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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 415 records · Page 23Linked to original sources
PubMed1993

[A case of limited form of Wegener's granulomatosis without detection of anti-neutrophil cytoplasmic antibody].

A 52-year-old woman was admitted to our hospital because of high fever and productive cough. Her chest X-ray showed multiple cavitary nodules in both lungs. Although we suspected Wegner's granulomatosis (WG), anti-neutrophil cytoplasmic antibody (ANCA) was not detected in her serum. Finally, an open lung biopsy was performed, and the limited form of Wegener's granulomatosis was diagnosed. With cyclophosphamide and steroid treatment, she markedly improved. We conclude that in patients suspected of having WG, it is necessary to perform open lung biopsy regardless of the detection of ANCA.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

[Soluble IL-2 receptor levels in rheumatic diseases].

We measured soluble interleukin-2 receptors (sIL-2R) in plasma and/or joint fluid (JF) from patients with rheumatoid arthritis (RA: 16 patients), Sjögren's syndrome (SS: 24 patients) and Behçet's disease (BD: 23 patients). Plasma sIL-2R levels were significantly higher in RA patients (956 +/- 994 U/ml, p < 0.01) and SS patients (1025 +/- 1112 U/ml, p < 0.01) than 20 healthy subjects (338 +/- 159 U/ml), but not significantly increased in BD patients (408 +/- 329 U/ml). sIL-2R levels higher than the mean of healthy subjects +2 standard deviations were observed in 3 BD patients (13.0%), 7 RA patients (43.8%) and 10 SS patients (41.7%). sIL-2R levels positively correlated with erythrocyte sedimentation rates and C-reactive protein levels in RA patients, or IgM levels in SS. There was no significant correlation between plasma sIL-2R levels and disease activity, clinical symptoms, or other laboratory parameters in BD patients. However, sIL-2R concentrations in the JF from 4 BD patients (1644 +/- 198 U/ml: p < 0.05) or 16 RA patients (3946 +/- 5424 U/ml: p < 0.01) were significantly higher than corresponding plasma sIL-2R concentrations. Above results indicate that lymphocytes are being activated in patients with RA or SS and in the inflammatory lesions of BD patients, while the whole immunologic activation are relatively lower in BD than RA and SS.

Adult↗
PubMed1993

[Disadvantages of "Gelseal graft" as a vascular prosthesis].

In clinical use, the Gelseal Triaxial graft have been shown to have several problems, such as pyrexia, pleural effusion and seroma formation around the graft. To investigate the cause of these complications, we examined mechanical and biological properties of the graft. The water permeability was found to be 0 ml at 120 mmHg in an in vitro study. Scanning electron microscopical observation revealed that gelatin in the graft wall was not uniform and easily detached from the luminal surface. The amount of impregnated gelatin in the graft was found to be 6.73 mg/cm2. In addition, this graft contained 297 and 73 pg endotoxin in extract/g of graft wt at 25 degrees C 72 hrs as assessed by Toxicolor and Endospecy pyrogen tests, respectively. The grafts were implanted in the descending aorta of 8 dogs for 2 weeks in an animal study. Three out of 8 animals died of graft occlusion. Both macroscopic and microscopic evaluations of the explants from 5 dogs showed that neither fibroblasts nor capillary blood vessels had infiltrated in some area of the graft wall. Serous fluid was found to be retained between the graft and the surrounding host tissue in three cases. These results indicated that the Gelseal graft was easy to implant due to zero porosity, but the coated gelatin was not clean and gelatin was easily detachable. Hence, the graft would be prone to some complications such as pyrexia, immune response, thromboembolism, seroma, and pleural effusion. One must be aware of the potential disadvantages of the Gelseal grafts before using it in patients.

Animals↗
PubMed1993

[A case of endocarditis caused by Candida glabrata].

A 45-year-old diabetic man had aortic valve replacement for Candida glabrata endocarditis. Postoperatively he was treated with fluconazole and amphotericin B. Despite therapy, C. glabrata was isolated from his blood. He collapsed suddenly and died of heart failure 70 days after operation. Autopsy revealed suture line insufficiency and perivalvular leakage. On histologic examination many colonies of fungi were found in the aortic valvular annulus and an embolus to the mesenteric artery.

Aortic Valve↗
PubMed1993

[Endoscopic classification of healing process in tracheobronchial tuberculosis].

Out of 404 patients with pulmonary and/or tracheobronchial tuberculosis treated during the last 10 years at Kurume University Hospital and St. Mary Hospital, in 41 patients, who had been histopathologically or bacteriologically diagnosed as having active tracheobronchial tuberculosis, tracheobronchial lesions were examined by use of bronchofiberscope. Most patients were treated by a combination of three antituberculous agents (INH, RFP and SM or EB). In 31 patients out of the 41 patients, broncho-fiberscopic examinations were performed twice or more. We observed the ulcerous lesions of bronchial tuberculosis at various stages of healing, and could classify the ulcerous lesions into the following three stages. Active Stage: stage A; ulcer formation without regenerating epithelium, Healing Stage: stage H; ulcer formation with regenerating epithelium, Scarring Stage: stage S; and no ulcer formation. Only the lesions of stage A were observed before treatment. In many patients during the first and second month of treatment, the lesions were stage A or H. It was found that healing of the lesions of tracheobronchial tuberculosis progressed through the stages A, H, and S, in this order. The smear positive rates in sputum were 88.5% in stage A, 12.9% in stage H and 5.0% in stage S. The culture positive rates in sputum were 88.5% in stage A, 20.0% in stage H, and 0% in stage S. We conclude that at least 3 months were generally required for the healing of tracheobronchial tuberculosis with ulcerous lesion. However, it seems that the period of time for healing of ulcerous lesions is shorter in patients who are treated by aerosol therapy with SM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages.

Analysis of mice carrying mutant T-cell antigen receptor (TCR) genes indicates that TCR-beta gene rearrangement or expression is critical for the differentiation of CD4-CD8- thymocytes to CD4+CD8+ thymocytes, as well as for the expansion of the pool of CD4+CD8+ cells. TCR-alpha is irrelevant in these developmental processes. The development of gamma delta T cells does not depend on either TCR-alpha or TCR-beta.

Animals↗
PubMed1992

Neurotoxins: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroisoquinoline and 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline as substrates for FAD-containing monooxygenase of porcine liver microsomes.

The activity of FAD-containing monooxygenase (FMO) (EC 1.14.13.8) of porcine liver microsomes was examined with the neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline (MDTIQ), as substrates. FMO catalyses these neurotoxins. The kinetic parameters of FMO for the neurotoxins and electron donors were determined. Km values for MPTP, TIQ and MDTIQ were determined to be 47 microM, 6.9 mM and 5.6 mM, respectively. The Km for the electron donor, NADPH, was variable from 31 to 200 microM depending on the substrate used. The activities of FMO for these neurotoxins were comparable with that for dimethylaniline.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Multivalent ligand binding by serum mannose-binding protein.

The serum-type mannose-binding protein (MBP) is a defense molecule that has carbohydrate-dependent bactericidal effects. It shares with mammalian and chicken hepatic lectins similarity in the primary structure of the carbohydrate-recognition domain, as well as the ligand-binding mode: a high affinity (KD approximately nM) is generated by clustering of approximately 30 terminal target sugar residues on a macromolecule, such as bovine serum albumin, although the individual monosaccharides have low affinity (KD 0.1-1 mM). On the other hand, MBP does not manifest any significant affinity enhancement toward small, di- and trivalent ligands, in contrast to the hepatic lectins whose affinity toward divalent ligands of comparable structures increased from 100- to 1000-fold. Such differences may be explained on the basis of different subunit organization between the hepatic lectins and MBP.

Acute-Phase Proteins↗
PubMed1992

Effects of interleukin 1 alpha on the activities and gene expressions of the cytochrome P450IID subfamily.

The mechanism by which recombinant human interleukin 1 alpha (rhIL-1 alpha) inhibits the activities of drug-metabolizing enzymes of rat liver microsomes, especially debrisoquine monooxygenase and bufuralol monooxygenase (both cytochrome P450IID supported reactions), as well as other enzymes, was investigated by injecting IL-1 alpha into rats. rhIL-1 alpha suppressed the activities of various P450-linked monooxygenase systems such as aminopyrine N-demethylase, benzphetamine N-demethylase, and 7-ethoxycoumarin O-deethylase. It also suppressed the activities of debrisoquine monooxygenase and bufuralol monooxygenase. On the other hand, IL-1 alpha had little effect on the activity of p-nitroanisole N-demethylase. The suppression of debrisoquine monooxygenase and bufuralol monooxygenase activities was caused by a decrease in the amounts of immunoreactive P450IID protein and its mRNA. The reduction rates in the level of immunoreactive P450IID protein and its mRNA were comparable. These results suggest that at the mRNA level, the enzymatic activities of debrisoquine monooxygenase and bufuralol monooxygenase are down-regulated by IL-1 alpha.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1992

Absorbance spectral change of the cytochrome P-450S21-phenylisocyanide complex upon binding of reduced NADPH-cytochrome-P-450 reductase.

Reduction of cytochrome P-450S21 (SF) (SF, substrate-free; purified from bovine adrenocortical microsomes) with sodium dithionite (Na2S2O4) in the presence of phenylisocyanide produced a ferrous cytochrome P-450S21 (SF)-phenylisocyanide complex with Soret absorbance maxima at 429 and 456 nm. On the other hand, when a preformed ferric cytochrome P-450S21 (SF)-NADPH-cytochrome-P-450 reductase (Fp2) complex was reduced chemically or enzymatically under the same conditions, the absorbance spectrum of the ferrous cytochrome P-450S21 (SF)-phenylisocyanide complex changed drastically, as characterized by an increase in absorbance intensity at 429 nm and a decrease at 456 nm. Similar spectral changes were observed by addition of reduced Fp2 to the preformed ferrous cytochrome P-450S21 (SF)-phenylisocyanide complex. Experiments to reduce a ferric cytochrome P-450S21 (SF)-phenylisocyanide complex with sodium dithionite in the presence of various amounts of Fp2 showed that; (1), the spectral change reached maxima for both absorption increase at 429 nm and decrease at 456 nm when cytochrome P-450S21 and Fp2 were previously mixed at the cytochrome P-450S21:Fp2 ratio of 1:5; (2), the spectral change was suppressed in 300 mM potassium phosphate buffer (pH 7.4). These results suggest that the absorbance spectral change is due to a conformational change around the heme moiety induced by association with reduced Fp2.

Adrenal Cortex↗
PubMed1992

Effects of cholesterol side-chain groups and adrenodoxin binding on the vibrational modes of carbon monoxide bound to cytochrome P-450scc: implications of the productive and nonproductive substrate bindings.

Effects of the bindings of cholesterol and its hydroxylated analogues on the Fe-CO stretching and the C-O stretching vibrations of cytochrome P-450scc-CO complex were examined by resonance Raman and FT-IR spectroscopies to reveal the spatial relationship between the steroid side-chain groups and the heme-bound C-O moiety at the active center. These C-O and Fe-CO vibrations exhibited considerable variations depending on the steroids used; however, analyses on the nu Fe-CO vs nu C-O plot for cytochrome P-450scc indicated the absence of the negative correlation between these two vibrations, which is common among various Fe(2+)-porphyrin-CO complexes having imidazole ligands. Rather, we noticed the existence of two groups depending on substrates, the one exhibiting C-O infrared absorption bands in the region from 1930 to 1940 cm-1 and higher enzymatic turnover numbers in the reconstituted enzymatic systems and the other exhibiting C-O infrared absorption bands in the region above 1945 cm-1 and lower enzymatic turnover numbers. Thus, the former substrate group is likely to be fitted into the substrate binding site in the efficient "productive substrate binding" structure, whereas the latter group may be bound to the enzyme in the structure not suitable for the efficient enzymatic reaction ("nonproductive substrate binding" conformation).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1992

Characterization of the cytochrome P-450IID subfamily in bovine liver. Nucleotide sequences and microheterogeneity.

To elucidate the molecular mechanisms underlying drug detoxification, the structures of the members of the microsomal cytochrome P-450IID subfamily were analyzed by isolating, mapping and sequencing cytochrome P-450IID (CYP2D) cDNA clones from bovine liver. The screening was performed under nonstringent conditions so that most of the P-450IID subfamily members could be obtained. 114 of the 147 positive clones were classified into four groups on the basis of their restriction-enzyme maps. The maps of the four groups were highly similar, however, the clones of one group contained an insertion of approximately 500 bp in the coding region. Analysis of partial nucleotide sequences of several representative clones from each group showed that the bovine P-450IID subfamily in liver consisted of several, not many, highly similar members, differing by less than 7% in their nucleotide sequences. The location of the insertion found in the minor group corresponded to intron 7 and the GT/AG rule was found at the exon/intron boundary, suggesting that intron 7 was retained in this group. The complete nucleotide sequences of two clones from the major group were examined to determine the structures of the P-450IID subfamily in bovine liver. A full-length cDNA clone (1615 bp) and a partial cDNA clone (1538 bp) contained open reading frames encoding 500 and 487 amino acid residues, respectively. The partial clone lacked the nucleotide sequence corresponding to the first 13 N-terminal amino acid residues. The deduced amino acid sequences of the two clones were 98% similar, and 80% and 68% similar to those from human CYP2D6 and rat CYP2D1, respectively. Comparisons of the amino acid sequences of the P-450IID subfamily members showed the highly conserved C-terminal region of their molecules and the high similarity between the members in one species, especially in cattle and man.

Amino Acid Sequence↗
PubMed1992

Electronic and stereochemical characterizations of intermediates in the photolysis of ferric cytochrome P450scc nitrosyl complexes. Effects of cholesterol and its analogues on ligand binding structures.

Low temperature photolysis of nitric oxide from the nitrosyl complexes of ferric cytochrome P450scc was examined by EPR spectroscopy to elucidate the stereochemical interaction between heme-bound ligand and side-chain of cholesterol or its hydroxylated analogues at the substrate-binding site. The photoproducts of the NO complexes trapped at 5 K exhibited new EPR absorptions providing information on the steric crowding of the distal heme moiety. Without substrate, the photoproduct exhibited a broad EPR absorption at g-8 due to magnetic dipole-dipole interaction between the photo-dissociated NO (S = 1/2) and the ferric iron (S = 5/2). This indicates that the photo-dissociated NO can move far away from the heme iron in the less restricted distal heme moiety of the substrate-free cytochrome P450scc. In the presence of substrates, such as cholesterol, 20(S)-hydroxycholesterol, 22(S)-hydroxycholesterol, 22(R)-hydroxycholesterol, and 25-hydroxycholesterol, the EPR spectra of the photoproducts exhibited many variations having broad g-8 absorptions and/or the widespread signals together with zero-field absorption. Among the steroid complexes used, 20(S)-hydroxycholesterol complex exhibited a conspicuously widespread EPR signal with a distinct zero-field absorption due to a spin-coupled interaction between the ferric iron (S = 5/2) and the photolyzed NO (S = 1/2). These results indicate that the 20(S)-hydroxycholesterol complex has restricted substrate-binding structure and that the hydroxylation of the cholesterol side-chain at the 22R position is necessary to proceed the side-chain cleavage reaction properly in cytochrome P450scc.

Adrenal Cortex↗
PubMed1992

Localization of metastasis suppressor gene(s) for prostatic cancer to the short arm of human chromosome 11.

Previous studies using somatic cell hybridization of highly metastatic and nonmetastatic rat prostatic cancer cells demonstrated that the resultant hybrids were nonmetastatic if all of the parental chromosomes were retained. Somatic hybrid segregants which underwent nonrandom chromosomal losses reexpressed high metastatic ability. These results demonstrated that there are gene(s) the expression of which can suppress metastatic ability of prostatic cancer cells. To identify the location of homologous gene(s) in the human, specific human chromosomes were introduced into highly metastatic rat prostatic cancer cells using the microcell-mediated chromosome transfer. Introduction of human chromosome 11 into highly metastatic rat prostate cancer cells results in suppression of metastatic ability without suppression of the in vivo growth rate or tumorigenicity of the hybrid cells. Spontaneous deletion of portions of human chromosome 11 in some of the clones delineated the minimal portion of human chromosome 11 capable of suppressing prostatic cancer metastases as the region between 11p11.2-13 but not including the Wilms' tumor-1 locus.

Animals↗
PubMed1992

Debrisoquine 4-monooxygenase and bufuralol 1'-monooxygenase activities in bovine and rabbit tissues.

The tissue distributions of debrisoquine 4-monooxygenase and bufuralol 1'-monooxygenase activities in microsomes from bovine and rabbit tissues were analysed. Debrisoquine 4-monooxygenase and bufuralol 1'-monooxygenase activities were found in liver, and at low levels in cerebral cortex, kidney cortex, lung, small intestine and spleen. Other tissues, such as kidney medulla, adrenocortex, adrenomedulla, blood vessels, thyroid gland, heart, ovary, uterus and testis, showed low levels of bufuralol 1'-monooxygenase activity but not detectable debrisoquine 4-monooxygenase activity. The bufuralol/debrisoquine monooxygenase activity ratios were higher in kidney and lung, and lower in cerebral cortex and spleen than in liver. Both monooxygenase activities in several bovine tissues including liver were inhibited strongly by phenylisocyanide (0.1 mM) and quinidine (0.5 mM), moderately by metyrapone (1 mM), and not at all by KCN (1 mM). NaN3 (5 mM) and sodium cholate (0.5% w/v) inhibited debrisoquine 4-monooxygenase activity strongly and moderately, but bufuralol 1'-monooxygenase activity moderately and strongly, respectively. No effect of a hydroxyl radical scavenger or of superoxide dismutase on either monooxygenase activity was observed. It was concluded from these results, as well as the NADPH dependency of the reactions, that the two monooxygenase reactions observed in these tissues were catalysed by cytochrome P450s.

Animals↗