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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 181 records · Page 10Linked to original sources
PubMed1998

Clinical significance of immunoglobulin A antiphospholipid antibodies: possible association with skin manifestations and small vessel vasculitis.

OBJECTIVE: To clarify whether immunoglobulin A (IgA) antiphospholipid antibodies (aPL) are an independent risk factor for specific manifestations of collagen vascular diseases. METHODS: We determined IgG, IgM, and IgA anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC) in 77 patients with various collagen diseases. Fifty-four patients who had positive results for either or both antibody classes were compared to 23 patients with systemic lupus erythematosus who had none of these antibodies. The association between the antibodies and clinical manifestations (thrombosis, fetal loss, thrombocytopenia, biological false positive test for syphilis, cutaneous manifestations, central nervous system involvement, and renal involvement) was analyzed. RESULTS: Of 54 patients with aPL, 33 showed significantly high levels of IgA aCL. Among them, IgA aCL coexisted with other aCL isotypes or LAC in 24 patients. The 9 patients with IgA aCL alone frequently had vasculitis associated manifestations, although thrombotic events and recurrent fetal loss were rare. Multivariate linear regression analysis showed that IgA aCL were independently associated with thrombocytopenia, skin ulcers, chilblain lupus, and vasculitis. There was also an association between IgM aCL and skin ulcers or chilblain lupus. CONCLUSION: Clinical manifestations of patients with IgA aCL differ from those of patients with IgG aCL. Determination of all 3 aCL isotypes and LAC is important to assess the risk of specific clinical manifestations in patients with aPL.

Adult↗
PubMed1998

[Three cases of Munchausen's syndrome mimicking connective tissue diseases].

Three young women were admitted to our hospital because of severe anemia and fever of unknown origin. The patients had a long history of frequent hospitalizations and operations. During hospitalization, the patients complained of hematemesis, hematuria and fever, which were sometimes discrepant with their physical and laboratory findings. After the careful observation, the patients were diagnosed as Munchausen syndrome because of either discovery of the tools used to make their symptoms or the patient's confession that these symptoms were made by herself. The patients with Munchausen syndrome sometimes show various symptoms and signs of multisystem inflammatory diseases, which mimick the clinical feature of connective tissue diseases. It is important for rheumatologists to be aware of the existence of Munchausen syndrome among the differential diagnosis of connective tissue diseases.

Adult↗
PubMed1997

Intravascular ultrasound findings after successful primary angioplasty for acute myocardial infarction: predictors of abrupt occlusion.

OBJECTIVES: This study sought to evaluate the intravascular structure as depicted by intravascular ultrasound after successful primary angioplasty (i.e., without thrombolytic therapy) for acute myocardial infarction and to investigate the related predictors of acute coronary occlusion. BACKGROUND: The usefulness of primary angioplasty for acute myocardial infarction is still limited by early reocclusion. There are few data regarding the intravascular ultrasound findings after primary angioplasty. METHODS: Intravascular ultrasound was performed in 27 patients after successful primary angioplasty. Repeat coronary angiography was performed 15 min later, on the following day and 1 month after angioplasty. RESULTS: Abrupt occlusion occurred in 8 of 27 patients. Angiographic variables in patients with versus those without abrupt occlusion were not significantly different. Intravascular ultrasound disclosed a significantly smaller lumen area ([mean +/- SD] 2.49 +/- 0.72 vs. 5.06 +/- 1.52 mm2, p < 0.001) and a significantly greater percent plaque area (80.5 +/- 9.1% vs. 63.7 +/- 7.8%, p < 0.001) in patients with abrupt occlusion. There was no significant difference in external elastic membrane cross-sectional area. We classified the ultrasound appearance of the intravascular structure as smooth, irregular or filled. Abrupt occlusion occurred in none of 6 patients with a smooth intravascular structure, 24% of 17 patients with an irregular structure and in all 4 with a filled structure (p < 0.05). In the latter group, the lumen was filled with bright speckled or low echogenic material, although angiography revealed excellent coronary dilation in all these arteries. CONCLUSIONS: Intravascular ultrasound revealed a narrow lumen in coronary arteries showing abrupt occlusion after successful primary angioplasty, even though angiography disclosed successful dilation. Arteries with a lumen filled with bright speckled or low echogenic material frequently develop abrupt occlusion.

Aged↗
PubMed1997

Existence of two heme B centers in cytochrome b561 from bovine adrenal chromaffin vesicles as revealed by a new purification procedure and EPR spectroscopy.

We have established a new purification procedure of cytochrome b561 from bovine adrenomedullary chromaffin vesicles. The heme content analysis of the purified sample indicated the presence of 1.7 molecules of heme B/cytochrome b561 molecule. EPR spectroscopy of the purified enzyme in oxidized state showed that there were three types of low spin heme species. Two of them showed usual EPR signals at gz = 3.14 and gz = 2.84 arising from the same heme and were interconvertible depending on pH. The other species showed a highly anisotropic low spin signal at gz = 3.70, with a lower redox potential than the others, and a temperature-sensitive character. These properties are very similar to low potential cytochrome b (bL or b566) of the mitochondrial complex III, indicating that the gz = 3.70 species is derived from a heme component different from the one that shows the usual low spin EPR signals. Based on our new structural model, these two heme B prosthetic groups are likely to be located on both sides of the membranes in close contact with the ascorbic acid- and semidehydroascorbic acid-binding sites, respectively, to facilitate the electron transfer across the membranes. This molecular architecture may provide a structural basis for the transmembrane electron transfer catalyzed by this hemoprotein.

Adrenal Medulla↗
PubMed1997

Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors.

Matrilysin is believed to play important roles in tumor progression and metastasis. In the present study, we analyzed matrilysin-producing cells in various human cancer tissues by immunohistochemistry and in situ hybridization. Tumor cells in colorectal carcinomas, pancreatic carcinomas, transitional-cell carcinomas of the kidney and small-cell lung carcinomas were frequently positive for matrilysin. In addition, we found that endothelial cells of arterioles and venules adjacent to matrilysin-positive tumors expressed matrilysin mRNA and protein. The endothelial cells adjacent to matrilysin-negative tumors and those in normal tissues were negative for matrilysin. Furthermore, analyses by casein zymography, Western blotting and RT-PCR showed that matrilysin was weakly expressed by cultured human umbilical vein endothelial cells. Our results suggest that the expression of matrilysin in vascular endothelial cells and in tumor cells may be regulated by common soluble factors, and that endothelial cell-derived matrilysin may contribute to tumor angiogenesis and tumor metastasis.

Animals↗
PubMed1997

Optical and electron paramagnetic resonance absorption spectra of complexes of nitric oxide synthase I with isocyanides.

Neuronal nitric oxide synthase (NOS I) was purified from porcine brains, and optical and EPR spectra of the complexes of NOS I with isocyanides were investigated. The complex of oxidized NOS I with tert-butylisocyanide exhibited optical absorption peaks at 437 and 560 nm in the difference spectrum, whereas with tert-butylisocyanide and phenylisocyanide, optically reduced NOS I-isocyanide complexes with absorbance maxima at 433, 451, 541 and 573 nm were produced. The dissociation constants of the NOS I-isocyanide complexes were optically determined, the constants being significantly larger than those of microsomal cytochromes P-450. Phenylisocyanide did not affect the optical spectrum of oxidized NOS I. A high concentration of phenylisocyanide also had no effect on the EPR spectrum of oxidized NOS I. The optical spectra of the reduced NOS I-isocyanide complexes were pH-dependent. With increasing pH, the intensity of the absorbance at 451 nm of the complexes increased and that of the absorbance at 433 nm decreased in parallel. Upon the addition of a saturating concentration of L-arginine, the difference spectra of the reduced NOS I-phenylisocyanides complex showed a drastic change, i.e., an increase in optical intensity at 433 nm and a concomitant decrease in the intensity at 451 nm. In titration experiments with L-arginine, spectral binding, Ks = 2.5 microM, was determined from the absorbance increase at 433 nm. No spectral change was observed on the addition of the same concentration of D-arginine. N(omega)-nitro-L-arginine methyl ester (NAME), a potent inhibitor of NOS I, had a similar effect to L-arginine, but the time course of the spectral change was very slow. These results suggest that: (1) the heme-iron pocket of NOS I will be narrower than those of the microsomal and mitochondrial cytochromes P-450; and (2) the binding of L-arginine and its analogue to their binding sites caused conformational changes around the ferrous heme moiety of NOS I.

Animals↗
PubMed1997

Cancer risk after renal transplantation in Japan.

Excess of cancer in patients receiving renal transplantation is well-known in Western countries, but information in Japan remains limited. Our study examined whether excess risk is found in patients receiving renal transplantation in Japan. Between 1970 and 1995, 1155 males and 589 females underwent renal transplantation in 6 hospitals, and a total of 12,982 person-years of observation was accumulated. Malignancies developed in 2.6% of patients; O/E ratio was 2.78. Median interval from renal transplantation to tumor development was 58 months. The interval in the patients receiving medication with cyclosporine-A (CyA) (median, 42.5 months) was significantly shorter than that with non-CyA (median, 95.5 months). Median age at the diagnosis of malignancy was 40 years, which is much younger than that in the general population. Relative risk was highest in renal cancer, followed by thyroid cancer, malignant lymphoma and uterine cancer. A distribution of malignancies was different from that reported from Western countries. These findings showed the excess risk of malignancies in Japan with renal transplants, especially in male patients, similar to that observed in Western countries, though the types of malignancy were different.

Adolescent↗
PubMed1997

Machado-Joseph disease gene product identified in lymphocytes and brain.

Machado-Joseph disease (MJD) is associated with the expansion of an unstable CAG repeat. The existence of an abnormal gene product in MJD was previously suggested with the expanded polyglutamine stretch-specific antibody. However, the product of the normal allele has not previously been identified. We generated monoclonal antibodies against the fusion protein (codon 225-310) of the MJD gene product and then identified the MJD1 gene product in normal lymphoblastoid cells as a approximately 50-kDa protein by immunoblot analysis. The electrophoretic mobility differences among the normal allele products corresponds to the molecular size difference produced by the polyglutamine stretch and the polymorphism at the C-terminus. Moreover, abnormal immunoreactive bands which were larger than the normal ones were found as a approximately 60-kDa protein exclusively in the MJD samples. The cytoplasm and the nuclei of neurons and glial cells were stained by these antibodies with immunocytochemistry. As in other CAG repeat diseases, the abnormal and normal allele products were almost equally expressed in lymphoblastoid cells and the brain of MJD patients.

Alleles↗
PubMed1997

Purification and characterization of a novel cytosolic NADP(H)-dependent retinol oxidoreductase from rabbit liver.

Rabbit liver cytosol exhibits very high retinol dehydrogenase activity. At least two retinol dehydrogenases were demonstrated to exist in rabbit liver cytosol, and the major one, a cytosolic NADP(H)-dependent retinol dehydrogenase (systematic name: retinol oxidoreductase) was purified about 1795-fold to electrophoretic and column chromatographic homogeneity by a procedure involving column chromatography on AF-Red Toyopearl twice and then hydroxyapatite. Its molecular mass was estimated to be 34 kDa by SDS-PAGE, and 144 kDa by HPLC gel filtration, suggesting that it is a homo-tetramer. The enzyme uses free retinol and retinal, and their complexes with CRBP as substrates in vitro. The optimum pH values for retinol oxidation of free retinol and CRBP-retinol were 8.8-9.2 and 8.0-9.0, respectively, and those for retinal reduction of free retinal and retinal-CRBP were the same, 7.0-7.6. Km for free retinol and Vmax for retinal formation were 2.8 microM and 2893 nmol/min per mg protein at 37 degrees C (pH 9.0) and the corresponding values with retinol-CRBP as a substrate were 2.5 microM and 2428 nmol/min per mg protein at 37 degrees C (pH 8.6); Km for free retinal and Vmax for retinol formation were 6.5 microM and 4108 nmol/min per mg protein, and the corresponding values with retinal-CRBP as a substrate were 5.1 microM and 3067 nmol/min per mg protein at 37 degrees C, pH 7.4. NAD(H) was not effective as a cofactor. 4-Methylpyrazole was a weak inhibitor (IC50 = 28 mM) of the enzyme, and ethanol was neither a substrate nor an inhibitor of the enzyme. This enzyme exhibits relatively broad aldehyde reductase activity and some ketone reductase activity, the activity for aromatic substitutive aldehydes being especially high and effective. Whereas, except in the case of retinol, oxidative activity toward the corresponding alcohols was not detected. This novel cytosolic enzyme may play an important role in vivo in maintaining the homeostasis of retinal, the substrate of retinoic acid synthesis, at least in rabbit liver, since a high concentration of retinol in liver and the lower Km of the enzyme for retinol force the oxidative reaction, while higher activity of retinal reductase at physiological pH forces the reductive reaction.

Alcohol Oxidoreductases↗
PubMed1997

A Japanese family carrying a novel mutation in the Emery-Dreifuss muscular dystrophy gene.

We report on a Japanese family affected by Emery-Dreifuss muscular dystrophy carrying a novel mutation of the emerin (STA) gene. The cardinal clinical feature of the family was cardiac conduction block and mild myopathy. A deletion of 11 bp with a frameshift was identified in exon 6, causing truncation of the predicted protein. The relationship between mutation and phenotype is discussed.

Adolescent↗
PubMed1997

Evidence for two successive pericentric inversions in sex lampbrush chromosomes of Rana rugosa (Anura: Ranidae).

The objective of this study was to clarify the course of inversions by which a ZW sex chromosome dimorphism has become established in Rana rugosa. Fortunately, R. rugosa preserves three different forms of sex chromosomes in the several isolated populations. In both males and females, the homomorphic sex chromosomes from Hiroshima were closely similar to Z, while those from Isehara were slightly different from the Z. Females from Hirosaki demonstrated heteromorphic sex chromosomes. In this study, the configuration and pairing behavior of sex lampbrush chromosomes were examined in the female offspring produced from a cross between a female from Hiroshima and a male from Isehara, as well as the female offspring of a female from Hirosaki and the male from Isehara. For the sex lampbrush chromosomes from Hiroshima and Isehara, chiasmata were exclusively formed between the distal regions of the long arms of one sex chromosome and the terminal regions of the short arms of the other. As a result, landmarks arranged in reverse order were observed in the achiasmatic regions of these chromosomes. For the sex lampbrush chromosomes from Isehara and Hirosaki, on the other hand, chiasma formation was mainly confined to the lower half of the chromosomes corresponding to the long arms, and the landmarks in the achiasmatic regions of these chromosomes were disposed in the opposite direction to each other. These results seem to indicate that in the primitive sex chromosomes of the Hiroshima type two pericentric inversions occurred, leading to the differentiation of the W chromosomes. This is the first report to substantiate the process of sex chromosome differentiation experimentally.

Animals↗
PubMed1997

Use of a bovine jugular vein graft with natural valve for right ventricular outflow tract reconstruction: a one-year animal study.

OBJECTIVE: We evaluated a bovine jugular vein graft with a natural trileaflet valve for right ventricular outflow tract reconstruction in a canine study for an entire year. METHODS: Heparinized bovine jugular vein grafts with a natural valve cross-linked with a hydrophilic polyepoxy compound of 18 to 20 mm in internal diameter were implanted in the right ventricular-pulmonary arterial position in eight dogs, and the main natural pulmonary artery was ligated. Anticoagulants were not used after implantation. Five grafts were retrieved on day 182 after implantation and the other three grafts on days 196, 375, and 385, respectively, and were inspected by macroscopic and microscopic observation. Cardiac catheterization, followed by angiography and echocardiography, was done just before graft retrieval. RESULTS: No graft kinking or regurgitation of the valve was observed. Echocardiography showed natural valve motion without thickening of the leaflets. Blood pressure in the conduits ranged from 18/9 to 31/4 mm Hg, in the right ventricle from 18/4 to 40/0 mm Hg, and the gradient varied from 0 to 14 mm Hg. The explanted conduits maintained their original shape, softness, and pliability with good coaptation of valves, without calcification or degenerative changes, except for one leaflet with slight deformation. In microscopic observation, endothelial cells lined the luminal surface of the conduit except for the areas adjacent to the valve. CONCLUSION: The graft worked perfectly as a right ventricular-pulmonary arterial valved conduit without anticoagulant therapy for a long time.

Animals↗
PubMed1997

Machado-Joseph disease gene products carrying different carboxyl termini.

Three cDNA clones for the Machado-Joseph disease gene (MJD1) were isolated, two of which have a new exon sequence and a distinct 3' terminal nucleotide sequence resulting in a new carboxyl terminal domain in the translated product. The nucleotide sequence of the other one is similar to the previously published one except for five polymorphisms, one of which is a single nucleotide substitution resulting in a change from the stop codon (TAA; allele A) to a tyrosine residue (TAC; allele C). Genetic analysis results suggest that Japanese MJD mutations are associated with allele A.

Amino Acid Sequence↗
PubMed1997

Direct inhibitions of the activities of steroidogenic cytochrome P-450 mono-oxygenase systems by anticonvulsants.

The effects of anticonvulsants on the activities of cytochromes P-450(17alpha,lyase) (CYP17), P-450arom (CYP19), P-450C21 (CYP21), P-450SCC (CYP11A1), and P-450(11beta) (CYP11B1) mono-oxygenase systems were studied using rat testicular microsomes, human placental microsomes, bovine adrenocortical microsomes, bovine adrenocortical mitochondria and purified cytochrome P-450(11beta). Phenytoin, clonazepam and carbamazepine inhibited the steroidogenesis catalysed by these cytochrome P-450 mono-oxygenase systems and the Ki values for each anticonvulsant were determined. Neither hydantoin nor sodium valproate inhibited the activities of steroidogenic cytochromes P-450. When the activities of cytochromes P-450arom and P-450C21 were measured in the presence of anticonvulsants, the Ki values (0.15 mM) for phenytoin were close to the plasma concentration of phenytoin under therapeutic conditions. Phenytoin, clonazepam and carbamazepine directly inhibited the monooxygenase activities of cytochromes P-450, because they did not affect the activities of NADPH-cytochrome P-450 reductase, NADPH-adrenoferredoxin reductase and adrenoferredoxin.

Adrenodoxin↗
PubMed1997

Effects of an immunosuppressive agent, tacrolimus (FK-506), on the activities of cytochrome P-450-linked monooxygenase systems in rat liver microsomes.

The effects of an immunosuppressive agent, tacrolimus (FK-506), on the activities of cytochrome P-450-linked monooxygenase systems with respect to three cytochrome P-450 isozymes in rat liver microsomes were investigated. FK-506 non-competitively inhibited the aniline p-hydroxylase, p-nitroanisole O-demethylase and lidocaine N-deethylase activities of cytochrome P-450-linked monooxygenase systems, these activities being mainly catalyzed by cytochromes P-450 CYP2E1, CYP2C11 and CYP3A4, respectively, and the Ki values of the activities for FK-506 were determined to be 605, 491 and 97 microM, respectively. The inhibition of cytochrome P-450-linked monooxygenase systems by FK-506 seemed to involve the direct inhibition of cytochromes P-450 because the NADPH-cytochrome c reductase and NADPH-ferricyanide reductase activities of NADPH-cytochrome P-450 reductase were not affected by the presence of 1 mM FK-506 at all. A spectrophotometric study showed that a reverse type I spectral change was induced on the addition of FK-506 to rat liver microsomes, and the Ks value was apparently 125 microM. On the other hand, the EPR spectra of cytochromes P-450 in rat liver microsomes were not affected by 1 mM FK-506. These results suggest direct interaction between FK-506 and cytochrome P-450 apoproteins, except for the heme iron regions of cytochromes P-450, resulting in inhibition of the drug-metabolism activities catalyzed by cytochromes P-450.

Aniline Hydroxylase↗
PubMed1997

Molecular cloning of sheep and goat ferredoxin reductase messenger ribonucleic acids, and identification of an alternatively spliced form of sheep ferredoxin reductase.

Complementary DNA clones of mRNAs for sheep and goat NADPH-ferredoxin reductases (ferredoxin NADP+ oxidoreductase, EC 1.18.1.2) were isolated by the reverse transcriptase polymerase chain reaction method, and the complete nucleotide sequences of the coding and 3'-flanking regions of these cDNA clones were determined. Comparative analysis using the deduced amino acid sequences of NADPH-ferredoxin reductases clarified the interspecific conservation of the ferredoxin-binding and flavin adenine dinucleotide (FAD)-binding regions, confirming the results reported previously. During this study, we happened to identify an alternatively spliced mRNA that completely lacks exon 3, just adjacent to the FAD-binding region of the sheep NADPH-ferredoxin reductase cDNA clone. In the screening of other alternatively spliced mRNAs of NADPH-ferredoxin reductases derived from several steroidogenic organs, such as adrenocortices, testes, and ovaries of sheep and goats, only one kind of alternatively spliced mRNA as described above was detected in sheep adrenocortices. Then, we constructed Escherichia coli expression systems for these two forms of mRNA and analyzed their enzymatic properties. We found that the ability of the alternatively spliced NADPH-ferredoxin reductase protein to transfer electrons to ferredoxin is completely abolished because FAD binding is inhibited.

Alternative Splicing↗