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Biomedical subjects

Y Nishida

Publications and source records attributed to Y Nishida.

At least 109 records · Page 6Linked to original sources
PubMed1999

Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers.

AIMS: Interindividual differences in the pharmacokinetics of venlafaxine, a new antidepressant, were shown during early clinical trials in Japan. Venlafaxine is metabolized mainly by CYP2D6 to an active metabolite, O-desmethylvenlafaxine (ODV). Therefore, the influence of the CYP2D6 genotypes on venlafaxine pharmacokinetics was examined in a Japanese population. METHODS: Twelve adult Japanese men in good health participated in this study. Genomic DNA was isolated from peripheral lymphocytes, and the CYP2D6 genotypes were determined by codon 188C/T, 1934G/A, 2938G/A and 4268G/C mutations using endonuclease tests based on PCR and by Xba I-RFLP analysis. Subjects were categorized into the following 3 groups (n=4 in each group); Group1: CYP2D6*10/*10, *5/*10, Group2: CYP2D6*1/*10, *2/*10 and Group3: CYP2D6*1/*1, CYP2D6*1/*2. Venlafaxine (25 mg, n=6; 37.5 mg, n=6) was administered orally at 09.00 h following an overnight fast. Plasma concentrations of venlafaxine and ODV were monitored by h.p.l.c. for 48 h. RESULTS: The Cmax and AUC of venlafaxine were 184% and 484% higher in the group 1 subjects than in the group 3 subjects, and 101% and 203% higher in the group 1 than in the group 2, respectively. CONCLUSIONS: These results suggest that CYP2D6*10 influences the pharmacokinetics of venlafaxine in a Japanese population.

Adult↗
PubMed1999

Combined small and transitional cell carcinoma of the urinary bladder with CA19-9 production.

It is well known that extrapulmonary small cell carcinoma, which exhibits morphological features similar to those observed in the lung, occurs in various organs. Clinically, most cases manifest aggressive biological behavior. A case of small cell carcinoma of the urinary bladder producing a high level of serum carbohydrate antigen (CA) 19-9, in which expression was confirmed in cancer cells of small as well as transitional cell carcinoma in the same tumor mass by immunostaining is reported. This paper documents combined small and transitional cell carcinoma of the urinary bladder with CA19-9 production, although it has already been reported that adenocarcinoma or transitional cell carcinoma in various organs frequently expresses CA19-9. Observations suggest that the histogenesis of some cases of combined small and transitional cell carcinoma in the urinary bladder may be the same, as both can produce CA19-9.

Aged↗
PubMed1999

Effect of lipoproteins on mesangial cell proliferation.

BACKGROUND: Triglyceride (TG)-rich lipoproteins have been reported to promote atherosclerosis, but little is known about their role in kidney disease or about their effects on mesangial cells. Accordingly, the purpose of this study was to investigate which lipoproteins could influence mesangial cell proliferation in vitro. We assessed the effect of various lipoproteins [very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low density lipoprotein (LDL), oxidized LDL, and high-density lipoprotein (HDL)] on the proliferation of cultured human mesangial cells and also assessed the influence of these lipoproteins on cytokine production. METHODS: We investigated the effect of various lipoproteins on cultured human mesangial cells using 3H-thymidine incorporation and cell counting assays and investigated the levels of several cytokines [interleukin (IL)-6, platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, and tumor necrosis factor-alpha] in mesangial cell culture supernatants after stimulation by the lipoproteins. RESULTS: Not only LDL but also TG-rich lipoproteins (VLDL and IDL) promoted the proliferation of mesangial cells up to certain concentrations, but cell growth was actually decreased at higher concentrations. Oxidized LDL caused a concentration-dependent decrease of 3H-thymidine incorporation, and HDL had no proliferative effect at any concentration. Exposure to VLDL, IDL, LDL, or a high concentration of HDL enhanced the secretion of IL-6, PDGF-AB, and TGF-beta by mesangial cells, whereas TNF-alpha secretion was stimulated by oxidized LDL. CONCLUSIONS: TG-rich lipoproteins, LDL, and oxidized LDL may be involved in mesangial cell proliferation and injury in patients with mesangial proliferative glomerulonephritis.

Cell Division↗
PubMed1999

Expression of polo-like kinase (PLK) in the mouse placenta and ovary.

The polo-like kinase (PLK) is a mammalian serine/threonine kinase involved in cell cycle regulation. Much evidence for the role of PLK in the cell cycle has come from studies of cultured cells; however, little is known about its function or even expression in vivo. The present study examined the features of PLK expression in the mouse placenta and ovary. Immunohistochemical studies showed that PLK is highly expressed in the basement membrane of the endometrial gland, in some endothelial cells, in endometrium after embryo implantation, in trophoblastic tissue invading the decidua, in the ovarian stroma and in some lutein bodies. In contrast, PLK was not detectable by immunohistochemistry in endometrial stroma before decidualization, in decidua, in trophoblastic tissue not invading the decidua or in ovarian follicles. PLK expression seemed to be correlated with the expression of proliferation cellular nuclear antigen (PCNA) in many placental and ovarian cells, reflecting a role in cellular proliferation. Nevertheless, in ovarian stroma and lutein bodies where PCNA was not expressed, PLK was strongly expressed. This finding indicates that PLK may have some post mitotic functions in certain specialized cell types.

Amino Acid Sequence↗
PubMed1999

Effect of pH and glucose on cultured human peritoneal mesothelial cells.

OBJECTIVE: We investigated the effects of various pH and glucose concentrations on the growth of human peritoneal mesothelial cells and on coagulation and fibrinolytic factors. MATERIALS AND METHODS: Cells were cultured at various pH values in Ham's F-12 medium containing 1.0% foetal calf serum and supplemented with D-glucose or D-mannitol at various concentrations. After 4-48 h, cell proliferation and 3H-thymidine incorporation were determined. Coagulation and fibrinolytic factors were measured after 48 h. RESULTS: Glucose caused concentration-dependent inhibition of cell growth at all pH values, but the deleterious effect of low pH on cell proliferation was faster and stronger than that of high glucose. At a similar osmolality, mannitol caused less inhibition of cell proliferation than glucose. There was a glucose concentration-dependent increase of thrombin-antithrombin III complex production at all pH values. At pH 5.2, tissue-type plasminogen activator production was far lower than at higher pH values, and production of the plasminogen activator inhibitor showed a glucose concentration-dependent increase. At pH 6.5 or 7.3, however, the plasminogen activator inhibitor production decreased and tissue-type plasminogen activator production increased in a glucose concentration-dependent manner. CONCLUSIONS: Low pH and/or high glucose culture medium had an inhibitory effect on peritoneal mesothelial cells, with the effect of high glucose being partially related to hyperosmolality. These cells may modulate peritoneal coagulant and fibrinolytic activity, with the balance between coagulation and fibrinolysis being disturbed by low pH and/or high glucose.

Antithrombin III↗
PubMed1999

Effects of oral administration of interferon-alpha on antibody production in mice with induced tolerance.

In vivo systemic effects and the immunomodulating potential of the oral administration of murine interferon-alpha (IFN-alpha) were investigated through mRNA expression of both IFN-alpha-inducible factors, interferon regulatory factor-1 (IRF-1) and 2,5-adenylate synthetase [2-5(A) synthetase] and 2-5(A) synthetase enzymatic activity in spleen and antibody production. The daily administration of IFN-alpha (0.1, 1, 10, and 100 IU/body) for 1 week augmented IRF-1 and 2-5(A) synthetase mRNA expression levels, as well as 2-5(A) synthetase enzymatic activity in spleen cells but not in cervical lymph nodes. The in vivo immunomodulating potential of the oral administration of IFN-alpha was also evaluated through antibody production in mice with induced tolerance. Ovalbumin (OVA) was administered intraperitoneally (i.p.) to induce systemic antibody production on day 0 when OVA feeding was initiated. The OVA was fed every 2-3 days for a total of 14 doses to suppress serum antibody levels. Oral administration of murine IFN-alpha was initiated on day 0 and was continued for 5 consecutive days weekly for 5 weeks (24 doses). On every sampling date (days 10, 17, 24, and 32), specific antibody levels in the IFN-alpha-administered groups were significantly higher than those in the control (nonadministered) group. This was especially noted in early phases (days 10 and 17) of antibody production when the levels of antibody in serum from the IFN-alpha-administration groups were equivalent to those of the nontolerance group. Altogether, it is suggested that oral use of IFN-alpha can elicit immunomodulating actions (e.g., antibody levels) by affecting the systemic immune system(s).

2',5'-Oligoadenylate Synthetase↗
PubMed1999

Genetic analysis of rolled, which encodes a Drosophila mitogen-activated protein kinase.

Genetic and molecular characterization of the dominant suppressors of D-raf(C110) on the second chromosome identified two gain-of-function alleles of rolled (rl), which encodes a mitogen-activated protein (MAP) kinase in Drosophila. One of the alleles, rl(Su23), was found to bear the same molecular lesion as rl(Sem), which has been reported to be dominant female sterile. However, rl(Su23) and the current stock of rl(Sem) showed only a weak dominant female sterility. Detailed analyses of the rl mutations demonstrated moderate dominant activities of these alleles in the Torso (Tor) signaling pathway, which explains the weak dominant female sterility observed in this study. The dominant rl mutations failed to suppress the terminal class maternal-effect mutations, suggesting that activation of Rl is essential, but not sufficient, for Tor signaling. Involvement of rl in cell proliferation was also demonstrated by clonal analysis. Branching and integration of signals in the MAP kinase cascade is discussed.

Amino Acid Sequence↗
PubMed1999

De novo synthesis of sphingolipids is required for cell survival by down-regulating c-Jun N-terminal kinase in Drosophila imaginal discs.

Mitogen-activated protein kinase (MAPK) is a conserved eukaryotic signaling factor that mediates various signals, cumulating in the activation of transcription factors. Extracellular signal-regulated kinase (ERK), a MAPK, is activated through phosphorylation by the kinase MAPK/ERK kinase (MEK). To elucidate the extent of the involvement of ERK in various aspects of animal development, we searched for a Drosophila mutant which responds to elevated MEK activity and herein identified a lace mutant. Mutants with mild lace alleles grow to become adults with multiple aberrant morphologies in the appendages, compound eye, and bristles. These aberrations were suppressed by elevated MEK activity. Structural and transgenic analyses of the lace cDNA have revealed that the lace gene product is a membrane protein similar to the yeast protein LCB2, a subunit of serine palmitoyltransferase (SPT), which catalyzes the first step of sphingolipid biosynthesis. In fact, SPT activity in the fly expressing epitope-tagged Lace was absorbed by epitope-specific antibody. The number of dead cells in various imaginal discs of a lace hypomorph was considerably increased, thereby ectopically activating c-Jun N-terminal kinase (JNK), another MAPK. These results account for the adult phenotypes of the lace mutant and suppression of the phenotypes by elevated MEK activity: we hypothesize that mutation of lace causes decreased de novo synthesis of sphingolipid metabolites, some of which are signaling molecules, and one or more of these changes activates JNK to elicit apoptosis. The ERK pathway may be antagonistic to the JNK pathway in the control of cell survival.

Acyltransferases↗
PubMed1999

p38 mitogen-activated protein kinase can be involved in transforming growth factor beta superfamily signal transduction in Drosophila wing morphogenesis.

p38 mitogen-activated protein kinase (p38) has been extensively studied as a stress-responsive kinase, but its role in development remains unknown. The fruit fly, Drosophila melanogaster, has two p38 genes, D-p38a and D-p38b. To elucidate the developmental function of the Drosophila p38's, we used various genetic and pharmacological manipulations to interfere with their functions: expression of a dominant-negative form of D-p38b, expression of antisense D-p38b RNA, reduction of the D-p38 gene dosage, and treatment with the p38 inhibitor SB203580. Expression of a dominant-negative D-p38b in the wing imaginal disc caused a decapentaplegic (dpp)-like phenotype and enhanced the phenotype of a dpp mutant. Dpp is a secretory ligand belonging to the transforming growth factor beta superfamily which triggers various morphogenetic processes through interaction with the receptor Thick veins (Tkv). Inhibition of D-p38b function also caused the suppression of the wing phenotype induced by constitutively active Tkv (TkvCA). Mosaic analysis revealed that D-p38b regulates the Tkv-dependent transcription of the optomotor-blind (omb) gene in non-Dpp-producing cells, indicating that the site of D-p38b action is downstream of Tkv. Furthermore, forced expression of TkvCA induced an increase in the phosphorylated active form(s) of D-p38(s). These results demonstrate that p38, in addition to its role as a transducer of emergency stress signaling, may function to modulate Dpp signaling.

Animals↗
PubMed1999

Mutations producing premature termination of translation and an amino acid substitution in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis associated with parkinsonism.

OBJECTIVES: Mutational analysis of the sterol 27-hydroxylase (CYP27) gene was performed on three patients from two Japanese families who had cerebrotendinous xanthomatosis (CTX) associated with parkinsonism. METHODS: Clinical evaluations, brain MRI studies, and laboratory analyses were completed on the three patients. The CYP27 gene was analysed for mutations by PCR amplification of gene segments followed by direct sequencing. RESULTS: Two different, homozygous mutations were identified in these families. One is a novel transition, substituting T for G at Glu162 (GAG) resulting in a stop codon (TAG). The other is also a transition, substituting T for C at Arg441 (CGG) resulting in Trp (TGG). The second is located in two amino acids ahead of the heme ligand binding site (Cys443) of the protein likely rendering it non-functional. It is the most common CTX mutation in Japanese patients. CONCLUSIONS: CTX with parkinsonism is caused by mutations with a severe impact on enzyme function. The two mutations described here are likely to cause loss of function because they are chain terminating or affect an essential site in the protein.

Adult↗
PubMed1999

The effect of da-fang-feng-tang on treatment of type II collagen-induced arthritis in DBA/1 mice.

Da-Fang-Feng-Tang (DFFT), which is believed to be effective for treating human rheumatoid arthritis (RA), was given to DBA/1 mice at the onset of type II collagen-induced arthritis (CIA) to examine its effect. Granules of the crude DFFT extract were administered by gastric gavage at a dose of 1.6 g/kg/day for 12 weeks, starting the day CIA began. The levels of anticollagen IgG antibody were significantly decreased in the sera of the DFFT-treated group compared with the control group from weeks 2 to 7 after the onset of CIA. The severity of arthritis in the DFFT-treated group was markedly alleviated when compared with the control group. In addition, histological examination of the DFFT-treated group showed less cartilage and bone erosion. These results suggest that administration of DFFT suppressed the development of CIA in mice and support the belief that DFFT is effective in treating human RA.

Animals↗
PubMed1999

Influence of mild exercise at the lactate threshold on glucose effectiveness.

The effect of a single bout of mild exercise on glucose effectiveness (S(G)) and insulin sensitivity (S(I)) was studied in six young male subjects by using a minimal model. An intravenous glucose tolerance test was performed under two conditions as follows: 1) 25 min after a bout of exercise on a cycle ergometer at the lactate threshold level for 60 min (Ex) and 2) without any prior exercise (Con). Leg blood flow (LBF) was also measured by strain-gauge plethysmography simultaneously with blood sampling. S(I) did not significantly change after exercise (18.1 +/- 1.5 vs. 17.7 +/- 1.9 x 10-(5) min/pM), whereas S(G) significantly increased (0.016 +/- 0.002 vs. 0.025 +/- 0.002 min(-1), P < 0.01). The increased blood flow after exercise remained high during the time period for measurement of the glucose disappearance constant and may be a determinant of S(G). The incremental lactate area under the curve until insulin loading was also significantly higher in Ex than in Con (2.6 +/- 0.9 vs. -3.5 +/- 1.5 mM/min, P < 0.05). These results suggest that increased S(G) after mild exercise may be due, at least in part, to increased LBF and lactate production under a hyperglycemic state.

Adult↗
PubMed1999

Apolipoprotein E polymorphism in IgA nephropathy.

BACKGROUND/AIM: To clarify the role of the apolipoprotein E (Apo E) phenotype in IgA nephropathy, we investigated its relationship with histological damage and clinical factors. METHODS: The subjects were 104 consecutive patients (41 men and 63 women) with IgA nephropathy. The Apo E phenotype was identified by plasma isoelectric focusing and immunoblotting, and the frequencies of Apo E alleles were calculated. RESULTS: The frequencies of the phenotypes and the alleles were as follows: 2/2 = 0, 2/3 = 0.086, 3/3 = 0.654, 2/4 = 0. 010, 4/3 = 0.211, 4/4 = 0.010, 3/5 = 0.029, epsilon2 = 0.048, epsilon3 = 0.817, epsilon4 = 0.120, and others = 0.015. There were no significant differences between the IgA nephropathy patients and healthy individuals in the frequencies of Apo E phenotypes and the alleles. However, the Apo E2 phenotype was significantly more common among patients with severe histological damage than in those with mild damage. The serum triglyceride levels were significantly elevated, and the Apo E2 phenotype was significantly more prevalent in patients with severe histological damage as compared with those with mild damage. CONCLUSION: The Apo E2 phenotype appears to be associated with the severity of histological damage in IgA nephropathy.

Adult↗
PubMed1999

Endothelium-derived contracting factor in carotid artery of hypertensive Dahl rats.

The present study is designed to investigate whether acetylcholine (ACh) elicits an endothelium-derived contracting factor (EDCF) and whether it contributes to decreased relaxant response induced by ACh in Dahl rats. Dahl salt-sensitive (DS) and -resistant (DR) rats were fed a 0.4% NaCl or an 8% NaCl diet for 4 weeks. High sodium intake significantly increased blood pressure in DS rats but not in DR rats. The carotid rings were suspended for isometric tension recording. ACh caused an endothelium-dependent contraction in carotid rings from hypertensive DS rats but not from normotensive Dahl rats. Atropine, indomethacin, SQ29548, or ONO-3708 (prostaglandin H(2) [PGH(2)]/thromboxane A(2) [TXA(2)] receptor antagonist) abolished ACh-induced contraction, and OKY-046 (inhibitor of TXA(2) synthetase) partially attenuated the contraction. High sodium intake significantly enhanced contraction evoked by U46619, a PGH(2)/TXA(2) receptor agonist, in both DS and DR rats. In contrast, ACh-induced relaxation was significantly depressed in the rings from hypertensive DS rats, and ONO-3708 partially improved the depressed relaxation. Administration of ONO-8809 (an orally active PGH(2)/TXA(2) receptor antagonist; 30 micrograms per body per day) for 4 weeks neither reduced blood pressure nor improved the depressed ACh-induced relaxation in hypertensive DS rats. These results suggest that ACh causes release of EDCF in carotid rings of hypertensive DS rats, which is likely to be PGH(2) and TXA(2). The EDCF contributed in part to the depressed ACh-induced relaxation.

Acetylcholine↗
PubMed1999

Contribution of a metal-peroxide adduct to neurodegeneration is due to its oxidative protease activity.

Many hypotheses have been developed to explain aging and age-related neurodegenerative disorders; one of the most compelling is the role of oxidative stress to induce changes in protease activity in brains of patients of Alzheimer's disease and prion disease. At the moment however, there is no clear answer how protein degradation may be achieved in the brain. We have observed that several metal compounds can degrade proteins in the presence of hydrogen peroxide, and elucidated the reaction scheme based on the new theoretical point for the reactivity of a metal-peroxide adduct with eta 1-coordination mode. In this article we would like to point out the importance of a copper(II)-peroxide adduct to promote neurodegenerative diseases such as prion disease and amyotrophic lateral sclerosis through its oxidative protease function.

Aging↗
PubMed1999

Myotonic dystrophy associated with insulinoma.

We describe a 51-year-old man with myotonic dystrophy (MyD) associated with insulinoma. In addition to the typical symptoms of MyD, he showed hypoglycemic attacks after meals. The radiological examination and selective blood sampling revealed an insulinoma in the head of the pancreas. The tumor was resected and histopathologically diagnosed as an insulinoma. In Southern blot analysis, CTG repeat of the myotonin protein kinase gene in the insulinoma showed the longest expansion, followed by normal tissue of the pancreas, muscle and white blood cells. Therefore, microsatellite instability was the most prominent in the tumor cells.

Biomarkers, Tumor↗
PubMed1999

Potassium supplementation increases sodium excretion and nitric oxide production in hypertensive Dahl rats.

The present study was designed to investigate whether antihypertensive and natriuretic effects of K were achieved by elevation of nitric oxide (NO) production in Dahl salt-sensitive (DS) rats. The rats were placed in individual metabolic cage and fed a high sodium diet with or without K supplementation for 4 weeks. K supplementation counteracted the blood-pressure raising effect of NaCl. K supplementation significantly enhanced sodium excretion and reduced sodium retention, increased the urinary nitrite plus nitrate excretion and kidney constitutive NO synthase activity in salt-loaded DS rats. These effect did not occur in the rats fed a low sodium diet with K supplementation. These results suggest that K supplementation attenuates development of hypertension with reduction of sodium retention in salt-loaded DS rats, which is mediated by the recovery of salt-induced NO production mechanism.

Animals↗