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Biomedical subjects

N Taniguchi

Publications and source records attributed to N Taniguchi.

At least 217 records · Page 12Linked to original sources

Dantrolene sodium reverses the increase in cAMP response element and TPA responsive element DNA-binding activity in the rabbit brain following haloperidol administration and heat stress.

Using electrophoretic mobility-shift assay (EMSA), we examined DNA-binding activity of cAMP response element (CRE), onto its responsive element CRE, as well as TPA responsive element (TRE) in the medial hypothalamus and striatum of the experimental rabbits administered with haloperidol under heat stress exposure and studied the effects of dantrolene sodium to the transcriptional factor. In EMSA with nuclear extracts from the rabbit brain, the DNA-binding activities of CRE and TRE in medial hypothalamus and striatum increased following haloperidol and heat stress. These increases were maintained by coadministration with atropine. The treatment with dantrolene sodium markedly reversed such increases. The alterations of activities of these transcriptional factors may reflect the therapeutic effect of dantrolene sodium.

Animals↗

High concentration of glucose increases mitogenic responsiveness to heparin-binding epidermal growth factor-like growth factor in rat vascular smooth muscle cells.

The effect of a high extracellular glucose concentration on the mitogenic response of rat vascular smooth muscle cells (SMCs) to heparin-binding epidermal growth factor-like growth factor (HB-EGF) was investigated. The mitogenic effect of HB-EGF was significantly greater in SMCs cultured in high glucose (25 mmol/L) than in cells cultured in low glucose (5.5 mmol/L) or at high osmolarity (5.5 mmol/L glucose plus 19.5 mmol/L mannitol). The mitogenic effect of epidermal growth factor (EGF), which shares the EGF receptor with HB-EGF, was not affected by glucose concentration. The mitogenic effect of HB-EGF was greater when incubated with heparan sulfate (HS) isolated from SMCs cultured in high glucose than with HS from cells cultured in low glucose. HS synthesized by cells in high glucose was of smaller molecular size and less sulfated than HS synthesized by cells in low glucose. The abundance of mRNA encoding HS-N-deacetylase/N-sulfotransferase (HS-NdAc/NST), a regulatory enzyme in the biosynthesis of HS, was decreased by high glucose in a protein kinase C-independent manner. These observations suggest that the enhanced mitogenic response to HB-EGF in SMCs cultured in high glucose may be attributable to changes in cell-associated HS. Downregulation of HS-NdAc/NST gene expression by high glucose may be related to the altered HS biosynthesis.

Animals↗

Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T lymphocytes.

Atherosclerotic lesions contain substantial numbers of activated T lymphocytes in addition to monocytes/macrophages. T cell-derived cytokines and growth factors may play a role in atherogenesis; however, stimuli responsible for T-cell activation in atherogenesis have not been fully elucidated. In this study, we provide evidence that lysophosphatidylcholine (lyso-PC), a polar phospholipid component increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate gene expression and secretion of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in cultured T lymphocytes isolated from human peripheral blood. Effects of lyso-PC on T lymphocytes appear to be selective and specific, since lyso-PC also increases interleukin (IL)-2 receptor expression but does not affect mRNA levels for IL-2 or IL-4. Lyso-PC-induced upregulation of HB-EGF and IL-2 receptor mRNA in peripheral T cells is mostly dependent on exogenous IL-2 in conditioned medium. The effect of lyso-PC on HB-EGF induction was more potent in CD4+ cells than in CD8+ cells, although lyso-PC increases IL-2 receptor expression dramatically in both CD4+ cells and CD8+ cells. Lyso-PC similarly increased HB-EGF expression in Jurkat cells, a cell line for human CD4+ T lymphocytes. These results in vitro suggest that lyso-PC may be an important stimulus for T cells in atherogenesis in vivo to upregulate HB-EGF and that T cell-derived smooth muscle growth factors may modulate atherosclerotic progression.

Biological Assay↗

Comparative ultrasonographic and angiographic study of carotid arterial lesions in Takayasu's arteritis.

The purpose of this study was to compare the usefulness of ultrasonography to that of angiography for studying arterial lesions in Takayasu's arteritis. Ultrasonographic and angiographic findings from 44 carotid arteries of 22 patients with Takayasu's arteritis (2 men and 20 women; mean age, 41.2 years) were compared. Angiography was used to classify the patency of the carotid arteries into three groups: nonstenotic, stenotic, and occlusive. Ultrasonography was also used to classify the same arteries into four groups: nonstenotic, mildly stenotic, moderately stenotic, and occlusive. Thickness of the wall (intima-media complex) of the carotid artery was measured with high-frequency transducers. Angiography showed 23 carotid arteries to be nonstenotic; 12, stenotic; and 9, occlusive; whereas ultrasonography showed 16 to be nonstenotic; 18, mildly stenotic; 7, moderately stenotic; and 3, occlusive. Results of the two diagnostic modalities correlated closely (P < 0.0001). Ultrasonography, aided by color flow imaging, detected six instances of a marginal but definite blood flow that angiography had failed to reveal. Arterial wall thickness correlated closely with the severity of ultrasonographic stenosis (P < 0.005). This thickness was 1.3 +/- 0.4 mm in the nonstenotic group, 1.6 +/- 0.5 mm in the mildly stenotic group, 2.2 +/- 0.8 mm in the moderately stenotic group, and 1.9 +/- 0.2 mm in the occlusive group. Even the walls of the nonstenotic arteries were significantly thicker than those of the normal carotid arteries (0.7 +/- 0.1 mm, P < 0.01). Ultrasonography appeared to be more useful than angiography in estimating stenotic severity of the carotid artery in Takayasu's arteritis. Characteristic ultrasonic findings included luminal stenosis or occlusion on two-dimensional ultrasonograms, decrease in or lack of flow shown by color Doppler flow imaging, and concentric thickening of the carotid arterial walls. Ultrasonographic mural thickness was the most sensitive indicator of early, latent inflammation.

Adult↗

Nitric oxide in the rat spinal cord in Freund's adjuvant-induced hyperalgesia.

To elucidate the involvement of nitric oxide in spinal nociceptive processing, the correlation of thermal withdrawal latency with nitric oxide synthase-stained neurons in the rat lumbar dorsal horn was analyzed after adjuvant-induced inflammation. From 4 hr through 5 days after subcutaneous injection of complete Freund's adjuvant into the hind paw, a marked thermal hyperalgesia was observed for heat stimulus applied to the affected region. NADPH-diaphorase- and nitric oxide synthase-positive neurons increased significantly in the superficial layers of the dorsal horn ipsilateral to the inflamed hind paw at day 3 of adjuvant-induced inflammation. No change in NADPH-diaphorase-positive neurons was observed at 1 hr and 1 day of adjuvant-induced inflammation. The intravenous administration of N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg), an inhibitor of nitric oxide synthase, significantly blocked the adjuvant-induced thermal hyperalgesia at day 3 of inflammation, but not at day 1; and it had no effect in non-inflamed rats. This anti-hyperalgesic effect of L-NAME at day 3 of inflammation was reversed by the prior administration of L-arginine (600 mg/kg, i.p.), a substrate of nitric oxide synthase. These data suggest that nitric oxide producing neurons in the spinal dorsal horn are involved in maintaining and facilitating the hyperalgesia associated with chronic nociception.

Animals↗

Chorioamnionitis reduces placental endocrine functions: the role of bacterial lipopolysaccharide and superoxide anion.

Chorioamnionitis has been shown to be one of the most important factors in inducing preterm delivery. The present study was undertaken to examine the effects of chorioamnionitis on placental endocrine functions. Preterm placentas with histologic chorioamnionitis produced smaller amounts of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) than those without chorioamnionitis (P < 0.001). To examine the mechanism involved in the suppression of placental endocrine functions induced by chorioamnionitis, we initially confirmed the expression of lipopolysaccharide (LPS) receptor, i.e. the CD14 molecule, on trophoblasts by Northern blot analysis and immunohistochemistry. We then stimulated purified trophoblasts with LPS, which is the major agent which induces inflammatory responses in the host via the LPS receptor. The trophoblasts stimulated with LPS produced reduced amounts of hCG, hPL, and progesterone in a time- and dose-dependent fashion in spite of the induced manganese-superoxide dismutase (SOD) synthesis. Stimulation of trophoblasts with hypoxanthine and xanthine oxidase resulted in suppressed hCG production, while the simultaneous addition of SOD into the culture medium reversed the suppression of hCG production. LPS in the placenta with chorioamnionitis might directly stimulate trophoblasts through the LPS receptor (CD14), thus reducing placental endocrine functions. Superoxide anions which exogenously act on trophoblasts might be generated by simultaneous stimulation of neutrophils and monocytes at the feto-maternal interface by LPS, and additively reduce placental endocrine functions.

Adult↗

Roles of purine nucleotides and adenosine in enhancing NOS II gene expression in interleukin-1 beta-stimulated rat vascular smooth muscle cells.

The production of nitric oxide (NO) by vascular smooth muscle cells (VSMC) is stimulated by interleukin-1 beta (IL-1 beta). This is enhanced in a dose-dependent manner by ADP, although it alone failed to induce nitrite accumulation. Purine nucleotides and their nonhydrolizable analogues as well as adenosine also exhibit variable enhancing effects. This enhanced nitrite formation was due to induction of the NO synthase (NOS II) gene as judged by Northern hybridization using an NOS II specific probe and by Ca2+ independency of the NOS II activity. 8-(p-Sulfophenyl)-theophylline, a blocker of adenosine receptors, suppressed the enhanced NO production by adenosine and ADP to the level of that with IL-1 beta alone. These data indicate that activation of the adenosine receptor on VSMC may enhance production of NOS II by modulating a signal transducing pathway of IL-1 beta. Although cAMP is a candidate as the second messenger, it was not significantly elevated by either ADP or adenosine treatment in IL-1 beta-stimulated cells. This mechanism might be stimulated under conditions with release of various purine and their derivatives.

Adenosine↗

Differentiation of renal cell carcinomas from angiomyolipomas by ultrasonic frequency dependent attenuation.

PURPOSE: We determined the usefulness of ultrasonic frequency dependent attenuation in differentiating hyperechoic renal cell carcinoma from angiomyolipoma. MATERIALS AND METHODS: Frequency dependent attenuation values were determined in 29 renal cell carcinomas and 13 angiomyolipomas. RESULTS: Frequency dependent attenuation values were significantly lower in renal cell carcinomas than in angiomyolipomas (0.42 versus 0.76 dB./cm./MHz.). Two of the renal cell carcinomas were as hyperechoic as the angiomyolipomas but they were clearly differentiated by the low frequency dependent attenuation. Two other renal cell carcinomas exhibited high values because of the abundance of fibrous tissue. However, they were readily diagnosed by the typical low echoic B-mode images. Frequency dependent attenuation did not differ between histological types of renal cell carcinoma. One angiomyolipoma that was poor in fat and rich in muscle components had an exceptionally low frequency dependent attenuation. Therefore, frequency dependent attenuation values can be regarded as an inversion of computerized tomography numbers. CONCLUSIONS: Frequency dependent attenuation measurement is a promising diagnostic aid in differentiating hyperechoic renal cell carcinomas from angiomyolipomas.

Adult↗

[Record and preservation of ultrasound images and computer-assistant analysis--estimation of digital filing system and texture analysis].

Digital filing systems have advanced with computer technology and are among the most interesting modalities for recording and preserving ultrasound images. The benefits are reduced expense, superior imaging, and ease in searching previous records compared with those factors in conventional constant film, videotape, and other storage systems. Computer-assisted analysis of digital images for automatic differentiation of diseases has recently been studied. Conventional quantitative estimation methods of tissue characterization or histogram are not easy to apply to clinical studies because these methods are time-consuming, and require a specialized machine for this propose. We propose a new method of texture analysis of echo images. This new method depends on the echo-texture of the organ, and can clearly differentiate liver cirrhosis from normal liver. These new digital techniques for clinical studies may facilitate examination.

Diagnosis, Computer-Assisted↗

Classification system of complications in neuroleptic malignant syndrome.

Our group treated 13 cases of neuroleptic malignant syndrome (NMS) over a period of 8 years. Based on the clinical severity of complications, the cases were classified into three types: mild, with no complications; moderate, with only respiratory disturbance; and severe, with respiratory disturbance and renal failure. The major complications affecting the prognosis of NMS are respiratory disturbance and renal failure. Renal failure is also associated with the occurrence of disseminated intravascular coagulation and rhabdomyolysis. The proposed classification system for NMS patients is useful in selecting the appropriate therapeutic strategy for this disorder. The clinical data were analyzed to determine the factors in the process of deterioration in NMS.

Adolescent↗

[Alcoholic effect on male sexual function].

Though an adequate volume of ethanol relieves nervousness and enhances sexual desire, acute administration of a great deal of ethanol suppresses central nervous system and causes sensory torpor and penile erectile dysfunction. Long term and excessive intake of ethanol causes central and/or peripheral neuropathy and sexual dysfunction; atrophy of testicles, low serum level of testosterone, impaired spermatogenesis and penile erectile dysfunction. It also invades various organs in digestive tract, cardiovascular system, central and peripheral nervous system and causes functional disorders in these organs. Successful treatment of patients with penile erectile dysfunction should be performed with treatment of these underlying and associated disease.

Adult↗

NS-49, an alpha 1A-adrenoceptor agonist, selectively increases intraurethral pressure in dogs.

The effects of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane sulfonanilide hydrochloride), an alpha 1A-adrenoceptor-selective agonist, on intraurethral pressure and blood pressure were investigated in anesthetized dogs. In addition, the contractile effects of NS-49 on the isolated dog urethra and carotid artery were compared with those of non-selective alpha 1-adrenoceptor agonists. Intravenously (i.v.) administered NS-49 at 0.3 microgram/kg or more significantly increased intraurethral pressure in a dose-dependent manner. Much higher doses of NS-49 were needed to increase blood pressure. In contrast, ST-1059 (1-(2',5'-dimethoxyphenyl)-2-aminoethanol) (an active metabolite of midodrine) at 30 micrograms/kg or more significantly increased both intraurethral pressure and blood pressure. NS-49 was 11-fold more selective for intraurethral pressure than ST-1059, NS-49, ST-1059, phenylephrine and noradrenaline caused concentration-dependent contraction of the isolated dog urethra. NS-49 caused only a slight contraction of the dog carotid artery even at high concentrations, whereas the reference drugs caused contractions of the artery with high efficacy. The alpha 1A-adrenoceptor-selective antagonists 5-methyl-urapidil and WB-4101 also showed high affinity for alpha 1-adrenoceptors in the dog urethra in inhibiting [3H]prazosin binding. In conclusion, the alpha 1A-selective agonist NS-49 selectively increased intraurethral pressure in dogs, and produced selective contraction of the dog urethra. These results suggest that the alpha 1A-adrenoceptor subtype is responsible for the contraction of the urethra and the regulation of intraurethral pressure, and that NS-49 might be useful for the treatment of stress incontinence with little effect on the cardiovascular system.

Adrenergic alpha-Agonists↗

"Free" iron in neonatal plasma activates aconitase: evidence for biologically reactive iron.

Plasma from certain preterm and term babies has recently been shown to contain low molecular mass iron (LMrFe) that can be chelated and measured in the bleomycin assay. The chemical nature of such iron, when detected in biological fluids, is still unclear with suggestions that it may not be a redox active form of iron until it becomes bound to bleomycin. Here we show that all plasma samples, from umbilical cord bloods, containing bleomycin-detectable iron, activated the enzyme aconitase in a cell-free system. It is, therefore, highly likely that LMrFe detected in the bleomycin assay is a biologically redox active form of iron.

Aconitate Hydratase↗

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level.

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.

Animals↗

Reducing sugars trigger oxidative modification and apoptosis in pancreatic beta-cells by provoking oxidative stress through the glycation reaction.

Several reducing sugars brought about apoptosis in isolated rat pancreatic islet cells and in the pancreatic beta-cell-derived cell line HIT. This apoptosis was characterized biochemically by inter-nucleosomal DNA cleavage and morphologically by nuclear shrinkage, chromatin condensation and apoptotic body formation. N-Acetyl-L-cysteine, an antioxidant, and aminoguanidine, an inhibitor of the glycation reaction, inhibited this apoptosis. We also showed directly that proteins in beta-cells were actually glycated by using an antibody which can specifically recognize proteins glycated by fructose, but not by glucose. Furthermore, fluorescence-activated cell sorting analysis using dichlorofluorescein diacetate showed that reducing sugars increased intracellular peroxide levels prior to the induction of apoptosis. Levels of carbonyl, an index of oxidative modification, and of malondialdehyde, a lipid peroxidation product, were also increased. Taken together, these results suggest that reducing sugars trigger oxidative modification and apoptosis in pancreatic beta-cells by provoking oxidative stress mainly through the glycation reaction, which may explain the deterioration of beta-cells under conditions of diabetes.

Acetylcysteine↗

Localization of heparin-binding epidermal growth factor-like growth factor in human coronary arteries. Possible roles of HB-EGF in the formation of coronary atherosclerosis.

BACKGROUND: Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a newly identified member of the EGF family. Our previous in vitro studies showed that HB-EGF is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs), suggesting the role of HB-EGF in the pathogenesis of atherosclerosis. The purposes of the present study were to investigate the localization of HB-EGF in both normal and atherosclerotic human coronary arteries and to elucidate the possible roles of this growth factor in the formation of atherosclerotic lesions. METHODS AND RESULTS: The immunohistochemical localization of HB-EGF, SMCs, macrophages, and EGF receptors (EGFRs) was examined in human coronary arteries obtained at autopsy. The medial SMCs of coronary arteries in neonates, infants, and children consistently synthesized HB-EGF protein. In normal adults, however, the relative number of HB-EGF-positive medial SMCs decreased gradually with age after about 30 years of age. In nonatherosclerotic coronary arteries with diffuse intimal thickening, SMCs of the intima, especially those located in the area of the medial side of the intima, were strongly positive for HB-EGF protein. In atherosclerotic plaques of coronary arteries with eccentric intimal thickening, both SMCs and macrophages in and around the core lesions, in addition to the intimal and medial SMCs located adjacent to the plaque, produced HB-EGF protein. A strong immunostaining of EGFRs was observed in these SMCs, suggesting a close association of HB-EGF and EGFR expression. CONCLUSIONS: These data suggest that HB-EGF might play important roles in the migration of SMCs from the media to the intima, the proliferation of intimal SMCs, and the interaction between SMCs and macrophages in the process of coronary atherogenesis.

Adult↗

Amino-terminal processing of cell surface heparin-binding epidermal growth factor-like growth factor up-regulates its juxtacrine but not its paracrine growth factor activity.

Human heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) expressed on Chinese hamster ovary (CHO) cells is synthesized as a 19-kDa major, and 22- and 27-kDa minor, membrane-anchored precursors (proHB-EGF). In contrast, the 27-kDa species is major and the 19- and 22-kDa ones are minor in mouse proHB-EGF. The juxtacrine growth factor activities of human and mouse proHB-EGFs on CHO cells toward EP170.7 cells in co-culture are significantly different. To investigate the relationship between the juxtacrine growth factor activities and the molecular species, we prepared human-mouse chimeras. Chimeras that have the human amino-terminal sequence with a mouse EGF-like domain showed approximately 8-fold up-regulation of the juxtacrine growth factor activity and the predominance of a 19-22-kDa major species. In contrast, chimeras that have the mouse amino-terminal sequence with a human EGF-like domain showed approximately 5-fold down-regulation of the juxtacrine activity and the predominance of the 27-kDa major species. A Gly32.HB-EGF (117-amino acid form), which is amino-terminally extended, induced the same mitogenic activity as that of Arg73.HB-EGF (75-amino acid form), which is amino-terminally truncated. These results strongly suggested that amino-terminal processing of human proHB-EGF would be required for up-regulation of its juxtacrine growth factor activity, but not for its paracrine activity.

Amino Acid Sequence↗