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S Kuroshima

Publications and source records attributed to S Kuroshima.

At least 19 recordsLinked to original sources
PubMed1990

Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation.

Adenine phosphoribosyltransferase (APRT) deficiency causing 2,8-dihydroxyadenine urolithiasis and renal failure is present at a high frequency among the Japanese but not other ethnic groups. A special type of mutant allele, designated APRT*J, with a nucleotide substitution at codon 136 from ATG (Met) to ACG (Thr) is carried by approximately 79% of all Japanese 2,8-dihydroxyadenine urolithiasis patients. We analyzed mutant alleles of 39 APRT deficient patients using a specific oligonucleotide hybridization method after in vitro amplification of a part of the genomic APRT sequence. We found that 24 had only APRT*J alleles. Determination of the haplotypes of 194 APRT alleles from control Japanese subjects and of the 48 different APRT*J alleles indicated that normal alleles occur in four major haplotypes, whereas all APRT*J alleles occur in only two. These results suggest that all APRT*J alleles have a single origin and that this mutant sequence has been maintained for a long period, as calculated from the frequency of the recombinant alleles.

Adenine Phosphoribosyltransferase↗
PubMed1990

Identification of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APART*Q0) leading to 2,8-dihydroxyadenine urolithiasis.

Homozygous deficiency of a purine salvage enzyme, adenine phosphoribosyltransferase (APRT), causes urolithiasis and renal failure. There are two known types of homozygous APRT deficiencies; type I patients completely lack APRT activity while type II patients only partially lack such activity. All type II patients possess at least one APRT*J allele with a substitution from ATG (Met) to ACG (Thr) at codon 136. Type I patients are considered to possess two alleles (APRT*Q0) both of which code for complete deficiencies. Thus, some patients with type II APRT deficiencies may have a genotype of APRT*J/APRT*Q0. As no individuals with such a genotype have previously been identified, we performed extensive analysis on four members of a family by (1) the T-cell method for the identification of a homozygote, (2) the B-cell method for the identification of heterozygotes, and (3) oligonucleotide hybridization after in vitro amplification of a part of genomic APRT sequence for the identification of APRT*J and non-APRT*J alleles. We report here the first evidence that 2,8-dihydroxyadenine urolithiasis developed in a boy aged 2 years with a genotype of APRT*J/APRT*Q0.

Adenine↗
PubMed1989

Detection of an amino acid substitution in the mutant enzyme for a special type of adenine phosphoribosyltransferase (APRT) deficiency by sequence-specific protein cleavage.

Generally, if mutant and normal proteins have similar molecular weights and electric charges, they cannot easily be distinguished from one another. We have developed a unique method by which a mutant enzyme of adenine phosphoribosyltransferase (APRT) can easily be distinguished from normal enzyme with nearly identical molecular weight and electric charge. DNA sequencing data have suggested that in this special type of disease (Japanese-type APRT deficiency) there is an amino acid substitution from Met to Thr at position 136 of APRT. Since normal APRT has only one Met residue, the Japanese-type mutant APRT should be a methionine-free protein. Using both an amino acid sequence-specific antiserum against APRT, and specific cleavage of peptide at the methionine residue with BrCN, we could distinguish between normal and mutant proteins. Thus, normal but not mutant APRT was cleaved with BrCN, indicating that the mutant APRT is a methionine-free protein. All tested patients with the Japanese-type APRT deficiency were found to synthesize exclusively methionine-free APRT. Usefulness of this method is not restricted to a single family, as 79% of all the patients with this disease among Japanese, and more than half of all the patients with this disease reported in the world, are likely to have this unique mutation. Thus, not only sequence-specific cleavage of DNA with restriction endonucleases but also that of protein with a chemical agent has been shown to be sometimes useful for the diagnosis and analysis of a genetic disease by careful examination of normal and mutant amino acid sequences.

Adenine Phosphoribosyltransferase↗
PubMed1987

Selection of human cells having two different types of mutations in individual cells (genetic/artificial mutants). Application to the diagnosis of the heterozygous state for a type of adenine phosphoribosyltransferase deficiency.

We have previously reported the establishment and characterization of B cell lines from patients and family members with various types of adenine phosphoribosyltransferase (APRT) deficiencies. These cell lines contain, at the APRT locus, three different alleles (APRT*1, APRT*Q0, and APRT*J) that are clearly distinguishable from each other. From five genetically heterozygous cell lines with two different genotypes (APRT*1/APRTQ0 and APRT*1/APRT*J), we have selected 48 clones resistant to 2,6-diaminopurine. Resistance to this adenine analogue is a characteristic of cells having defects in both of the APRT alleles in individual cells. The mutant clones from a cell line from a complete-type heterozygote had APRT activities close to zero (mean = 0.04 nmol/min per milligram protein) in the cell extracts, while 15 clones from four cell lines from the four Japanese-type heterozygotes had significant enzyme activities (mean = 3.88 nmol/min per milligram protein). Kinetic studies on two of the mutants from two Japanese-type heterozygous cell lines have shown that affinity to substrate 5-phosphoribosyl-1-pyrophosphate was reduced, indicating that APRT in those clones reflected the characteristics of the Japanese-type enzyme. The data presented here indicate that clones we obtained are genetic/artificial mutants, each having a genetic mutation in a single allele (APRT*J or APRT*Q0) and an artificially produced mutation in the other previously functional allele (APRT*1). The present procedure provided the only diagnostic method for Japanese-type APRT heterozygotes (APRT*1/APRT*J).

Adenine Phosphoribosyltransferase↗
PubMed1987

Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase deficiencies.

Adenine phosphoribosyltransferase (APRT) deficiency leading to 2,8-dihydroxyadenine (DHA) urolithiasis has been considered a rare cause of urolithiasis and renal insufficiency. We have examined samples from 19 Japanese families with DHA lithiasis. In 79% of the families, patients only partially lacked hemolysate APRT activities, clearly contrasting with the complete deficiency in all the patients from non-Japanese families so far reported. All patients with DHA lithiasis were homozygotes for defective APRT genes, whether the deficiency was complete or partial. In family studies we found two symptomatic and four asymptomatic homozygous family members. The segregation figures are compatible with the hypothesis of a simple autosomal recessive mode of inheritance. By analyzing the data stored by a large clinical laboratory in Japan, we estimated that 0.00368% of the general population has DHA lithiasis. These data indicate that more than 1% of the general population possess mutant alleles of the APRT gene as heterozygotes. Our present studies indicate that most of the patients with this disease are undiagnosed in Japan, and probably in other countries also.

Adenine↗
PubMed1987

Cross-resistance to ouabain in a murine leukemia cell variant selected for cis-dichlorodiammineplatinum(II) resistance.

A murine leukemic cell line (R1.1) variant (R1.1/CDDPR-E8) resistant to cis-dichlorodiammineplatinum(II)(CDDP) was also found to be resistant to ouabain, a postulated specific inhibitor of sodium-potassium ATPase. The variant established by the culture of parental cells in step by step increasing concentrations of CDDP, exhibited 11-fold higher resistance to CDDP than the parental R1.1 cells. The present study suggests that a mutational change leading to an alteration in cell membrane characteristics associated with ouabain has also changed the sensitivity of cells against CDDP. Alternatively, the present data may indicate that the cytotoxicity of CDDP is closely linked to its effects on cell membrane.

Animals↗