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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 433 records · Page 24Linked to original sources
PubMed1999

[Metabolism of 123I-FP-CIT in humans].

The metabolism of N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-FP-CIT) in healthy humans was studied. Plasma and urine samples, obtained after i.v. administration of 123I-FP-CIT, were analyzed using the two-dimensional thin-layer chromatography technique. Eleven radiochemical components were detected in both plasma and urine, and four of them were the parent 123I-FP-CIT and its metabolites, N-(3-fluoropropyl)-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-acid), 2 beta-carboxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-nor-acid) and 2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-nor-CIT). These four identified radiochemical components occupied about 80% or more in ratio of the radiochemical components in the plasma and urine. In the metabolites of 123I-FP-CIT, the high polar metabolites--123I-acid and 123I-nor-acid--were found to be the major components, while lipophilic 123I-nor-CIT was a minor component. Free iodide (123I-) was not found in the plasma or urine. Thus, the main metabolic reactions which 123I-FP-CIT undergoes in humans seem to be hydrolysis of the ester bond and N-dealkylation. In vivo deiodination of 123I-FP-CIT was found to be minimum. Current results suggest that the metabolites of 123I-FP-CIT hardly influence evaluation of the dopamine transporter in the human brain.

Adult↗
PubMed1999

[Increased serum soluble Fas ligand in hyperthyroid Graves' disease].

The interaction of Fas with its ligand (FasL) regulates a number of physiological and pathophysiological process of cell death or apoptosis. Recent studies suggest that Fas and Fas ligand (FasL) interactions among thyrocytes from patients with Hashimoto disease which is caused by thyroid autoimmunity may contribute to clinical hypothyroidism. The role of Fas-FasL interaction in the pathophysiology of Graves' disease has not well been determined. The serum levels of soluble Fas (sFas) and FasL (sFasL) were measured in 48 Japanese patients with Graves' disease (U; untreated hyperthyroidism, T; hyperthyroidism under treatment, E; euthyroidism under treatment and R; remission), destructive thyroiditis (D), subacute thyroiditis (S) and 40 normal controls using commercially available ELISA kits. The levels of sFas (mean +/- SD, ng/ml) were 0.93 +/- 0.30 in normal controls (n = 32), 2.41 +/- 1.28 in U (n = 19), 2.44 +/- 0.79 in T (n = 16), 2.37 +/- 0.55 in E (n = 12), and 2.30 +/- 0.11 in R (n = 6), 2.42 +/- 0.37 in D (n = 3) and 2.68 +/- 0.17 in S (n = 3). There were no significant differences of sFas levels among any groups. While, the mean levels of sFasL (ng/ml) of normal controls were 0.058 +/- 0.02 (n = 40), and those of patients with hyperthyroid Graves' disease (U; 0.34 +/- 0.09 and T; 0.26 +/- 0.05), were significantly higher than those in normal controls (p < 0.005) and with subacute thyroiditis (0.097 +/- 0.001, vs U; p < 0.01, vs T; p < 0.05) but not different from those in E, R and D (E; 0.34 +/- 0.09, R; 0.25 +/- 0.07 and D; 0.31 +/- 0.11, respectively). There was a significant correlation between serum thyrotropin receptor antibody (TRAb) and free thyroxine levels (p < 0.01) while there were no correlation between sFas and sFasL levels and TRAb or free thyroxine levels. The results indicate that the Fas-FasL system contributes to the pathophysiology of hyperthyroid Graves' disease although serum sFas and sFasL levels do not appear to be useful indicators in evaluating disease activity.

Autoimmunity↗
PubMed1999

[Practical compensation method of downscattered component due to high energy photon in 123I imaging].

We looked into the problem that the quantitative values of 123I data vary according to collimator type. First, we made the assumption that the quantitative values of 123I data are degraded by the scattered photons from the 529 keV component which contaminate the 159 keV imaging data. Then, the 123I Dual Window (IDW) method was proposed to improve the quantitative values of the 123I data. The IDW method uses the energy window on the high-energy side to estimate the amount of scattered 529 keV photons which contaminate the 159 keV data. Since only a dual-energy window acquisition and a simple image processing are needed, the IDW method can be performed in most conventional gamma camera systems. In the torso phantom studies, the IDW method reduced the error in the semi-quantitative value 'heart/mediastinum (H/M) ratio' in 123I-MIBG myocardial scintigraphy from 22% to 1%. The results of the phantom studies indicate that the IDW method can improve the quantitative values of 123I data.

3-Iodobenzylguanidine↗
PubMed1999

[Phase 1 clinical study of 123I-FP-CIT, a new radioligand for evaluating dopamine transporter by SPECT (II): Tracer kinetics in the brain].

The kinetics of 123I-FP-CIT in the brain for healthy subjects were studied. Twelve dynamic SPECT data sets (0- to 6-hr after an intravenous injection) from a Phase 1 clinical trial of 123I-FP-CIT were analyzed. Tracer concentrations in the striatum, midbrain, cerebellum and cerebral cortex were measured on the SPECT images co-registered with the corresponding MR images. High tracer accumulation was observed in the striatum, which peaked at 60 min post-injection, followed by slow elimination (3%/hr). The kinetics were similar both in the cerebellum and in the cerebral cortex, which peaked at 15 min post-injection, followed by rapid elimination. Tracer accumulation in the midbrain was higher than in the cerebellum and cerebral cortex. The striatal specific/nonspecific binding ratio ((striatal-occipital)/occipital concentration ratio) was stable at 3-hr post-injection and later at a value of 3, suggesting that the specific binding of 123I-FP-CIT could be evaluated from a single SPECT image at 3- to 6-hr post-injection. The specific/nonspecific binding ratio at 4-hr post-injection showed a negative correlation with aging (r = -0.70, p = 0.01), with a decrease rate of 11%/decade (95% confidence interval: 3%-19%/decade).

Adult↗
PubMed1998

Cloning of a thermostable ascorbate oxidase gene from Acremonium sp. HI-25 and modification of the azide sensitivity of the enzyme by site-directed mutagenesis.

A gene encoding a thermostable ascorbate oxidase (ASOM) was cloned from Acremonium sp. HI-25 and sequenced. The gene comprised 1709 bp and was interrupted by a single intron of 57 bp. ASOM consisted of 551 amino acids including a signal peptide with a molecular mass of 61200, and contained four histidine-rich regions with high sequence homology to the corresponding regions of other multicopper oxidases. The ASOM gene was expressed in Aspergillus nidulans under the Aspergillus oryzae Taka-amylase A gene promoter. The recombinant enzyme (An-ASOM) exhibited almost the same enzymatic properties as ASOM. The ASOM gene was mutated by site-directed mutagenesis with reference to the amino acid sequences of plant enzymes to generate enzymes with altered azide sensitivity. Site-directed mutagenesis at the trinuclear active copper site resulted in an increase in azide resistance; the Ala465Leu and Phe463Trp/Ala465Leu mutants exhibited approximately 10 and 20% increases in azide resistance, respectively.

Acremonium↗
PubMed1998

Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice.

Stat3, a member of STAT, is activated by a variety of cytokines such as IL-6 family of cytokines, granulocyte CSF, epidermal growth factor, and leptin. A recent study with mice genetically deficient in the Stat3 gene has revealed its important role in the early embryogenesis. To assess the function of Stat3 in adult tissues, we disrupted the Stat3 gene specifically in T cells by conditional gene targeting using Cre-loxP system. In Stat3-deficient T cells, IL-6-induced proliferation was severely impaired. IL-6 did not enhance cell cycle progression, but prevented apoptosis of normal T cells. In contrast, IL-6 did not prevent apoptosis of Stat3-deficient T cells. Antiapoptotic protein, Bcl-2, was normally up-regulated in response to IL-6 even in Stat3-deficient T cells. These results demonstrate that Stat3 activation is involved in IL-6-dependent T cell proliferation through prevention of apoptosis independently of Bcl-2.

Amino Acid Sequence↗
PubMed1998

Vasoactive intestinal peptide potentiates and directly stimulates catecholamine secretion from rat adrenal chromaffin cells.

The actions of vasoactive intestinal polypeptide (VIP) on catecholamine secretion and changes in [Ca2+]i in single rat chromaffin cells were studied using amperometry and Indo-1. Application of VIP prior to acetylcholine (ACh) or co-application of VIP and ACh enhanced secretion by 94% and 153% respectively, compared to ACh alone. [Ca2+]i was increased by 17% when VIP was preapplied and by 73% upon co-application. Exposure to VIP before stimulation with 60 mM K+ enhanced secretion by 68%, but not [Ca2+]i. VIP application prior to DMPP and nicotine had no effect on [Ca2+]i, but increased [Ca2+]i signals to muscarine by 18%. VIP co-application potentiated only [Ca2+]i responses to muscarine, by 28%. The effect of VIP on muscarine-induced [Ca2+]i signals was mimicked by 8-Br-cAMP, and both were blocked by H-89, a protein kinase A inhibitor. Long-lasting increases in secretion accompanied by a sustained rise in [Ca2+]i to VIP alone were seen in 55% of cells. Removal of Ca2+ or addition of La3+ inhibited both responses, while L-, N- and P-type Ca2+ channel blockers were ineffective. SK&F 96365 inhibited VIP-induced secretion completely and rises in [Ca2+]i by 75%. Neither 8-Br-cAMP nor 8-Br-cGMP evoked responses similar to VIP alone. Thus in rat chromaffin cells, VIP acts both directly as a neurotransmitter in provoking sustained catecholamine secretion in a cAMP-independent manner, and also by enhancing ACh-induced secretion, via a cAMP-dependent action involving muscarinic receptors.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

A novel three-dimensional crystal of bacteriorhodopsin obtained by successive fusion of the vesicular assemblies.

When the two-dimensional crystal of bacteriorhodopsin (bR), purple membrane, is incubated at high temperature (32 degreesC) with a small amount of the neutral detergent octylthioglucoside in the presence of the precipitant ammonium sulfate, a large fraction of the membrane fragments is converted into spherical vesicles with a diameter of 50 nm, which are able to assemble into optically isotropic hexagonal crystals when the precipitant concentration is increased. The vesicularization of purple membrane takes place under such a condition that the miscibility of the detergent to the aqueous phase becomes very low, and we suggest that it is initiated by insertion of the detergent molecules into the membrane. At low temperature, the transformation into the vesicular structure is inhibited and no large crystal is produced directly from membrane/detergent/precipitant mixtures. When a suspension of the spherical vesicles produced at the high temperature is cooled and concentrated below 15 degreesC, however, a birefringent hexagonal crystal is produced that diffracts X-rays beyond 2.5 A resolution. This new crystal belongs to the space group P622 with unit cell dimensions of a=b=104.7 A and c=114.1 A, and it is shown to be made up of stacked planar membranes, in each of which the bR trimers are arranged on a honeycomb lattice and the space among the proteins is filled with the detergent molecules and native lipids. These stacked membranes are suggested to be produced by successive fusion of the spherical vesicles. This implies that the crystallization is achieved without any step for complete solubilization of the protein. The present result offers a unique crystallization method that may be applicable to such membrane proteins that are liable to denature in the presence of an excess amount of detergent.

Bacteriorhodopsins↗
PubMed1998

Expression of Id1 results in apoptosis of cardiac myocytes through a redox-dependent mechanism.

We have constructed a recombinant adenovirus (Ad.Id1) that allows for efficient expression of the helix-loop-helix protein Id1. After infection with Ad.Id1, neonatal cardiac myocytes display a significant reduction in viability, which was proportional to the level of Id1 expression. A similar effect was observed in adult myocytes. Morphological and biochemical assays demonstrated that Id1 expression resulted in myocyte apoptosis. In contrast, expression of Id1 in endothelial cells, vascular smooth muscle cells, or fibroblasts did not affect the viability of these cells. Along with the induction of apoptosis, the expression of Id1 in neonatal cardiac myocytes resulted in an increase in the level of intracellular reactive oxygen species. The source of these reactive oxygen species appears to be the mitochondria. Reducing the ambient oxygen concentration or treatment with a cell-permeant H2O2 scavenger prevented Id1-stimulated apoptosis in cardiac myocytes. These results suggest that the expression of Id1 leads to the induction of apoptosis in cardiac myocytes through a redox-dependent mechanism.

Adenoviridae↗
PubMed1998

IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production.

IL-18 is a product of macrophages and with IL-12 strikingly induces IFN-gamma production from T, B, and NK cells. Furthermore, IL-18 and 1L-12 synergize for IFN-gamma production from Th1 cells, although this combination fails to affect Th2 cells. In this study, we show that IL-12 and IL-18 promptly and synergistically induce T and B cells to develop into IFN-gamma-producing cells without engaging their Ag receptors. We also studied the mechanism underlying differences in IL-18 responsiveness between Th1 and Th2 cells. Pretreatment of T or B cells with IL-12 rendered them responsive to IL-18, which induces cell proliferation and IFN-gamma production. These IL-12-stimulated cells had both high and low affinity IL-18R and an increased IL-18R mRNA expression. In particular, IL-12-stimulated T cells strongly and continuously expressed IL-18R mRNA. However, when T cells developed into Th1 cells after stimulation with anti-CD3 and IL-12, they lowered this IL-12-induced-IL-18R mRNA expression. Then, such T cells showed a dominant response to anti-CD3 by IFN-gamma production when they were subsequently stimulated with anti-CD3 and IL-18. In contrast, Th2 cells did not express IL-18R mRNA and failed to produce IFN-gamma in response to anti-CD3 and IL-18, although they produced a substantial amount of IFN-gamma in response to anti-CD3 and IL-12. However, when Th1 and Th2 cells were stimulated with anti-CD3, IL-12, and IL-18, only the Th1 cells markedly augmented IFN-gamma production in response to IL-18, suggesting that IL-18 responsiveness between Th1 and Th2 cells resulted from their differential expression of IL-18R.

Animals↗
PubMed1998

Stem cell factor augments Fc epsilon RI-mediated TNF-alpha production and stimulates MAP kinases via a different pathway in MC/9 mast cells.

Mast cells express the receptor tyrosine kinase kit/stem cell factor receptor (SCFR) which is encoded by the proto-oncogene c-kit. Ligation of SCFR induces its dimerization and activation of its intrinsic tyrosine kinase activity leading to activation of Raf-1, phospholipases, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinases. However, little is known about the downstream signals initiated by SCFR ligation except for activation of extracellular signal-regulated kinases. The murine mast cell line, MC/9, synthesizes and secretes TNF-alpha following the aggregation of high affinity Fc receptors for IgE (Fc epsilonRI). Ligation of SCFR or Fc epsilonRI on MC/9 cells resulted in the activation of all three MAP kinase family members, extracellular signal-regulated kinases, c-Jun amino-terminal kinase (JNK), and p38. Stem cell factor (SCF)-induced activation of JNK and p38 was insensitive to wortmannin, cyclosporin A, and FK506 whereas activation of these kinases through Fc epsilonRI was sensitive to these drugs. Coligation of SCFR augmented Fc epsilonRI-mediated activation of MAP kinases, especially JNK activation, and SCF augmented Fc epsilonRI-mediated TNF-alpha production in MC/9 cells, although SCF alone did not induce TNF-alpha production. This augmentation by SCF was regulated at the level of transcription, at least in part, since the promoter activity of TNF-alpha was enhanced following addition of SCF. These results demonstrate that SCF can augment Fc epsilonRI-mediated JNK activation and cytokine gene transcription but via pathways that are regulated differently than the ones activated through Fc epsilonRI.

Adjuvants, Immunologic↗
PubMed1998

Alzheimer's disease with asymmetric parietal lobe atrophy: a case report.

A 52-year-old, right-handed female presented with visuospatial dysfunction including left hemineglect, incomplete Balint's syndrome, and environmental agnosia, together with left-sided motor symptoms such as unskillful movement, dystonic postures, and myoclonus in the left hand, without significant dementia. Symptoms progressed to akinetic mutism prior to her death 10 years after onset of illness. Imaging studies such as MRI, SPECT, and PET studies showed severe, predominantly right-sided involvement of parietal and parieto-occipital areas. The motor signs might originate from the right parietal lesions such as area five or somatosensory area. Neuropathologic studies including immunocytochemistry showed tau-positive neurofibrillary tangles and abundant neuritic plaques with amyloid deposits, confirming the diagnosis of Alzheimer's disease. An analysis of serum apolipoprotein E revealed epsilon3/epsilon3 homozygosity. This case represents a variant of Alzheimer's disease conspicuous for progressive motor signs and visuospatial dysfunction with a striking laterality, reflecting asymmetric parietal involvement. Alzheimer's disease with asymmetric parietal atrophy is difficult to be clinically distinguished from corticobasal degeneration characterized by progressive unilateral motor signs and focal cortical signs.

Agnosia↗
PubMed1998

Nerve growth factor treatment prevents the increase in superoxide produced by epidermal growth factor in PC12 cells.

Stimulation of pheochromocytoma (PC12) cells with the mitogen epidermal growth factor (EGF) produced a rapid and robust accumulation of intracellular reactive oxygen species (ROS), an accumulation which, in other systems, has been shown to be essential for mitogenesis. Brief pretreatment of the cells with nerve growth factor (NGF) suppressed the EGF-mediated ROS increase. EGF failed to produce elevations in ROS in a PC12 variant stably expressing a dominant-negative p21(ras) construct (PC12-N17) or in cells pretreated with the MEK inhibitor PD098059. NGF failed to suppress the increase in ROS in the PC12 variant nnr5, which lacks p140(trk) receptors. The suppression of the increase in ROS by NGF was restored in nnr5 cells stably expressing p140(trk) (nnr5-trk), but NGF failed to prevent the increase in ROS in nnr cells expressing mutant p140(trk) receptors that lack binding sites for Shc and phospholipase Cgamma. Among several inhibitors of superoxide-generating enzymes, only the lipoxygenase inhibitor, nordihydroguaiaretic acid reduced EGF-mediated ROS accumulation. The inhibitory action of NGF on ROS production was mimicked by the nitric oxide donor, sodium nitroprusside, and was blocked by an inhibitor of nitric-oxide synthetase, L-nitroarginine methyl ester. These results suggest a novel mechanism for the rapid interruption of mitogenic signaling by the neurotrophin NGF.

Animals↗
PubMed1998

Antitumor effect of CD40 ligand: elicitation of local and systemic antitumor responses by IL-12 and B7.

The interaction between CD40 ligand (CD40L, CD154) and its receptor CD40 has been implicated in the establishment of cell-mediated immunity as well as humoral immune responses. To examine the role of CD40L in eliciting antitumor immunity, we introduced murine CD40L gene into P815 mastocytoma (CD40L-P815). CD40L-P815 cells underwent prompt rejection when inoculated s.c. into syngenic DBA/2 mice or athymic BALB/c nu/nu mice, which was mediated by NK cells and dependent on endogenous IL-12. The primary rejection of CD40L-P815 cells in DBA/2 mice elicited CD8+ T cell-mediated protective and systemic immunity against parental tumor cells, which was induced by CD4+ T cells and endogenous B7. These results indicated a potent antitumor effect of CD40L that is mediated by potentiation of host Ag-presenting cell functions, and introduction of CD40L will be useful as a new strategy of immuno-gene therapy against tumors.

Animals↗
PubMed1998

Identification of a novel bone morphogenetic protein-responsive gene that may function as a noncoding RNA.

Bone morphogenetic proteins (BMPs)/osteogenic proteins (OPs), members of the transforming growth factor-beta superfamily, have a wide variety of effects on many cell types including osteoblasts and chondroblasts, and play critical roles in embryonic development. BMPs transduce their effects through binding to two different types of serine/threonine kinase receptors, type I and type II. Signaling by these receptors is mediated by the recently identified Smad proteins. Despite the rapid progress in understanding of the signaling mechanism downstream of BMP receptors, the target genes of BMPs are poorly understood in mammals. Here we identified a novel gene, termed BMP/OP-responsive gene (BORG), in C2C12 mouse myoblast cell line which trans-differentiates into osteoblastic cells in response to BMPs. Expression of BORG was dramatically induced in C2C12 cells by the treatment with BMP-2 or OP-1 within 2 h and peaked at 12-24 h, whereas transforming growth factor-beta had a minimal effect. BMP-dependent expression of BORG was also detected in other cell types which are known to respond to BMPs, suggesting that BORG is a common target gene of BMPs. Cloning and sequence analysis of BORG cDNA and the genomic clones revealed that, unexpectedly, the transcript of BORG lacks any extensive open reading frames and contains a cluster of multiple interspersed repetitive sequences in its middle part. The unusual structural features suggested that BORG may function as a noncoding RNA, although it is spliced and polyadenylated as authentic protein-coding mRNAs. Together with the observation that transfection of antisense oligonucleotides of BORG partially inhibited BMP-induced differentiation in C2C12 cells, it is possible that a new class of RNA molecules may have certain roles in the differentiation process induced by BMPs.

Animals↗
PubMed1998

Early development of Epstein-Barr virus-associated T-cell lymphoma after a living-related renal transplantation.

We herein report a case of Epstein-Barr virus (EBV)-associated T-cell lymphoma that developed within a month after a kidney transplantation. The recipient was a 37-year-old man who had evidence of a previous EBV infection. Cyclosporine, methylprednisolone, and azathioprine were used for immunosuppression, and acute rejection was treated with high-dose methylprednisolone. The lactate dehydrogenase level started to increase on day 24 and thereafter peaked on day 37 while also demonstrating progressive jaundice and a bleeding tendency. A transplant nephrectomy was done on day 37; however, the patient could not recover and eventually died of respiratory failure as a result of diffuse pulmonary edema. A pathological examination of the resected kidney revealed a diffuse proliferation of large atypical lymphoid cells in the parenchyma. Immunohistochemically, the tumor cells were positive for CD45 and T-cell marker, CD45RO, but negative for B-cell markers. EBV-encoded RNA was demonstrated within the neoplastic cells by in situ hybridization.

Adult↗
PubMed1998

Recombinant murine interleukin-12 facilitates induction of cardiac myosin-specific type 1 helper T cells in rats.

Autoimmunity after viral myocarditis is considered to be one of the causes of dilated cardiomyopathy. Cytokines are assumed to play an important role in the pathogenesis. We recently reported that interleukin (IL)-2 and interferon (IFN)-gamma mRNA are expressed in the myocardium of rats with experimental autoimmune myocarditis (EAM). However, the role of cytokines in autoimmune myocardial injury in detail is still not clear. Reverse transcription-polymerase chain reaction identified IL-12 (p40) mRNA in antigen-presenting cells in the initial phase of EAM. Cardiac myosin-specific T lymphocytes (MSTLs) were cultured with cardiac myosin peptide (CMP) in the presence of IL-2 and/or IL-12 and were transferred to other naive rats. The results showed that EAM could be effectively induced by transfer of MSTLs cultured with IL-12, whereas transfer of MSTLs cultured with IL-2 was less effective. However, IL-2 acts synergistically with IL-12, and MSTLs cultured with both cytokines most efficiently induce EAM. In vitro experiments showed that MSTLs cultured with both IL-12 and IL-2 produced a much greater amount of IFN-gamma than did MSTLs cultured with either IL-12 or IL-2 alone. The amount of IFN-gamma production was correlated with pathogenicity of MSTLs. Transfer experiments after sorting further demonstrated that the transfer was affected by CD4+ helper T (Th) cells but not by CD8+ cytotoxic T lymphocytes. IL-12 and IL-2 synergistically enhance the pathogenicity of MSTLs. Furthermore, a type 1 Th (Th1) cytokine, IFN-gamma, which is a potent regulatory cytokine of autoimmunity, is produced by MSTLs. IL-12 and IL-2 potentiate the expansion of cardiac myosin-specific Th1 cells and play an important role in the development of autoimmune myocardial injury.

Animals↗