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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 649 records · Page 36Linked to original sources

Quantitative analysis of the mitochondrial cytochrome P-450-linked monooxygenase system: NADPH-hepatoredoxin reductase, hepatoredoxin, and cytochrome P-450s27 in livers of patients with cerebrotendinous xanthomatosis.

We studied the mitochondrial cytochrome P-450-linked monooxygenase system in livers of two patients with cerebrotendinous xanthomatosis (CTX). The three components of this system, which catalyzes steroid 27-hydroxylation, NADPH-hepatoredoxin reductase, hepatoredoxin, and cytochrome P-450s27, were stained on a nitrocellulose sheet with antibodies against NADPH-adrenodoxin reductase, adrenodoxin, and cytochrome P-450scc, respectively, from bovine adrenocortical mitochondria. The concentrations of hepatoredoxin in the patients were not significantly different from a control, but the level of NADPH-hepatoredoxin reductase was three times that of the control. Cytochrome P-450s27 was not detected in the patients, but it was present (22.8 pmol/mg of protein) in the control liver. This implies that a defect of mitochondrial cytochrome P-450s27 prevents steroid 27-hydroxylation of hepatic mitochondria in patients with CTX.

Adrenal Cortex↗

Effects of cholesterol and adrenodoxin binding on the heme moiety of cytochrome P-450scc: a resonance Raman study.

The effects of cholesterol and adrenodoxin binding on resonance Raman spectra of cytochrome P-450scc in both oxidized and CO-reduced states were examined. Upon cholesterol binding, oxidized cytochrome P-450scc showed a significant shift of spin equilibrium from low-spin to high-spin state. Addition of adrenodoxin caused a complete conversion of cholesterol-bound oxidized cytochrome P-450scc to a pure high-spin state that was considered to be in the hexacoordinated state judged by the v10 mode at 1620 cm-1 and v3 mode around 1485 cm-1. Cholesterol in substrate binding site may oppose a linear and perpendicular binding of carbon monoxide to the reduced heme iron, leading to the distorted Fe-C-O linkage. This is based on the following observations: (1) an increase of the Fe-CO stretching frequency to 483 from 477 cm-1 upon addition of cholesterol; (2) an enhanced photodissociability of bound carbon monoxide of CO complex of cytochrome P-450scc in the presence of cholesterol. As another aspect of the effect of cholesterol on the CO complex form of cytochrome P-450scc, the enhanced stability of the native form ("P-450" form) was observed. There was no additional effect of reduced adrenodoxin on the Raman spectra of the CO-reduced form of cytochrome P-450scc.

Adrenal Cortex↗

Characterization of two cysteine residues in cytochrome P-450scc: chemical identification of the heme-binding cysteine residue.

It was found that there were only two cysteine residues in highly purified cytochrome P-450scc molecule from bovine adrenocortical mitochondria by titration with 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) in denatured conditions. Only one cysteine residue at position 303 of cytochrome P-450scc could be specifically modified with DTNB in the native state. The resulting cytochrome P-450scc-5-thio-2-nitrobenzoic acid complex (cytochrome P-450scc-TNB) showed no distinct differences in absorption spectra, cholesterol binding, or electron transferring from adrenodoxin, compared to those of untreated cytochrome P-450scc. These observations indicated that the 303rd cysteine residue does not play a role in heme binding, cholesterol (substrate) binding or adrenodoxin binding. The other cysteine residue at 461 could be modified with DTNB only in a denatured condition. These assignments of cysteine residues were made by the subsequent S-cyanylation with KCN followed by incubation in 6 M guanidine hydrochloride at alkaline pH, which causes enhanced cleavage of peptide bonds adjacent to the cyanylated cysteine residues. Analyses of fragmented polypeptides by SDS-polyacrylamide gel electrophoresis confirmed that there were only two cysteine residues in the molecule and indicated that the cleavage rate of the peptide bond between 460 and 461 becomes high only when both cysteine residues (303 and 461) are cyanylated. These results clearly established that the 461st cysteine residue in cytochrome P-450scc plays a role as the heme fifth ligand on the basis of the general agreement that a thiolated cysteine residue coordinates to the heme iron.

Adrenal Cortex↗

Purification and biochemical characterization of hepatic ferredoxin (hepatoredoxin) from bovine liver mitochondria.

Hepatic ferredoxin (hepatoredoxin) was purified from bovine liver mitochondria. The monomeric molecular mass of the hepatoredoxin was larger than that of adrenocortical ferredoxin (adrenodoxin) from bovine adrenocortical mitochondria at 14 kDa. We studied the amino acid residues and NH2-terminal sequence of this protein. The hepatoredoxin was organ-specific protein. The optical absorption spectrum of oxidized hepatoredoxin had two peaks, at 414 and 455 nm in the visible region. Hepatoredoxin formed an immunoprecipitin line against anti-adrenodoxin immunoglobulin in Ouchterlony double diffusion, and an immunochemical staining band in Western blotting.

Adrenodoxin↗

Association between HLA and Sjögren's syndrome in Japanese patients.

Japanese patients with primary Sjögren's syndrome (SS), patients with SS and rheumatoid arthritis (SS-RA), and patients with SS and connective tissue disease without RA (nonrheumatoid connective tissue disease [SS-CTD]) were typed for HLA antigens. Patients with primary SS and those with SS-RA had higher frequencies of DRw53 than did those who had SS-CTD; however, the group with SS-CTD showed a negative correlation with DRw52. These data indicate that Japanese and white patients with SS have different HLA specificities, and that genetic factors involved in the development of SS-CTD might be different from those in primary SS and SS-RA.

Arthritis, Rheumatoid↗

Plasma membranes purified from myeloid leukemia cells before and after differentiation. I. Characterization of spectrin-like proteins and increased association of actin.

Two-step sucrose density gradient centrifugation was used to isolate the plasma membrane of a myeloid leukemia cell line (Ml). Calspectin (or fodrin) was identified in the Triton-insoluble fraction from the plasma membrane, and the molecular size and actin- and calmodulin-binding activity were studied. During differentiation of this cell line, which accompanied the induction of cell motility and phagocytic activity, the membrane-bound actin increased dramatically, whereas calspectin increased only slightly. Therefore, calspectin does not appear to have a major function in the increased binding of actin filaments to the plasma membrane, a requirement for the induction of cell motility.

Acid Phosphatase↗

Anti-thrombotic effect of KC-404, a novel cerebral vasodilator.

KC-404 prevented mice from death and rats from A-V block, both induced by rapid i.v. injection of adenosine diphosphate (ADP), at high doses (5-100 mg/kg, i.v.). KC-404, at relatively lower doses (0.5-2 mg/kg, i.v.), inhibited the electroencephalographic (EEG) change in rat rapidly administered with arachidonic acid (AA) into the internal carotid artery. KC-404 (0.3-3 mg/kg, p.o.) inhibited the necrotic change of lower leg, paw or finger of rat when injected with sodium laurate into the femoral artery. KC-404 at doses up to 100 mg/kg, p.o. did not alter bleeding time in rat. Thus, KC-404 is expected to be of therapeutic value in cerebrovascular disorders accompanying thrombus in cerebral vasculature.

Adenosine Diphosphate↗

Zonal distribution of cytochromes P-450 and related enzymes of bovine adrenal cortex--quantitative assay of concentrations and total contents.

The zona glomerulosa, zona fasciculata, zona reticularis, and medulla were separated from bovine adrenal glands and cytochromes P-450 and related enzymes in each zone were investigated immunochemically by Western blotting using antisera from chickens or rabbits against cytochromes P-450scc, P-450(11)beta, P-450s21, and b5, NADH-cytochrome b5 reductase, NADPH-cytochrome P-450 reductase, NADPH-adrenodoxin reductase, and adrenodoxin. Concentrations of cytochrome P-450(11)beta, NADPH-cytochrome P-450 reductase, and cytochrome b5 per milligram of protein of homogenate were higher in the zona glomerulosa than in the other zones; the levels of the other components were higher in the zona fasciculata. The total enzyme content of all components was the highest in the zona fasciculata. The amount of adrenodoxin was about 10 times that of NADPH-adrenodoxin reductase in each zone.

Adrenal Cortex↗

A new platelet antigen system, Yuka/Yukb.

We report a new platelet antigen (Yukb) involved in a case of neonatal alloimmune thrombocytopenia (NAITP). This antigen is considered to be a product of an allele of the Yuk gene, another allele of which codes for Yuka which was involved in 2 cases of NAITP. The Yuka and Yukb antigens are not expressed on thrombasthenic platelets which suggests that these antigens are present on platelet glycoprotein IIb and/or IIIa. The gene frequencies for Yuka and Yukb in the Japanese population were estimated to be 0.0083 and 0.9917, respectively.

Alleles↗

Yuka, a new platelet antigen involved in two cases of neonatal alloimmune thrombocytopenia.

We report a new platelet antigen (Yuka) defined by the sera of 2 mothers whose babies developed alloimmune thrombocytopenia. These antiplatelet antibodies were IgG detected by Mixed Passive Hemagglutination (MPHA). In the study of two families, the Yuka antigen was found to be inherited as an autosomal dominant trait. The frequency of the Yuka phenotype in the Japanese population was estimated to be 1.7% (5/300).

Blood Platelets↗

Effect of hard metal dust on ventilatory function.

The effect of hard metal dust generated in shaping on ventilatory function has been studied, in particular, the relation between levels of exposure to cobalt and changes in ventilatory function. In 15 healthy young men a significant decrease in FVC occurred after a six hour exposure to hard metal dust containing cobalt at a mean concentration of 38 micrograms/m3 (range 14-76 micrograms/m3). No dose-effect relation could be discerned between the decrease in FVC and the hard metal concentration or the cobalt concentration. All the subjects complained of irritation of the airways. On the other hand, in 42 shaping workers exposed to cobalt at an average concentration of 85 micrograms/m3 no significant decreases in ventilatory function were detected after seven hour exposures to hard metal, although in 42 shapers, who had been exposed to cobalt at a mean concentration of 126 micrograms/m3, the FEV1% was significantly decreased compared with matched controls. This finding suggests that hard metal dust containing cobalt at a mean concentration of 126 micrograms/m3 causes chronic bronchial obstruction.

Adult↗

Cavernous hemangioma of scrotum and penile shaft.

We report a 13-year-old boy with two independently detected cavernous hemangiomas of the scrotum and the penile shaft. A right scrotal cavernous hemangioma was incidentally found at the age of 6 years by a histological examination of a right scrotal hematoma attributed to contusion. The patient noticed a soft tumor of the penile shaft at the age of 10 and gradual enlargement of the tumor during the next 3 years. He consulted our department at the age of 13. An ultrasonic echogram revealed a heterogeneous tumor, a hemangioma, having dimensions of 3.5 X 2.5 X 1.5 cm and no connection of the corpus cavernosum penis. The tumor was completely removed surgically by means of circumcision on March 30, 1984, and histological examination demonstrated a cavernous hemangioma.

Adolescent↗

Changes in intracellular K+ and Na+ ion concentrations during cell growth and differentiation.

We compared intracellular K+ and Na+ ion concentrations during cell growth and differentiation of a mouse myeloid leukemia M1 cell line. Cells undergoing mitosis had higher K+ concentrations than quiescent cells. Treatment with a K+ channel blocker and furosemide enhanced cell growth and produced a slight increase in the intracellular K+ concentration. Treatment with reagents that reduced the intracellular K+ concentration stopped cell growth. Induction of differentiation in this cell line produced a decrease in the K+ concentration, which always was accompanied by an increase in the Na+ concentration. Treatment with ouabain, which decreased the intracellular K+ concentration, did not, however, induce differentiation in the M1 cell line. The data suggest that cell growth and differentiation in the M1 cells are accompanied by changes in the intracellular K+ and Na+ concentrations but that the changes in the contents of these monovalent cations do not necessarily induce differentiation in this cell line.

Animals↗

State of systemic hemodynamics in a case of juxtaglomerular cell tumor.

A renin-producing juxtaglomerular cell tumor was found in a 27 year-old woman. The infusion of angiotensin II analogue produced a marked decrease in arterial pressure. Oral administration of captopril also reduced her blood pressure. Although the renal vein renin did not indicate the laterality of the tumor, unilateral partial nephrectomy cured the disease. This is the first case report to describe measurement of several hemodynamic parameters before and after surgical removal of a juxtaglomerular cell tumor.

Adult↗

Bursal role in the synthesis of gamma-chain messenger ribonucleic acid in young chickens.

Incomplete bursectomy was performed in 3-day-old chickens by treatment with .5% testosterone propionate on the 3rd day of incubation. The purpose of this experimental approach was to determine the role of the bursa of Fabricius in the translation activity of messenger ribonucleic acids (RNA) coding immunoglobulin-isotypes. The bursal poly(A) RNA, prepared from bursae of normal and hormone-treated chickens, directed the synthesis of 72, 43, 38, and 25-kilodalton molecules as revealed by immune precipitation and sodium dodecylsulphate acrylamide gel electrophoresis. However, unlike the messenger RNA from normal bursae, the messenger from bursae of hormonal-treated embryos failed to direct the synthesis of 68-kilodalton gamma-polypeptide.

Animals↗

[Combination chemotherapy for bronchogenic carcinoma based on cell type].

Based on the cell types in bronchogenic carcinoma, we treated 123 patients with different regimens of combination chemotherapy. The chemotherapy regimens consisted of CAP (cyclophosphamide + adriamycin + platinum) for 60 patients with adenocarcinoma and large cell carcinoma, PP (peplomycin + platinum) for 29 patients with squamous cell carcinoma and CAV (cyclophosphamide + adriamycin + vincristine) for 35 patients with small cell carcinoma. These regimens were repeated every 4 weeks for at least 2 cycles. The response rates for CAP, PP and CAV were 18.3% (11 PR), 20.7% (6 PR) and 60% (10 CR + 11 PR), respectively. Median survival time (MST) was 12.5 months for CAP, 8.5 months for PP and 9.5 months for CAV. Responders had a significantly (P less than 0.002) improved survival (MST, 15.5 months) compared to non-responders (MST, 7.5 months) in small cell carcinoma. However, there was no significant difference between responders and non-responders in CAP and PP. Survival of patients with PS 0-1 was significantly better than that with PS 2-3 in all treated patients. Nausea and vomiting were severe in patients treated with platinum-based polychemotherapy. There was no renal failure although a transient increase of serum creatinine was noted in CAP and PP. Myelosuppression was mild to moderate in all patients treated with CAP, PP and CAV.

Adenocarcinoma↗