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Biomedical subjects

I Nishigaki

Publications and source records attributed to I Nishigaki.

At least 19 recordsLinked to original sources

Glycated protein-iron chelate increases lipid peroxide level in cultured aortic endothelial and smooth muscle cells.

Formation of an iron chelate of glycated protein was demonstrated by the appearance of an absorption peak at approximately 270 nm after mixing glycated bovine serum albumin with FeCl3. This peak disappeared and a new peak appeared at approximately 420 nm to form an isosbestic point at approximately 340 nm by the addition of deferoxamine mesylate, an iron-chelating agent, to the mixture, thus confirming the formation of the iron chelate of the glycated protein in the mixture. The lipid peroxide level was increased markedly in endothelial cells and slightly in smooth muscle cells from bovine aorta incubated in the medium containing glycated fetal bovine serum-iron chelate. Morphological observation by phase-contrast microscopy and scanning electron microscopy revealed that the glycated fetal bovine serum-iron chelate caused intense damage to the endothelial cells. These results indicate that glycated protein-iron chelate provokes lipid peroxidation, which explains at least in part the mechanism of atherogenesis found in diabetic patients.

Animals↗

Possible contributions of mastocytosis, apoptosis, and hydrolysis in pathophysiology of randomized skin flaps in humans and guinea pigs.

To understand better the pathophysiology of random skin flaps, randomized skin flaps of human (3 cases) and guinea pig (53 cases) were investigated. Proximal (normal), proximomedial (viable), mediodistal (between viable and necrotic parts), and distal (necrosis) locations of the skin flaps were biopsied. Lipid peroxidase, hydrolytic enzymes of cytosol (Ca(2+)-dependent cysteine protease: calpain), and lysosome (acid phosphatase) of skin were used as markers. Measurements were taken of the flap blood flow; the numbers of capillaries, postcapillary venules, pericapillary arterioles, leukocytes, and mast cells per unit square of dermis. Apoptotic cells were identified by specific staining. Flaps were sampled at postoperative weeks 1 and 3 (human) and hours 1 and 6, and days 1 to 7 (guinea pig). The values for normal skin were regarded as the control. Obstruction (by leukocytes) of venous microvessels, rather than arterial microvessels, was the major cause of temporary hypoxia in the proximomedial location, constant hypoxia (venous stasis) in the mediodistal location, and ischemia in the distal location. Increases in the number of mast cells (mastocytosis) and microvessels (angiogenesis) were significant only in the viable parts of the flaps. This phenomenon and the rate of blood flow increased with time in viable locations (guinea pig). Epidermal necrosis, dermal fibrosis, and apoptosis were evident mostly in the mediodistal location. Elevated levels of leukocytes, lipid peroxidase, acid phosphatase, and calpain, combined with necrotic changes, were seen mostly in the distal skin location. There is a strong possibility that the following factors are involved: lipid piroxidation and hydrolysis in necrosis of the distal flap location after ischemia; constant hypoxia in fibrosis and apoptosis in the mediodistal location; and initial or temporary hypoxia in mastocytosis-induced angiogenesis in the viable location. The results presented here indicate that guidelines for further investigations include combined suppression of leukotaxis, lipid peroxidase, and hydrolysis, or the application of mast cell growth factors in an effort to salvage the flap maximally.

Animals↗

Anti-proliferative effect of 2-methoxyestradiol on cultured smooth muscle cells from rabbit aorta.

The proliferation of cultured smooth muscle cells from rabbit aorta was inhibited markedly by 2-methoxyestradiol, considerably by 2-hydroxyestradiol, and only slightly by 17 beta-estradiol. The effects at doses from 1 to 40 nmol/ml were cytostatic rather than cytocidal. 2-Methoxyestradiol could be useful to suppress excessive proliferation of arterial smooth muscle cells, and thus to prevent the progression of atherosclerosis.

2-Methoxyestradiol↗

[Three interesting pediatric cases with penicillin-resistant Streptococcus pneumoniae infection].

Since penicillin-resistant Streptococcus pneumoniae first recognized in 1967, the rate of penicillin-resistant strains has been increasing worldwide. There have been up to 50% from pediatric specimens in Japan. We reported three pediatric cases with penicillin G resistant Streptococcus pneumoniae infection to show some important clue from these cases for clinical practice against resistant pneumococcal infection. The first case was a typical acute mastoiditis, although we have experienced only masked mastoiditis recently. The second case was meningitis with septicemia, which did not show any abnormality in the first obtained cerebrospinal fluid. The third case was recurrent bronchitis in a child with cerebral palsy. The minimum inhibition concentrations of these isolated strains were 0.25 microgram/ml in the second case an 2.0 microgram/ml in the first and third cases.

Adolescent↗

A case of lipoprotein glomerulopathy successfully treated with probucol.

A 54-year-old woman presented proteinuria and severe hyperlipoproteinemia, She had type III hyperlipoproteinemia with the phenotype E2/2. Renal biopsy specimen revealed lipoprotein thrombi within the glomerular capillary lumina without tubulointerstitial lesion and deposition of IgA in the mesangium and peripheral capillary loops, indicating lipoprotein glomerulopathy with IgA nephropathy. Treatment with probucol resulted in the improvement of both hyperlipoproteinemia and proteinuria with the disappearance of the lipoprotein thrombi in the glomerular capillary without any change in the mesangial IgA deposition. The data suggest that probucol may be effective against the early stage of lipoprotein glomerulopathy with less lipoprotein thrombi and without tubulointerstitial damage.

Female↗

Purification of aromatic L-amino acid decarboxylase from bovine brain with a monoclonal antibody.

Aromatic L-amino acid decarboxylase was purified from bovine brain for the first time by affinity chromatography using a monoclonal antibody to the enzyme, and it was compared with the decarboxylase purified from bovine adrenal medulla by the same procedure. The monoclonal antibody was produced from a hybridoma established for the enzyme highly purified from bovine adrenal medulla. The Mr values of brain and adrenal-medulla enzyme were both estimated to be approx. 100,000 by gel-permeation chromatography. SDS/polyacrylamide-gel electrophoresis revealed a single band with an apparent Mr of 50,000. Western immunoblot analysis showed that the antibody recognized each enzyme. With regard to substrate specificity, pH-dependence and effect of pyridoxal 5'-phosphate as a cofactor, both enzymes were similar.

Adrenal Medulla↗

Familial retinoblastoma (mother and son) with 13q14 deletion.

We present here the first familial cases (a mother and son) of dominantly inherited retinoblastoma with a 13q14 deletion [46,XY or XX, del(13)(q14.1q21.2)]. Their esterase D activities in red blood cells were as low as 50% of the normal control and the haplotype of esterase D was a type 1-0 in the mother and a type 2-0 in the son. They had peculiar facies characterized by a high forehead, low and broad nasal root, a short and bulbous nose, a long philtrum, and open mouth with a thin upper lip, and prominent earlobes. Chromosome and esterase D analysis should be performed in patients with retinoblastoma even if retinoblastoma seems to be transmitted through an autosomal dominant inheritance. This family indicates that one of the causes of dominantly inherited retinoblastoma is a chromosome deletion of part of the 13q14 band whether it is detectable by chromosome analysis or not.

Adult↗

Deficiency of AMP deaminase in erythrocytes.

Six individuals with complete deficiency of erythrocyte AMP deaminase have been discovered. They are all healthy and have no hematological disorders. The deficiency is only in isozyme E, which is the erythrocyte type isozyme, and is inherited as an autosomal recessive trait. The frequency of the mutant gene is surprisingly high, one heterozygote in about 30 of the population in Japan, Seoul, and Taipei. The ATP level is approximately 50% higher in AMP-deficient erythrocytes compared to that of control cells. Degradation of adenine nucleotide is slower in the deficient erythrocytes than in the control erythrocytes.

AMP Deaminase↗

Activity of red cell esterase D in 50 cases of retinoblastoma patients and their family members.

Esterase D was qualitatively and quantitatively analyzed in the red blood cells from 50 retinoblastoma patients who had been followed-up at Juntendo University and their family. In only one case with deletion of chromosome No. 13 (q12.3-q21.2), was the esterase D activity (type 2) 1.47 Unit/gHb which was approximately 50% of the level in normals. Additional retinoblastoma patients and their family members, 77 parents and 25 siblings, showed a normal range of esterase D level in their own phenotypes. These facts confirmed that the deletion of an esterase D locus was infrequent (approximately 2% in our series) in retinoblastoma patients. It was also compatible with the published data that the range of deletion of chromosome was No. 13 (q12.3-q21.2) involving 13q14.

Carboxylesterase↗

Red cell NADH diaphorase variants in Japanese.

Human red cell NADH diaphorase isozyme patterns were examined in 5,046 healthy adult Japanese by starch gel electrophoresis. Twenty had Dia 2-1 and 3 had Dia 4-1 phenotypes. The incidence of Dia variants in patients with mental retardation, cerebral palsy, epilepsy and Down's syndrome was also examined and compared with that of healthy people. It was noticed that thin-layer isoelectric focusing on polyacrylamide gel was very useful for discriminating variant bands from 'aging bands'.

Dihydrolipoamide Dehydrogenase↗

Effect of amphetamine on brain catecholamines, brain beta-endorphin, serum prolactin, catechol-O-methyltransferase and monoamine oxidase of various organs in the rat.

Rats were treated with amphetamine to induce an amphetamine psychosis which resembles paranoid schizophrenia. Brain catecholamines, brain beta-endorphin, serum prolactin as well as catechol-O-methyltransferase and monoamine oxidase were subsequently measured. The norepinephrine levels were significantly lower in brain regions of rats treated with amphetamine whereas levels of dopamine and beta-endorphin remained the same. No significant changes were found in the levels of catechol-O-methyltransferase, monoamine oxidase and serum prolactin. In view of recent findings by other investigators in this field, our results suggest an important role of the adrenergic system in the pathogenesis of amphetamine psychosis.

Amphetamine↗

Complete deficiency of AMP deaminase in human erythrocytes.

Four individuals with complete absence of erythrocyte AMP deaminase have been discovered. The subjects appear to be perfectly healthy and there was no evidence of hemolysis. The deficiency was found only in erythrocytes and as expected, mononuclear cells and platelets showed normal level of activity. The activities of all the other purine metabolizing enzymes that were tested were normal. The deficiency is inherited as an autosomal recessive trait.

AMP Deaminase↗

Isoelectric focusing studies of human red cell esterase D: evidence for polymorphic occurrence of a new allele EsD7 in Japanese.

The isoelectric focusing study of esterase D in Japanese revealed evidence of a new polymorphic allele (EsD7) which is difficult to find by conventional starch gel electrophoresis only. A comparison with the occurrence of a subdivision of EsD2 in Caucasians (EsD5) suggests a remarkable difference in allele distribution of esterase D among races. Quantitative analysis showed a relatively low value of enzyme activity for this new allele. It is therefore emphasized that in addition to conventional electrophoresis, enzyme assay and further detection by isoelectric focusing are essential in analyzing the esterase D system.

Alleles↗

Genetic analysis of human lymphocyte proteins by two-dimensional gel electrophoresis: VI. Identification of esterase D in the two-dimensional gel electrophoresis pattern of cellular proteins.

C33k polypeptide, which is a cytosol polypeptide with molecular weight of 33 000 and approximate pI value of 7.5, has three common electrophoretic phenotypes and is an abundant polypeptide in peripheral blood lymphocytes, fibroblasts and red blood cells. Family and population studies indicate that the three phenotypes of C33k polypeptide are determined by two common alleles at a single autosomal locus. The gene frequencies of the two common alleles were 0.642 and 0.358, respectively, in a Japanese population. Since esterase D has a subunit size and gene frequencies similar to those of C33k polypeptide, the phenotypes of C33k polypeptide and esterase D were compared in 18 families totaling 72 members. Perfect concordance of the phenotypes between C33k polypeptide and esterase D was observed in all 72 members. In addition, a gene dosage effect on the expression of the phenotype of C33k polypeptide was observed in the red blood cell lysate from a patient with partial 13q trisomy who was reported to have two doses of EsD1 and one dose of EsD2. These data indicate that the polymorphic C33k polypeptide is esterase D, which is assigned to chromosome 13q14. This finding is useful for the detection of proteins coding for by chromosome 13q14-linked genes in the studies on human gene mapping using somatic hybrid cell lines and two-D gel electrophoresis.

Blood Proteins↗