen (Der p2).

BACKGROUND: Der p 2, composed of 129 amino acids, is one of the major allergens of Dermatophagoides pteronyssinus. Several groups reported epitope mapping of IgE antibody but not of IgG or IgG subclass antibodies in Der p 2. OBJECTIVE: The purpose of this study was to compare the epitopes recognized by Der p 2-specific IgE antibodies with those recognized by IgG4 antibodies. METHODS: Recombinant fusion proteins containing a full-length peptide or overlapping five fragments of Der p 2 were prepared and analyzed for their reactivity with IgE and IgG subclass antibodies in sera from patients with mite allergy by means of Western blot procedure. RESULTS: IgE antibodies in 12 of 13 sera tested bound to full-length Der p 2 (1-129). In 11 of these 12 sera, IgE antibodies bound to one or more of fragments 41-80, 64-105, or 81-129 but not to those of 1-40 or 20-63. Of the 11 sera in which the IgE antibodies to the fragments were detected, only four contained detectable levels of IgG4 antibodies reactive to the fragments. The binding spectra of the IgG4 antibodies against the fragments were rather wide and differed from those of IgE antibodies. CONCLUSION: Results revealed that there are differences in epitope recognition between IgE and IgG4 antibodies; IgE antibodies recognize restricted parts of Der p 2 antigen compared with IgG4.

Animals↗
PubMed1996

Differences in titres of IgE, IgG4 and other IgG subclass anti-Der p 2 antibodies in allergic and non-allergic patients measured with recombinant allergen.

BACKGROUND: The mite allergens are recognized as major causes of allergic disease such as bronchial asthma, allergic rhinitis and atopic dermatitis. The functions of allergen-specific IgG subclass antibodies are not defined. OBJECTIVE: In order to clarify the relationship between IgE and IgG subclasses, we examined serum levels of the Dermatophagoides pteronyssinus group 2 (Der p 2)-specific antibodies of IgE, IgG total and IgG subclasses in children with mite allergy. METHODS: We prepared a recombinant Der p 2 fusion protein and examined serum levels of Der p 2 antigen-specific antibodies by enzyme-linked immunosorbent assay (ELISA) systems developed in our laboratory using a recombinant Der p 2 as target antigen. Sera from 240 children with mite allergy and 25 controls were measured. RESULTS: The serum levels of specific IgE and, to lesser degree, IgG4 were higher in allergic children than non-allergic controls, while in the levels of the other IgG subclasses there was no difference between the two groups. There was no correlation between levels of specific IgE and IgG4 or in those between specific IgG4 and other IgG subclasses. CONCLUSION: Results indicate that the induction of Der p 2-specific IgG4 in allergic diseases is independent to IgE as well as other IgG subclasses.

Adolescent↗
PubMed1996

[Gene therapy for adenosine deaminase deficiency].

Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is a fatal recessive disorder caused by mutations in the gene encoding ADA. Based on the first clinical trial of two young girls with ADA-deficient SCID by recombinant retrovirus-mediated gene transfer at the National Institute of Health of USA, we prepared to treat a four-year-old boy with ADA-deficient SCID who had been treated with PEG-ADA for 3 years. Approval to perform the clinical trial of gene therapy by using his peripheral blood T lymphocytes as the target and recombinant retroviral vector (LASN) as the vector for ADA gene transfer was obtained from both of the Ministry of Health and Welfare and the Ministry of Education, Science, Sports and Culture on 13 February, 1995. The first clinical trial of gene therapy for the patient was initiated on 1 August 1995. He received 8 x 10(8) LASN-transduced lymphocytes in an injection administered intravenously on 8 August and 2.5 x 10(9) transduced lymphocytes on 4 September without any side reactions. The procedure, safety and efficacy of clinical trial of gene therapy were discussed.

Adenosine Deaminase↗
PubMed1995

Overexpression of retinoic acid receptor alpha suppresses myeloid cell differentiation at the promyelocyte stage.

Retinoic acid receptor (RAR) alpha is required to heterodimerize with retinoid X receptor (RXRs) in order to regulate myeloid differentiation. If so, it is expected that overexpression of normal RAR alpha may perturb the RAR alpha/RXR heterodimer formation and also the differentiation of myeloid cells. We have described here the morphology and the RA response of human RAR alpha cDNA transduced murine bone marrow cells using a retroviral vector. Most of RAR alpha transduced cells displayed promyelocyte like morphology and their proportion of c-kit expressing population was increased remarkably compared with the control (Neor gene transduced cells). Furthermore, this morphology was observed even after these cells were brought into the semisolid culture containing IL-3 alone. Interestingly, immature RAR alpha transduced cells differentiated into mature granulocytes under the condition of the high concentration of RA(10(-6) M). We did not observe any effect of RAR alpha on monocytes. These results indicate that overexpression of normal RAR alpha is sufficient for inducing maturation arrest of myeloid cell lineage that is similar to the phenotype found in the acute promyelocytic leukemia bearing PML-RAR alpha translocation.

3T3 Cells↗
PubMed1995

Decreased cytoplasmic immunoglobulin A production during Epstein-Barr virus immortalization on lymphocytes from patients with ataxia-telangiectasia.

Previously, we have reported significantly lower immunoglobulin (Ig) A production in supernatants of cultured lymphoblastoid cells using enzyme-linked immunosorbent assay from patients with ataxia-telangiectasia (AT) when compared to that of age- and sex-matched healthy individuals. Here, we further assess the degree of cytoplasmic Ig production in these cells and also analyze it during the early phase of Epstein-Barr virus immortalization. All classes of cytoplasmic IgM, IgG, and IgA productions were demonstrated in cells from healthy controls. In contrast, cells from patients with AT showed only cytoplasmic IgM and IgG with low or nondetectable levels of IgA during and after the immortalizing process. These results suggest B lymphocytes bearing IgA are functionally immature and/or defective in patients with AT.

Adolescent↗
PubMed1995

A 15-base pair (bp) palindromic insertion associated with a 3-bp deletion in exon 10 of the gp91-phox gene, detected in two patients with X-linked chronic granulomatous disease.

Molecular genetic studies were carried out on two maternal cousins with X-linked chronic granulomatous disease (X-CGD). Sequencing analysis of polymerase chain reaction (PCR)-amplified DNA fragments from both patients revealed a 15-base pair (bp) insertion associated with a 3-bp deletion in exon 10 of the cytochrome b heavy chain (gp91-phox) gene. Results of genomic PCR with primers flanking the insertion/deletion site confirmed the mutation, and also demonstrated that their mothers were carriers for the disease. Palindromic sequences were found in the 15-bp insertion as well as in the flanking 3-bp deletion site, which may play a role in the mechanism of this mutation.

Adolescent↗
PubMed1995

Recurrent pneumococcal meningitis in a patient with transient IgG subclass deficiency.

We report the case of a 3 year old boy who exhibited recurrent serious infections with a transient imbalance of IgG subclass in the second year of life. He suffered from pneumococcal meningitis at 3 months, hepatitis at 9 months, and purulent arthritis at 11 months of age. The second episode of pneumococcal meningitis occurred at 14 months. Serum IgG level was normal for age. Low level of IgG2, undetectable level of IgG4 and negligible level of pneumococcus-specific IgG1-G2 antibodies were found. No other primary immunodeficiency was apparent. Serum IgG2-G4 levels but not pneumococcus-specific IgG1-G2 titers increased by the age of 30 months. At that time, he was inoculated with a polyvalent pneumococcal vaccine along with acellular diphtheria-pertussis-tetanus vaccine. He acquired the immunity against these agents, and had no episodic infections in the following 2 years. This observation stresses the existence of transient IgG subclass deficiency associated with delayed development of the anti-polysaccharide antibody response.

Child, Preschool↗
PubMed1995

[Establishment of superoxide production assay system using Epstein-Barr virus transformed cell line with chemiluminescence].

We established the system to detect superoxide produced by Epstein Barr virus lymphoblastoid cell line (EB-LCL). Superoxide production of EB-LCL was evaluated by measuring chemiluminescence (CL) enhanced with addition of horseradish peroxidase (HRP). Using this system, we measured CL of EB-LCL established from 13 patients with chronic granulomatous disease (CGD) and 8 normal individuals. Significant elevation of CL was observed in all control EB-LCLs, however, no remarkable CL was seen in any patients' EB-LCLs. We examined the effect of recombinant human interferon gamma (rh-IFN-gamma) and granulocyte colony stimulating factor (G-CSF) on CL of EB-LCL in vitro. With addition of rh-IFN-gamma, CL of normal control EB-LCL was significantly enhanced (p < 0.05), on the other hand, G-CSF was shown to have no effect. No significant CL was observed in any CGD patients' EB-LCLs even with addition of rh-IFN-gamma or G-CSF. It was suggested that superoxide produced by EB-LCL detected in this system was dependent on the same NADPH oxidase system which presents in phagocyte.

B-Lymphocytes↗
PubMed1994

Successful intravenous immunoglobulin therapy for recurrent pneumococcal otitis media in young children.

Serum immunoglobulin levels and naturally occurring antibody titres against Streptococcus pneumoniae were measured in seven children aged 1-1.9 years with recurrent pneumococcal acute otitis media (AOM). Three of them had low IgG2 levels. Mean antibody levels of anti-pneumococcal IgG1 and anti-pneumococcal IgG2 were significantly lower in patients when compared to those of healthy controls and children who had less frequent episodes of AOM. Following treatment with intravenous immunoglobulin (IVIG) for 6 months, anti-pneumococcal IgG1 and IgG2 antibody levels increased and the number of episodes of AOM decreased in all patients. Following the discontinuation of IVIG therapy, no AOM episode occurred. Serum levels of anti-pneumococcal IgG1 and IgG2 were normal, which were measured in three subjects at 5, 6, and 12 months after the cessation of IVIG therapy. These results suggested that delayed maturation of anti-pneumococcal antibody production caused recurrent AOM and this condition was corrected by IVIG therapy.

Acute Disease↗
PubMed1994

Molecular genetic studies of two families with X-linked chronic granulomatous disease: mutation analysis and definitive determination of carrier status in patients' sisters.

Molecular genetic studies of two families with X-linked chronic granulomatous disease (X-CGD) were performed. The patients showed abnormal patterns on Southern blot analysis using cytochrome b heavy chain (CYBB) cDNA as a probe. Both patterns differed and neither has ever been observed in normal individuals. We applied the results to the diagnosis of the carrier state in the patients' sisters. The results clearly demonstrated that each patient's sister possessed the same abnormal allele as the patient's CYBB gene, as detected by Southern analysis. Thus, the results confirm that both of the patients' sisters are carriers of the disease. Further molecular analysis of the patients' mutation revealed that they were a point mutation, and a partial deletion of the CYBB gene, respectively. These mutations have not previously been reported.

Amino Acid Sequence↗