[ESWL therapy of pancreatic calculi].
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Adult↗
Biomedical subjects
K Goto
Publications and source records attributed to K Goto.
Level of ETB receptor mRNA is down-regulated by endothelins through decreasing the intracellular stability of mRNA molecules.
Using ROS17/2 rat osteosarcoma cells as a model system, we examined the possibility that endothelin (ET)-induced down-regulation of ETB receptor was accompanied by a decrease in levels of ETB receptor mRNA. Northern blot analysis showed that low doses of ET-1 and ET-3 caused a transient decrease in ETB receptor mRNA in the cells. The maximum decrease in the levels of ETB receptor mRNA (80%) occurred after 2-4 h of exposure of the cells to ETs and was followed by a gradual recovery to control levels by 24 h. The effects were dose-dependent (EC50-1 nM), and ET-1 and ET-3 were almost equipotent in eliciting the response. The addition of either ionomycin, a Ca2+ ionophore, or phorbol dibutyrate, a protein kinase C activator, mimicked the effect of ETs. These results suggested that ETs-induced down-regulation of ETB receptor mRNA was mediated by the activation of ETB receptor and that it may have involved ETB receptor coupled second messenger pathways. We also showed that ETB receptor mRNA had a long intracellular life span which suggested that ETs-induced down-regulation of ETB receptor mRNA may have been due to a decrease in the stability of mRNA, rather than inactivation of the transcription of mRNA.
Animals↗
Action of endothelin-1 on rat astrocytes through the ETB receptor.
We investigated the effect of ET-1 on the state of rat cerebral astrocytes (AC) differentiation. AC ceased to proliferate and changed into its differentiated state by treatment with dibutyryl cyclic AMP (DBcAMP). The cell growth activity in DBcAMP-treated AC was stimulated by ET-1 in a dose-dependent manner. Over similar dose ranges, ET-1 suppressed the glutamine synthetase activity in DBcAMP-treated AC. The molar potency of ET-1 in this action was at least 3 orders of magnitude higher than that in mitogenic action in AC under the proliferative state previously reported. Northern blot analysis revealed that ETB receptor mRNA level in DBcAMP-treated AC was markedly higher than that in AC untreated with DBcAMP. Consistently, binding studies showed that the Bmax value for [125I]ET-1 in DBcAMP-treated AC was 16 times higher than that in AC untreated with DBcAMP. These results suggest that ET-1 potently induced a retraction of the differentiation state of AC from fully the specialized state and that the high responsiveness of differentiated AC to ET-1 was partly attributed to the high level expression of the ETB receptor.
Animals↗
Cloning and expression of rat preproendothelin-3 cDNA.
We report here the cloning and expression of a rat full-length cDNA encoding preproendothelin-3 (preproET-3). The predicted rat preproET-3 consisted of 167 amino acid residues. As in other ET-family peptides, the mature rat ET-3 was predicted to be produced through unusual processing from a 41-residue intermediate, the big ET-3 in rat. Transient transfection of COS-7 cells with the cloned preproET-3 cDNA resulted in the production of mature ET-3 and this production was inhibited by phosphoramidon, a metaloprotease inhibitor. This suggested that a phosphoramidon sensitive mechanism was involved in the production of ET-3 in the transfected COS-7 cells. Northern blot analysis showed that an approximately 3.0-kb rat preproET-3 mRNA was expressed in rat tissues, including the eye ball, submandibular gland, brain, kidney, jejunum, stomach and spleen. A 2.0-kb and a 3.3-kb mRNA were also detected in the eye ball and small intestine, respectively. The distinct distribution of rat preproET-3 mRNA from that of preproET-1 mRNA suggested that ET-1 and ET-3 played different roles.
Amino Acid Sequence↗
Calcitonin gene-related peptide in the regulation of cardiac function.
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Animals↗
Physiology and pharmacology of endothelins.
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Endothelins↗
Age- and sex-related variation of plasma endothelin-1 concentration in normal and hypertensive subjects.
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Adult↗
Sequential changes in electroencephalogram continuity in very premature infants.
This study was conducted to quantify sequential changes in electroencephalogram (EEG) continuity for 24 h in very premature infants. For a total of 122 days, continuous 2-channel EEG recording was conducted for 28 premature infants from 26 to 33 weeks of conceptional age (CA). None of the infants showed evidence of neurological impairment during hospitalization. Normal neurological outcome was noted at a minimum 12 months of age. By classifying each 5.5 min epoch according to EEG continuity, the number of contiguous epochs of each series of discontinuous type (DTs) and the number of epochs between two series of discontinuous type (IDTIs) were counted at each CA. The duration of DT decreased with increasing CA. The mean duration remained at 13-16 min after 29 weeks CA. The mean duration of each IDTI increased with CA, up to about 1 h at 33 weeks. A constant period of DTs was noted at longer intervals with increasing CA. These changes appear related to the development of sleep state organization with CA.
Brain↗
Increased plasma concentration of endothelin-1 in cholesterol-fed rats.
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Animals↗
Vasoconstrictor effects of endothelin-1 on myocardium microcirculation studied by the Langendorff perfusion method: differential sensitivities among microvessels.
An intravital fluorescence microscope system was used to investigate the pharmacological effects of endothelin-1 (ET-1) on the coronary microcirculation in the isolated beating hearts of rats. The heart was perfused by retrograde aortic steady flow with an oxygenated Krebs-Ringer solution containing FITC-dextran. Changes in diameters of coronary microvessels accompanying the cumulative injection of ET-1 in the perfusate were observed and recorded with a video camera system. Coronary perfusion pressure was also measured during each experiment. Bolus injections of ET-1 (1-300 pmole) elicited a dose-dependent increase in perfusion pressure from 54 +/- 6 mm Hg (mean +/- SEM; n = 10, before the ET-1 injection) to 144 +/- 9 mm Hg (n = 8, at the ET-1 dose of 300 pmole). A dose-dependent narrowing of microvessels was also observed. This vasoconstriction was especially prominent in small-sized arterioles; the maximum vasoconstriction of the smaller arterioles was significantly higher than that of the larger arterioles (P less than 0.05). The response induced by ET-1 dose of 3-10 pmole was significantly larger in arterioles than in postcapillary venules in the diameter range between 10 and 40 microns. The vasoconstriction produced by ET-1 was inhomogeneous. Some part of bifurcations of arterioles showed a prominent localized vasoconstriction, and occasionally showed a complete luminal obstruction. Such a segmental vasospasm might be attributed to localized sensitivities of arterioles to ET-1. These findings suggest that ET-1 may have an important role in governing the coronary resistance and regulating the capillary flow in the myocardium.
Animals↗
Localization of gene expression of calreticulin in the brain of adult mouse.
The localization of gene expression of calreticulin, a calcium-binding protein in the endoplasmic reticulum, was examined throughout the entire brain of adult mice by in situ hybridization. Calreticulin mRNA is expressed widely and heterogeneously in discrete neurons throughout the brain, but the white matters expressed it weekly or faintly. In the olfactory bulb, the mRNA is expresses moderately in the mitral cells, but weakly in the periglomerular cells and internal granule cells. In the cerebrum, the gene is expressed intensely in the piriform cortex, but weakly in neocortex, the entorhinal cortex and the amygdaloid nuclei. In the hippocampal formation, calreticulin mRNA is expressed intensely in the CA1-CA3 regions but less intensely in the granule cells of the dentate gyrus. The caudate-putamen, thalamic and hypothalamic nuclei, and mammillary nuclei express the mRNA weakly or faintly. In the mesencephalon, pons and medulla, moderate expression of the mRNA is detected in the pontine nuclei and the locus ceruleus. Weak expression of the mRNA is detected in several discrete nuclei and zones such as the substantia nigra, the superior colliculus and the central gray. Expression signals of calreticulin mRNA are faint in the inferior olive. In the cerebellum, calreticulin mRNA is expressed moderately in the Purkinje cells whereas no significant expression is detected in the granule cells. The plexus choroideus of the lateral, third and fourth ventriculi express calreticulin mRNA intensely although no distinct expression of the mRNA is discerned in the ependyma.
Animals↗
Gene cloning, sequence, expression and in situ localization of 80 kDa diacylglycerol kinase specific to oligodendrocyte of rat brain.
A 3.1 kbp cDNA clone encoding diacylglycerol (DG) kinase of 80 kDa (80K-DG kinase) was isolated from a rat brain cDNA library. The deduced amino acid sequence was 82% homologous to previously identified porcine 80K-DG kinase and contained zinc finger-like sequences, E-F hand motifs and ATP-binding sites similar to the porcine counterpart. By in situ hybridization histochemistry of rat brain at postnatal week 3, the expression signals for 80K-DG kinase mRNA appeared predominantly on somata of discrete cells in the white matter, and the expression pattern was similar to that of the myelin-specific proteins. In immunohistochemistry using the antibody against bacterially expressed DG kinase-fusion protein, numerous fibrous or dot-like structures exhibiting the immunoreactivity were concentrated in the white matter and they were arranged to radiate in the cerebral cortex and the cerebellar granular layer in a pattern almost identical to that of oligodendrocytes. No neuronal cells exhibited the immunoreactivity. The present finding thus strongly suggests that 80K-DG kinase is expressed specifically in the oligodendrocytes, but not neurons, and may be involved in the myelin formation and metabolism. In addition, the intense hybridization signals and the immunoreactivity for this protein were detected in the entire medulla of the thymus and the periarterial lymphatic area of the splenic white pulp both of which represent T-cell-dependent areas.
Amino Acid Sequence↗
Enhancement of host defense by Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, a novel synthetic compound. A comparison with recombinant human granulocyte colony-stimulating factor in 5-fluorouracil-treated mice.
The effect of a novel synthetic compound, Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, on recovery from long-lasting leukopenia induced by 5-fluorouracil was compared with that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). When mice were administered i.p. with 5-FU (200 mg/kg) on days 0 and 7, intravenous administration of Y-25510 (100 and 1000 micrograms/kg) prevented the decrease in the peripheral leukocyte and neutrophil number and accelerated the recovery from leukopenia. Subcutaneous administration of rhG-CSF (50 micrograms/kg) did not prevent leukopenia but accelerated the recovery from leukopenia. In particular, peripheral neutrophil number increased over a normal level. The administration of Y-25510 (10, 100 and 1000 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, lymphocytes, neutrophils and monocytes. The administration of rhG-CSF (50 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, and neutrophils but not that of lymphocytes and monocytes. In fractions of bone marrow cells on day 21, the administration of Y-25510 (1000 micrograms/kg) showed a tendency of restoring the decrease in neutrophil number. In conclusion, the administration of Y-25510 prevented leukopenia and accelerated the recovery from leukopenia in the 5-FU-treated mice. It is suggested that the mechanism of the restorative action of Y-25510 is different from that of rhG-CSF. In a number of immature bone marrow cells Y-25510 has a potent stimulatory effect on the recovery from the decrease in number of hematopoietic cells, keeping a balance in number of each blood cell.
Adjuvants, Immunologic↗
A revised method of conservative palatoplasty.
A revised method of conservative palatoplasty was performed on 21 patients with isolated cleft palate. The operation was principally based on von Langenbeck's method. The major modifications were that the mucosal layer was dissected instead of the mucoperiosteum and lateral mucosal deficits produced by medial displacement of the dissected mucosal flaps were covered with transpositioned buccal mucosal flaps. Postoperative early results were compared with those of the 23 patients treated by Perko's mucosal flap operation. Our method was found to bring about a relatively long velum comparable to Perko's method and wound healing was more uneventful. Results at the age of 5 years were compared with those of the patients treated by Wardill's mucoperiosteal flap operation as well as with those treated by Perko's method. There were no statistically significant differences among the three groups in the maxillofacial development and speech results.
Child, Preschool↗
Severe type Hunter's syndrome. Polysomnographic and neuropathological study.
The clinico-pathological and polysomnographical findings of an adult male patient with severe type of Hunter's syndrome are presented. He died of respiratory failure aged 19, which was much older than the average in this disease. Mucopolysaccharidosis was suspected at the age of one year, and diagnosed by leucocyte enzyme assay at 4 years of age. Mental and physical activity gradually deteriorated until his death. He often showed central type sleep apnea during the sleep stage 2, in addition to common obstructive apnea in Hunter's syndrome. The autopsy showed marked fibrous thickening of the endocardium and valves, enlargement of the liver and spleen, dilatation of the lateral ventricles and diffuse atrophy of the brain. Histologically, diffuse cytoplasmic vacuolations were found in fibroblast-like cells in the thickened endocardium and vascular walls, in Kupffer cells, and in many neurons of the central and peripheral nervous systems. Most neuronal inclusions were considered to be a ganglioside, and in other cells to be a mucopolysaccharide, by their ultrastructure. Massive accumulation of ganglioside in the neurons in the respiratory center might be reflected on central type sleep apnea.
Adult↗
Intraarterial infusion chemotherapy with [Sar1,Ile8]angiotensin II for bladder cancer.
Thirty-three patients with primary bladder cancer (nine stage T1 with multifocal tumors and 24 stage T2-4) were treated with intraarterial infusion chemotherapy including cisplatin, doxorubicin, and [Sar1,Ile8]Angiotensin II(AT II). Of the 32 evaluable patients, 12 had pathologically proven complete response (CR), 19 showed partial response (PR), and one showed no change (NC); the overall response rate (CR + PR) was 97%. The blood pressure increased in response to the administration of [Sar1,Ile8]AT II in all the patients; the mean increase in the systolic blood pressure was 36 mmHg. Most of the side effects were mild to moderate in severity, transient in nature, and included nausea/vomiting (100%), alopecia (84%), leukopenia (66%), headache (9%), nephrotoxicity (6%), diarrhea (3%), skin pigmentation (3%), and neurotoxicity (3%). One patient who dropped out of the study developed hemiplegia as a result of cerebral infarction. The findings indicate that it is necessary to exercise caution in selecting the patients to be subjected to this therapy. We conclude that intraarterial infusion chemotherapy combined with a vasoconstrictor has a significant effect not only against multifocal superficial bladder cancer but also against invasive bladder cancer.
1-Sarcosine-8-Isoleucine Angiotensin II↗
A pertussis toxin-sensitive mechanism of endothelin action in porcine coronary artery smooth muscle.
1. Endothelin-1 (ET-1)-induced contraction of porcine coronary artery strips may be mediated via at least two intracellular signalling mechanisms, the activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels and the stimulation of phosphoinositide breakdown. Here we have investigated the possible involvement of pertussis toxin (PT)-sensitive guanosine-5'-triphosphate (GTP)-binding proteins (G-proteins) in ET-1-induced activation of these two signalling pathways in porcine coronary artery smooth muscle. 2. Increase in extracellular K+ concentration (10, 15 mM) shifted the dose-response relationship for the ET-1-induced contraction to the left. 3. The dihydropyridine Ca2+ channel blocker, nifedipine (10(-8) M), induced a rightward shift in the dose-response curve for ET-1. Pretreatment of the arterial strips with PT (0.1 microgram ml-1) induced a similar rightward shift of the ET-1 dose-response curve but not of the KCl response. Nifedipine (10(-8) M) did not further attenuate the ET-1-induced contraction in the PT-pretreated strips. 4. The pretreatment with PT significantly reduced 45Ca2+ uptake of the arterial strips stimulated by ET-1, but had no effect on ET-1-induced production of inositol phosphates. 5. The contractile response of the arterial strips to phorbol dibutyrate, an active phorbol ester, was not significantly affected by 10(-8) M nifedipine. 6. We confirmed that the pretreatment of the tissue with PT induced ADP-ribosylation of a 41 kDa membrane protein. 7. These findings indicate that activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels by ET-1 in this tissue is mediated via a PT-sensitive G-protein in a manner apparently independent of the ET-1-induced activation of protein kinase C. It is concluded that the action of ET-1 in porcine coronary artery is mediated via two distinct signal transduction pathways, which are coupled to PT-sensitive and PT-insensitive GTP-binding proteins, respectively.
Adenosine Diphosphate Ribose↗
Effects of endothelin-1 and conversion of big endothelin-1 in the isolated perfused rabbit lung.
We examined the effects of endothelin-1 (ET-1) on pulmonary hemodynamic and transvascular fluid filtration and the conversion of big endothelin-1 (big ET-1), a precursor of ET-1, in isolated perfused rabbit lungs at constant vascular and airway pressures. Furthermore we examined whether ET-1 contributes to cyclooxygenase metabolism. The perfusate flow decreased significantly after bolus administration of 1 or 0.1 nmol of ET-1. Lung weight did not increase throughout the experimental period. Big ET-1- (1 nmol) induced decrease in the flow was slow in developing, although the maximum response was comparable to that induced by the same dose of ET-1. The concentration of bit ET-1 in the perfusate progressively decreased, while that of ET-1 increased in a time-dependent manner. Phosphoramidon, an inhibitor of metalloproteinase, suppressed the pressor effect of big ET-1 (P less than 0.01) and the increase in the concentration of ET-1 in the perfusate (P less than 0.05). The present findings provide the first evidence suggesting that the potent vasocontractile effect of big ET-1 in pulmonary circulation can be attributed to the production of ET-1 by the conversion from big ET-1 in the vascular bed. ET-1-induced perfusate flow changes were not affected by indomethacin, and the concentration of 6-ketoprostaglandin F1 alpha, a metabolite of prostacyclin, did not increase after ET-1 administration.
Animals↗