[Opioid receptors--structures, functions and distributions].
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Amino Acid Sequence↗
Biomedical subjects
M Satoh
Publications and source records attributed to M Satoh.
EM574, an erythromycin derivative, is a potent motilin receptor agonist in human gastric antrum.
Erythromycin and its derivatives are known to induce phase III-like contractions, which are similar to those induced by motilin, in the human gastrointestinal tract during the interdigestive state, but few detailed in vitro studies have been reported. We evaluated EM574, an erythromycin derivative, as a motilin receptor agonist in the human gastric antrum in vitro, using contraction studies of muscle strips and isolated myocytes, receptor binding assay and tissue section autoradiography. EM574 stimulated contractions of muscle strips in a concentration-dependent manner (10(-7)-10(-5) M), and this contractile effect was unaffected by pretreatment with atropine or tetrodotoxin. Isolated myocytes contracted in response to EM574 with a peak shortening at 10(-7) M, which was comparable to the response to motilin. EM574 displaced specifically 125I-motilin bound to smooth muscle homogenates with a Kd value of 7.8 x 10(-9) M, compared with 4.5 x 10(-9) M for motilin. Film autoradiograms showed that 125I-motilin-binding sites were localized in the muscle layers, and that the labeling disappeared in the presence of a 1000 times molar concentration of EM574. We conclude that EM574 directly stimulates smooth muscle cell contraction by acting on motilin receptors in the human gastric antrum in vitro.
Autoradiography↗
[A case of pulmonary actinomycosis; histological diagnosis obtained from transbronchial lung biopsy specimen].
We report the first case of pulmonary actinomycosis that was diagnosed by histological findings of transbronchial lung biopsy specimen. A 60-year-old man was admitted because of cough and bloody sputa. His chest roentgenogram and CT scan revealed a cavitary opacity in the apex of the left lung. Histological findings of the biopsy specimen showed multiple basophilic actinomyces granules accompanied by an acute inflammatory exudate, confirming the diagnosis of pulmonary actinomycosis. We prescribed antibiotic treatment and a good response was obtained.
Actinomycosis↗
[Experimental techniques for developing new drugs acting on dementia (3)--Experimental methods on the long-term potentiation].
Long-term potentiation (LTP) in the hippocampus is a long-lasting enhancement of excitatory synaptic transmission that follows brief tetanic stimulation of afferent fibers, and a candidate of neuronal substrata of learning and memory. Therefore, intensive studies have been done to elucidate the mechanism of LTP and to search for drugs having effects on LTP production. So far, we have found that LTP in mossy fiber-CA3 system of guinea pig hippocampal slices was susceptible to some neurotransmitters and nootropics, which are shown to improve learning deficiency in rodents. In the present paper, we detailed recording devices, experimental procedures and analysis of data in our laboratory. Using this experimental system, the effects of cholinergic agents on LTP of field EPSP in a mossy fiber-CA3 system were examined. A muscarinic M1-receptor antagonist pirenzepine and an M2 antagonist, AF-DX 116, at an examined concentration inhibited and facilitated, respectively, the LTP induction with no change in field EPSP amplitude evoked by test stimuli in the absence of tetanus. Thus, our experimental methods described here appear feasible for developing medication for dementia.
Animals↗
Onset of polymyositis with autoantibodies to threonyl-tRNA synthetase during pregnancy.
A 24-year-old black woman developed polymyositis with autoantibodies to threonyl-tRNA synthetase in the 2nd trimester of her 3rd pregnancy. This was complicated by fetal loss and the development of severe relapsing myositis resistant to corticosteroid and azathioprine therapy. These features were also common in other cases in the literature. Antisynthetase antibodies had not been reported in myositis occurring during pregnancy and may be of interest regarding the pathogenesis of inflammatory myopathy complicating pregnancy.
Adult↗
Genetic and immunological differences between Japanese patients with diffuse scleroderma and limited scleroderma.
OBJECTIVE: To study the association between HLA-DR and scleroderma (SSc), subsets of SSc, and autoantibodies in SSc. METHODS: HLA-DR antigens were determined in 45 Japanese patients with SSc. The association between HLA-DR and SSc, subsets of SSc, and autoantibodies was analyzed in 22 patients with SSc excluding mixed connective tissue disease (MCTD)/overlap syndrome (OL). RESULTS: When the 20 patients with MCTD and 3 patients with OL were excluded from the original patient group, a significant increase of HLA-DR2 was observed (59 vs 29% of controls, p < 0.01). The frequency of DR2 increased to 69% in patients with diffuse SSc (p < 0.01). DR1, which was not found in diffuse SSc, was found in 2 of 9 patients with limited SSc. The frequency of DR2 was significantly higher in patients with antitopoisomerase I (10/12, 83%, p < 0.05). In contrast, DR1 was found only in 2 patients with anticentromere antibodies (ACA), and all 5 patients with ACA had no HLA-DR2 (p < 0.01). CONCLUSION: Our results suggest that different HLA-DR markers may be associated with the production of distinct autoantibodies in diffuse SSc and limited SSc.
Antibodies↗
Systemic lupus erythematosus. Antibodies to DNA, DNA-binding proteins, and histones.
Pathogenic autoantibodies to DNA are frequently associated with autoantibodies to chromatin-associated proteins such as histones or the Ku (p70/p80) antigens. In view of the increasing evidence that autoantibody production is antigen-driven, and because DNA is packaged with proteins in the cell, we suggest that anti-DNA antibodies may arise in response to DNA-protein complexes rather than naked DNA. Recent studies of the specificities of autoantibodies directed against the components of nucleosomes and transcriptional complexes are consistent with this hypothesis. The possible clinical significance of immune recognition of various types of chromatin complexes in autoimmune disease is discussed.
Antibodies, Antinuclear↗
[Quadricuspid aortic valve: three case reports and review of the literature].
Three patients with grade 3 aortic regurgitation caused by rare congenital quadricuspid valve underwent aortic valve replacement. Patients were two females (51 and 45 years old) and a 51 year-old male. The first case showed 2 equal larger and 2 equal smaller valves. In the latter two cases, 4 equal sized cusps were noted. Fibrous trabeculations bridging the aortic wall and the commissures, giving an appearance of a hammock, were noted in the third case. Small fenestations were also noted in two cusps in this case. These findings may suggest dysplastic feature of the quadricuspid aortic valve. Hypertension seemed to have played an important role in the occurrence of regurgitation in their 4th or 5th decade of life. Their postoperative courses were uneventful.
Aortic Valve↗
[A case of lung cancer with axillary nodal involvement].
A 57-year-old man with lung cancer was reported. Primary tumor was located at left S1+2, and directly invaded to chest wall (from 1st. rib to 4th rib). Hypercalcemia and delirium were observed. Whole body examination showed that no distant metastasis except for nodal swelling of left axillary region. Left upper lobectomy combined with chest wall resection was performed. Hilar, mediastinal and axillary nodes were also dissected. Histological examination revealed that nodal involvement was not present at neither hilar or mediastinal region, but was present in axillary node. It was thought that lymphatic extension had occurred from trough chest wall to axillary nodes but not through mediastinal rout. So systematic dissection of locally invaded region as well as hilar and mediastinal region was recommended in each cases.
Axilla↗
The effect of percutaneous ethanol injection therapy on small solitary hepatocellular carcinoma is comparable to that of hepatectomy.
OBJECTIVES: Forty patients with solitary hepatocellular carcinoma (HCC) smaller than 20 mm in diameter were admitted to our hospitals from March 1986 to December 1989. Of that 40 patients, 17 were treated with hepatectomy, 12 with percutaneous ethanol injection therapy, and 11 with the combination of percutaneous ethanol injection therapy and transcatheter arterial embolization. METHOD: Following up the patients after their first treatment for 2 months to 6 yr, as of April 30, 1993, we evaluated the effects of hepatectomy, percutaneous ethanol injection therapy, and the combination of percutaneous ethanol injection therapy and transcatheter arterial embolization. RESULTS: Of the 23 patients who did not undergo surgery, eight died from recurrence of HCC and one died from ruptured varices. Of the 14 surviving patients, 10 experienced recurrences during the follow-up period. Of the 17 patients who underwent surgery, one died in hospital and four died from recurrence of carcinoma. Of the remaining 12 patients, nine experienced recurrences. The cumulative survival and recurrence rates were similar in operated and nonoperated patients. There was no significant difference in these rates in patients treated with versus without transcatheter arterial embolization. CONCLUSION: Our results showed that the efficacy of hepatectomy and the efficacy percutaneous ethanol injection therapy for small solitary HCC were similar. However, percutaneous ethanol injection therapy was safer and less expensive than hepatectomy.
Carcinoma, Hepatocellular↗
Cytokines affecting survival and differentiation of an astrocyte progenitor cell line.
The effects of various cytokines on survival and differentiation of an astrocyte progenitor cell line (AP-16) were examined. Epidermal growth factor (EGF) deprivation caused death of AP-16 cells by apoptosis. Transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) prevented the apoptosis occurring in the absence of EGF. Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) induced glial fibrillary acidic protein (GFAP) and decreased A2B5 antigen in AP-16 cells, indicating that these cytokines induced AP-16 cells to differentiate into astrocytes.
Animals↗
In situ hybridization study of kappa-opioid receptor mRNA in the rat brain.
Distribution of kappa-opioid receptor mRNA in rat brain was examined by in situ hybridization technique. kappa-Opioid receptor mRNA was expressed in various brain regions, especially intensely in the neocortex (layer V and VI), caudate-putamen, nucleus accumbens, preoptic area, paraventricular thalamic nucleus, amygdala, several nuclei of hypothalamus, ventral tegmental area and substantia nigra pars compacta.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Prevention of carcinogenicity of anticancer drugs by metallothionein induction.
We examined the efficacy of metallothionein induction in the prevention of the carcinogenic action of cis-platinum and melphalan administered repeatedly to mice over a relatively long period. The increased pulmonary metallothionein induced by bismuth or zinc compounds during the period of chemotherapy with cis-platinum or melphalan protected the mice from carcinogenesis of these drugs in the lung. These results suggested the efficacy of metallothionein inducers in suppression of carcinogenicity considered as a secondary effect of anticancer agents in cancer chemotherapy.
Animals↗
Role of somatostatin in the augmentation of hippocampal long-term potentiation by FR121196, a putative cognitive enhancer.
N-(4-Acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide (FR121196), a newly introduced putative cognitive enhancer of a derivative of piperazine, was investigated for its effects on long-term potentiation in guinea-pig hippocampal slices. The magnitude of long-term potentiation of population spikes recorded in CA3 pyramidal neurons was significantly augmented by perfusing FR121196 (10(-9)-10(-6) M) for 25 min before and during tetanic stimulation of the mossy fibers; the basal amplitude of population spikes before tetanus was hardly affected by the drug. The dose-response curve was bell-shaped with a maximal augmentation at 10(-7) M. Similar activity and bell-shaped dose-response curve were observed with methamphetamine (10(-8)-10(-6) M). Physostigmine (10(-8)-10(-6) M) also facilitated long-term potentiation of this pathway and the magnitude of augmentation was concentration-dependent. Scopolamine (10(-6) M) per se had little effect on the magnitude of long-term potentiation in the mossy fiber-CA3 pathway, but significantly attenuated its enhancement by FR121196 (10(-7) M) and physostigmine (10(-6) M), although it failed to influence that by methamphetamine (10(-7) M). In hippocampal slices from animals treated with cysteamine, which was shown to deplete hippocampal somatostatin, FR121196 (10(-7) M) hardly affected long-term potentiation generation, whereas physostigmine (10(-6) M) and methamphetamine (10(-7) M) augmented it significantly. These results suggest that FR121196 enhances the development of long-term potentiation in the mossy fiber-CA3 pathway through activation of somatostatinergic neurons in the hippocampal formation.
Animals↗
Cloning and expression of a cDNA for the rat kappa-opioid receptor.
We cloned a cDNA for the rat kappa-opioid receptor from a rat thalamus cDNA library. The deduced amino acid sequence consists of 380 residues with features shared by members of the G protein-coupled receptor family. The specific binding of [3H]bremazocine to the membrane of COS-7 cells transfected with the cDNA was displaced by kappa-specific opioid ligands, but not by mu- and delta-specific ligands. Xenopus oocytes injected with the in vitro transcribed mRNA responded to opioid ligands with the same subtype specificity. Northern blot analysis demonstrated that kappa-opioid receptor mRNA is expressed in a regionally specific manner in rat brain.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Bidirectional modulation of long-term potentiation by carbachol via M1 and M2 muscarinic receptors in guinea pig hippocampal mossy fiber-CA3 synapses.
Participation of muscarinic M1 and M2 receptors in the modulation of long-term potentiation (LTP) was studied in the mossy fiber-CA3 synapse of guinea pig hippocampal slices. The magnitude of tetanus-induced LTP was attenuated in the presence of 0.01-0.1 microM carbachol, at which concentration the pre-tetanus amplitude of field excitatory postsynaptic potential (fEPSP) was not affected. The attenuation of LTP by the low concentration of carbachol was reversed by an M2 muscarinic antagonist, AF-DX 116, but not by an M1 antagonist, pirenzepine. On the contrary, a high concentration (10 microM) of carbachol decreased the pre-tetanic amplitude of fEPSP, however, the magnitude of LTP was significantly larger than that in control slices in which pre-tetanic amplitude of fEPSP was reduced to the level of carbachol-treated slices by reducing the intensity of stimulation or extracellular Ca2+ concentration. The augmentation of LTP by 10 microM carbachol was blocked by pirenzepine but not by AF-DX 116. These results suggest that the synaptic plasticity in the guinea pig hippocampal mossy fiber-CA3 synapse is inhibited and facilitated by muscarinic agonist through muscarinic M2 and M1 receptors to inhibit and facilitate the LTP, respectively.
2-Amino-5-phosphonovalerate↗
Ischemic tolerance due to the induction of HSP70 in a rat ischemic recirculation model.
Various studies have demonstrated an increase in heat shock protein 70 (HSP70) synthesis in the brain following transiently induced ischemia, suggesting a protective role for HSP70 against ischemic insult. In this study, we determined the time course of HSP70 mRNA and protein induction in rat hippocampus following ischemia using Pulsinelli's four-vessel occlusion model, and suggested a protective role for HSP70 induction in limiting ischemic damage to neurons and delayed neuronal death. In Northern blotting analysis using human HSP70 DNA as a probe, the accumulation of HSP70 mRNA after 5 min ischemia became evident at 4 h, and continued until 16 h, while after 30 min ischemia, HSP70 mRNA appeared at 2 h, and continued above control level until 24 h after treatment. In immunoblot analysis using anti-HSP70 antibody, induction of HSP70 protein appeared 24 h and reached a maximum 48 h after 5 min ischemia. In immunohistochemical analysis using anti-HSP70 antibody, staining was not detected in CA1 neurons until 16 h after 5 min ischemia, but staining in CA1 gradually increased 1 day after ischemia and reached a maximum level 2 days after ischemia. Similar time profiles in the staining pattern of HSP70 protein were observed in CA3 and CA4 neuronal cells following 30 min ischemia. When rats pretreated with 5 min ischemia (non-lethal for CA1 pyramidal neurons) were exposed to a 30 min, lethal period of ischemia, 2 days after pretreatment, considerable staining of HSP70 was observed. Pretreated rats had much less neuronal damage in the CA1 sector than did rats subjected to lethal, 30 min ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptation, Physiological↗
Participation of spinal cord substance P in hyperalgesia induced by repeated cold stress.
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Animals↗