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Biomedical subjects

T Yokoi

Publications and source records attributed to T Yokoi.

At least 199 records · Page 11Linked to original sources
PubMed1994

Stereoselective pharmacokinetics and interconversions of flosequinan enantiomers containing chiral sulphoxide in rat.

1. In order to study the pharmacokinetics of flosequinan enantiomers ((+-)-7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) containing chiral sulphur, plasma levels of (+)-(R)- and (-)-(S)-flosequinan (R-FSO and S-FSO) and two metabolites (flosequinan sulphide (FS) and flosequinan sulphone (FSO2)) were measured after oral and i.v. administration of racemic flosequinan (rac-FSO), R-FSO and S-FSO in male rat. 2. The pharmacokinetic parameters of the enantiomers were different after oral and i.v. administration of R-FSO and S-FSO. The plasma clearance of R-FSO was higher than S-FSO. 3. The major metabolites of boh R-FSO and S-FSO was FSO2. A minor metabolite, FS, was also detected in plasma. 4. Interconversions occurred after the oral and i.v. administration of R-FSO and S-FSO. The amount of interconversion from S-FSO and R-FSO was greater than that from R-FSO to S-FSO. The rate of interconversion after oral administration was higher than that after i.v. administration. 5. After i.v. administration of FS, R-FSO and S-FSO were detected in plasma, suggesting that the interconversion occurred via formation of FS. 6. The pharmacokinetic parameters of R-FSO after administration of rac-FSO differed from that after administration of R-FSO, indicating the interaction between each enantiomer.

Administration, Oral↗
PubMed1994

Effects of cyclosporin-A and D-penicillamine on the development of hepatitis and the production of antibody to protein disulfide isomerase in LEC rats.

Long Evans Cinnamon (LEC) rats, which spontaneously develop hepatitis, produce an autoantibody to protein disulfide isomerase (PDI) before the development of clinical signs of hepatitis. Anti-PDI antibody may be associated with immunological hepatitis. Thus, the purpose of this study was to investigate the effects of some drugs on the development of hepatitis and the occurrence of the antibody in LEC rats. Cyclosporin-A, an immunosuppressant, and D-penicillamine, which promotes copper excretion, were orally administered to LEC rats for 23 weeks. Mortality, blood biochemical parameters and the titer of serum anti-PDI antibody were measured. In control LEC rats, four of eight rats died before 20-weeks-old. Only one of seven rats in the cyclosporin-A-treated group died at the age of 20 weeks. When rats were treated with D-penicillamine, the development of clinical signs of hepatitis was inhibited, and all rats survived. Cyclosporin-A-treated rats showed increases in blood biochemical parameters similar to those in control rats. The titer of anti-PDI antibody in control rats was higher the non-survivors than survivors. These findings suggest the association of the anti-PDI antibody with lethality, but not with the apparent development and progression of hepatitis as measured by blood biochemical parameters in LEC rats.

Administration, Oral↗
PubMed1994

Sex-related differences in the expression of cytochrome P450 in hamsters: cDNA cloning and examination of the expression of three distinct CYP2C cDNAs.

Sex-related differences in the expression of cytochrome P450 isozymes in hamsters were investigated. Three distinct cDNA clones (assigned as CYP2C25, CYP2C26, and CYP2C27) were isolated from liver cDNA libraries from male and female hamsters, using rat CYP2C11 cDNA as a probe. Sequence analysis revealed that these three forms were very similar to each other (> 90% identity of nucleotide sequences) and belong to the CYP2C gene subfamily. The CYP2C25, CYP2C26, and CYP2C27 cDNA clones consisted of an open reading frame encoding 490 amino acids. CYP2C25, CYP2C26, and CYP2C27 proteins expressed in Saccharomyces cerevisiae catalyzed the hydroxylation of tolbutamide and the N-demethylation of aminopyrine and benzphetamine. Only CYP2C25 showed testosterone hydroxylase (16 beta) activity. Northern blot analyses with specific oligonucleotide probes demonstrated that expression of CYP2C27 was male specific and male predominant in kidneys and livers, respectively. No sex-related difference was observed in the expression of CYP2C25 and CYP2C26. These results support our previous findings that sex-related differences in the expression of liver microsomal cytochromes P450 occur in hamsters.

Aminopyrine↗
PubMed1994

[A case of interstitial pneumonia antedating rheumatoid arthritis--differentiation from idiopathic BOOP].

A 49-year-old female presented with productive cough, fever and chest pain, and was admitted to Nagoya University Hospital. Her chest X-rays, taken previously and on admission, showed infiltrative shadows in both upper lung fields and left-sided pleural effusion. Rheumatoid factors were positive in serum and the pleural effusion. Antibiotics were ineffective. Transbronchial lung biopsy revealed intraalveolar fibrosis as well as interstitial inflammation. Idiopathic BOOP was suspected on the basis of clinical findings together with the histological features. However, open lung biopsy revealed lymphoid hyperplasia with germinal center formation. The patient was diagnosed as having lung involvement antedating rheumatoid arthritis, despite the absence of joint symptoms at present.

Arthritis, Rheumatoid↗
PubMed1993

Identification of protein disulfide isomerase and calreticulin as autoimmune antigens in LEC strain of rats.

Long Evans Cinnamon (LEC) rats, showing spontaneous hereditary hepatitis and hepatic carcinoma, were found to possess autoimmune antibodies to liver microsomal proteins, particularly to proteins with the molecular weight of 56kD and 55kD. The antibodies occurred in association with acute lethal hepatitis in the LEC rats in our previous study. Two-dimensional immunoblot analysis of the antigenic proteins revealed that the 56kDa and 55kDa proteins showed 4.2 and 4.0 pI values and were estimated to be protein disulfide isomerase (PDI) and calreticulin, respectively, from NH2-terminal amino acid sequence analysis. These proteins were further identified by immunoblot analyses using purified proteins and specific antibodies. PDI was a major autoimmune antigenic protein.

Amino Acid Sequence↗
PubMed1993

Rat liver flavin-containing monooxygenase (FMO): cDNA cloning and expression in yeast.

A rat liver cDNA clone, RFMO1, coding for a flavin-containing monooxygenase (FMO) was isolated. This cDNA clone encoded a protein of 532 amino acids. The deduced amino acid sequence was 84, 82 and 82% identical to those of the pig, human (Form 1) and rabbit (Form 1) liver FMOs, while it was only 52, 50, 54, 56 and 54% identical to the human (Form II), human (Form 2) and rabbit liver FMOs (Form 2) and rabbit and guinea pig lung FMOs. RNA blot analysis showed that rat liver FMO was also expressed in lung and kidney and to a lesser extent in the heart and brain. An expression plasmid, pAMFMO, was constructed and the FMO protein expressed in yeast (AH22). This FMO protein catalyzed thiobenzamide S-oxidation, and NADPH oxidation associated with the S- or N-oxidation of thiourea, N,N-dimethylaniline, trimethylamine, imipramine, chlorpromazine, N,N-dimethylhydrazine, thioacetamide as substrates. The S-oxidation activities of thiobenzamide and thiourea were enhanced by n-octylamine, a known enhancer of FMO, and inhibited by alpha-naphthylthiourea, a known inhibitor of FMO. This is the first report in which FMO with catalytic activities was stably expressed.

Amines↗
PubMed1993

Acute exacerbation in idiopathic pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases.

We treated three patients with idiopathic pulmonary fibrosis who had an acute clinical exacerbation. We analyzed their clinical, radiographic, therapeutic, and pathologic findings. Their initial symptoms were influenza-like illness or cough with fever, and all had leukocytosis and elevation of C-reactive protein. Infectious events were ruled out by extensive bacteriologic and serologic examination. The patients' lung injury scores progressed rapidly to severe lung injury compatible with adult respiratory distress syndrome. Findings from bronchoalveolar lavage fluid showed marked neutrophilia and elevation of albumin concentrations. All patients showed various degrees of improvement following corticosteroid therapy. Histologic findings from open lung biopsy specimens showed both usual interstitial pneumonia (UIP) and organizing acute lung injury pattern. Whether these two forms of interstitial pneumonia (UIP and acute lung injury pattern) are variants of one disease or are unrelated and also the effectiveness of corticosteroid therapy on such conditions remain to be determined by further studies.

Acute Disease↗
PubMed1993

The effect of topical tretinoin on the photodamaged skin of the Japanese.

Fifteen middle aged or elderly patients with chronic solar damage of the skin, eight patients with melasma and three patients with xeroderma pigmentosum were treated with topical tretinoin for 6 months. There was a significant improvement in fine surface lines in periorbital region, but no significant improvement was observed in deep furrows. No significant change was induced in melasma despite the improvement in smoothness of the skin surface. Global improvement was also seen in one patient with xeroderma pigmentosum. With regard to the functions of the stratum corneum that was assessed on the flexor surface of the forearms, values of water content as well as transepidermal water loss were found to increase one month after start of the application of tretinoin cream. On the other hand, there was no significant change in the amino acid content of the stratum corneum when measured after 4 months of the treatment. It is concluded that tretinoin cream is capable of partly reversing fine surface lines in photodamaged facial skin of the Japanese. However the irritation induced by 0.1% tretinoin cream was unexpectedly severe in the Japanese as compared to that reported in Caucasians.

Administration, Topical↗
PubMed1993

Inhibition of beta-glucuronidase by natural glucuronides of kampo medicines using glucuronide of SN-38 (7-ethyl-10-hydroxycamptothecin) as a substrate.

1. 7-Ethyl-10-[4-(piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11), a potent anticancer agent currently under development for clinical use, is metabolized in vivo to 7-ethyl-10-hydroxycamptothecin (SN-38), which is subsequently conjugated to 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38-glucuronide). The SN-38-glucuronide was hydrolysed by beta-glucuronidase from E. coli to aglycones and glucuronic acid. 2. Four purified natural glucuronides including baicalin, wogonoside, luteolin-3'-glucuronide, and glycyrrhizin, inhibited beta-glucuronidase using SN-38-glucuronide as substrate. The inhibition potencies of these natural glucuronides toward beta-glucuronidase were similar to that of saccharic acid 1,4-lactone. 3. These results indicate that plant materials of Kampo (Japanese herbal) medicines containing these glucuronides could be used in vivo to decrease the enterohepatic circulation of SN-38 and possibly that of other drugs.

Antineoplastic Agents, Phytogenic↗
PubMed1993

[A new method for quantitative measurement of rCBF using graphic plot analysis: application to 123I-IMP dynamic study].

To estimate regional cerebral blood flow (rCBF) using the dynamic data, a new graphic plot analysis is proposed. By assuming a two-compartment model for the tracer kinetics, we derived the linear relationship as Y(t) = 1/K1 + theta t, where Y(t) is the ratio of time-integrated blood activity to brain tissue activity, t is the scan time, and theta is a proportional constant. A plot of Y(t) against the scan time t yields a straight line and the y-intercept of the line represents the value of inverse rCBF K1. This method was applied to five normal subjects with N-isopropyl-p(123I)iodoamphetamine. The mean value of K1 in the gray matter was 42.1 +/- 6.8 ml/100 g/min. We also produced the rCBF images within a few seconds using the present method. The present graphical method gives a reliable and rapid estimation of rCBF.

Amphetamines↗
PubMed1993

[A case of round atelectasis related to spontaneous pneumothorax in a patient with neurilemmomatosis].

A 60-year-old man was admitted to our department for investigation of abnormal shadows on his chest X-ray. He had been diagnosed as having neurilemmomatosis in 1987. His chest X-ray showed nodular shadows in left S5 and S8 and localized spontaneous pneumothorax in left lung field. The nodular shadows, which were in contact with thickening of the pleura, showed curved shadows of bronchi and vessels (so-called comet tail sign). We suspected that they were round atelectasis, but to confirm the diagnosis and to treat the pneumothorax, limited resection of the lung and resection of the bulla were performed. The diagnosis of round atelectasis was confirmed by histological findings. Round atelectasis related to spontaneous pneumothorax is a very rare condition; however, we consider this to be an important case for understanding the pathogenesis of round atelectasis.

Humans↗
PubMed1993

[A new graphic method for evaluation of distribution volume on N-isopropyl-p-[123I]iodoamphetamine (IMP) SPECT].

We developed a new graphic method using N-isopropyl-p-[123I]iodoamphetamine (IMP) and SPECT of the brain, the graph on which all three parameters, cerebral blood flow, distribution volume (Vd) and delayed count to early count ratio (Delayed/Early ratio), were able to be evaluated simultaneously. The kinetics of 123I-IMP in the brain was analyzed by a 2-compartment model, and a standard input function was prepared by averaging the time activity curves of 123I-IMP in arterial blood on 6 patients with small cerebral infarction etc. including 2 normal controls. Being applied this method to the differential diagnosis between Parkinson's disease and progressive supranuclear palsy, we were able to differentiate both with a glance, because the distribution volume of the frontal lobe significantly decreased in Parkinson's disease (Mean +/- SD; 26 +/- 6 ml/g). This method was clinically useful. We think that the distribution volume of 123I-IMP may reflect its retention mechanism in the brain, and the values are related to amine, especially to dopamine receptors and its metabolism.

Aged↗
PubMed1993

[A case report of epithelioid hemangioendothelioma of the lung].

A 15-year-old woman presented with an abnormal chest X-ray taken at a medical check up. Her chest X-ray disclosed multiple nodular shadows in bilateral lung fields. A transbronchial biopsy was non-diagnostic and an open biopsy was performed. The tumor was histologically diagnosed as epithelioid hemangioendothelioma on the basis of associated with immunoreactivity to factor-VIII related antigen by immunohistochemistry and the presence of Weibel-Pallade bodies on electron microscopy. She has been followed-up in her home town without significant change.

Adolescent↗
PubMed1993

A new graphic plot analysis for cerebral blood flow and partition coefficient with iodine-123-iodoamphetamine and dynamic SPECT validation studies using oxygen-15-water and PET.

To estimate regional cerebral blood flow (rCBF) and brain-blood partition coefficient (lambda) using a dynamic measurement, a new graphic plot analysis is proposed. By assuming a two-compartment model for tracer kinetics, we derived the linear relationship as Y(t) = K1 - k2 X(t), where Y(t) is the ratio of brain tissue activity-to-time-integrated arterial blood activity and X(t) is the ratio of time-integrated brain tissue activity-to-time-integrated arterial blood activity. A plot of Y(t) against X(t) yields a straight line and the y- and x-intercept of the regression line represent rCBF (K1) and lambda, respectively. The slope is a washout constant (-k2). This method was applied to 14 subjects with N-isopropyl-p-iodine-123 iodoamphetamine ([123I]IMP). The mean values of K1 and lambda for normal subjects were 41.3 +/- 6.7 ml/100 g/min and 29.6 +/- 6.5 ml/g, respectively, in the gray matter. A comparative study with positron emission tomography (PET) using an H2(15)O autoradiographic method revealed good correlation between IMP K1 and PET rCBF [r = 0.822; K1 = 0.842 rCBF + 0.030 (ml/g/min)]. The values of K1 using the graphical method were in excellent agreement with those using a nonlinear least-squares fitting technique (r = 0.992 for K1; r = 0.941 for lambda). The estimated K1 values in the graphical method were not changed when scanning times were varied. We conclude that a two-compartment model is acceptable for IMP kinetics within a scan time of 60 min. The graphical method gives a reliable and rapid estimation of rCBF when applied to dynamic data.

Amphetamines↗
PubMed1993

[A case of bronchiolitis obliterans organizing pneumonia associated with ulcerative colitis].

A 53-year-old male was admitted to our hospital with fever and chest pain. A chest X-ray film showed infiltrative shadows in the right upper and middle lung field. In spite of administration of antibiotics, the chest X-ray film revealed gradually increasing infiltrates and a new shadow appeared in the left upper lung field. The open lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP). There was marked roentgenographic improvement in response to steroid therapy. Very few cases of BOOP associated with ulcerative colitis have been reported.

Bronchiolitis Obliterans↗
PubMed1992

Apoptotic cell death of primed CD45RO+ T lymphocytes in Epstein-Barr virus-induced infectious mononucleosis.

The expansion of activated T cells, characterized by the expression of CD45RO as well as HLA-DR antigens, is a central feature in acute infectious mononucleosis (IM) induced by primary infection of Epstein-Barr virus (EBV). However, the fate of these activated T cells in this disease is not clearly understood. We found that, on simple culture, a large proportion of T cells isolated from acute IM patients died rapidly, but only a few T cells from normal individuals did. Morphologic observations and DNA fragmentation analysis showed that the loss of viability of IM T cells after incubation was mediated by apoptosis. IM T cells undergoing apoptosis resided exclusively in the CD45RO+ populations of both CD4+ and CD8+ T cells, most of which were shown to coexpress apoptosis-related Fas antigen. Some cytokines such as interleukin-2 (IL-2), IL-5, and IL-6 could rescue IM T cells from apoptotic cell death. The results seemed to imply that most of primed (CD45RO+) T cells in acute IM might be subject to apoptotic cell death, possibly when leaving from the local sites actively producing certain soluble factors required for their survival. Our studies suggest the programmed cell death of peripheral mature T cells as a mechanism of antigen-driven selection.

Antigens, CD↗
PubMed1992

Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia.

Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN-gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy.

Adolescent↗