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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 595 records · Page 33Linked to original sources

Guanine nucleotide-induced Ca2+ release in permeabilized murine thymocytes.

GTP and IP3 induced Ca2+ release from an internal store in permeabilized murine thymocytes loaded with Ca2+ by ATP. Ca2+ release was dependent on the concentration of GTP: half-maximal release with 0.5 microM and maximal release with 10 microM. The GTP effect was completely abolished by 100 microM GTP gamma S, GMPPNP and UTP. None of the other nucleotides used except ITP induced Ca2+ release. When GTP was added after the effect of IP3 had virtually subsided, and vice versa, further Ca2+ release occurred, which led to the conclusion that the mechanism of GTP-mediated Ca2+ release may be different from that of IP3-mediated release.

Animals↗

Electron paramagnetic resonance study of ferrous cytochrome P-450scc-nitric oxide complexes: effects of 20(R),22(R)-dihydroxycholesterol and reduced adrenodoxin.

Electron paramagnetic resonance (EPR) spectra of ferrous-nitric oxide (14NO and 15NO) cytochrome P-450scc complexed with 20(R),22(R)-dihydroxycholesterol were measured at 77 K with X-band (9.35 GHz) microwave frequency. The EPR spectra clearly showed the spin system to have rhombic symmetry (gx = 2.068, gz = 2.001, gy = 1.961, and Az = 1.89 mT for 14NO) and were distinct from those of 20(S)-hydroxycholesterol complexes. The unique nature of the 20(S)-hydroxycholesterol complexes indicates that 20(S)-hydroxycholesterol is not a proper intermediate in the cholesterol side-chain cleavage reaction. In addition, among various steroid complexes of ferrous-NO species having rhombic symmetry, the EPR spectra of 20(R),22(R)-dihydroxycholesterol complexes were significantly different from those of 22(R)-hydroxycholesterol complexes, suggesting that upon 20S-hydroxylation of 22(R)-hydroxycholesterol the conformation of the active site changes so as to facilitate subsequent cleavage of the C20-C22 bond of the cholesterol side chain. Addition of reduced adrenodoxin to the ferrous-NO cytochrome P-450scc complex in the presence of cholesterol caused a complete shift of the gx = 2.070 signal to gx = 2.075, indicating a reorientation of cholesterol in the substrate-binding site of the enzyme upon adrenodoxin binding. Without reduced adrenodoxin, the process of reorientation of cholesterol in the substrate-binding site was very slow, requiring more than 50 h of incubation at 0 degrees C. The present observations suggest that adrenodoxin may have another positive role in the cholesterol side-chain cleavage reaction, in addition to transferring an electron to the heme of cytochrome P-450scc.

Adrenal Cortex↗

Crystallization of cytochrome P-450scc from bovine adrenocortical mitochondria.

Cytochrome P-450scc (P-450scc), a cholesterol side-chain cleavage enzyme from bovine adrenocortical mitochondria, has been crystallized for the first time. Upon removal of glycerol from the solution of the native enzyme complexed with pyridoxal 5'-phosphate (PLP) by microdialysis against distilled water, reddish and planar crystals appeared. The crystals of native P-450scc were also obtained by the same procedure. We identified the crystals as the P-450scc-PLP complex or native P-450scc by absorption spectroscopy and SDS-polyacrylamide gel electrophoresis, and characterized them under a polarization microscope.

Adrenal Cortex↗

Adrenoferredoxin-binding peptide of NADPH-adrenoferredoxin reductase.

The amino-acid sequence at the adrenoferredoxin-binding site of NADPH-adrenoferredoxin reductase ferredoxin:NADP+ oxidoreductase, EC 1.18.1.2) from bovine adrenocortical mitochondria was investigated chemically. NADPH-adrenoferredoxin reductase has an essential lysine residue at the adrenoferredoxin-binding site. A polypeptide at the adrenoferredoxin-binding site was isolated by high-pressure liquid chromatography from NADPH-adrenoferredoxin reductase modified with pyridoxal 5'-phosphate and cleaved with cyanogen bromide. The amino-acid sequence of the adrenoferredoxin-binding peptide was identified. The peptide accounted for 95% of the sugar content of the NADPH-adrenoferredoxin reductase.

Adrenal Cortex↗

Synthesis of methyl glycoside derivatives of tri- and penta-saccharides related to the antithrombin III-binding sequence of heparin, employing cellobiose as a key starting-material.

Two key synthons for the title pentasaccharide derivative, methyl O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-acetyl- 2-azido - 3-O- benzyl-2-deoxy-beta-D-glucopyranoside and O-(methyl 2,3-di-O-benzyl-4-O- chloroacetyl-beta-D-glucopyranosyluronate)-(1----4)-3,6-di-O-acetyl-2-az ido-2- deoxy-alpha-D- glucopyranosyl bromide, were prepared from a common starting material, cellobiose. They were coupled to give a tetrasaccharide derivative that underwent O-dechloroacetylation to the corresponding glycosyl acceptor. Its condensation with the known 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide afforded a 77% yield of suitably protected pentasaccharide, methyl O-(6-O- acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)- O- (methyl 2,3- di-O-benzyl-beta-D-glucopyranosyluronate)-(1----4)-O-(3,6-di-O-acetyl-2- azido-2 - deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L- idopyranosyluronate)- (1----4)-6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranoside. Sequential deprotection and sulfation gave the decasodium salt of methyl O-(2- deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1----4)-O-(be ta-D- glucopyranosyl-uronic acid)-(1----4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-alpha-D-gluco pyranosyl)- (1----4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1----4)-2-deoxy-2- sulfamido-6-O- sulfo-beta-D-glucopyranoside (3). In a similar way, the trisaccharide derivative, the hexasodium salt of methyl O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D- glucopyranosyl)- (1----4)-O-(beta-D-glucopyranosyluronic acid)-(1----4)-2-deoxy-2-sulfamido-3,6- di-O- sulfo-alpha-D-glucopyranoside (4) was synthesized from methyl O-(6-O-acetyl-2- azido- 3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2,3-di-O- benzyl-beta- D-glucopyranosyluronate)-3,6-di-O-acetyl-2-azido-2-deoxy-alpha-D- glucopyranoside. The pentasaccharide 3 binds strongly to antithrombin III with an association constant almost equivalent to that of high-affinity heparin, but the trisaccharide 4 appears not to bind.

Antithrombin III↗

Role of actin filaments in shape formation of mesenteric mesothelial cells of the bullfrog.

The role of actin filaments in the development of cellular shape in the mesenteric mesothelium of the bullfrog was studied by using a simple, new technique for making en face preparations of mesothelial sheets. By using these mesothelial cell preparations, the distribution of actin was determined by means of fluorescence microscopy with 7-nitrobenz-2-oxa-1,3-diazole (NBD)-phallacidin and that of myosin by means of immunofluorescence microscopy. Although fluorescence produced by both NBD-phallacidin and antimyosin staining was found exclusively along the margins of the cells, its intensity was altered in correspondence with changes in cell shape. For instance, tadpole-type mesothelial cells with either an irregular or very slender cell shape showed very weak fluorescence. On the other hand, frog-type mesothelial cells with a polygonal shape showed intense fluorescence at their margins and had circumferential bundles of actin filaments at their apices. Furthermore, intercellular junctions between the mesothelial cells developed as the cell shape became polygonal during metamorphosis. The present study showed that development of circumferential bundles of actin filaments and intercellular junctions may serve to establish and maintain the definitive polygonal cellular pattern in the mesenteric mesothelium of the bullfrog.

Actins↗

Isolation and purification of mature bovine adrenocortical ferredoxin with an elongated carboxyl end.

Mature bovine adrenocortical ferredoxin (adreno-ferredoxin) was extracted from fresh adrenal glands at pH 9.0. Extraction and purification at this alkaline pH protected the mature adreno-ferredoxin molecule from proteolytic degradation. The mature adreno-ferredoxin was extensively purified by a rapid procedure including two kinds of column chromatography, hydrophobic and ion exchange. The purified adreno-ferredoxin was homogeneous on the basis of two HPLC analyses, hydrophobic and ion exchange, and had the highest purity so far reported. Then it was digested by trypsin and the carboxyl-terminal peptide was isolated from the tryptic digest by a novel column chromatographic method using a cation-exchange HPLC column, TSK-gel SP-5PW. The carboxyl-terminal amino acid was isoleucine, so the adreno-ferredoxin had 127 amino acid residues, the longest polypeptide so far determined chemically for bovine adreno-ferredoxin. Only Glu-128 was lacking within the carboxyl-terminal elongated peptide that was found by nucleotide sequencing of the adreno-ferredoxin gene. There was no evidence obtained on whether the deletion of Glu-128 was due to so-called carboxyl-terminal processing or to proteolytic degradation during storage and purification.

Adrenal Cortex↗

Monte Carlo calculations of doses to tiles irradiated by 60Co and 252Cf simulating atomic bomb gamma-ray fluences.

Dose calculations for tiles exposed to the Hiroshima atomic bomb radiations were undertaken. A Monte Carlo code, ABOMB, was developed which considers the characteristics of atomic bomb gamma-ray fluences and geometrical configurations. ABOMB was applied to tile dose calculations for the available photon sources with definite fluences. Its validity was tested by comparing the depth-dose curves calculated for 60Co and 252Cf beams with the equivalent experimental data obtained in the laboratory. Selection of parameters, contribution of backscattering, and computing time also were considered. Present calculations are considered to be accurate with uncertainties less than +/- 10%, and may be useful for correcting or reinforcing atomic bomb gamma-ray doses, together with tile dose measurements by thermoluminescent (TL) dosimetry.

Californium↗

Abnormalities of pulmonary blood flow during cold exposure in systemic lupus erythematosus.

The aim is to determine whether pulmonary blood flow is altered during cold exposure of the hands in individuals with systemic lupus erythematosus (SLE). Cold exposure was induced by immersion of the hands, one at a time, in 10 degrees C water in nine SLE patients in whom pulmonary fibrosis had been ruled out by a routine examination. Lung perfusion was measured by continuous venous infusion of krypton 81 m. Cold exposure to at least one of the hands caused an 8 to 22% decrease of pulmonary blood flow in five of the nine patients. A 10 to 33% increase in flow developed in three of the nine patients during cold exposure of the hands. We conclude that these abnormalities in pulmonary blood flow during cold exposure were revealed in SLE patients with scarcely any clinical symptoms.

Adult↗

Complete duplication of male urethra. Two case reports.

Complete urethral duplication is a rare anomaly in boys. About 60 cases have been reported in the literature, of which approximately one-third were managed with a surgical procedure of total excision of the accessory urethra. Another third were managed by partial excision, and the rest were managed conservatively. Here 2 cases are presented, and the surgical treatment is discussed.

Child↗

An autopsied case of systemic lupus erythematosus with pulmonary hypertension--a case report.

The authors report an autopsied case of systemic lupus erythematosus (SLE) with pulmonary hypertension. The patient was a forty-five-year-old female who had been troubled by obstinate Raynaud's phenomenon for ten years before the definite diagnosis of pulmonary hypertension was made. Microscopic examination of the pulmonary vasculature yielded findings consistent with plexogenic pulmonary arteriopathy. However, the deposition of immune complexes in the pulmonary vascular endothelium was not detected by enzyme antibody study. This case suggests, therefore, that "pulmonary Raynaud's phenomenon" is a possible pathogenesis of pulmonary hypertension in patients with SLE.

Autopsy↗

Semisynthetic beta-lactam antibiotics. IV. Synthesis and antibacterial activity of 7 beta-[2-(hetero aromatic methoxyimino)-2-(2-aminothiazol-4-yl)acetamido]cephalosporins.

A series of 7 beta-[2-(hetero aromatic methoxyimino)-2-(2-aminothiazol-4-yl)acetamido]- cephalosporins have been synthesized and bacteriologically evaluated. Several substances in this series showed exceptional in vitro activity, especially those with a five-membered hetero aromatic substituent moiety at the 7-position and a quaternary ammonium group as the 3-function of the cephem nucleus. The most active derivative, 7 beta-[2-(imidazol-4-ylmethoxyimino)-2-(2-aminothiazol-4-yl)a cetamido]-3-(pyridiniomethyl)ceph-3-em-4-carboxylate (13a) was the most evenly balanced with respect to activity against Gram-positive and Gram-negative bacteria. Furthermore, 13 was stable to various types of beta-lactamases and had high affinities for penicillin binding protein-3 and -1Bs of both Escherichia coli and Pseudomonas aeruginosa.

Bacteria↗

[Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

Adult↗