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Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 451 records · Page 25Linked to original sources

Histopathological and morphometrical comparison of granulomatous lesions in BALB/c and C3H/HeJ mice inoculated with Mycobacterium paratuberculosis.

Susceptibility to Mycobacterium paratuberculosis strain ATCC 19698 infection was compared histologically and morphometrically in BALB/c (Bcgs) and C3H/HeJ (Bcgr) mice. The granulomatous lesions, containing M. paratuberculosis, in the liver and spleen of BALB/c mice increased progressively until 32 weeks after intraperitoneal inoculation. In contrast, both the granulomatous lesions and number of bacteria decreased drastically in C3H/HeJ mice beginning at 6 weeks after inoculation. There were histological differences in granulomatous lesions between BALB/c and C3H/HeJ mice, indicating differing functional activity of cellular immunity. Intestinal lesions similar to those seen consistently in bovine paratuberculosis were observed first at 6 weeks after infection and later became disseminated widely, especially in BALB/c mice. Our results suggest that the innately susceptible BALB/c mice and the innately resistant C3H/HeJ mice may be useful and convenient models for further studies of immunoregulation and antimicrobial therapy of paratuberculosis.

Animals↗

Effects of various protease inhibitors on the intestinal absorption and degradation of insulin in rats.

The effects of protease inhibitors on the intestinal absorption of insulin were investigated in situ in closed small and large intestinal loops in rats, and the stability of insulin was examined in homogenates of the small and large intestine. The intestinal absorption of insulin was evaluated by its hypoglycemic effect. When insulin alone was administered into small or large intestinal loops, no marked hypoglycemic response was observed in either region. Of the coadministered protease inhibitors, soybean trypsin inhibitor (1.5, 10 mg/ml) marginally promoted insulin absorption from the large intestine, whereas aprotinin (10 mg/ml) did to a moderate degree. However, a significant hypoglycemic effect was obtained following large intestinal administration of insulin with 20 mM of Na-glycocholate, camostat mesilate and bacitracin, when compared with the controls. In contrast, we found little hypoglycemic effect following small intestinal coadministration of insulin with these protease inhibitors. In the stability experiment, bacitracin, camostat mesilate and Na-glycocholate were effective in reducing insulin degradation in both small and large intestinal homogenates. It was found that the reduction in the proteolytic rate of insulin was related to the decrease in plasma glucose concentration by these protease inhibitors in the large intestine. These findings suggest that coadministration of protease inhibitors would be useful for improving the large intestinal absorption of insulin.

Animals↗

Different modulation of protein kinase C isozymes in dibutyryl cyclic AMP-differentiated PC12h cells.

PC12h cells can be differentiated into sympathetic neuron-like cells by various agents, including nerve growth factor, basic fibroblast growth factor, cyclic AMP analogues, and protein kinase C (PKC) activators. To study the involvement of PKC in the process of PC12h cell differentiation by cyclic AMP treatment, PKC isozymes (alpha, beta I, beta II, and gamma) were analyzed using column chromatography and immunoblotting. Two PKC isozymes, PKC(alpha) and PKC(beta II), were predominantly detected in PC12h cells. When stimulated by dibutyryl cyclic AMP, PKC(alpha) levels declined in the cytosolic fraction of the cells, whereas PKC(beta II) levels increased. Increased PKC(beta II) levels were also detected in the particulate fraction, whereas particulate PKC(alpha) levels did not change. The total PKC activity decreased in the cytosolic fraction following cyclic AMP stimulation of PC12h cells, whereas it stayed constant in the particulate fraction. Fractionation on a hydroxyapatite column showed a decreased level of PKC(alpha) activity and a transient increase followed by a decreased level of PKC(beta II) activity. This discrepancy between increased PKC(beta II) immunoreactivity and reduced PKC(beta II) activity suggested the presence of nonactivatable PKC(beta II) in cyclic AMP-treated PC12h extract. These findings indicate that PKC(alpha) and PKC(beta II) are differentially regulated during the differentiation of PC12h cells. In addition, the differentiation of PC12h cells triggered by cyclic AMP seems to involve characteristic alterations of PKC isozymes.

Animals↗

Increased endothelium-dependent vascular relaxation in ethanol-fed rats.

We investigated the mechanism underlying increased relaxation of aortic strips to acetylcholine in rats chronically treated with ethanol. Rats were divided into three groups and maintained on liquid diets containing ethanol (35% of total calories) as the ethanol-fed group or an equicaloric volume of sucrose instead of ethanol as the sucrose-fed group for 10 weeks. The control group was also maintained on modified American Institute of Nutrition diet for the same period. Vascular strips of isolated rat aortas were mounted in organ chambers to record isometric tension. The endothelium-dependent relaxation responses to acetylcholine and calcium ionophore A23187 were greater in ethanol-fed rats than in control and sucrose-fed rats. However, the relaxation response to sodium nitroprusside or nifedipine did not differ among the three groups. Acetylcholine, calcium ionophore A23187, and sodium nitroprusside caused an increase in the cGMP contents of rat aortic strips that was similar among the three groups. These results suggest that a cGMP-independent relaxation mechanism is involved in the increased relaxation response to acetylcholine after chronic treatment with ethanol.

Acetylcholine↗

Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system.

Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I interferon (IFN) system; the former functions as a transcriptional activator, and the latter represses IRF-1 function by competing for the same cis elements. More recent studies have revealed new roles of the two factors in the regulation of cell growth; IRF-1 and IRF-2 manifest antioncogenic and oncogenic activities, respectively. In this study, we determined the structures and chromosomal locations of the human IRF-1 and IRF-2 genes and further characterized the promoters of the respective genes. Comparison of exon-intron organization of the two genes revealed a common evolutionary structure, notably within the exons encoding the N-terminal portions of the two factors. We confirmed the chromosomal mapping of the human IRF-1 gene to 5q31.1 and newly assigned the IRF-2 gene to 4q35.1, using fluorescence in situ hybridization. The 5' regulatory regions of both genes contain highly GC-rich sequences and consensus binding sequences for several known transcription factors, including NF-kappa B. Interestingly, one IRF binding site was found within the IRF-2 promoter, and expression of the IRF-2 gene was affected by both transient and stable IRF-1 expression. In addition, one potential IFN-gamma-activated sequence was found within the IRF-1 promoter. Thus, these results may shed light on the complex gene network involved in regulation of the IFN system.

Animals↗

Evidence for a critical role for the cytoplasmic region of the interleukin 2 (IL-2) receptor gamma chain in IL-2, IL-4, and IL-7 signalling.

The high-affinity interleukin 2 receptor (IL-2R) consists of at least three distinct subunits: the IL-2R alpha chain (IL-2R alpha), beta chain (IL-2R beta), and gamma chain (IL-2R gamma). It has been shown that the cytoplasmic region of IL-2R beta, but not of IL-2R alpha, is essential for IL-2 signalling to the cell interior. In the present study, we examined the functional role of the IL-2R gamma cytoplasmic region in the IL-3-dependent mouse hematopoietic cell line BAF-B03, which expresses the endogenous IL-2R alpha and IL-2R gamma, or its subline F7, which additionally expresses human IL-2R beta cDNA. We show that overexpression of a mutant IL-2R gamma, lacking all but 7 amino acids of its cytoplasmic region, results in the selective inhibition of IL-2-induced c-fos gene activation and cellular proliferation in F7 cells. When two chimeric receptor molecules in which the cytoplasmic regions of IL-2R beta and IL-2R gamma had been swapped with each other (IL-2R beta/gamma and IL-2R gamma/beta) were coexpressed in BAF-B03, the cells responded to IL-2. These results indicate the critical importance of the IL-2-induced functional cooperation of the two cytoplasmic regions. Finally, we provide evidence that the IL-2R gamma cytoplasmic region is also critical for the IL-4 and IL-7-induced growth signal transduction in BAF-B03.

Animals↗

Functional dissection of p56lck, a protein tyrosine kinase which mediates interleukin-2-induced activation of the c-fos gene.

Members of the newly identified receptor family for cytokines characteristically lack the intrinsic protein tyrosine kinase domain that is a hallmark of other growth factor receptors. Instead, accumulating evidence suggests that these receptors utilize nonreceptor-type protein tyrosine kinases for downstream signal transduction by cytokines. We have shown previously that the interleukin-2 receptor beta-chain interacts both physically and functionally with a Src family member, p56lck, and that p56lck activation leads to induction of the c-fos gene. However, the mechanism linking p56lck activation with c-fos induction remains unelucidated. In the present study, we systematically examined the extent of c-fos promoter activation by expression of a series of p56lck mutants, using a transient cotransfection assay. The results define a set of the essential amino acid residues that regulate p56lck induction of the c-fos promoter. We also provide evidence that the serum-responsive element and sis-inducible element are both targets through which p56lck controls c-fos gene activation.

Base Sequence↗

TGF-beta-induced macrophage colony-stimulating factor gene expression in various mesenchymal cell lines.

We report here that transforming growth factor-beta (TGF-beta) can increase the expression level of macrophage colony-stimulating factor (M-CSF) mRNA in a variety of mesenchymal cell lines derived from osteoblasts, bone marrow stromal cells, fibroblasts, and myoblasts. The M-CSF activity in the conditioned medium of mouse osteoblast-like MC3T3-E1 cells was increased by TGF-beta as well as interleukin-1 (IL-1) treatment. The increase of M-CSF mRNA expression was observed as early as 2 h after TGF-beta or IL-1 addition and was superinduced by cycloheximide treatment. Nuclear run-off assays revealed that the increase in M-CSF mRNA by TGF-beta as well as IL-1 occurred, at least in part, at the transcriptional level. Platelet-derived growth factor (PDGF) also enhanced the M-CSF production in MC3T3-E1 cells. Furthermore, TGF-beta and IL-1 distinctly induced both PDGF-A and PDGF-B chain mRNA in MC3T3-E1 with different time courses. Our present studies suggest that PDGF autocrine loop-dependent and loop-independent pathways could modulate the M-CSF production stimulated by TGF-beta or IL-1 and account for the complexity of the cytokine network involving M-CSF in vivo under various physiological and pathological conditions.

Animals↗

The role of brain-derived neurotrophic factor in transient forebrain ischemia in the rat brain.

Brain-derived neurotrophic factor (BDNF) may play a role in the pathophysiology of neuronal cell death after cerebral ischemia. We investigated alterations in BDNF gene expression and the effect of BDNF on neuronal death after transient forebrain ischemia in the rat brain. Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries and by producing systemic hypotension for 8 minutes. The alterations in the BDNF messenger ribonucleic acid content in the hippocampus and the cerebral cortex were examined by Northern blot analysis, using a phosphorus-32-labeled mouse BDNF complementary deoxyribonucleic acid probe. Recombinant Chinese hamster ovary cells with BDNF-secreting capacity were established by expression vector transfection with BDNF complementary deoxyribonucleic acid. The effect of BDNF on neuronal death in the hippocampal CA1 region after ischemia was then examined by using a continuous intraventricular infusion of 200 microliters of normal (Group II, n = 6) or 30-times concentrated recombinant Chinese hamster ovary cell culture medium containing BDNF (Group IV, n = 6). Normal (Group I, n = 6) or 30-times concentrated (Group III, n = 6) Chinese hamster ovary cell culture medium, not including BDNF complementary deoxyribonucleic acid, was infused into the same ischemic brains, which served as controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

4-acylaminophenol derivatives as novel lipoxygenase inhibitors: synthesis and inhibitory effect on 5-lipoxygenase and leukotriene B4 production.

Structure-activity relationships in the inhibitory effects of 4-acylaminophenol derivatives on the 5-lipoxygenase (5-LOX) from RBL-1 cells and leukotriene B4 (LTB4) production by guinea pig neutrophils were studied. When the N-acyl group was n-octanoyl or 2-thiophenecarbonyl and the size of the two ortho substituents of phenol was varied, the substituents bulkier than isopropyl, i.e., 2,6-di-tert-butyl and 2,6-dicyclohexyl, substantially weakened the inhibitory activity in both enzymatic and cellular systems. Among the 2,6-dimethyl derivatives with an acyl group of various carbon-chain lengths (C1-13), those with a n-alkyl chain of C5 to C12 showed similarly potent inhibitory activities toward 5-LOX with an IC50 ranging from 0.27 to 0.66 microM; in contrast, maximal inhibitory activities toward LTB4 production were observed in a narrower range of the serial compounds: i.e., those with a n-hexyl, n-heptyl, or n-octyl chain on the carbonyl carbon formed by far the most inhibitory group of the series and the inhibitory activity sharply decreased on either side of the chain length. Nearly all the active compounds also inhibited cyclooxygenase (COX), but the IC50 values for COX inhibition were more than ten times higher than the corresponding IC50 values for 5-LOX inhibition in most cases, indicating that the acylaminophenols are relatively selective 5-LOX inhibitors.

Aminophenols↗

Development of Theileria sergenti schizonts in the lymph node of experimentally infected cattle.

Schizogony of Japanese Theileria sergenti of cattle was studied by light and electron microscopy. Schizonts were detected in the draining lymph node between 4 and 8 days after sporozoite inoculation. Macroschizonts (the phase of nuclear division having invaginations) were formed 6 days after inoculation. Subsequently, microschizonts (the phase of merozoite formation displaying rosette-like appearance) were observed 8 days after inoculation. Multiple infections of a host cell with sporozoites were suggested to occur since different stages of schizonts were simultaneously detected in the same cell. Host cells of schizonts were considerably enlarged by parasitism. However, morphological characteristics of the developmental stages of T. sergenti schizonts resembled those of malignant Theileria species (e.g. T. parva). Schizogony of T. sergenti observed in this study seems to be the primary generation.

Animals↗

A risk-benefit assessment of drugs used in the management of glaucoma.

All antiglaucoma drugs are able to lower intraocular pressure (IOP) to variable degrees. However, all of them can possibly produce ocular and/or systemic adverse effects, some of which are not acceptable. Therefore, the drug or the combination of drugs which is efficacious enough to achieve the target IOP and have no or negligible adverse effects should be identified for each glaucoma patient, considering their ocular (e.g. the stage of glaucomatous damage, refraction) and systemic (e.g. age, cardiovascular disease) conditions.

Adrenergic Agonists↗

Effects of endothelin-1 on intraocular pressure and aqueous humor dynamics in the rabbit eye.

The effects of endothelin-1 (ET-1) on intraocular pressure (IOP) and aqueous humor dynamics were studied in the rabbit eye. The intravitreal injection of 10(-5) M ET-1 (20 microliters) produced a biphasic IOP response consisting of an initial rise of 1 to 2 hours in duration, and a subsequent prolonged reduction lasting for more than 96 hours. Aqueous humor dynamics were determined 24 hours after the 10(-5) M ET-1 injection. Aqueous humor formation, measured fluorophotometrically, was decreased by 58%. Total outflow facility increased by 94%, according to measurement by two-level constant pressure perfusion. The change of uveoscleral outflow determined by fluorescein-dextran perfusion was not significant. The decrease in aqueous flow and the increase in total facility accounted for most of the IOP reduction after the ET-1 injection. Endothelin, which is endogenously present in the eye, may play a role in the regulation of intraocular pressure.

Animals↗

Class II-restricted presentation of an immunoglobulin heavy-chain-gene product by a gene-transfected B-cell line.

The presentation of an antigen endogenously processed by B lymphocytes was investigated. The expression plasmid vectors, harboring genomic rearranged V genes from two monoclonal B cells and genomic mu-constant region gene, were constructed. Two B-cell lines, the MOPC104E myeloma mu-heavy chain expressing AMB line and the control hybridoma mu-heavy chain expressing AHB line, were established by gene transfection into A20.2J B lymphoma cell line. The cloned transfectant cell lines expressed surface and cytoplasmic IgM. Radioimmunoprecipitation analysis of surface IgM revealed that both cell lines used transfected mu-heavy chain and host-derived kappa-light chain. The T-cell line, MRT-2, specific for the MOPC104E protein, proliferated on AME B cell lines but not on control AHB-cell lines. MRT-2 proliferation was inhibited by anti-I-Ed,k,p,r but not by anti-I-Ad monoclonal antibody. Although the AME-transfectant lines secrete IgM into the culture medium, double chamber-type culture-experiments revealed that MRT-2 proliferation is not mediated by the uptake of secreted IgM. The results suggest that B cells process and present their own immunoglobulin heavy-chain V-region peptides to T cells in the context of MHC class-II molecules.

Amino Acid Sequence↗

Protein-tyrosine kinase p72syk is activated by platelet activating factor in platelets.

It has been demonstrated that activation of platelets by platelet-activating factor (PAF) results in a dramatic increase in tyrosine phosphorylation of several cellular proteins. We report here that p72syk is a potential candidate for the protein-tyrosine phosphorylation following PAF stimulation in porcine platelets. Immunoprecipitation kinase assay revealed that PAF stimulation resulted in a rapid activation of p72syk which peaked at 10 s. The level of activation was found to be dose dependent and could be completely inhibited by the PAF receptor antagonist, CV3988. Phosphorylation at the tyrosine residues of p72syk coincided with activation of p72syk. Pretreatment of platelets with aspirin and apyrase did not affect PAF induced activation of p72syk. Furthermore, genistein, a potent protein-tyrosine-kinase inhibitor, diminished PAF-induced p72syk activation and Ca2+ mobilization as well as platelet aggregation. These results suggest that p72syk may play a critical role in PAF-induced aggregation, possibly through regulation of Ca2+ mobilization.

Animals↗

Effects of vanadate on prostacyclin and endothelin-1 production and protein-tyrosine phosphorylation in human endothelial cells.

The ability of vanadate, an inhibitor of protein-tyrosine phosphatases, to affect the production of prostacyclin (PGI2) and endothelin-1 (ET-1) and protein-tyrosine phosphorylation in human umbilical vein endothelial cells (HUVEC) was studied. The addition of vanadate to monolayers of cultured HUVEC caused a sustained release of PGI2 from HUVEC in a time- and dose-dependent manner. When aspirin-treated HUVEC, which have lost the ability to increase PGI2 production in response to arachidonate, were incubated with vanadate, the cells recovered their ability to increase PGI2 production in response to arachidonate. This recovery of inducible PGI2 production in aspirin-treated HUVEC was completely inhibited either by cycloheximide, a protein synthesis inhibitor, or by actinomycin D, an RNA synthesis inhibitor. In contrast, the same concentration of vanadate suppressed the basal release of ET-1 from HUVEC. Vanadate also caused an increase in protein-tyrosine phosphorylation in HUVEC. These data indicate that vanadate induces opposite effects on PGI2 and ET-1 production with a concomitant increase in protein-tyrosine phosphorylation in HUVEC.

Endothelins↗

[Wegener's granulomatosis--report of four cases including two in patients who died of myocardial infarction].

The prognosis for Wegener's granulomatosis (W-G) is good if it is diagnosed early and a combination of corticosteroids and cytotoxic drugs is given. During the past fourteen years, we were encountered four cases of W-G, three were systemic and one was limited. Of the three patients, with systemic disease, two died of myocardial infarction caused by a delay in diagnosis and one died of fulminant renal and respiratory failure. Only the one patient with a limited form of the disease survived for more than 5 years. We emphasize the importance of early diagnosis with consideration of the systemic features of W-G.

Acute Kidney Injury↗