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Biomedical subjects

N Shimozawa

Publications and source records attributed to N Shimozawa.

At least 127 records · Page 7Linked to original sources
PubMed1994

Molecular cloning and functional expression of a human peroxisomal acyl-coenzyme A oxidase.

cDNA encoding the human peroxisomal acyl-coenzyme A oxidase (AOX) was cloned and sequenced. The longest cDNA insert isolated has 3083 bases and encodes the entire protein of 661-amino acids, including the carboxyl-terminal sequence (Ser-Lys-Leu) known as a minimal peroxisome-targeting signal. At the amino acid level, the significantly high homology (89%) to rat AOX was found. In the cDNA-expression experiment, significant amount of AOX was accumulated in human skin fibroblast and the expressed AOX was catalytically active, while only a limited amount was found in Zellweger syndrome patient's fibroblast not having normal peroxisomes.

Acyl-CoA Oxidase↗
PubMed1994

Identification of a nonsense mutation in ALD protein cDNA from a patient with adrenoleukodystrophy.

The molecular basis of X-linked adrenoleukodystrophy (ALD) was investigated. Six (A to 50) fragments of cDNA for ALD protein (Mosser et al. Nature 361: 726-730, 1993) from an adult patient with adrenomyeloneuropathy were amplified by PCR and mutations were screened by Mutation Detection Enhancement gel electrophoresis. A single base substitution (2154 C-->T, which resulted in the formation of a termination codon for glutamine (Q590STOP) and deletes Pst I site (CTGCAG-->CTGTAG), was detected. Eight other ALD patients did not have this mutation. A family study revealed the presence of both the mutant and normal alleles in the mother, a sister and a niece, indicating that these individuals were carriers. A nephew with childhood ALD who died 10 years earlier had the same mutant allele as detected by Pst I restriction assay. This report is the first description of a mutant allele for ALD, at the cDNA level, and presents confirmatory evidence of ALD protein as the primary etiology of ALD.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1994

Proliferative responses towards native, heat-denatured and pepsin-treated ovalbumin by peripheral blood mononuclear cells from patients with hen's egg-sensitive atopic dermatitis.

In order to clarify the mechanism of food-antigen recognition, the proliferative responses of peripheral blood mononuclear cells (PBMCs) to native, heat-denatured or pepsin-treated ovalbumin (OA) were investigated in 16 hen's egg-sensitive patients with atopic dermatitis (AD). Seven of them had hypersensitivity to boiled hen's egg and others had not. The responses of PBMCs to heat-denatured OA were lower than those to native OA in the patients without hypersensitivity to boiled hen's egg. However, there were no differences of the responses of PBMCs between heat-denatured OA and native OA in the patients with hypersensitivity to boiled hen's egg. Moreover, the reduction of the responses of PBMCs to pepsin-treated OA was recognized in six out of seven patients. The primary structure of OA did not change by heating or pepsin treatment according to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). These results suggested that the secondary structure of OA changed in connection with the reduction of the responses of PBMCs to denatured OA. In addition, we demonstrated the suppressive effect of anti-HLA-DR and anti-HLA-DQ monoclonal antibodies on the proliferative response of PBMCs to OA. The results suggested that the proliferative responses of PBMCs to OA were restricted by HLA-DR or HLA-DQ in hen's egg-sensitive patients with AD.

Antibodies, Monoclonal↗
PubMed1994

High-intensity proton and T2-weighted MRI signals in the globus pallidus in juvenile-type of dentatorubral and pallidoluysian atrophy.

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder. An expanded CAG trinucleotide repeat sequence motif in a gene on the short arm of chromosome 12 has recently been identified in patients with DRPLA. Juvenile-type DRPLA is characterized by childhood onset and progressive myoclonic epilepsy (PME). According to the pathological study, the degeneration of the globus pallidus is more marked in this than in other types. We observed high-intensity signals in the globus pallidus on proton and T2-weighted magnetic resonance imaging (MRI) in a patient clinically diagnosed as juvenile-type DRPLA who had the expanded CAG trinucleotide repeat motif in the DRPLA gene. The globus pallidus may be affected in the early stages of this type of DRPLA, and MRI may be useful for the early diagnosis of DRPLA.

Atrophy↗
PubMed1994

Intravenous immunoglobulins suppress immunoglobulin productions by suppressing Ca(2+)-dependent signal transduction through Fc gamma receptors in B lymphocytes.

A high dose intravenous immunoglobulin (IVIG) therapy is used in the treatment of a wide range of autoimmune disorders. However, the mechanisms of the action of IVIGs remain poorly understood. To analyse the mechanisms of effects of IVIGs on immunoglobulin (Ig) production of B cells, the effects of IVIGs on B lymphoblastoid cell lines transformed by Epstein-Barr virus (LCLs) were investigated. The productions of IgG or IgM of LCLs were dose-dependently suppressed by polyethylene glycol (PEG)-treated IVIG or pH 4-treated IVIG though the productions were not or only slightly suppressed by pepsin-treated IVIG. The suppression by IVIGs was blocked by anti-human IgG Fc or anti-Fc gamma RII. C mu gene expression and mu s C terminal gene expression of LCLs were suppressed by PEG-treated IVIG, whereas neither C mu gene expression nor mu s C terminal gene expression of LCLs were suppressed by pepsin-treated IVIG. Although the increase in intracellular calcium concentration in LCLs was not suppressed by pepsin-treated IVIG, the increase was suppressed by PEG-treated IVIG. This suppressing effect of PEG-treated IVIG on intracellular calcium concentration of LCLs was blocked by anti-human IgG Fc or anti- Fc gamma RII. Our results suggest that IVIGs suppressed the Ca(2+)-dependent signal transduction through Fc gamma R on B-cell membrane, consequently, the transcription of C mu mRNA, especially secreted mu mRNA was suppressed in the B cells.

B-Lymphocytes↗
PubMed1994

A wild-type mu s C-terminal gene is expressed in Bloom's syndrome cells.

Selective IgM deficiency is found commonly in patients with Bloom's syndrome (BS). Serum IgM concentrations were low though serum IgG and IgA concentrations were normal in both patients with BS included in the study. In a previous study the authors showed that selective IgM deficiency in BS is due to an abnormality in the maturation of surface IgM-bearing cells into IgM-secreting cells and a failure of secreted mu (mu s) mRNA synthesis. The membrane-bound mu (mu m) and mu s mRNA are produced from transcripts of a single immunoglobulin mu gene by alternative RNA processing pathways. The control of mu s mRNA synthesis depends on the addition of poly(A) to mu s C-terminal segment. The study described here demonstrated that there was no mutation or deletion in the sequence including mu s C-terminal coding sequence, the RNA splice site (GG/TAAAC) at the 5' end of mu s C-terminal segment, and the AATAAA poly(A) signal sequence, and second GT-rich element immediately down-stream of the cleavage site in both patients.

Adult↗
PubMed1994

Peroxisome assembly factor 1: nonsense mutation in a peroxisome-deficient Chinese hamster ovary cell mutant and deletion analysis.

A cDNA encoding 35-kDa peroxisome assembly factor 1 (PAF-1), a peroxisomal integral membrane protein, was cloned from Chinese hamster ovary (CHO) cells and sequenced. The CHO PAF-1 comprised 304 amino acids, one residue shorter than rat or human PAF-1, and showed high homology to rat and human PAF-1: 90 and 86% at the nucleotide sequence level and 92 and 90% in amino acid sequence, respectively. PAF-1 from these three species contains a conserved cysteine-rich sequence at the C-terminal region which is exactly the same as that of a novel cysteine-rich RING finger motif family. PAF-1 cDNA from a peroxisome-deficient CHO cell mutant, Z65 (T. Tsukamoto, S. Yokota, and Y. Fujiki, J. Cell Biol. 110:651-660, 1990), contained a nonsense mutation at the codon for Trp-114, resulting in premature termination. Truncation in PAF-1 of either 19 amino acids from the N terminus or 92 residues from the C terminus maintained the peroxisome assembly-restoring activity when tested in both the Z65 mutant and the fibroblasts from a Zellweger patient. In contrast, deletion of 27 or 102 residues from the N or C terminus eliminated the activity. PAF-1 is encoded by free polysomal RNA, consistent with a general rule for biogenesis of peroxisomal proteins, including membrane polypeptides, implying the posttranslational transport and integration of PAF-1 into peroxisomal membrane.

Amino Acid Sequence↗
PubMed1994

Comparison of allergic diseases and specific IgE antibodies in different parts of Japan.

We investigated the differences of allergic diseases and specific IgE antibodies to inhaled or ingested allergens between two cities in a Japanese pediatric population. One of the two cities is Itoman, which is a subtropical city in Okinawa prefecture; the other is Gifu, which is a Temperate Zone city in Gifu prefecture. The prevalence of asthma or wheezy bronchitis was significantly higher in Itoman; however, the prevalence of atopic dermatitis was significantly higher in Gifu. Furthermore, the positive percentages of specific IgE antibodies to inhaled allergens such as house dust, and Dermatophagoides farinae were higher in Itoman. The positive percentages of specific IgE antibodies to ingested allergens such as egg white, cow milk, and soybean were higher in Gifu. These results suggest that the differences in prevalence of allergic diseases and allergens may depend on differences in the triggering environmental factors between different parts of Japan.

Administration, Inhalation↗
PubMed1994

Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis.

We describe four infants with a novel subtype of an isolated deficiency of one of the peroxisomal beta-oxidation enzymes with detectable enzyme protein. The patients showed characteristic clinical and biochemical abnormalities, including hypotonia, psychomotor retardation, hepatomegaly, typical facial appearance, accumulation of very-long-chain fatty acids, and decreased lignoceric acid oxidation. However, beta-oxidation enzyme proteins were detected by immunoblot analyses, and large peroxisomes were identified by immunofluorescence staining. In order to identify the underlying defect in these patients, complementation analysis was introduced using fibroblasts from these patients and patients with an established deficiency of either acyl-CoA oxidase or bifunctional enzyme, as identified by immunoblotting. In the complementing combinations, fused cells showed increased lignoceric acid oxidation, resistance against 1-pyrene dodecanoic acid/UV selection, and normalization of the size and the distribution of peroxisomes. The results indicate that two patients with a more severe clinical course were suffering from bifunctional enzyme deficiency and that the other two infants, who were siblings and had a less severe clinical presentation, were the first patients with acyl-CoA oxidase deficiency with detectable enzyme protein.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1993

Suppressive effects of elimination diets on T cell responses to ovalbumin in hen's egg-sensitive atopic dermatitis patients.

We investigated the effect of elimination diets on T cell responses to ovalbumin (OA) in hen's egg-sensitive atopic dermatitis (AD) patients. The proliferative responses of both peripheral blood mononuclear cells (PBMCs) and T cells with monocytes to OA decreased after elimination diets, but those to Candida albicans or phytohemagglutinin (PHA) did not decrease after elimination diets. The proliferative responses of CD4+ T cells with monocytes to OA decreased after elimination diets. In these patients, clinical symptoms of AD improved. These results indicate that T cells, especially CD4+ T cells, respond to food antigens in food-specific lymphocyte responses, and that elimination diets may be able to initiate reduction of the responsiveness of food-sensitive T cells, especially CD4+ T cells. Moreover, the surface marker phenotypes of the T cells responding to OA were analysed. Our results showed that CD4+CD45RA+ T cells tended to increase. The increase in circulating CD4+CD45RA+ T cells might function as systemic suppression against immune responses in the skin.

Adolescent↗
PubMed1993

Expression of secreted immunoglobulin heavy chain genes and immunoglobulin-secreting cells in human lymphocytes.

The numbers of immunoglobulin-secreting cells in peripheral blood mononuclear cells and the expression of mRNA for secreted type of immunoglobulin heavy chains were investigated in healthy children, compared with the percentages of surface immunoglobulin-bearing cells and the expression of mRNA for membrane-bound type of immunoglobulin heavy chains, respectively. Although a difference between expression of mu s mRNA and mu m mRNA was unclear, mu mRNA was well transcribed. The expression of gamma s mRNA or alpha s mRNA was markedly higher than that of gamma m mRNA or alpha m mRNA. However, although the detection methods could be of different sensitivities, the percentage of IgM-, IgG-, or IgA-secreting cells was markedly low, compared with the percentage of surface IgM-, IgG-, or IgA-bearing cells, respectively. Therefore, additional regulation of the pattern of the immunoglobulin gene expression may be exerted at the translational and post-translational stages.

Antibody-Producing Cells↗