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Biomedical subjects

T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 127 records · Page 7Linked to original sources
PubMed2000

[Modulation of cytokine production from human mononuclear cells by several agents].

We investigated the effects of drugs, especially anti-pulmonary disease agents, on the production of cytokines from human peripheral blood mononuclear cells (PBMC). Roxithromycin (RXM), a macrolide antibiotic with the structure of 14-member macrocycline ring increased adherent cells (monocyte/macrophages), whereas it suppressed the proliferation of PBMC stimulated with phytohemagglutinin (PHA). RXM suppressed the production of IL-1 beta and TNF-alpha from lipopolysaccharide (LPS)-stimulated PBMC in a dose-dependent manner. Levofloxacin, a fluorinated quinolone, increased IL-2 production by PBMC stimulated with PHA. The production of GM-CSF and soluble IL-2 receptor was suppressed at high concentrations of LVFX. LVFX suppressed IL-1 beta production, but did not the production of TNF-alpha and IL-8 production. A beta-adrenoceptor agonists (beta-agonist), procaterol, clenbuterol, fenoterol and terbutaline suppressed the production of TNF- and IL-1 beta. TNF-alpha production was almost completely suppressed by dibutyryl cyclic AMP (dbcAMP), whereas IL-1 beta production appeared to be partially refractory even at the highest concentration examined. Both procaterol and theophylline elevated cAMP levels in LPS-stimulated PBMC, but the effect of procaterol was limited. The inhibition of the production of TNF-alpha and IL-1 beta by procaterol was additively potentiated with theophylline. Of examined phosphodiesterase (PDE) isozyme inhibitors type IV PDE inhibitors were more effective in inhibiting the production of TNF-alpha and IL-1 beta by LPS-stimulated PBMC than a nonselective, type III or type III/IV inhibitor. The addition of the beta-agonist increased the inhibitory effect of tested PDE inhibitors on the production of TNF-alpha and IL-1 beta Type IV, type III and nonselective PDE inhibitors were effective in inhibiting the production of IFN-gamma and IL-2 in a dose-dependent manner. In contrast, the production of IL-4 and IL-5 was inhibited by only the highest concentration of type IV inhibitor, and other agents had no effect on the production. Similarly, dbcAMP inhibited the production of IFN-gamma and IL-2 more potently than that of IL-4 and IL-5. The addition of the beta-agonist increased the inhibitory effect of tested PDE inhibitors on the production of IFN-gamma and IL-2 production. These findings indicate that these agents have an immunodulatory action on the production of cytokines by PBMC and also indicate that they could be potent pharmacological agents for the treatment of diseases in which several cytokines are important etiological factors.

4-Quinolones↗
PubMed2000

The physiological activity and in vivo distribution of dinitrosyl dithiolato iron complex.

Nitric oxide (NO) is recognized as an endogenous mediator of vascular tone, a neurotransmitter and an immune effector molecule. Furthermore, it has been implicated in the development of various diseases. Because NO is extremely labile in the biological milieu, its activities can be effected not only by NO itself but also by relatively stable physiologic NO carriers or NO donors. Dinitrosyl iron complexes have been recognized as endogenous NO carrier molecules as well as S-nitrosothiols. The complex has been found in cells and the tissues of mammals and bacteria via its readily detectable, characteristic electron paramagnetic resonance (EPR) signals. Endogenously produced dinitrosyl iron complex with thiolate ligands (DNIC) has a critical biological potential; and it can function as a physiologic regulatory factor in a biological system, especially the immune and cardiovascular systems. We have been studying the in vivo behavior and distribution of DNIC to elucidate its physiological roles and pharmacokinetics. In this article, an attempt is made to provide an overview of the history, physiology and in vivo behavior of DNIC.

Animals↗
PubMed2000

Gene cloning, purification, and characterization of two cyanobacterial NifS homologs driving iron-sulfur cluster formation.

Iron-sulfur proteins are essential in the photosynthetic system and many other biological processes. We have isolated and characterized enzymes driving the formation of iron-sulfur clusters from Synechocystis sp. PCC6803. Two genes (slr0387 and sll0704), showing similarity to nifS of Azotobacter vinelandii, were cloned, and their gene products (SsCsdl and SsCsd2) were purified. They catalyzed the desulfuration of L-cysteine. Reconstitution of a [2Fe-2S] cluster of cyanobacterial ferredoxin proceeded much faster in the presence of L-cysteine and either of these enzymes than when using sodium sulfide. These results suggest that SsCsdl and SsCsd2 facilitate the iron-sulfur cluster assembly by producing inorganic sulfur from L-cysteine. Synechocystis sp. PCC6803 has no gene coding for a protein with similarity to the N-terminal domain of NifU of A. vinelandii, which is believed to cooperate with NifS to assemble iron-sulfur clusters. Thus, the cluster formation in the cyanobacterium probably proceeds through a mechanism that is different from that in A. vinelandii.

Bacterial Proteins↗
PubMed2000

Short-term effects of prednisolone on neuromuscular transmission in the isolated mdx mouse diaphragm.

To determine the mechanism of the beneficial effects of prednisolone on Duchenne muscular dystrophy (DMD), we examined the short-term effects of prednisolone on neuromuscular transmission by using conventional microelectrode methods in the mdx mice. High (56 micromol/liter) and low (2.8 micromol/liter) concentrations of prednisolone were applied to a bath containing phrenic nerve-diaphragm preparations from mdx mice, and several parameters related to neuromuscular transmission were recorded. The high dose of prednisolone significantly decreased parameter n on quantal release by nerve impulse and decay time-constant of end-plate potentials, which showed adverse effect on neuromuscular transmission. The low dose of prednisolone did not significantly increase quantal content, but could assist the compensatory reaction to maintain the safety margin of neuromuscular transmission in the mdx mice. Our results suggest that the latter effect represents one of the possible mechanisms of the therapeutic effects of prednisolone on DMD.

Animals↗
PubMed2000

A method for identifying underlying causes of death in epidemiological study.

To obtain the underlying causes of death in individuals of a cohort (male only), the items of date of birth, date of death and address code at the time of death were linked between the data of resident cards and the death tapes of National Vital Statistics supplied by the Ministry of Health and Welfare. As a result, the persons who have the same information for above mentioned three items between the resident cards and the death tapes accounted for 97.4%. If the persons who had the same information for three items except one item were considered to be identical, they accounted for 99.4%. It would be concluded that underlying cause of death can be obtained by record linkage of death tapes of National Vital Statistics with three informations in residence cards, dates of birth, dates of death and address codes at the time of death, even without names of the individual in the death tapes. The matched rate would be high enough for epidemiological studies.

Cause of Death↗
PubMed2000

Antitumor effect of alpha-galactosylceramide (KRN7000) on spontaneous hepatic metastases requires endogenous interleukin 12 in the liver.

Hepatic metastasis is a major clinical problem in cancer treatment. We examined antitumor activity of alpha-galactosylceramide (KRN7000) on mice with spontaneous liver metastases of reticulum cell sarcoma M5076 tumor cells (spontaneous metastasis model). In this model, all mice that were s.c. challenged with one million tumor cells developed a solid s.c. mass by day 7 and died of hepatic metastases. In the current study, we administered 100 microg/kg of KRN7000 to the model mice on days 7, 11, and 15. This treatment suppressed the growth of established liver metastases and resulted in the prolongation of survival time. Fluorescence-activated cell sorter analysis of phenotypes of spleen cells, hepatic lymphocytes, and regional lymph node cells around the s.c. tumor revealed that CD3+NK1.1+ (NKT) cells increased in hepatic lymphocytes of the KRN7000-treated mice. Cytotoxic activity and IFN-gamma production of hepatic lymphocytes were augmented in comparison with those of spleen cells and regional LN cells. At the same time, interleukin (IL)-12 production of hepatic lymphocytes was markedly enhanced. Neutralization of IL-12 using a blocking monoclonal antibody diminished the prolonged survival time. These results showed that the in vivo antitumor effects of KRN7000 on spontaneous liver metastases were dependent on the endogenous IL-12 production, where NKT cells in the liver are suggested to be involved. Adjuvant immunotherapy using KRN7000 could be a promising modality for the prevention of postoperative liver metastases.

Adjuvants, Immunologic↗
PubMed2000

[Locoregional adoptive immunotherapy using LAK cells and IL-2 against liver metastases from digestive tract cancer].

We investigated the clinical efficacy of locoregional and systemic adoptive immunotherapy (AIT) with or without interleukin-2 (IL-2) against solid metastatic lesions from digestive tract cancer. Eighteen patients, who were treated with more than 10(10) lymphokine-activated killer (LAK) cells, were enrolled in this study. Seven of the 18 patients received hepatic arterial infusion (HAI) of LAK cells with or without IL-2 against metastatic liver tumors (locoregional therapy group). The remaining 11 patients received systemic transfer of LAK cells with IL-2 against metastatic lesions located in organs other than the liver (systemic therapy group). Three of 7 locoregional therapy group patients showed clinically significant tumor regressions that were evaluated as being equivalent to partial response (PR). Two of the 11 systemic therapy group patients showed significant tumor regressions, but this response rate was much lower than that of the locoregional therapy group. The 2 effective cases in the systemic therapy group were esophageal cancer patients. Locoregional AIT with or without IL-2 against liver metastases from digestive tract cancer could be an effective therapeutic modality in some patients who are refractory to conventional therapies (e.g., chemotherapy and radiotherapy). It is necessary to find a new way to augment the anti-tumor effect of this therapy in combination with prior or concomitant chemotherapy.

Adult↗
PubMed1999

Quantitative determination of a potent lipopolysaccharide antagonist, E5564, in rat and dog plasma by high-performance liquid chromatography with fluorescence detection.

The assay method was established for the quantification of a potent lipopolysaccharide (LPS) antagonist, E5564, in rat and dog plasma using HPLC. E5564 and the I.S. (an analogue of E5564) were extracted and derivatized with 9-Anthryldiazomethane (ADAM reagent) to be given fluorescence. LC-MS analysis indicated that single molecule of E5564 was coupled with two molecules of ADAM reagent at one on each of the phosphorus groups. After solid-phase extraction, ADAM derivatives of E5564 and the I.S. were separated on an ODS column using methanol/ethanol containing sodium acetate as a mobile phase at 1.2 ml/min (gradient elution), and detected by a fluorescence detector (excitation: 254 nm, emission: 415 nm). The intra-day and inter-day precision were less than 14.4%, and accuracy were within +/-13.0% in the concentration range of 30 to 20,000 ng/ml plasma in both species. E5564 was stable for at least 13 days in rat and dog plasma at -20 degrees C, and the processed sample was stable for up to 14 days at 4 degrees C. This validated method was successfully applied to the evaluation of the pharmacokinetics of E5564 in rats and dogs after single bolus intravenous doses.

Animals↗
PubMed1999

Autosomal dominant familial spinal and bulbar muscular atrophy with gynecomastia.

The proband, a 53-year-old man, developed progressive spinal and bulbar muscular atrophy and gynecomastia at the age of 50. His father had weakness of lower limbs, and his son had a nasal voice, ocular movement abnormalities, and gynecomastia, whereas two of the proband's brothers showed either gynecomastia or tongue fasciculations. None of the patients showed any expansion of CAG repeat in the androgen receptor gene or any hormonal abnormality. Thus, this family is affected by a form of autosomal dominant spinal and bulbar muscular atrophy with gynecomastia.

Chromosome Aberrations↗
PubMed1999

Physicochemical Properties of 2-Vinylpyridine Telomers Possessing Multihydrocarbon Chains in Aqueous Solution and at the Silica/Aqueous Solution Interface.

Physicochemical properties of multialkylated surfactants of partially quaternized 2-vinylpyridine telomers having multihydrocarbon side chains (nRm-2VPQ: n, number of chains; m, alkyl chain length) in aqueous solutions were investigated. The critical micelle concentration (cmc) and surface tension at the cmc were 13 µmol dm(-3) and 52 mNm(-1) for 2.1R(8)-2VPQ, 7.1 µmol dm(-3) and 37 mNm(-1) for 2.5R(12)-2VPQ, and 4.7 µmol dm(-3) and 40.0 mNm(-1) for 3.4R(12)-2VPQ, respectively. The aggregation numbers at the cmc determined by the light scattering method were 4 +/- 1 for 2.1R(8)-2VPQ, 45 +/- 10 for 2.5R(12)-2VPQ, and 11 +/- 1 for 3.4R(12)-2VPQ. Thus, the number of chains and the alkyl chain length of the telomers affected the micellar properties in aqueous solutions. At the interface of the silica/aqueous solution, the adsorbed amounts of the telomers increased sharply at their low concentrations and reached a plateau by forming a monolayer and a subsequent bilayer. Silica suspensions also showed a dispersion-flocculation-redispersion sequence with the telomer concentration, where the maximum sedimentation rate was influenced by the number of chains and the alkyl chain length of the telomers. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Workplace exposure to environmental tobacco smoke and high density lipoprotein cholesterol among nonsmokers.

There are few epidemiologic studies among adult nonsmokers on the effects of workplace environmental tobacco smoke on high density lipoprotein cholesterol (HDL-C). The authors investigated this relation, using data from health examinations conducted in 1995 on 3,062 Japanese nonsmokers in a total of 27 municipal offices with few smoking restrictions. Multiple regression analysis with adjustments for age, body mass index, alcohol drinking, and sports activities showed that in women, and in men lacking both alcohol consumption and sports activities characteristics, there were inverse linear relations between workplace smoking indices and HDL-C levels. Multivariate logistic regression showed that nonsmoking women in the upper two thirds of offices ranked by smoking intensity had an increased risk of low HDL-C levels (<45 mg), taking those in the lowest third of offices as reference (the medium third: odds ratio = 1.7; 95% confidence interval: 1.2, 2.5; the highest third: odds ratio = 1.6; 95% confidence interval: 1.1, 2.4). The results indicated that workplace environmental tobacco smoke exposure is associated with HDL-C among nonsmokers. However, the lack of data on home exposure limits causal inferences about the effects of workplace exposure.

Adult↗
PubMed1999

Nitrosothiol formation catalyzed by ceruloplasmin. Implication for cytoprotective mechanism in vivo.

Ceruloplasmin (CP) is a major multicopper-containing plasma protein that is not only involved in iron metabolism through its ferroxidase activity but also functions as an antioxidant. However, physiological substrates for CP have not been fully identified nor has the role of CP been fully understood. The reaction of nitric oxide (NO) with CP was investigated in view of nitrosothiol (RS-NO) formation. First, formation of heavy metal- or CP-catalyzed RS-NO was examined with physiologically relevant concentrations of NO and various thiol compounds (RSH) such as glutathione (GSH). Among the various heavy metal ions and copper-containing enzymes and proteins examined, only copper ion (Cu(2+)) and CP showed potent RS-NO (S-nitrosoglutathione)-producing activity. Also, RS-NO-forming catalytic activity was evident for CP added exogenously to RAW264 cells expressing inducible NO synthase in culture, but this was not the case for copper ion. Similarly, CP produced endogenously by HepG2 cells showed potent RS-NO-forming activity in the cell culture. One-electron oxidation of NO appears to be operative for RS-NO production via electron transfer from type 1 copper to a cluster of types 2 and 3 copper in CP. Neurological disorders are associated with aceruloplasminemia; besides RS-NO, S-nitrosoglutathione particularly has been shown to have neuroprotective effect against oxidative stress induced by iron overload. Thus, we suggest that CP plays an important catalytic role in RS-NO formation, which may contribute to its potent antioxidant and cytoprotective activities in vivo in mammalian biological systems.

Animals↗
PubMed1999

Simultaneous determination of donepezil (aricept) enantiomers in human plasma by liquid chromatography-electrospray tandem mass spectrometry.

A rapid, sensitive and enantioselective LC-MS-MS method using deuterium-labeled internal standard was developed and evaluated for the simultaneous quantitative determination of donepezil enantiomers in human plasma without interconversion during clean-up process and measurement. The use of an avidin column allowed the separation of donepezil enantiomers, which were specifically detected by MS-MS without interference from its metabolites and plasma constituents. Evaluation of this assay method shows that samples can be assayed with acceptable accuracy and precision within the range from 0.0206 ng/ml to 51.6 ng/ml for both R-donepezil and S-donepezil. This analytical method was applied to the simultaneous quantitation of donepezil enantiomers in human plasma.

Calibration↗
PubMed1999

Estrogen replacement therapy decreases platelet-activating factor-acetylhydrolase activity in post-menopausal women.

OBJECTIVE: To examine the effects of estrogen replacement therapy on plasma platelet-activating factor-acetylhydrolase (PAF-AH) activity and the lipoprotein profile in post-menopausal women. METHOD: Eight post-menopausal women received conjugated equine estrogen (0.625 mg/day) orally for a period of 10 weeks. PAF-AH activity and lipid levels were measured in plasma samples obtained from each subject prior to treatment and after 2, 6, and 10 weeks of estrogen therapy. RESULTS: Within 2 weeks of initiating estrogen treatment, a significant reduction in PAF-AH activity (-26%) was observed. Estrogen also caused significant decreases in total cholesterol (-8%), low-density lipoprotein-cholesterol (-24%), and the ratio of apolipoprotein B to A-II (-19%). On the other hand, levels of both high-density lipoprotein-cholesterol (18%) and triglyceride (31%) were elevated. CONCLUSION: Estrogen exerts a favorable effect on the lipoprotein profile, but decreased plasma PAF-AH activity may facilitate platelet aggregation thereby opposing protective effect of estrogen-replacement therapy with respect to thrombotic complications.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Cloning and functional characterization of the 5'-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene. Essential role of 5'-untranslated region in tissue-specific expression.

The human monocyte chemoattractant protein-1 receptor designated hCCR2 is an essential co-receptor in cell entry by the human immunodeficiency virus as well as a receptor for monocyte chemoattractant protein-1, a member of the family of C-C chemokines that mediate monocyte chemotaxis. To elucidate the molecular mechanisms underlying the transcriptional regulation of hCCR2, we cloned and sequenced the hCCR2 gene; it was approximately 8 kilobase pairs in length and consisted of three exons divided by two introns. In the 5'-flanking region, there were the typical mammalian promoter consensus elements, a CAAT box and a TATA box, resulting in a single transcription initiation site. In addition, we found clustered tissue-specific cis-regulatory elements such as GATA consensus sequences, Oct-1 binding sequences, and CAAT/enhancer-binding protein binding sequences. Luciferase assays with various promoter deletions and gel mobility shift assays indicated that three cis-regulatory elements located within the region from -89 to +118 are required for basal activity in THP-1 cells. One element is an octamer sequence 36-base pair upstream from the TATA box; it binds mainly to Oct-1 and is capable of increasing transcriptional activity. The other two elements, which are tandem recognition sites of the CAAT/enhancer-binding protein family, are located in the 5'-untranslated region and account for the transcriptional activation as well as the tissue specificity of hCCR2.

5' Untranslated Regions↗