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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 649 records · Page 36Linked to original sources
PubMed1996

[Effect of hypercholesteremia on vascular endothelial function and albumin excretion rate in patients with diabetes mellitus].

Tissue-type plasminogen activator (tPA) is an endothelium-derived vasoactive substance which is released to the blood stream by exercise, blood occlusion, and desmopressin (DDAVP). The increased capacity of the plasma tPA level raised by these factors is thought to reflect in vivo endothelial function. On the other hand, endothelial dysfunction has been reported in patients with hypercholesteremia as well as in those with diabetes mellitus. Therefore, diabetic patients with hypercholesteremia were administered 5 mg of simvastatin daily for one month and plasma tPA responses evoked by DDAVP were examined before and after treatment for hypercholesteremia. While the treatment of simvastatin for one month significantly reduced serum cholesterol levels from 257 +/- 12 mg to 206 +/- 10 mg (no change in HbA1c was observed during the study), plasma tPA levels and % delta vWF (von Willebrand factor) following DDAVP infusion significantly increased from 11.4 +/- 1.2 ng/ml to 13.4 +/- 1.4 ng/ml and from 69.3 +/- 23.4% to 126.5 +/- 47.4%, respectively. However, neither increase in plasma levels of guanosine 3', 5'-cyclic monophosphate (cGMP) nor change in the depressive response of blood pressure was observed following DDAVP infusion after the treatment of simvastatin. In addition, no change in urinary albumin excretion rate was observed with the treatment of hypercholesteremia. Therefore, it was suggested that improvement in hypercholesteremia may ameliorate vascular endothelial dysfunction in diabetic patients with hypercholesteremia and that hypercholesteremia may enhance endothelial dysfunction in these patients.

Albuminuria↗
PubMed1996

[Intractable hiccup in two severely handicapped patients during phenytoin therapy].

Two severely handicapped patients developed intractable hiccup during phenytoin therapy. In these two patients, serum phenytoin levels revealed 32.6 micrograms/ml and 17.6 micrograms/ml, respectively. Since large doses of phenytoin cause delayed latencies, and depressed or lost of brainstem auditory evoked potentials, it can be speculated that intractable hiccup could occur through dysfunction of brainstem by phenytoin.

Adult↗
PubMed1996

Radioimmunoprecipitation assay for glutamic acid decarboxylase antibodies evaluated clinically with sera from patients with insulin-dependent diabetes mellitus.

We evaluated a new, commercially developed radioimmunoprecipitation assay for measuring glutamic acid decarboxylase (GAD) antibodies by using recombinant human GAD65. The intra- and interassay CVs were 8.0% (n = 20) and 8.6% (n = 15), respectively. We found GAD antibodies in 74% (23 of 31; 95% confidence interval 55-88%), 70% (14 of 20; 46-88%), and 65% (28 of 43; 49-79%) of patients at, respectively, < or = 1 year, 1-2 years, and 2-4 years after the onset of insulin-dependent diabetes mellitus (IDDM) and in 30% (30 of 99; 21-40%) of patients with long-term diabetes (4-22 years). We also detected GAD antibodies in 8% (9 of 106; 4-16%) of patients with non-insulin-dependent diabetes mellitus (NIDDM). The frequency of GAD antibodies in the NIDDM group was markedly higher in the insulin-deficient patients [67% (6 of 9; 30-93%)], who initially were nonketotic and non-insulin-dependent for > or = 6 months but later became insulin dependent, than in the non-insulin-deficient patients [3% (3 of 97; 1-9%)]. This new commercial assay is easy to use and provides a specific and sensitive method for evaluating GAD antibodies in IDDM.

Adolescent↗
PubMed1996

[Neutrophil elastase and elastin-derived peptides in BAL fluid and emphysematous changes on CT scans].

We examined the relationship between neutrophil elastase, elastin-derived peptides in bronchoalveolar lavage (BAL) fluid, and the development of pulmonary emphysema. The level of neutrophil elastase was higher in asymptomatic current smokers with emphysematous changes on computed tomographic scans than in current smokers without emphysematous changes, and was found to be correlated with the level of elastin-derived peptides in BAL fluid. Subjects with high levels of neutrophil elastase in BAL fluid had faster annual declines in FEV1. We conclude that the level of neutrophil elastase in BAL fluid can be used to differentiate asymptomatic cigarette smokers who are at risk for pulmonary emphysema from those who are not.

Aged↗
PubMed1996

Human T lymphotropic virus type I (HTLV-I)-specific T helper cell responses from HTLV-I seronegative patients with chronic myelopathy and MS in Japan.

Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to Adult T cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although most HAM/TSP patients have high anti-HTLV-I antibody titers in their sera, HTLV-I infected but seronegative patients with neurological diseases have been reported. To clarify whether seronegative, HTLV-I related neurological disease may exist, we have developed a method that measures the production of interleukin-2 (IL-2) from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I infected persons. This method is sensitive enough to detect exposure to HTLV-I before seroconversion or even before detection by PCR. We examined 12 patients with chronic progressive myelopathy and eight patients with multiple sclerosis (MS) in central Japan, where the prevalence rate of HTLV-I is between one and four percent among asymptomatic blood donors, using the IL-2 production assay. None of them were positive by the assay, suggesting seronegative HTLV-I myelopathy is very rare among patients with chronic progressive myelopathy and MS in Japan.

Adult↗
PubMed1995

Purification and characterization of a novel xylulose 5-phosphate-activated protein phosphatase catalyzing dephosphorylation of fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase.

We have shown previously (Nishimura, M., Fedorov, S., and Uyeda, K. (1994) (J. Biol. Chem. 269, 26100-26106) that the administration of high concentrations of glucose stimulates dephosphorylation of Fru-6-P,2-kinase: Fru-2,6-bisphosphatase in perfused liver, and xylulose (Xu) 5-P activates the dephosphorylation reaction. To characterize the protein phosphatase, we have purified the Xu 5-P-activated protein phosphatase to homogeneity from livers of rats injected with high glucose. Several protein phosphatases in the livers were separated by DEAE-cellulose chromatography, but only one peak of the enzyme was activated by Xu 5-P. The protein phosphatase was inhibited by okadaic acid (IC50 = 1-3 nM) and did not require Mg2+ or Ca2+, suggesting that the enzyme was type 2A. The enzyme was a heterotrimer (M(r) = 150,000) and consisted of structural (A, 65 kDa) catalytic (C, 36 kDa), and regulatory (B, 52 kDa) subunits. Amino acid sequences of five tryptic peptides derived from the B subunit showed similarity with those of the B alpha isoform of rat protein phosphatase 2A, but five out of 73 residues were different. The protein phosphatase catalyzed dephosphorylation of Fru-6-P,2-kinase:Fru-2,6-Pase, phosphorylase alpha, and pyruvate kinase, and the Km values were 0.8 microM, 3.7 microM, and 2.2 microM, respectively. Among these substrates dephosphorylation of only the bifunctional enzyme was activated by Xu 5-P, and the K alpha value for Xu 5-P was 20 microM. Xu 5-P was the only sugar phosphate which activated the PP2A among all the sugar phosphates examined. These results demonstrated the existence and isolation of a unique heterotrimeric protein phosphatase 2A in rat liver which catalyzed the dephosphorylation of Fru-6-P,2-kinase:Fru-2,6-Pase and was activated specifically by Xu 5-P. The Xu 5-P-activated protein phosphatase 2A explains the increased Fru 2,6-P2 level in liver after high glucose administration.

Amino Acid Sequence↗
PubMed1995

Changes in physical properties of vacuolar membrane during transformation of protein bodies into vacuoles in germinating pumpkin seeds.

Changes in membrane molecular dynamics associated with the transformation of protein body membranes into vacuolar membranes during pumpkin seed germination, were monitored by EPR-spin probe technique. Using highly purified membrane preparations as well as 5-SASL and 16-SASL spin labels, parameters like general membrane lipid fluidity, order parameter, semicone angle, rotational correlation times tau 2B and tau 2C, ratio of immobilized to mobile lipids were determined and the activation energy for rotational diffusion of 16-SASL was calculated. Analysis of these parameters at different temperatures indicated a more rigid nature of protein body membrane comparing to vacuolar membrane, as a result of a more restricted motional freedom of lipids. These differences are discussed in terms of protein composition and various functional specialization of both types of membranes.

Cyclic N-Oxides↗
PubMed1995

Cloning and gene mapping of the mouse homologue of the CBFA2T1 gene associated with human acute myeloid leukemia.

The human CBFA2T1 (also known as MTG8) gene, on chromosome 8, has been identified through its involvement in the t(8;21) chromosomal translocation, frequently found in acute myeloid leukemia. We report here the isolation and characterization of the mouse homologue of the CBFA2T1 gene, Cbfa2t1h. Nucleotide sequence analysis of Cbfa2t1h cDNA clones revealed an open reading frame encoding a protein of 577 amino acids with an extremely high degree of amino acid identity (99.3%) to the human protein. The nucleotide sequence is also highly conserved between mouse and human in the 5'- and 3'-untranslated regions (87.0, 92.0, and 93.7% identities for 5'-untranslated, coding, 3'-untranslated regions, respectively). The 3'-untranslated region of Cbfa2t1h contains a (CA)n dinucleotide repeat, and the polymerase chain reaction amplification of the (CA)n repeat region revealed fragment length polymorphism among mouse strains. Using this polymorphism, we have mapped Cbfa2t1h to mouse chromosome 4 close to the centromere using SMXA recombinant inbred strains and 106 intersubspecific backcross progenies of the (DBA/2 x Mae) x Mae cross. The chromosomal location was also confirmed by fluorescence in situ hybridization.

Acute Disease↗
PubMed1995

Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82.

Previously, we have shown that CD81 and CD82, two members of the transmembrane 4 superfamily, form multimolecular membrane complexes by associating with each other and with CD4 or CD8 in T cells. In the present study, we further analyzed the molecular basis of the CD4 association with CD81 and CD82 by co-precipitation experiments. First, we examined the regions of CD4 involved in the association with CD81 and CD82 by employing chimeric proteins generated from CD4 and CD2. It was confirmed that CD4, but not CD2, was capable of binding with CD81 and CD82 in transfected cells. We found that the cytoplasmic region of CD4 was sufficient for the chimeric proteins to co-precipitate CD81, while both the cytoplasmic and extracellular regions of CD4 were required for them to efficiently co-precipitate CD82. We next found, by using truncated CD4 lacking the C-terminal 31 amino acids or mutated CD4 with the cysteine residues at 394 and 397 replaced by serine, that the p56lck binding site or the covalent modification with palmitic acid was not necessary for CD4 to associate with CD81 and CD82. Finally, we found that the binding of p56lck to CD4 strongly inhibited its association with CD81 and CD82. It is, therefore, suggested that CD4 exists at least in two physical states, one associated with p56lck and another associated with CD81 and CD82 in the absence or uncoupling of p56lck.

Acylation↗
PubMed1995

Electrophysiologic alterations in the rabbit nodal cells induced by membrane lipid peroxidation.

To investigate cellular electrophysiologic alterations due to lipid peroxidation of the cell membrane by free radicals as a possible cause of coronary reperfusion arrhythmias, we studied the effects of t-butyl hydroperoxide on the spontaneous action potential and membrane currents of the rabbit sinoatrial and atrioventricular node preparations (0.2 x 0.2 x 0.1 mm). 1-5 min of superfusion with t-butyl hydroperoxide (100-500 microM) caused a transient increase in the spontaneous firing frequency by 9%, accompanied by a 4% increase in the action potential amplitude and a 33% increase in the maximal rate of depolarization (P < 0.05, n = 6). t-Butyl hydroperoxide then gradually suppressed physiological automaticity, but induced abnormal repetitive firing due to early and delayed after-depolarizations. 15 min of superfusion with t-butyl hydroperoxide caused a complete standstill of nodal cells at a resting potential of -46 +/- 3 mV (n = 12). Such effects of t-butyl hydroperoxide on the spontaneous action potential were attenuated by pretreating the cells with butylated hydroxytoluene, a lipid peroxidation inhibitor. Voltage clamp experiments using double microelectrode methods revealed that t-butyl hydroperoxide transiently increased the Ca2+ current by 22% after 5 min of superfusion but subsequently reduced it to 46% of the control value after 15 min (P < 0.05, n = 6). Similar biphasic changes were observed in the delayed rectifying K+ current and hyperpolarization-activated inward current (n = 6). Background current was progressively increased without any change in its reversal potential (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Study of the enantioselective binding between BOF-4272 and serum albumins by means of high-performance frontal analysis.

High-performance frontal analysis (HPFA) was incorporated in an on-line HPLC system for the study of the enantioselective binding of BOF-4272, a new xanthine oxidase inhibitor, with human, bovine and rat serum albumins. This HPLC system consists of a HPFA column (diol-silica column), an extraction column (C4 column) and a chiral separation column (beta-cyclodextrin immobilized silica column), which were connected in series via two column switching valves. After the direct injection of a solution of 0.5-400 microM racemic BOF-4272 and 550 microM serum albumin onto the HPFA column, BOF-4272 was eluted, under a mild mobile phase condition (phosphate buffer, pH 7.4, ionic strength 0.17), as a zonal peak containing a plateau region. The drug concentration in the plateau region is the same as that for the unbound drug concentration in the sample solution. A given volume of this plateau region was transferred into the extraction column, and subsequently the extracted BOF-4272 was transferred into the chiral separation column to determine the unbound concentration of each enantiomer. The binding between BOF-4272 and the serum albumins was enantioselective and species dependent. The unbound concentration of the (+)-isomer in rat serum albumin solution was 1.04-1.14 times larger than that of the antipode, while the unbound concentration of the (-)-isomer in bovine serum albumin solution was 1.04-1.16 times larger than that of the antipode. The enantioselectivity of the binding between BOF-4272 and human serum albumin was concentration dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Molecular cloning of a novel C or gamma type chemokine, SCM-1.

From human PBMC stimulated with PHA, we have isolated cDNA clones encoding a novel cytokine named SCM-1, which is significantly related to the CC and the CXC chemokines but has only the 2nd and the 4th of the four cysteines conserved in these proteins. Its gene is also distinctly mapped to human chromosome 1. SCM-1 is strongly induced in human PBMC and Jurkat T cells by PHA stimulation. Among various human tissues, SCM-1 is expressed most strongly in spleen. SCM-1 is found to be 60.5% identical to lymphotactin, a recently described murine lymphocyte-specific chemokine, which also retains only two cysteines. SCM-1 and lymphotactin may thus represent the human and murine prototypes of a novel C or gamma type chemokine family.

Amino Acid Sequence↗
PubMed1995

Four ferredoxins from Japanese radish leaves.

We detected three ferredoxin components, a, b, and c, in green shoots of Japanese radish seedlings by hydrophobic HPLC analysis using a phenyl-5PW column. All components were also present in mature leaves. Component a was further separated into two components, a1 and a2, by reversed-phase HPLC after carboxymethylation. The existence of four ferredoxins in the photosynthetic tissue of a single plant species is reported here for the first time. Each individual ferredoxin component was isolated, and its primary structure was analyzed for comparison with the two leaf ferredoxins, L-Fds A and B, isolated by Wada et al. (J. Biochem. 105, 619-625 (1989)). The primary structures of components a1, a2, and b were all found in 12 possible structures of L-Fd A deducible from its microheterogeneities. This led us to conclude that L-Fd A is a mixture of three ferredoxins corresponding to components a1, a2, and b. The complete primary structure of component c was established by sequencing of the whole protein and of peptides generated by protease digestion. The N-terminal structure of component c was identical with L-Fd B up to the 11th amino acid residue, suggesting that this component is the same ferredoxin as L-Fd B.

Amino Acid Sequence↗
PubMed1995

Fc receptors in liver sinusoidal endothelial cells in NZB/W F1 lupus mice: a histological analysis using soluble immunoglobulin G-immune complexes and a monoclonal antibody (2.4G2).

In systemic lupus erythematosus accompanied by the abnormal appearance of circulating immune complexes (ICs), Fc gamma receptor (FcR)-mediated IC handling in macrophages including Kupffer cells has been shown previously. However, sinusoidal endothelial cells (SECs) largely ingest soluble immunoglobulin (Ig) G-ICs through FcRs. In this study, the character, antigenic expression, and activity (i.e., ligand-binding capacity of SEC FcRs in NZB/NZW F1 lupus and NZW nonautoimmune mice) were immunohistochemically analyzed using monoclonal antibody (MAb) 2.4G2 to FcRs and peroxidase-antiperoxidase IgG as a ligand on cryosections. MAb 2.4G2 stained SECs and blocked the ligand binding of SEC FcRs in both mice strains. The staining intensities with MAb 2.4G2 in SECs and the FcR activities in SECs alone and all sinusoidal cells in both mice strains reached their maximum values at the age of 5 months. Staining intensities in NZB/W F1 were significantly higher at 1 and 2 months and lower at 9 months than those in NZW. The number of Kupffer cells detected by MAb F4/80 to macrophages in both mice strains gradually increased until 5 months, but their number in NZB/W F1 at 9 months was twice as large as that in NZW. In conclusion, SEC FcRs in mice are low-affinity FcRs that react with MAb 2.4G2. The data of FcR activity suggest no impairment of the FcR-mediated IgG-IC binding on SECs in NZB/W F1 in early life.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Family segregation analysis of inheritance of human minor histocompatibility antigen.

Disparities in minor histocompatibility antigens (mHAs) between HLA-identical donor and recipient pairs often cause graft-versus-host disease (GVHD) or graft rejection. Minor HAs are thought to be peptides that are associated with specific major histocompatibility complex (MHC) molecules and are presented to specific T cells. Despite the importance of mHAs in constructing a strong immunological barrier following tissue transplantation, little information on mHAs in humans is available. We have already reported establishment of the DR9-restricted mHA-specific CD4+ cytotoxic T cell (CTL) clone "A-6." To investigate the chromosomal localization of the gene encoding the mHA peptide recognized by clone A-6 in context with DR9, we performed a family segregation analysis. We concluded that the mHA-encoding gene was transmitted from parent(s) to some offspring.

B-Lymphocytes↗
PubMed1995

NGF receptor expression in sensory neurons develops normally in embryos lacking NGF.

Numerous in vivo and in vitro studies have shown that NGF increases the expression of its receptors, p75 and TrkA, in NGF-responsive cell lines and in NGF-responsive neurons of the developing and mature nervous system. To determine if endogenous NGF is required for the normal developmental increase in p75 and TrkA expression that occurs in sensory neurons shortly after they innervate their targets, we used quantitative RT/PCR to compare the levels of p75 and trkA mRNAs in the trigeminal ganglia of normal mouse embryos and embryos that are homozygous for a null mutation in the NGF gene. We show that the marked increase in p75 and trkA mRNA expression that occurs between E11 and E13 in normal embryos takes place on time and to the same extent in NGF-/- embryos. We also show that trigeminal neurons from E13 NGF+/+ and NGF-/- embryos have very similar dose responses for survival induced by NGF. These findings clearly show that the expression of both p75 and TrkA and the sensitivity of developing sensory neurons to NGF do not require and are not modulated by target-derived NGF during the early stages of target field innervation.

Animals↗
PubMed1995

Homologues of a vacuolar processing enzyme that are expressed in different organs in Arabidopsis thaliana.

Vacuolar processing enzymes (VPEs) are responsible for the maturation of seed proteins. These processing enzymes belong to a novel group of cysteine proteinases with molecular masses of 37 to 39 kDa. We isolated two genes of VPEs from a genomic library of Arabidopsis. The gene products were designated alpha-VPE and beta-VPE, and they were 56% identical in terms of amino acid sequence. The amino acid sequences of alpha-VPE and beta-VPE were also 55% and 67% identical to that of castor bean VPE, respectively. The gene for alpha-VPE had 7 introns, while that of beta-VPE had 8 introns. Northern blot analysis revealed that alpha-VPE is expressed in rosette leaves, cauline leaves and stems of Arabidopsis, while beta-VPE is predominantly expressed in the flowers and buds. Neither alpha-VPE nor beta-VPE is expressed in the siliques. This result strongly suggests that the isolated genes encode isozymes of VPE that are specific to vegetative organs.

Amino Acid Sequence↗