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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 253 records · Page 14Linked to original sources
PubMed1996

[Fas antigen (CD95) expressions and apoptosis of neoplastic cells from various lymphoid malignancies including adult T-cell leukemia/lymphoma].

We determined Fas antigen (CD95) expressions on neoplastic cells from various lymphoid malignancies including adult T-cell leukemia/lymphoma (ATL/L) by a flow cytometoric method. ATL/L cells generally expressed Fas antigen, while few Fas-positive cells were detected in the other lymphoid malignancies such as non-Hodgkin lymphomas, acute lymphoblastic leukemias, and chronic lymphocytic leukemias. The function of Fas antigen was considered normal, since anti-Fas monoclonal antibody induced apoptosis of ATL/L cells. However, clinical subtypes of ATL/L did not associate with the degrees of Fas antigen expression. When recent observations by others were also considered, the apoptosis of ATL/L cells seemed to be under a complex control mechanism which includes a Fas/Fas-ligand system, HTLV-I Tax protein, bcl-2 protein and interleukin-2 (IL-2)/IL-2 receptor system. In addition, the regulation of apoptosis by Fas/Fas-ligand system and bcl-2 protein might be different between T-and B-lineage lymphoid malignancies.

Apoptosis↗
PubMed1996

[An immunohistological study on expression of glutathione S-transferase pi (form) in dysplastic and neoplastic human uterine cervix lesions].

The glutathione S-transferase (GST) pi has been studied in association with the mechanisms of multidrug resistance and as a marker for malignant tumors. In this study, specimens from 92 cases of cervical neoplasms and 10 cases of normal squamous epithelium adhering to myoma were stained immunohistochemically with a rabbit polyclonal antibody to GST-pi. In 6 cases of normal squamous epithelium, the intermediate layer was positively stained with the GST-pi antibody. In all 20 cases of dysplasia, the cells with koilocytotic atypia were stained positively. In all 10 cases of carcinoma in situ and all 16 cases of stage Ia squamous cell carcinoma, various intensities of GST-pi staining were demonstrated. Forty-six specimens of stage Ib or more squamous cell carcinoma were positive for GST-pi binding except only one case. In general, squamous cell carcinoma of the uterine cervix is resistant to chemotherapeutic agents. GST-pi is most frequently stained in cervical squamous cell carcinoma as compared with ovarian or endometrial carcinoma. In conclusion, these results suggest that GST-pi may be a marker for cervical squamous cell carcinoma.

Adult↗
PubMed1996

[Prospective clinical study of the combination therapy of auranofin and methotrexate for rheumatoid arthritis--a multi-center study].

In a study to evaluate the usefulness of DMARDs combination therapy for RA, AF and MTX were concurrently given to RA patients who had responded poorly to over three months of monotherapy of either AF or MTX. The study was composed of two stages. In the first stage, patients were concurrently given AF and MTX for six months in order to evaluate the efficacy of combination therapy. In the second stage, patients who had responded to the earlier combination therapy were again put on monotherapy of the additive DMARD. Safety evaluation was conducted with 126 patients, and both efficacy and utility were evaluated in 100 patients. Lansbury index for RA significantly improved in both groups of patients starting with the AF and followed by the MTX combination (Group I) and those who started with MTX alone followed by the AF combination (Group II). The ratio of patients who achieved slight improvement or better in the overall improvement rating was significantly higher in Group I at 74.6%, vs. 51.1% in Group II patients. Ten patients (16.9%) and 2 patients (4.9%) were switched to their additive DMARD monotherapy of MTX and AF respectively, having responded to the combination therapy in stage I with slight improvement or a better rating. Adverse events were observed in 44 patients (34.9%), but the combination therapy neither increased the incidence of adverse events nor caused new adverse events. Combination therapy of AF and MTX appeared to be useful both in terms of efficacy and safety for patients who have experienced the dwindling effect of monotherapy.

Adult↗
PubMed1996

[Evaluation of sensitivity and specificity of confirmatory assays for lupus anticoagulant (LA) detection].

To evaluate the sensitivity and specificity of confirmatory assays for LA detection, we performed the platelet neutralization procedure (PNP), diluted Russell's viper venom time (dRVVT) confirmatory assay (the ratio of LA-screen and LA-confirm:S/C), and specific hexagonal phase neutralization test (StaLA) on, plasma samples 43 LA-positive in either the ratio of dilute APTT and APTT(dAPTT/APTT) or dRVVT(LA-screen). The sensitivity and the specificity were evaluated by 4 different analyses based on, 1) maximal plasma dilution, 2) correlation between the screening assays and these confirmatory assays, 3) ratio of LA-positive in the confirmatory assays, and 4) receiver operation characteristic (ROC) method. All 4 analyses showed that sensitivity was in the order of PNP > S/C > Staclot-LA. However, the order of the specificity evaluated by the ROC method was Staclot-LA > S/C > PNP. The APTT-based confirmatory assay, PNP can detect LA of the plasma samples that were all positive in the dAPTT/APTT ratio, while the LA-positive plasma samples in dRVVT-confirm were all positive in the dRVVT-screen assay. Our findings suggest that confirmatory assays should be based on the method giving an abnormal screening assay. Accordingly, we recommend the following combinations of screening and confirmatory assays in terms of specificity; 1) dAPTT/APTT ratio and Staclot-LA as the APTT-based assay, and 2) LA-screen and LA-confirm as the dRVVT-based assay.

Blood Coagulation Tests↗
PubMed1996

Laboratory diagnosis of Helicobacter pylori infection by polymerase chain reaction.

Although the detection of Helicobacter pylori (Hp) infection is important, it is a rather difficult task using only conventional diagnostic techniques. In this study, we have applied a polymerase chain reaction (PCR)-based assay for the diagnosis of Hp infection. RT-PCR for Hp ribosomal RNA was utilized, using the gastric biopsy specimens obtained endoscopically from 10 patients. PCR primers have been designed from the highly consensus region of the 7 different Hp rRNA sequences in GenBank. In the detection of Hp, PCR was more sensitive than culturing and showed 100% of the sensitivity and specificity compared with histology. Our primer pair could detect as few as 50 organisms per reaction. RT-PCR for Hp rRNA is a sensitive and specific method to detect Hp infection in the gastric mucosa.

Base Sequence↗
PubMed1996

[Incidence of synchronous or metachronous multiple primary cancers and aggregation of cancers in families of patients with endometrial cancer].

We evaluated the incidence of synchronous or metachronous multiple primary cancer, hereditary or familial cancer, and the familial aggregation of cancer in 142 patients who were treated for endometrial cancer at Tsukuba University Hospital in the period 1977 to 1995. Synchronous multiple primary cancers were identified in 6 of the 142 patients (4.2%). Eleven patients (7.7%) had a history of extraendometrial cancer. Patients with endometrial cancer had a significantly high incidence of a history of breast cancer. Endometrial cancer was diagnosed in two patients who were screened before menopause. Four patients with endometrial cancer (2.8%) subsequently developed extraendometrial forms of cancer. One patient (0.7%) was considered to have a hereditary form of cancer, and 5 patients (3.5%) had familial forms of cancer. A total of 86 cases of cancer were found among 53 kindred (37.3%). More detailed studies are needed to elucidate the aggregation of cancers in the families of patients with endometrial cancer in Japan. Patients with a history of breast cancer should be screened for the presence of endometrial cancer.

Adenocarcinoma↗
PubMed1996

[Hemolytic anemias observed in SLE].

Hemolytic anemia observed in patients with SLE include autoimmune hemolytic anemia (AIHA) and thrombotic microangiopathic hemolytic anemia (TMHA). AIHA is caused by anti-erythrocyte antibody, which can be detected by direct Coombs' test. Recently, anti-phospholipid antibody draw attention as a cause of AIHA in SLE. TMHA include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Patients with TTP show CNS symptoms and renal damage, while those with HUS develop renal insufficiency, but show minimal CNS symptoms. Clinical findings of TMHA are fever, hemolytic anemia, thrombocytopenia, CNS symptoms, and renal insufficiency, which are quite same as the findings of SLE itself. TMHA should be considered for differential diagnosis in acute exacerbation of SLE.

Anemia, Hemolytic↗
PubMed1996

Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis.

OBJECTIVE: To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism. METHODS: Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-prostaglandin F1 alpha, 2,3-dinor-6-keto-PGF1 alpha, and prostaglandin E2 were determined. In a randomized crossover study, 8 patients with biopsy proven lupus nephritis were given 4 days' oral administration of DP-1904 (400 mg/day bid) or indomethacin (50 mg/day bid). The effects of DP-1904 on prostanoid metabolism were studied. RESULTS: Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis compared with non-renal systemic lupus erythematosus (SLE)(p < 0.05); enhanced production of TXA2 was also estimated in patients with lupus nephritis. The urinary TXB2/6-keto-PGF1 alpha ratio was also increased in lupus nephritis compared with non-renal SLE (p < 0.01), indicating a prostanoid imbalance that may lead to impaired renal function and subsequent pathology. During administration of DP-1904, the urinary excretion of TXB2 was significantly decreased after 1 to 2 days. An increase in creatinine clearance as a measure of renal function was observed. In contrast, during the administration of indomethacin, urinary excretion of both TXB2 and 6-keto-PGF1 alpha decreased and there were no significant changes in the urinary TXB2/6-keto-PGF1 alpha ratio or creatinine clearance. Hemodynamic changes were associated with a slight increase in sodium excretion, but with no change in arterial blood pressure. No side effects were elicited during the 4 days of treatments. CONCLUSION: The abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function, which was mediated hemodynamically, and the altered metabolism was reversible and at least partially corrected by a TXA2 synthetase inhibitor, DP-1904.

Adult↗
PubMed1996

Fluorometric determination of total mRNA with oligo(dT) immobilized on microtiter plates.

We have developed a rapid and nonradioactive method of quantifying cytosolic mRNA from crude cell lysates by using plastic plates to which oligonucleotides containing poly(dT) sequences were previously immobilized. Captured mRNA on the plate was mixed with Yoyo-1 fluorescent indicator dye, and the resulting Yoyo-1 fluorescence of the mRNA-Yoyo-1 complex was measured in a fluorometer. Because Yoyo-1 signals were linearly increased in proportion to the amount of applied mRNA in the range 10-250 ng, the amount of mRNA in test samples can be determined by comparing their Yoyo-1 fluorescence with that of known concentrations of calibrator mRNA. Using this system, we found that the amount of cytosolic mRNA in undifferentiated U937 and HL-60 cells was 268.6 +/- 13.1 and 282.0 +/- 7.8 ng/10(6) cells, respectively, significantly (P < 0.01) more than that of phorbol ester-induced differentiated U937 and HL-60 cells (145.3 +/- 13.9 and 164.7 +/- 11.6), respectively. Therefore, the present system may be applicable to both medical molecular biology research and diagnostics.

Animals↗
PubMed1996

[Chronic pulmonary paracoccidioidomyosis in a Japanese Adult].

We encountered a case of chronic pulmonary paracoccidiodomycosis in Japan. A 53-year-old Japanese man, who had worked in Brazil from 1964 to 1969. Came to our hospital because of abnormal shadows on a screening chest roentgenogram. In 1989, he had been treated with fluconazole for mucocutaneous-lymphangitic paracoccidioidomycosis with oral ulceration and neak hymphadenitis. Chest roentgenograms and computed tomograms showed diffuse small nodular and emphysematous shadows. Microscopical examination of specimens obtained by transbronchial lung biopsy showed no abnormality. He was treated with oral fluconazole, and the abnormal radiographic shadows regressed. We believe that this was the first case of chronic pulmonary paracoccidiodomycosis in Japan.

Antifungal Agents↗
PubMed1996

[The ethanol elimination pharmacokinetics--the effects of genotypes of ALDH2 and CYP2E1 on the ethanol metabolism].

The effects of the genotypes of CYP2E1, ALDH2, ADH upon the blood ethanol and acetaldehyde levels were investigated. The predicting 95% confidence bounds determined on regression analysis of the data suggested that after venous injection of ethanol, the blood ethanol and acetaldehyde concentrations in a volunteer normal homozygous for ALDH2 (ALDH2*1/1) were significantly lower than that heterozygous (ALDH2*1/2). And the blood ethanol and acetaldehyde concentrations in a volunteer with C2 allele (C1/C2) were significantly lower than that in (C1/1). However, there were no significant differences in the blood ethanol and acetaldehyde concentrations between volunteers with ADH2*1/1 and ALDH2*1/2. It is possible that the ALDH2*1 and C2 alleles may correspond to the lower blood ethanol and acetaldehyde concentrations after intravenous administrations of 0.2 g /kg of ethanol.

Adult↗
PubMed1996

Modulation of peripheral blood lymphocyte subsets during methylprednisolone pulse therapy.

We determined fluctuations in circulating lymphocyte subsets induced by methylprednisolone pulse therapy (MPT) and the continuous administration of prednisolone (PSL) in 17 patients with autoimmune or systemic rheumatic disease. Two-color flow cytometry, using monoclonal antibodies to various lymphocyte subsets, was performed to identify a possible association between the clinical efficacy of treatment and modulative effects on each subset. Both MPT and continuous oral PSL showed suppressive effects on most of the lymphocyte subsets: CD4+, CD45RA or CD45RA+CD4+, CD8+, CD11b.CD8+, CD5+ B, and CD57+ or CD57 CD16+ cells. Modulation of lymphocyte subsets were more profound with MPT than with continuous oral PSL. The results are relevant to the different degrees of immuno-suppression effected by the two treatment modalities. We found that the number of CD45RA.CD4+ cells after MPT treatment correlated with the clinical efficacy of the treatment: the less CD45RA.CD4+ cell numbers decreased after MPT treatment, the greater was the clinical efficacy of the treatment. The results probably are associated with a rapid recovery of the subset after MPT treatment in the responders. Thus, the sequential monitoring of circulating lymphocyte subsets is useful in predicting the clinical effects of MPT treatment.

Adult↗
PubMed1996

Decay-accelerating factor (DAF, CD55)-negative T lymphocytes in the peripheral blood of Sjögren's syndrome patients.

OBJECTIVE: To clarify possible associations of decay-accelerating factor (DAF, CD55), expressed on circulating lymphocyte subsets and other hematologic cells, with corresponding cytopenias observed in primary Sjögren's syndrome (SS). METHODS: DAF expression on peripheral blood (PB) cells was determined in 21 patients with SS and 11 healthy controls by single or 2 color flow cytometry. RESULTS: In the PB from SS patients, anemia, monocytopenia, neutropenia, and lymphocytopenia were observed. Compared to the controls, the percentages of DAF-negative cells were higher in CD4+ and CD8+ T cell subsets from SS patients, but the expression of DAF was similar in the other PB cells, including CD19+ B cells, CD56+ NK cells, monocytes, granulocytes, and erythrocytes. The percentages of DAF-negative cells among the CD4+ and CD8+ cells were positively correlated in SS patients, but the numbers of cells in both subsets were decreased in those patients being treated with prednisolone. However, these proportional changes are thought to reflect a decrease in the numbers of DAF-positive CD4+ and CD8+ cells, because the absolute numbers of circulating DAF-positive CD4+ and CD8+ cells, but not DAF-negative cells, were significantly decreased in SS patients. In addition, DAF-negative cells were detectable in both CD45RA+ (naive) and CD45RO+ (memory) T cells from healthy individuals, and the expression of DAF was remarkably increased in both subsets after in-vitro activation with concanavalin-A. CONCLUSION: DAF-negative cells are proportionally increased among circulating CD4+ and CD8+ T cells in SS patients, although such changes are due to decreased numbers of DAF-positive cells within each subset. When considering previous observations, the DAF-negative CD4+ and CD8+ cells probably belong to activated T cell subsets in both SS patients and controls. However, the patterns of DAF expression seemed to be different between activated T cells recognized in the PB, and those induced by in vitro-stimulation.

Adult↗
PubMed1995

Electron paramagnetic resonance investigation of cytochrome P-450c21 from bovine adrenocortical microsomes: a new enzymatic activity.

Cytochrome P-450c21 (CYP21A1) purified from bovine adrenocortical microsomes was investigated by electron paramagnetic resonance (EPR) spectroscopy to clarify the interactions among heme active center, protein surroundings, water molecules and bound substrates or analogues. The low-spin EPR signals of the oxidized enzyme (as purified) consisted of two species; one at gz = 2.39, gy = 2.23, and gx = 1.925 (component A) and the other at gz = 2.42, gy = 2.23, and gx = 1.916 (component B). The component A is probably representing a product-bound form, whereas the component B indicates either occupation of the substrate-binding site with a substrate analogue or absence of steroid at the site. Upon addition of progesterone, the component A signal completely disappeared and the intensity of high-spin signal (g = 8.06, 3.54) increased. Addition of 17 alpha-hydroxyprogesterone caused a development of a new low-spin signal at gz = 2.42, gy = 2.21, and gx = 1.966 (component C) and a further increase in intensity of the high-spin signal (g = 8.06, 3.54). Addition of 20 beta-hydroxyprogesterone caused an increase in intensity of the component C signal (and the g = 8 high-spin signal) even stronger than did 17 alpha-hydroxyprogesterone. These observations suggest that 20 beta-hydroxyprogesterone binds to the cytochrome P-450c21 active center in a very similar manner as 17 alpha-hydroxyprogesterone does and, therefore, may be a metabolizable substrate. A new enzymatic pathway catalyzed by cytochrome P-450c21 was confirmed with a reconstituted enzymatic system consisting of cytochrome P-450c21, NADPH-cytochrome P-450 reductase and an NADPH-generating system. 20 beta-Hydroxyprogesterone was converted to progesterone via a putative 20 beta-oxidase reaction in a comparable turnover number to that of the 21-hydroxylation of 17 alpha-hydroxyprogesterone.

Adrenal Cortex↗
PubMed1995

Interaction of NADPH-adrenodoxin reductase with NADP+ as studied by pulse radiolysis.

The reduction of flavin in NADH--adrenodoxin reductase by the hydrated electron (eaq-) was investigated by pulse radiolysis. The eaq- reduced directly the flavin of the reductase to form a blue semiquinone of the enzyme. Subsequently, the semiquinone decayed by dismutation to form the oxidized and fully reduced forms of the enzyme with a second-order rate constant of 4.4 x 10(4) M-1 s-1. In the presence of equimolar NADP+, the decay of eaq- accompanied an absorption increase at 400 nm, the spectrum of which, formed transiently, is identical to that of NADP radical (NADP.). Subsequently, the transient species decayed concomitantly with the formation of the semiquinone. The rate constant in the formation of the semiquinone was independent of the concentration of the enzyme (6.1 x 10(4) s-1 at pH 7.5). From these results, it is concluded that eaq- reacts with NADP+ bound to the enzyme to form NADP. initially, and subsequently, an electron flows from the NADP. to the flavin by an intracomplex electron transfer. A similar result was obtained in the reaction of CO2- or N-methylnicotinamide radical with the NADP(+)-adrenodoxin reductase complex. These results suggest that the nicotinamide moiety of NADP+ bound to the enzyme is accessible to the solvent and masks the flavin completely.

Animals↗
PubMed1995

Mutations of p16Ink4/CDKN2 and p15Ink4B/MTS2 genes in biliary tract cancers.

p16Ink4 and p15Ink4B are cyclin-dependent kinase 4 inhibitors and link to the regulation of cell cycle in mammalian cells. The genes encoding these inhibitors are located at 9p21, which is a frequent site of allelic loss in various types of tumors. Twenty-five primary biliary tract cancers were examined for somatic mutations in p16Ink4/CDKN2, p15Ink4B/MTS2, p53, and K-ras genes and allelic loss of 9p21 by microsatellite analysis. Four biliary tract cancer cell lines were analyzed for homozygous deletions and point mutations. We found frequent homozygous deletions in p16Ink4/CDKN2 and p15Ink4B/MTS2 genes in the biliary tract cancer cell lines. Each cancer cell line had alteration of either p16Ink4/CDKN2, p15Ink4B/MTS2, or p53 genes. In primary tumors, 16 of 25 (64%) biliary tract cancers had point mutations in the p16Ink4/CDKN2 gene. These include 14 missense and 2 silent mutations. The frequency of mutations in gall bladder cancer and hilar bile duct cancer were 80% (8 of 10) and 63% (5 of 8), respectively. Each of codons 1, 80, and 111 was changed in two cases of these cancers. One of three intrahepatic bile duct cancers, one of two common bile duct cancers, and one of two ampullary cancers had mutations in the p16Ink4/CDKN2 gene. In contrast, no mutation in the p15Ink4B/MTS2 gene, one base change in the K-ras gene, and one loss of heterozygosity at the IFN alpha locus in 25 cancers and one base change in the p53 gene in 19 cancers were observed. These results suggest that p16Ink4/CDKN2, rather than p15Ink4B/MTS2 or p53 genes, and its inactivation may be important in biliary tract carcinogenesis.

Base Sequence↗
PubMed1995

An essential lysyl residue (Lys208) in the substrate-binding site of porcine FAD-containing monooxygenase.

The substrate (amine)-binding site of porcine FAD-containing monooxygenase (FMO) (EC 1.14.13.8) was examined using pyridoxal 5'-phosphate (pyridoxal-P) to modify lysyl residues. The enzymic activity of the FMO was inhibited competitively by pyridoxal-P. Upon reduction of pyridoxal-P-treated FMO with NaBH4, a new characteristic absorption peak of substituted pyridoxal-P appeared at 325 nm. The amino acid residue compositions of the native and pyridoxal-P-treated FMOs indicated that the lysyl residues were modified by pyridoxal-P. The about 74% inactivation of the enzymic activity on covalent pyridoxal-P treatment of the FMO was nearly completely prevented in the presence of the substrate, N,N-dimethylaniline. The FMO covalently modified with pyridoxal-P in the presence or absence of N,N-dimethylaniline was digested with trypsin treated with tosylphenylalanylchloromethane and the resultant peptide fragments were separated with a reverse-phase high-performance liquid chromatography system; only one peptide was specifically labeled with pyridoxal-P and was detected at 325 nm in the absence of N,N-dimethylaniline. The modified peptide was analyzed and identified as that comprising the amino acid residues 186-208. These results suggest that Lys208 plays an important role in the substrate (amine)-binding site of FMO.

Amino Acid Sequence↗