Search PubMed⌕ Search

Biomedical subjects

S Fujimori

Publications and source records attributed to S Fujimori.

At least 91 records · Page 5Linked to original sources
PubMed1988

Identification of a single nucleotide change in a mutant gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT Ann Arbor).

HPRT Ann Arbor is a variant of hypoxanthine (guanine) phosphoribosyl-transferase (HPRT: EC 2.4.2.8), which was identified in wo brothers with hyperuricemia and nephrolithiasis. In previous studies, this mutant enzyme was characterized by an increased Km for both substrates, a normal Vmax, a decreased intracellular concentration of enzyme protein, a normal subunit molecular weight and an acidic isoelectric point under native isoelectric focusing conditions. We have cloned a full-length cDNA for HPRT Ann Arbor and determined its complete nucleotide sequence. A single nucleotide change (T----G) at nucleotide position 396 has been identified. This transversion predicts an amino acid substitution from isoleucine (ATT) to methionine (ATG) in codon 132, which is located within the putative 5'-phosphoribosyl-1-pyrophosphate (PRPP)-binding site of HPRT.

Base Sequence↗
PubMed1988

The development of electroretinogram abnormalities and the possible role of polyol pathway activity in diabetic hyperglycemia and galactosemia.

This study examined the induction of electroretinogram abnormalities in hyperglycemia and the possible role of increased polyol pathway activity in the development of these changes. Both diabetic hyperglycemia and galactosemia caused the prolongation of peak latencies and in some cases a reduction in the amplitudes of oscillatory potentials on the b-wave. Diabetic hyperglycemia-associated abnormalities were prevented and normalized by insulin or ADN-138, an aldose reductase inhibitor. Galactosemia-induced abnormalities were inhibited by ADN-138, and were reversed either by ADN-138 treatment or by withdrawal of galactose from the diet. Polyol accumulation was prevented by insulin or ADN-138, and the elevated polyol level was reversed by insulin, ADN-138, or withdrawal of galactose in diabetic hyperglycemia and/or galactosemia. These results suggest that the increased polyol pathway activity in the hyperglycemia may be involved in the development of electroretinogram abnormalities similar to those in human diabetes; therefore, ADN-138 could be a useful drug for therapy of retinopathy in the early diabetic stage.

Animals↗
PubMed1988

Effect of a new aldose reductase inhibitor, 8'-chloro-2',3'-dihydrospiro [pyrrolidine-3,6'(5'H)-pyrrolo[1,2,3-de] [1,4]benzoxazine]-2,5,5'- trione (ADN-138), on delayed motor nerve conduction velocity in streptozotocin-diabetic rats.

The effects of a chemically new type of aldose reductase inhibitor, ADN-138, on delayed motor nerve conduction velocity (MNCV) and sciatic nerve sorbitol, fructose and myo-inositol levels were studied in streptozotocin-diabetic rats. MNCV in rats was significantly delayed after 3 weeks of diabetes and ADN-138 treatment was started at this point. Treatment of diabetics with ADN-138 at 5 and 20 but not 1 mg/kg/d for 3 weeks resulted in a significant increase in MNCV and reduced sorbitol levels to or below those of nondiabetic controls. However, fructose, though decreased in a dose-dependent manner, was not normalized. The reference drug, Sorbinil, showed similar effects on them. After the 3 weeks of ADN-138(20 mg/kg/d) treatment, diabetics were left on ADN-138 or continued further to be treated with it for 3 weeks. The withdrawal of ADN-138 prevented a further increase in MNCV and restored sorbitol and fructose to nontreated diabetic levels, and myo-inositol levels declined. In contrast, the ADN-138-continued group kept improving its MNCV and normalized sorbitol and myo-inositol. These results suggest that polyol accumulation is responsible for delayed MNCV and that the action of ADN-138 on MNCV reflected reversibility of metabolic function in diabetics.

Aldehyde Reductase↗
PubMed1988

A case of pacemaker lead fracture associated with thoracic outlet syndrome.

A pacemaker lead fracture in the left subclavian vein was caused by compression of the clavicle and the first rib; subsequent coil elongation at the same site on the right side was observed in the replacement lead in a patient with thoracic outlet syndrome. Venography showed narrowing of the subclavian vein at the site where the lead abnormalities were observed. This case illustrates that a lead in the subclavian vein can be easily damaged when a patient has thoracic outlet syndrome.

Aged↗
PubMed1988

Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese.

Complete adenine phosphoribosyltransferase (APRT) deficiency causes 2,8-dihydroxyadenine urolithiasis. In previous reports, analysis of the kinetic properties of APRT from APRT-deficient Japanese subjects revealed strikingly similar abnormalities suggesting a distinct "Japanese-type" mutation. In this paper, we report studies of 11 APRT-deficient lymphoblast cell lines. Nucleotide sequence analysis of APRT genomic DNA from WR2, a Japanese-type homozygote, identified a T to C substitution in exon 5, giving rise to the substitution of threonine for methionine at position 136. RNase mapping analysis confirmed this mutation in WR2 and revealed that six other Japanese-type homozygotes carry the same mutation on at least one allele. The remaining Japanese subject, who does not express the Japanese-type phenotype, did not demonstrate this mutation. Southern blot analysis showed that all seven Japanese-type subjects were confined to one TaqI restriction fragment length polymorphism (RFLP) haplotype. These studies provide direct evidence for the nature of the mutation in the Japanese-type APRT deficiency.

Adenine Phosphoribosyltransferase↗
PubMed1988

Renal handling of hypoxanthine and xanthine in normal subjects and in four cases of idiopathic renal hypouricemia.

Pyrazinamide (PZA) was used to study the renal handling of hypoxanthine, xanthine and uric acid in 2 normal subjects and in 4 patients with idiopathic renal hypouricemia; one patient was classified as having a postsecretory reabsorption defect, whereas the others were classified as having a presecretory reabsorption defect. In normal subjects, PZA suppressed strongly the excretion of xanthine as well as uric acid; however, it showed a weak effect on that of hypoxanthine. PZA suppressed all excretion of these 3 compounds in the patient with postsecretory reabsorption defect. PZA showed almost no effect on the excretion of either hypoxanthine, xanthine or uric acid in the patients with presecretory reabsorption defect.

Adult↗
PubMed1986

Altered kinetic properties of a mutant adenine phosphoribosyltransferase.

Three siblings in a Japanese family experienced recurrent 2,8-dihydroxyadenine urolithiasis despite the presence of adenine phosphoribosyltransferase (APRT) activities in the hemolysates (19.9% to 28.2% of normal value). However, studies on viable T cells from these patients indicated that APRT was not functional in viable cells. Further analysis of the partially purified enzymes from hemolysates disclosed that patient's APRT had a reduced affinity to 5-phosphoribosyl-1-pyrophosphate (PRPP). Seven healthy members of this family whose APRT functioned normally in viable T cells had the erythrocyte enzyme levels between the patients and normal individuals (38.2% to 65.6%), suggesting that they are carriers of the defective gene. These results indicate that the defective gene code a unique mutant APRT with a reduced affinity to PRPP, and the patients are homozygotes. The mutant enzyme was also shown to be more heat-stable than normal enzyme. However, since mutant enzyme, unlike normal enzyme, was insensitive to the stabilization effect of PRPP, the latter became more heat-stable than the former when the heat treatment was performed in the presence of PRPP. This type of defect with alterations in the kinetic and physical properties of APRT as described here is likely to be a common type of APRT deficiency in Japan.

Adenine Phosphoribosyltransferase↗
PubMed1985

Rapid method for the diagnosis of partial adenine phosphoribosyltransferase deficiencies causing 2,8-dihydroxyadenine urolithiasis.

More than half of the Japanese patients with 2,8-dihydroxyadenine urolithiasis only partially lack adenine phosphoribosyltransferase (APRT), while all the Caucasian patients with the same disease completely lack the enzyme. APRT activities in healthy heterozygotes for the complete APRT deficiencies were at the same levels as the Japanese patients, and simple enzyme assay does not distinguish between these two conditions. We have previously shown, using viable T-cells, that the enzyme was non-functional in the cells from the Japanese patients although they contain considerable APRT activities in the cell extracts. In the present investigations, we devised a rapid method using erythrocytes for the diagnosis of partial APRT deficiencies accompanied by severe impairment in adenine metabolism causing 2,8-dihydroxyadenine lithiasis. Thus, erythrocytes from three different families with 2,8-dihydroxyadenine urolithiasis associated with partial APRT deficiencies incorporated only minimal amounts of radioactive adenine, while normal erythrocytes incorporated significant amounts. These data indicate that severe impairment in adenine metabolism is shown not only in viable T-cells but also in viable erythrocytes. The present procedures provide a rapid method suitable for routine clinical use for the diagnosis of partial APRT deficiencies causing 2,8-dihydroxyadenine lithiasis.

Adenine↗
PubMed1985

Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies.

2,8-Dihydroxyadenine urolithiasis associated with partial deficiencies of adenine phosphoribosyltransferase (APRT) has been found only among Japanese families. All Caucasian patients with the same lithiasis are completely deficient in this enzyme. Partially purified APRT from one of the Japanese families with the lithiasis associated with a partial deficiency of APRT had a reduced affinity for 5-phosphoribosyl-1-pyrophosphate (PRPP). In the present investigations, we have shown that this characteristic is common in mutant enzymes from all the four separate Japanese urolithiasis families associated with partial APRT deficiencies so far tested. The mutant enzymes also had several other characteristics in common including increased resistance to heat in the absence of PRPP and reduced sensitivity to the stabilizing effect of PRPP. These data suggest that these families have a common mutant allele (APRT*J) at the APRT gene locus.

Adenine↗
PubMed1985

Severe impairment in adenine metabolism with a partial deficiency of adenine phosphoribosyltransferase.

Among three unrelated patients with recurrent 2,8-dihydroxyadenine urolithiasis, two completely lacked adenine phosphoribosyltransferase (APRT) in both erythrocytes and proliferative T cells. The third patient possessed significant enzyme activities in both hemolysates and T-cell extracts at levels comparable to heterozygotes for complete APRT deficiency. Despite significant APRT activities in cell extracts, cultured T cells from the third patient were at least 100-fold more resistant than normal T cells to an adenine analog, 6-methylpurine, whose cytotoxicity is dependent on APRT. These data indicate that APRT activity in T cells from the third patient is positive in cell extracts, but apparently not operating in viable cells. Although the cells from the patients with complete APRT deficiency were as resistant to 6-methylpurine as the cells from the third patient, the cells from the heterozygotes for complete APRT deficiency were almost as sensitive as normal T cells. Therefore, adenine metabolism in the third patient but not in the heterozygotes seems to be as severely impaired as in the patients with complete APRT deficiency, which is quite consistent with the clinical manifestations in these individuals.

Adenine↗
PubMed1984

5'-Methylthioadenosine in urine from normal subjects and cancer patients.

In an attempt to study, in human body, the metabolism of 5'-methylthioadenosine, a byproduct of the polyamine biosynthesis, we examined whether this nucleoside is excreted into urine, and, if so, whether the amount increases when the synthesis of polyamines increases. We found that 5'-methylthioadenosine is a natural nucleoside in human urine as evidenced by two separate chromatography systems as well as the analysis of the acetylated compound by gas chromatography-mass spectrometry. Preliminary study did not show the elevation of urinary 5'-methylthioadenosine level in malignant patients, suggesting that the cleaving enzyme, 5'-methylthioadenosine phosphorylase, very efficiently removes this nucleoside in vivo.

Adenosine↗