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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 325 records · Page 18Linked to original sources
PubMed1994

In vivo administration of H2 blockers, cimetidine and ranitidine, reduced the contents of the cytochrome P450IID (CYP2D) subfamily and their activities in rat liver microsomes.

1. The effects of in vivo administration of H2 blockers, cimetidine and ranitidine (0.6 mmol/kg body weight/day, for 5 days), on several P450 isozymes, the P450IID (CYP2D) subfamily, and their monooxygenase activities in rat liver microsomes were investigated. 2. In vivo administration of cimetidine and ranitidine decreased the contents of P450 isozymes and the activities of P450-linked monooxygenase systems; i.e., benzphetamine N-demethylase, aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase, debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase. 3. The inhibitory effect on the enzymatic activities of the P450IID (CYP2D)-linked monooxygenase systems was studied by Western blot analysis with serum containing anti-CYP2D6 IgG, i.e., LKM1 autoantibody. The amount of P450IID (CYP2D) in liver microsomes decreased more remarkably in the group administered ranitidine or cimetidine in vivo than in controls. 4. The effects of cimetidine and ranitidine on the activities of the P450IID (CYP2D)-linked monooxygenase systems were investigated in vitro. The activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase were inhibited in vitro by cimetidine or ranitidine at a higher concentration than that on in vivo administration of either H2 blocker. 5. The kinetic parameters for cimetidine or ranitidine as to the activities of debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase in liver microsomes were determined by means of Lineweaver-Burk plots. 6. The suppressive effects of cimetidine and ranitidine on the activities of P450IID (CYP2D)-linked monooxygenase systems in vivo were found to be due to a decrease of the content of the P450IID (CYP2D) protein.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1994

Correspondence of increased debrisoquine 4-monooxygenase activity with seizure-susceptibility in Mongolian gerbils.

Four drug-metabolizing activities in Wistar rat and Mongolian gerbil liver microsomes were investigated to clarify the biochemical basis of convulsions. No significant associations were observed between the susceptibility to the tonic-clonic seizures in Mongolian gerbils and the drug-metabolizing enzymatic activities of p-nitroanisole O-demethylase, aminopyrine demethylase and benzo[a]pyrene-3-monooxygenase. However, a significant association was observed with the debrisoquine 4-monooxygenase (cytochrome P-450db1-linked monooxygenase system) activity, which is known to metabolize exogenous and endogenous parkinsonism-inducing neurotoxins such as MPTP and TIQ, and to activate carcinogens during the detoxication of xenobiotics. The mean activity of debrisoquine 4-monooxygenase in the seizure-sensitive group (male, 380; female, 350 pmol/h/mg protein) remained significantly higher (about 4-5 times) than that in the seizure-resistant group (male, 90; female, 80 pmol/h/mg protein). More Mongolian gerbils were extensive metabolizers of debrisoquine in the seizure-sensitive group than in the seizure-resistant group. These results suggest a possibility that the cytochrome P-450db1-linked monooxygenase system may activate the potential neurotoxins which are associated with tonic-clonic seizures in the Mongolian gerbil.

Animals↗
PubMed1994

Epidermal growth factor induces biphasic activation of ornithine decarboxylase in human stomach-derived KATO-III cells.

Effect of epidermal growth factor (EGF) on ornithine decarboxylase (ODC) was examined in human gastric cancer-derived KATO-III cells, because 125I-EGF binding studies indicated a presence of specific binding sites for EGF on these cells. Upon stimulation with EGF, both ODC mRNA expression and ODC enzyme activity were significantly increased in KATO-III cells. However, unlike in other cellular systems, both EGF-induced ODC mRNA expression and ODC enzyme activation were biphasic with the peaks at 15 +/- 10 min and 2.1 +/- 1.5 hrs (mean +/- SE) for mRNA, and 3.1 +/- 1.5 and 7.7 +/- 1.8 hrs (mean +/- SE) for enzyme activity, respectively. Therefore, KATO-III cell line may provide a unique model for the biochemical analysis of EGF action on ODC activation.

Cell Line↗
PubMed1994

Flow cytometric analysis of cell-surface antigen expressions on acute myeloid leukemia cell populations according to their cell-size.

Acute myeloid leukemia (AML) cells which expanded from a single leukemic cell show certain degrees of morphological and biological heterogeneity. In the present study, we determined cell-surface antigen expressions (CD13, 33, 34 and 38, and HLA-DR) on AML cells based on their cell-size (large vs small cells) by flow cytometry. We found that the cell-surface antigens were more strongly expressed on the large leukemic cells than the small cells, regardless of FAB subtypes. Furthermore, our preliminary study demonstrated that AML patients who showed a relatively small difference in antigen expression between large and small leukemic cells had longer remission durations and survival periods, compared with those with a more prominent difference in antigen expression. Thus, the heterogeneity of AML cells determined by the combination of cell-surface antigen expressions and cell-size may be associated with clinically important biological behaviors.

Adult↗
PubMed1994

Gene frequencies and haplotypic associations within the HLA region in 916 unrelated Japanese individuals.

The gene frequencies and haplotypic associations within the HLA region have been investigated in 916 unrelated Japanese individuals. HLA class I and class II antigens were studied by conventional serology, and class II alleles, DRB1, DRB3, DQA1, DQB1 and DPB1 were typed by using polymerase-chain reaction amplification and sequence-specific oligonucleotide probe (PCR-SSOP) method. Thirty DRB1, 3 DRB3, 8 DQA1, 15 DQB1 and 13 DPB1 alleles were found in our population. DR-NJ25, a characteristic antigen in the native American and Asian populations, was observed at 3.0%. This antigen was observed mainly with the DRB1*1403 and 1406 alleles. Twenty-seven out of 30 DRB1 alleles found in this study had a high positive linkage disequilibrium with DQB1 alleles and 20 of them had an exclusive association with one specific DQA1-DQB1 combination. The strong association between DRB1 alleles and HLA-B antigens was the most striking finding in this study. Twenty-eight out of 30 DRB1 alleles had a positive linkage disequilibrium with 24 HLA-B antigens (p < 0.01). The other two alleles, DRB1*0404 and 1402, were very rare, and their frequencies were 0.2% and 0.1%, respectively. The data presented in this population study should be useful for the studies on anthropology, organ transplantation and disease susceptibility.

Gene Frequency↗
PubMed1994

Striking conservation of three extended HLA-DR13 haplotypes in the Japanese population.

HLA class II DNA typing was conducted for 1335 unrelated Japanese individuals. The study on the linkage disequilibrium revealed a striking conservation of HLA DR13 haplotypes. Among these Japanese, 155 were typed for HLA-DR13 serologically, and they were correspondent to three DRB1 alleles, DRB1*1301, 1302 and 1307 defined by using the polymerase-chain reaction and sequence-specific oligonucleotide probe (PCR-SSOP) method. The two alleles, DRB1*1301 and 1307 were exclusively associated with each specific DRB3-DQA1-DQB1 combination which was DRB1*1301-DRB3*0101-DQA1*0103-DQB1*0603, and DRB1*1307-DRB3*0202-DQA1*0501-DQB1*0301, respectively. DRB1*1302, the most common DR13 allele in Japanese, had two significant associations with DRB3*0301-DQA1*0102-DQB1*0604 (DRB1*1302A) and with DRB3*0301-DQA1*0102-DQB1*0605 (DRB1*1302B). In this study, no other DR13 class II combinations were found. Only the DRB1*1302A halotype was associated with the DPB1*0401 allele while the DRB1*1302B haplotype was not. The complete conservation of these DR13 class II haplotypes was found to extend toward the HLA class I region. They were HLA A3-B44-DRB1*1301, A33-B44-DRB1*1302A and A33-B17-DRB1*1302B. Japanese could be characterized with these three extended haplotypes which were remarkably different from those in Caucasian, Black and Asian other than Korean populations.

DNA Primers↗
PubMed1994

Long-term graft survival rate of zero-mismatch kidney transplants for HLA-DRB1.

The study of a two-locus association between HLA-B and -DRB 1 revealed a significant 43 linkage disequilibrium. Donor-recipient HLA-DRB1 was determined by these 43 linkages. Zero-mismatch for HLA-DRB1 had a significant effect on the graft survival rate in living related and cadaver transplants. The 5-year graft survival rate was 94% in the zero-mismatch group for HLA-DRB1, 96% for related transplants, 92% for cadaver cases, and 94% in HLA identical siblings. A statistically significant difference was found between the zero-mismatch group for HLA-DRB1 and mismatch groups for HLA-DRB1 or HLA-DR (P < 0.01). The zero-mismatch group for HLA-DRB1 had mismatches for HLA-A and/or HLA-B in 46 of 70 cases (66%). No significant differences in the rejection rate was observed between zero-mismatch and mismatch cases for HLA-A and/or -B in the zero-mismatch group for HLA-DRB1. In the second step, genotyping was conducted in 118 cases. The 5-year graft survival rate was 93% in the zero-mismatch group for HLA-DRB1 and 86% in mismatch group (not a significant difference). We concluded that zero-mismatch transplant for HLA-DRB1 had a better long-term graft survival rate regardless of HLA class I.

Cyclosporine↗
PubMed1994

The impact of hepatitis C virus infection on liver disease in renal transplant recipients.

To assess the prevalence of hepatitis C virus (HCV) infection in renal transplant recipients and its impact on posttransplant liver disease, the sera from 176 recipients who had been followed for 1-20 years (mean 8.3 years) were tested for HCV-specific antibody using enzyme immunoassay. HCV-specific antibody was detected in 53 patients (30.1%) including 2 patients also positive for hepatitis B surface antigen (HBsAg). Among 167 HBsAg-negative patients, the presence of HCV-specific antibody was associated with an increased incidence of chemically significant hepatitis (70.6% vs. 9.5% in anti-HCV-negative patients, P < 0.01). Hepatitis was more likely to be chronic in anti-HCV-positive patients than in anti-HCV-negative patients (P<0.05). Serious liver disease developed in 4 of 51 anti-HCV-positive, HBsAg-negative patients: liver failure causing death in 3 and hepatoma in 1. Liver biopsy specimens from anti-HCV-positive patients showed more aggressive histological lesions compared with those from anti-HCV-negative patients. We conclude that HCV infection is quite prevalent in our renal transplant recipients and plays a major role in posttransplant chronic liver disease.

Alanine Transaminase↗
PubMed1994

[Mechanism of efficacy of erythromycin on diffuse panbronchiolitis--effect of erythromycin on cytokine mRNA expression in human whole blood model].

Recently, "low-dose and long-term" erythromycin (EM) has been reported to be effective in treatment of diffuse panbronchiolitis (DPB), but its mechanism is still obscure. We studied the effect of EM on cytokine mRNA expression by using LPS-stimulated human whole blood as an experimental vivo model. IL-8 mRNA was expressed in biphasic fashion with peak expression at 6 hours and 20 hours from the start of LPS stimulation. When whole blood was pretreated with EM (2 micrograms/ml) for 1 hours. IL-8 mRNA expression was depressed at 20 hours (p < 0.025) from the start of LPS (1 microgram/ml) stimulation. However, when pretreated for 12 hours, it was not depressed. EM (2 micrograms/ml) also depressed IL-1 beta (p < 0.025) and TNF alpha (p < 0.05) mRNA expressions at 6 hours from the start of LPS stimulation. From the above results, it was suggested that the direct inhibition of IL-1 beta and TNF alpha production by EM resulted in subsequent depression of production of IL-8 that is a potent chemotactic factor for neutrophil, and consequently, EM acts to protect the bronchiole tissues of DPB patients from destruction by proteolytic enzymes released from neutrophils. This assumption seems to be supported by our previous observation that when patients with DPB were treated with EM a marked decrease in number of neutrophil in bronchoalveolar lavage fluid (BALF) was accompanied by clinical and radiographic improvement.

Adult↗
PubMed1994

[Antibiotics susceptibilities and other biological properties of methicillin-resistant Staphylococcus aureus: observation in the last 2 years in our university hospital].

We examined biological properties of strains of methicillin-resistant Staphylococcus aureus (MRSA) which were isolated in our ward in 1991 and 1992. A total of 47 MRSA strains were isolated in 1991 and 64 in 1992. The majority of these strains of MRSA were highly resistant to DMPPC, CEZ and IPM, and were intermediately resistant to MINO. All these strains were, however, sensitive to VCM. The number of coagulase type II strains increased from 22 (46.8%) to 51 (79.7%), and that of enterotoxin type A strains from 27 (57.4%) in 1991 to 47 (73.4%) in 1992. The number of strains which produce Toxic Shock Syndrome Toxin-1 (TSST-1) also increased from 19 (40.4%) to 45 (70.3%), and those strains that produce beta-lactamase decreased from 24 (51.1%) to 21 (32.8%). From the above results, we confirmed the recent change in types of the epidemic strains of MRSA. Namely, there was a marked increase in number of strains which produce type II coagulase type A enterotoxin and TSST-1. For the prevention of a patient to patient-, room to room- and ward to ward-spread, strict isolation was indicated both the infection patients, immunocompromised patients who were at high risk for the infection and the proved carriers. Treatment with VCM was started immediately if MRSA infection was thought plausible. These countermeasures seemed to succeed in reducing the incidence of the infection in our ward.

Anti-Bacterial Agents↗
PubMed1994

Upregulation of cell surface expression of T-lymphoid antigens and adhesion molecules on acute myeloid leukaemia cells after in vivo administration of granulocyte colony-stimulating factor.

We herein report a case of acute myeloid leukaemia (AML, FAB:M0) who showed upregulation of T-lymphoid antigens (CD2, CD7) and adhesion molecules (CD11a, CD11b, CD18) on leukaemic cells after in vivo administration of granulocyte colony-stimulating factor (G-CSF). To our knowledge, this is the first report which describes in vivo changes of cell surface antigen expression on AML cells after the administration of G-CSF.

Aclarubicin↗
PubMed1994

Cloning of cDNAs for new subtypes of murine low-affinity Fc receptor for IgE (Fc epsilon RII/CD23).

In humans, two subtypes of the low-affinity Fc receptor for IgE, Fc epsilon RIIa and Fc epsilon RIIb, have been identified. The two forms differ only in a short stretch of amino acids at the cytoplasmic amino terminus. On the other hand, only one Fc epsilon RIIa-like receptor was reported in the mouse, although the existence of another subtype of transcript has been suggested. A new cDNA subtype for murine Fc epsilon RII that has amino acid homology to the human subtype b at the amino terminus was cloned by polymerase chain reaction. When expressed transiently in COS cells, the cDNA is capable of generating a functional cell surface protein that is recognized by an anti-Fc epsilon RII antibody and that has affinity to IgE. In the spleen, although the expression level is considerably lower than that of subtype a, the transcript appears in B cells and in non-B cells upon stimulation with IL-4 and LPS, in contrast to the constitutive expression of the conventional Fc epsilon RII transcript. It is also detectable in several cell lines of B- or T-cell lineages. These results suggest that this gene may be the murine counterpart of human Fc epsilon RII subtype b. Another cDNA clone for the distinct Fc epsilon RII transcript has also been isolated. The cDNA also encodes a surface protein functional on COS cells, but its human counterpart has not been found.

Amino Acid Sequence↗
PubMed1994

Extracorporeal shock wave lithotripsy for ureteral stones using the Dornier lithotriptor MFL5000.

A total of 157 ureteral stones in 150 patients were treated by extracorporeal shock wave lithotripsy (ESWL) using the Dornier lithotriptor MFL5000. Stones were treated in situ in 149 cases and with a double-J ureteral stent bypass in 8 cases due to large stone burden or failure of the preceding in situ ESWL. The average number of ESWL sessions and shock waves were 1.6 and 4,446, respectively. Multiple sessions were required in 58 cases (36.9%) for satisfactory fragmentation. At a 3-month follow-up, 91.7% of the cases treated by in situ ESWL and 50% of those treated with a stent bypass were rendered stone-free, achieving an overall stone-free rate of 89.4%. Ureteroscopic extraction or open ureterolithotomy was performed in 4 cases with an impacted stone for the removal of the residual fragments. No serious complications related to ESWL were observed. In situ ESWL is an effective and noninvasive method of treating ureteral stones. Large and/or impacted stones can also be successfully treated by ESWL with or without a stent bypass, but ureteroscopic or surgical procedures may be necessary to salvage fragments packed in the ureteral edema.

Adult↗
PubMed1994

Association of Mycoplasma pneumoniae antigen with initial onset of bronchial asthma.

Although mycoplasmal airway infection frequently exacerbates bronchial asthma, the cause of the initial onset of asthma remains unclear at present. In this report, we describe a patient in whom a previous acute mycoplasmal respiratory infection led to an initial onset of bronchial asthma. One month after the onset of the illness, cough and wheezing appeared. Pulmonary function studies revealed an airway obstructive dysfunction. Oral administration of bronchodilators resulted in a marked improvement of the asthmatic symptoms. An airway hyperresponsiveness to methacholine was demonstrated even 2 yrs after the initial onset of the illness, and IgE antibody specific to Mycoplasma pneumoniae was detected in the serum by use of enzyme-linked immunosorbent assay. An immediate skin test for M. pneumoniae was positive in addition to multiple positive skin tests. A bronchial inhalation challenge test with M. pneumoniae antigen also yielded a positive result. We conclude that the effects of mycoplasmal respiratory infections on the airway are multifactorial and involve a complex interplay of airway inflammation and IgE-mediated hypersensitivity.

Adult↗