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Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 361 records · Page 20Linked to original sources
PubMed1994

Mucopolysaccharidosis IV A: molecular cloning of the human N-acetylgalactosamine-6-sulfatase gene (GALNS) and analysis of the 5'-flanking region.

Mucopolysaccharidosis IV A (MPS IV A) is the result of a genetic deficiency in a lysosomal hydrolase, N-acetylgalactosamine-6-sulfatase (GALNS). To investigate MPS IV A patients at the level of the genome, we analyzed the structure of the human GALNS-encoding gene. From the genomic library of a normal subject in lambda EMBL3, we isolated five overlapping clones covering the coding region of the GALNS cDNA and determined the structural organization. The gene is about 50 kb long and contains 14 exons. The 5'-flanking region lacks a canonical TATA box and CCAAT sequences, but is G+C-rich (70.5%), with four GC boxes, characteristic of a housekeeping gene promoter. The transcription initiation site was determined by primer extension analysis, using RNA from human liver and HeLa cells. Transcription was found to initiate at a few sites, the major ones being 58 and 22 bp upstream of the translation initiation codon. The 5'-flanking region had promoter activity by transient expression, determined using a CAT assay. In addition, this region retained promoter activity, even in reverse orientation. The region -98 to -1 upstream of the ATG codon was defined by deletion analysis to be a minimal promoter. One GC box in this region is likely to be a binding site of a regulatory element.

Base Sequence↗
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

Improved oral absorption of enteric coprecipitates of a poorly soluble drug.

An anticancer agent, N-[[[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]amino]carbonyl]-2 - nitrobenzamide (HO-221, 1), shows poor oral absorption and is only slightly soluble in water (0.055 microgram/mL at 37 degrees C). The coprecipitates with polyvinylpyrrolidone or a vinylpyrrolidone and vinylacetate copolymer (copolyvidone) showed a marked increase of the dissolution rate and attainment of temporary supersaturation of 1. The oral bioavailability of these preparations in dogs at a dose of 1 of 5 mg/kg was approximately 60%, which was 3.5 times greater than that of a micronized preparation. Further, the enteric coprecipitate with hydroxypropyl methylcellulose phthalate 200731, which showed a dissolution profile similar to that of the copolyvidone preparation at pH 6.5 but no dissolution at pH 1.2, revealed the almost complete oral absorption. Because intraduodenal administration of the copolyvidone coprecipitate showed a higher absorption than that of per oral administration, it was suggested that the partial precipitation of crystallites in the nonenteric coprecipitates occurred before reaching the absorption site, the small intestine.

Administration, Oral↗
PubMed1994

Inhibition of interferon-gamma and interleukin-2 production from lymphocytes stimulated with food antigens by an anti-allergic drug, Tranilast, in patients with food-sensitive atopic dermatitis.

N(3',4'-dimethoxycinnamoyl) anthranilic acid (Tranilast) inhibits antibody-mediated hypersensitivity reactions, and is an effective drug for patients with bronchial asthma or allergic rhinitis. Interferon-gamma (IFN-gamma) production of ovalbumin (OA)-stimulated peripheral blood mononuclear cells (PBMCs) from hen's egg-sensitive patients with atopic dermatitis (AD) was significantly higher than those of healthy controls. Tranilast inhibited this IFN-gamma production. Moreover, interleukin-2 (IL-2) production of OA-stimulated PBMCs from hen's egg-sensitive patients with AD was also inhibited by Tranilast. Our results suggest that Tranilast can be used to the patients with food sensitive AD.

Anti-Allergic Agents↗
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

Predictive values of cord blood IgE and cord blood lymphocyte responses to food antigens in allergic disorders during infancy.

Proliferative response of cord blood lymphocytes stimulated twice by food antigens and cord blood IgE concentration were measured in 131 full-term newborn infants for the prediction of allergic disorders. Through the follow-up study for 2 1/2 years, the value of stimulation index in proliferative response of cord blood lymphocytes to ovalbumin or bovine serum albumin was greater than 1.5 in 17 (sensitivity 53.1%) of 32 infants in whom allergic disorders developed and less than 1.5 in 81 (specificity 81.8%) of 99 infants who had no allergic disorders (cutoff limit of stimulation index 1.5). The sensitivity was increased (71.9%) by the combination of the cord blood IgE concentration (cutoff limit 1.0 IU/ml) and proliferative response of cord blood lymphocytes to food antigens (cutoff limit of stimulation index 1.5). The combination of the cord blood IgE concentration and proliferative response of cord blood lymphocytes to food antigens is useful for the prediction of allergic disorders. Interleukin-2 production of cord blood lymphocytes stimulated with food antigens was also measured in 24 newborn infants. Interleukin-2 activity in culture supernatants of ovalbumin- or bovine serum albumin-stimulated cord blood lymphocytes correlated well with proliferative response of cord blood lymphocytes to ovalbumin or bovine serum albumin.

Antigens↗
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

Identification of monocyte chemotactic factors in supernatants of ovalbumin-stimulated lymphocytes from patients with atopic dermatitis who are sensitive to hen's egg.

Monocyte chemotactic activities in supernatants of ovalbumin (OA)-stimulated peripheral blood mononuclear cell (PBMC) cultures were studied in patients with atopic dermatitis (AD) who were sensitive to hen's egg. The monocyte chemotactic activities in hen's egg-sensitive AD patients were significantly higher than those of non-atopic healthy controls and patients with immediate allergic symptoms. However, the monocyte chemotactic activities were not detected in bovine serum albumin-stimulated PBMC culture supernatants in patients with AD who were sensitive to hen's egg, but not to cow's milk. Furthermore, there was significant correlation between the monocyte chemotactic activities and proliferative responses of PBMCs to OA in hen's egg-sensitive AD patients, whereas there was no significant correlation between the monocyte chemotactic activities and radioallergosorbent test values. These results suggest that PBMCs stimulated with food antigens produce monocyte chemotactic factors which relate to the pathogenesis of AD in food-sensitive AD patients and that the pathogenesis of AD may be related to cell-mediated immune responses.

Adolescent↗
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

Thyroid cancer in a case with the Alagille syndrome.

A 19-year-old woman with the Alagille syndrome developed papillary thyroid carcinoma with lung metastasis. She was diagnosed as having Alagille syndrome at the age of 8. Following total thyroidectomy and lymph nodes dissection, iodine-131 therapy was conducted for local and distant metastases. This is the first report of a case of thyroid cancer accompanying Alagille syndrome.

Adult↗
PubMed1994

Significance of measurement of pre-S2 antigen for the prevention of vertical transmission of hepatitis B virus in infants born to HBsAg carrier mothers.

The significance of pre-S2 antigen (pre-S2 Ag) as a marker of hepatitis B virus (HBV) infection, especially in infants born to HBsAg carrier mothers who are HBeAg-negative or HBeAg-positive, was evaluated. Pre-S2 Ag was measured by enzyme immunoassay. HBsAg carrier mothers who were HBeAg-negative and HBeAb-positive were divided into two groups: group A, mothers whose infants were not infected with HBV (n = 10) and group B, mothers whose infants were infected with HBV (n = 13). Absorption rates of pre-S2 Ag in group A and B were 0.09 +/- 0.04 and 1.36 +/- 0.95, respectively. The values for pre-S2 Ag in group B were significantly higher than those in group A. Values for pre-S2 Ag among HBsAg carrier mothers who were HBeAg-positive and HBeAb-negative were also measured by reverse passive hemagglutination. In the same way, HBsAg carrier mothers who were HBeAg-positive and HBeAb-negative were divided into two groups: group C, mothers whose infants did not become HBsAg carriers (n = 15) and group D, mothers whose infants became HBsAg carriers (n = 11). The titers of pre-S2 Ag (reverse passive hemagglutination) in group C and D were 2(5.75) +/- 1.68 and 2(10.45 +/- 1.69), respectively. The values for pre-S2 Ag in group D were significantly higher than those in group C. The values for pre-S2 Ag as markers of infectivity became higher with increasing amounts of HBV-DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier State↗
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

Suppression of proliferative responses of lymphocytes to food antigens by an anti-allergic drug, ketotifen fumarate, in patients with food-sensitive atopic dermatitis.

Experimental studies have shown that ketotifen fumarate inhibits reaginic antibody-mediated hypersensitivity reactions. In this study, the proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA) in children with atopic dermatitis (AD), who are sensitive to hen's egg, were significantly higher than those of healthy children. The proliferative responses of PBMCs to OA were dose-dependently inhibited by ketotifen in patients with hen's egg-sensitive AD. Moreover, the inhibition resulted from the effects of ketotifen on T cells. In contrast, the proliferative responses of PBMCs to phytohemagglutinin and tetanus toxoid were not inhibited by ketotifen. These results suggest that ketotifen inhibits food antigen-specific proliferative responses of PBMCs in patients with food-sensitive AD.

Child, Preschool↗