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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 271 records · Page 15Linked to original sources
PubMed1995

Identification of essential lysyl and cysteinyl residues, and the amino acid sequence at the substrate-binding site of retinal oxidase.

Retinal oxidase, which synthesizes all-trans and 9-cis retinoic acid from all-trans and 9-cis-retinal, has been purified from rabbit liver cytosol. The substrate-binding site of the retinal oxidase was investigated with some chemical modification reagents. Lysyl-specific pyridoxal 5'-phosphate (PLP) and cysteinyl-specific p-chloromercuribenzoate (PCMB) competitively inhibited the activity of the retinal oxidase, and the inhibition could be prevented by the presence of all-trans-retinal or its derivatives. Treatment with sodium borohydride (NaBH4) resulted in covalent attachment of PLP to the lysyl residue of the retinal oxidase and the PLP modified-retinal oxidase was cut with cyanogen bromide, and the polypeptides modified with PLP were further digested with trypsin. Two of the peptides modified with PLP were purified from the digested polypeptide mixture and their amino acid sequences were determined.

Aldehyde Oxidoreductases↗
PubMed1995

Inhibition of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolic activity of porcine FAD-containing monooxygenase by selective monoamine oxidase-B inhibitors.

The MPTP metabolic activity of porcine FAD-containing monooxygenase (FMO) (EC 1.14.13.8) was inhibited considerably by deprenyl and pargyline, selective MAO-B inhibitors, and they showed typical competitive inhibition. Deprenyl and pargyline, amine derivatives were also examined as to whether they are substrates for the FMO. It was found that deprenyl and pargyline are excellent substrates for the FMO. The Ki and Km values of deprenyl and pargyline for the FMO are 14 microM and 9 microM, and 14.3 microM and 11.6 microM, at pH 8.0 and 25 degrees C, respectively.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Delayed graft function does not influence long-term outcome in cadaver kidney transplants without mismatch for HLA-DRB1.

The currently study focused on the influence of delayed graft function on the long-term graft success rate in cadaver kidneys without any mismatches for HLA-DRB1. Donor-recipient HLA-DRB1 was determined by the significant two-locus linkages of HLA-B and -DRB1. The overall 5-year graft success rate was 88% in an HLA-DRB1-compatible group, significantly higher than the 69% in an HLA-DRB1 mismatch group (P < 0.05) and the 66% in an HLA-DR mismatch (P < 0.01). Delayed graft function was observed in 182 of 223 transplants. This high incidence of 82% is due to the fact that, in Japan, kidney procurement may only occur after cardiac arrest. The incidence did not differ in each group. The 5-year success rate for grafts with delayed function was 87% in the HLA-DRB1-compatible group, again significantly superior to the 68% in the HLA-DRB1 mismatch group and the 63% in the HLA-DR mismatch cases (P < 0.05). There was, thus, no difference in graft success rate for each group, with or without delayed graft function. Consequently, we feel that delayed graft function has no impact on the long-term outcome in transplants without mismatches for HLA-DRB1.

Adult↗
PubMed1995

An interleukin-1 binding region oligopeptide from the human type I IL-1 receptor reduces acute inflammation, delayed hypersensitivity reaction, and lethal endotoxemia in animals.

The effect of an interleukin-1 binding region oligopeptide from the interleukin-1 receptor on various inflammatory responses was investigated in animal models. A synthetic peptide (KICIRIQIS) corresponding to 86-93 of the extracellular domain of the human type I interleukin-1 receptor was used. Carrageenan-induced rat paw edema, a model of acute inflammation, was dose dependently suppressed by intraperitoneal administration of the peptide. The delayed hypersensitivity reaction to sheep red cells was diminished by pretreatment of mice with the peptide at a relatively high dose. In a murine lethal endotoxemia model, animals treated with the interleukin-1 receptor peptide (10 mg/kg x 4) showed significantly better survival than vehicle-treated animals when the peptide was administered from 20 minutes after lipopolysaccharide injection. Improved survival was accompanied by suppression of lipopolysaccharide-induced production of colony-stimulating factor, although the peptide did not improve hypoglycemia. These findings suggest that the interleukin-1 receptor peptide may be a potential treatment for various inflammatory processes.

Acute Disease↗
PubMed1995

Changing autoantibody profiles with variable clinical manifestations in a patient with relapsing systemic lupus erythematosus and polymyositis.

The production of autoantibodies characteristic of different autoimmune disease subsets is thought to be controlled primarily by genetic factors, whereas non-genetic factors are generally believed to be of secondary importance. A patient with systemic lupus erythematosus (SLE) and polymyositis (PM) who experienced frequent relapses associated with changing clinical manifestations and autoantibody specificities is reported. Her initial presentation as SLE with anti-Sm antibodies shifted to the onset of PM with temporal production of a different set of autoantibodies. The latter antibodies disappeared when myositis resolved, followed by the reappearance of autoantibodies and clinical manifestations characteristic of SLE. The shifts of autoantibody profiles in association with variable clinical manifestations in this patient argue that environmental factors may play a more important role in autoimmunity than previously supposed, and that interplay between environmental triggers and genetic predisposing factors may lead to the constellation of autoimmune disease manifestations exhibited at a particular time.

Adult↗
PubMed1995

Massive pericardial effusion in scleroderma: a review of five cases.

Medical records of five patients with scleroderma (SSc), each of whom had pericardial effusion with an estimated volume of more than 200 ml, were reviewed to study the clinical and immunological significance of massive pericardial effusion in SSc. Diffuse SSc (4/5), with a wide area of pigmentation (4/5), flexion contracture (4/5), oesophageal hypomotility (5/5), pulmonary fibrosis (4/5) and autoantibodies to topoisomerase I (3/5) were the common features in this group. High protein, lactate dehydrogenase and low white blood cell count were the characteristics of pericardial fluid. None of the patients had signs of acute pericarditis. Four of the five cases died within 9 months of the diagnosis of pericarditis; two with renal failure, one with cardiac tamponade and another with sudden death. The pericarditis in diffuse SSc, especially in cases with anti-topoisomerase I, may be characterized by a chronic form of pericarditis with poor prognosis, often complicated by renal failure.

Adult↗
PubMed1995

The drug-drug interaction effects of haloperidol on plasma carbamazepine levels.

The metabolic interaction between carbamazepine (CBZ) and haloperidol (HP) was studied in Japanese schizophrenic patients treated with HP but not with CBZ and with both CBZ and HP. The serum CBZ concentrations in patients treated without HP were significantly decreased (p < 0.05), on average approximately 40%, as compared to those in patients treated with both CBZ and HP, whereas the serum HP concentrations in patients treated with both HP and CBZ were significantly decreased (p < 0.05), as compared to those in patients treated with HP but not with CBZ. The effect of HP, which prevents the serum CBZ level from decreasing, was shown in this study.

Anticonvulsants↗
PubMed1995

Thermoluminescence dosimetry of the Hiroshima atomic-bomb gamma rays between 1.59 km and 1.63 km from the hypocenter.

Gamma-ray kermas from the Hiroshima atomic bomb were measured by a thermoluminescence (TL) method using tile specimens collected from five locations on the rooftop of a building (Postal Saving Bureau), 1,591-1,635 m from the hypocenter. Four tile specimens each from five locations were sampled and quartz grains were extracted from them. TL of these grains were analyzed by the high temperature TL method and gamma-ray kermas were obtained. The results in tissue kerma, on average, are 21% higher (standard errors are 4.3-7.3%) than the DS86 estimation. The present data and the reported TL results indicate that the measured gamma-ray kermas begin to exceed the DS86 values at about 1.3 km and the discrepancy between them increases with ground distance. This discrepancy is attributed to errors in the DS86 neutron source spectrum and is supported by previous neutron activation measurements.

Gamma Rays↗
PubMed1995

Characterization of a novel human tumor necrosis factor-alpha mutant with increased cytotoxic activity.

Various novel recombinant human tumor necrosis factor-alpha (TNF) mutants were prepared using protein engineering techniques, and their cytotoxic activity was compared with that of the intact form of TNF (intact TNF). Mutant 471 (a TNF mutant molecule with the deletion of 7 amino acids at the amino-terminal and the substitution of Pro8Ser9Asp10 by ArgLysArg) had a 6-fold higher cytotoxic activity against murine L929 cells. The mutant TNF had an increased ability to bind to TNF receptor on murine L929 fibroblasts cells. A cross-linking study revealed that mutant 471 had an increased ability to form an active trimer. Mutant 471 also showed higher cytotoxic activity against human KYM myosarcoma cells and human MIA PaCa-2 pancreatic carcinoma cells. The possible cachectin activity of the mutant was almost the same as that of intact TNF. These results suggest that mutant 471 might be a more promising candidate as an anticancer agent than intact TNF.

Amino Acid Sequence↗
PubMed1995

Spontaneous production of various cytokines except IL-4 from CD4+ T cells in the affected organs of sarcoidosis patients.

We investigated surface antigens and spontaneous cytokine production of T cells from bronchoalveolar lavage fluid (BALF) and aqueous humor (AH) from pulmonary sarcoidosis patients for a better understanding of the role of T cells in granuloma formation. The levels of CD3, CD11b, and CD28 antigen expression on freshly isolated T cells in the BALF of patients were significantly lower than those in peripheral blood lymphocytes (PBL) of either sarcoidosis patients or healthy donors (HD). In contrast, the levels of CD80 (B7/B7-1) and CD86 (B70/B7-2) antigen expression were significantly higher on these T cells and alveolar macrophages in the BALF of patients. Fifty-three T cell clones (TCC) established from the BALF and AH of the three sarcoidosis patients displayed primarily either CD4+ CD11b+ CD28+ or CD4+ CD11b- CD28- phenotypes. Most (61-90%) of these TCC spontaneously produced greater amounts of IL-1 alpha, IL-10, tumour necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) than did TCC from the PBL from sarcoidosis patients or HD (P < 0.05). Interferon-gamma (IFN-gamma), IL-6, and IL-2, but not IL-4, were also produced by 40-48% of these TCC. These results suggest that CD4+ T cells of the affected organs of sarcoidosis patients are activated and involved in the immunopathogenesis of sarcoidosis through production of various cytokines.

Adult↗
PubMed1995

Intra- and interindividual variation in the pharmacokinetics of tacrolimus (FK506) in kidney transplant recipients--importance of trough level as a practical indicator.

BACKGROUND: Tacrolimus (FK506) is currently used as the primary immunosuppressant in clinical kidney transplantation in some centers. The purpose of this study was to evaluate the pharmacokinetics of this drug and to see if trough level, which has been used widely in therapeutic drug monitoring, can be used as an appropriate substitute for other pharmacokinetic measurement tests. METHODS: The blood concentration-time curve was studied in 10 kidney transplant recipients on 26 occasions after oral dosage of 2 to 18 mg every 12 hours. Whole blood concentration was measured by two-step immunoabsorption assay. Methylprednisolone was used as a concomitant immunosuppressive drug. RESULTS: The blood concentration-time curves showed remarkable interindividual variation. Intraindividual variation was also found, but the degree of variation was slight compared with interindividual variation. On 17 occasions of measurement in one patient, the dose was significantly correlated with trough (r = 0.684), Cmax (r = 0.838) and AUC0-12 (r = 0.817). In nine patients on nine occasions, however, the dose was not significantly correlated with trough (r = 0.351), Cmax (r = 0.270) or AUC0-12 (r = 0.355). tmax ranged from one to four hours (mean + SD; 2.8 + 1.3) and fluctuated in both intra- and interindividual measurements. In spite of a wide variation in the blood concentration-time-curve patterns, a highly significant linear relationship between trough and Cmax or AUC0-12 was observed in both intraindividual (Cmax, r = 0.876; AUC0-12, r = 0.926) and interindividual (Cmax, r = 0.943; AUC0-12, r = 0.984) measurements. CONCLUSIONS: We conclude that trough level is a practical acceptable indicator of the blood levels of tacrolimus, and can be used to monitor blood concentration.

Adult↗
PubMed1995

Sealing of a fabric vascular prosthesis with autologous adipose tissue: a preliminary report of its clinical application.

A new method of sealing fabric vascular prostheses with autologous adipose tissue was clinically applied as an alternative to preclotting with fresh blood. Thirty-six patients with peripheral arterial occlusive disease were implanted with highly porous fabric prostheses. The prostheses were prepared by sealing the fabric pores with autologous adipose tissue that had been chopped up into small pieces and enmeshed in the fabric by forceful injection of the tissue suspension through a syringe. There was no complication related to the sealed graft such as graft bleeding after implantation. In-hospital mortality occurred in 4 patients: 1 case each of pneumonia, pulmonary infarction, sepsis, and acute myocardial infarction. During the period of 274 +/- 190 days, 3 prostheses were found to be occluded. All the other grafts were patent. The overall patency rate was 91.4%. Postoperative angiography revealed neither intimal thickening at the anastomotic sites nor irregularity of the prosthetic surface. The method proved safe and useful for implantation of smaller caliber artificial grafts.

Adipose Tissue↗
PubMed1995

Growth regulation of endothelial cells by tissue fragments: analysis on mechanism of rapid endothelialization of tissue-seeded vascular prosthesis in a three-dimensional culture system.

Rapid endothelialization of the inner surface was reported in an autologous tissue-seeded vascular prosthesis. We applied a three-dimensional in vitro culture system to elucidate the precise mechanism of rapid endothelial coverage of a tissue-seeded vascular prosthesis. Human venous, omental, adipose and striated muscle tissue fragments were harvested from surgical specimens. They were embedded in collagen gel, and 2.0 x 10(5) bovine aortic endothelial cells (BAECs) were seeded on the gel. The number of BAECs was counted on Days 2 and 7. Growth rate of BAECs was facilitated on the collagen gel with omental and striated muscle tissue fragments (p < 0.05). Factor VIII-negative spindle cells migrated around tissue fragments, especially around the omental and striated muscle tissue fragments. Rapid endothelialization of a tissue-seeded vascular prosthesis may result from facilitation of EC proliferation by viable tissue fragments and migrated cells. These results confirm tissue fragments regulate EC growth, and are useful as bioengineering tools.

Animals↗
PubMed1995

CYP2E1 and ALDH2 genotypes and alcohol dependence in Japanese.

The genotypes of the CYP2E1 and ALDH2 loci of alcoholic (alcohol dependence) and nonalcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphism of CYP2E1 (C1/C2) and ALDH2 (ALDH2*1/ALDH2*2), and the susceptibility to alcoholism. There was no significant difference in C2 gene frequency between alcoholics (0.19) and nonalcoholics (controls) (0.20), whereas there was a significant difference in ALDH2 allele frequency, suggesting that, in Japanese, the C2 genotype of CYP2E1 may have nothing to do with the risk of developing alcohol dependence. However, the ALDH2*1 allele may influence drinking behavior and the development of alcohol dependence. Furthermore, racial interethnic differences in the frequency of the mutated allele of the CYP2E1 gene (C2) were found, like the ALDH2 gene. Japanese healthy controls showed a significantly higher frequency of the C2 allele than did Swedish healthy controls (0.05; reported by Persson et al., FEBS Lett. 319:207-211, 1993).

Alcohol Drinking↗
PubMed1995

Periarticular osteopenia in adjuvant induced arthritis: role of interleukin-1 in decreased osteogenic and increased resorptive potential of bone marrow cells.

OBJECTIVE: To clarify the local osteogenic and bone resorptive potential of periarticular bone in adjuvant induced arthritis (AIA). METHODS: Formation of fibroblast colony forming units (FCFU; osteogenic precursor cells) and osteoclast-like cells in bone marrow culture was studied in AIA rats. Osteoclast-inducing activity in the AIA rat bone marrow was assayed by the addition of the marrow supernatant from rats with AIA to control cultures. Bone mineral density was determined by dual x ray absorptiometry. RESULTS: Marrow from AIA rats and that from animals receiving recombinant human interleukin-1 (IL-1) beta for seven days grew significantly fewer FCFU than control marrow. Formation of osteoclast-like cells was increased in bone marrow cultures from rats with AIA, especially when bone marrow cells were cultured in the presence of marrow supernatant. Formation of resorption lacunae on ivory slices was increased in the marrow cultures from rats with AIA, especially from the right (adjuvant inoculated) tibia. AIA rat marrow supernatant promoted osteoclast-like cell formation in control culture, and this was significantly suppressed by an anti-IL-1 antibody. Rats with AIA showed a significant decrease in the bone mineral density of the periarticular regions of the tibia and femur. CONCLUSION: An uncoupled state in bone resorption-formation linkage, possibly mediated through an increase of IL-1 in the bone marrow, may contribute to the development of periarticular osteopenia in inflammatory arthritis.

Animals↗