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Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 271 records · Page 15Linked to original sources

Induction of tyrosine aminotransferase of primary cultured rat hepatocytes depends on the organization of microtubules.

We investigated the relationship between the expression of tyrosine aminotransferase (TAT) and cytoskeletal systems of cultured rat hepatocytes by using serum-free culture conditions and changing three factors: 1) the concentration of calcium, 2) the dish-coating material, and 3) the cell-plating density. In hepatocytes in low-calcium medium, induction of TAT by dexamethasone and glucagon was maintained, although cell-cell adhesion was lost. Hepatocytes on Matrigel formed a nonspreading, spherical shape that provided them with the full extent of TAT activity without cell-cell adhesion. Hepatocytes plated on collagen at low cell density spread and changed shape, and the induction of TAT activity was markedly reduced. By using confocal laser-scanning microscopy, we analyzed the three-dimensional organization of cytoplasmic microtubules of hepatocytes maintaining the ability of TAT induction. Hepatocytes plated on collagen at low cell density possessed the radial filamentous structure of cytoplasmic microtubules. When the spherical shape of hepatocytes was maintained by cultivating cells on Matrigel, a ring-like structure of cytoplasmic microtubules beneath the plasma membrane was dominant. Moreover, the induction of TAT activity of hepatocytes in a standard culture system was strongly inhibited by the addition of 1 microM colchicine. These studies suggest that the organization of cytoplasmic microtubules may participate in the shape-related regulation of cell function.

Actins↗

Influence of microbial stimulation on hypergammaglobulinemia and autoantibody production in pristane-induced lupus.

Pristane induces a lupus-like syndrome characterized by autoantibody production and glomerulonephritis in nonautoimmune strains of mice. Although it has been suggested that this syndrome results from nonspecific immune activation, there is little evidence so far that B cells are activated nonspecifically by pristane or that this promotes autoimmunity. In this study, we examined whether polyclonal hypergammaglobulinemia occurs in pristane-induced lupus, and its relationship to the production of anti-DNA, nRNP/Sm, and Su autoantibodies. In conventionally housed mice, there was a marked increase in total IgM and IgG3 2 weeks after i.p. pristane injection, followed by increased IgG1, IgG2a, and IgG2b levels. IgM levels were higher in pristane-treated specific pathogen-free (SPF) mice than in conventionally housed mice, whereas IgG and IgA levels were reduced. Pristane induced anti-nRNP/Sm and Su autoantibodies in SPF mice, but their onset was delayed and levels were lower than those in conventionally housed mice. There was no consistent relationship between total IgG1, 2a, and 2b hypergammaglobulinemia and production of anti-nRNP/Sm and Su autoantibodies. Moreover, the total Ig levels were similar in the anti-nRNP/Sm-positive and -negative groups. In contrast, production of IgM anti-ssDNA antibodies paralleled IgM hypergammaglobulinemia in some, but not all, mice. These studies indicate that pristane-induced lupus is associated with marked hypergammaglobulinemia, the magnitude of which is influenced by the microbial environment. However, anti-nRNP/Sm and Su autoantibody production is at least partly independent of polyclonal B cell activation. The data strongly suggest that pristane-induced lupus is not exclusively the consequence of nonspecific immune stimulation. They also point to the importance of microbial stimulation in the development of hypergammaglobulinemia in this inducible lupus model.

Animals↗

A distinct subtype of "metatropic dysplasia variant" characterised by advanced carpal skeletal age and subluxation of the radial heads.

BACKGROUND: "Metatropic dysplasia variants" are a group of bone dysplasias whose skeletal abnormalities are similar to, but milder than, those of classical metatropic dysplasia. The genetic and phenotypic heterogeneity has not been thoroughly elucidated. OBJECTIVE: The objective was to designate a distinct subtype of these metatropic dysplasia variants. MATERIALS AND METHODS: The subjects were four Japanese patients, two sporadic cases and two siblings, who all had identical skeletal changes. The radiological features in these patients were compared with those of previously reported metatropic dysplasia variants. RESULTS: Moderate platyspondyly with pear-shaped and/or anterior-tongued vertebral bodies, halberd pelvis, and dumbbell deformity of the tubular bones were regarded as hallmarks of metatropic dysplasia variants. The peculiar skeletal change in our patients was advanced carpal skeletal age in childhood, unlike most patients reported as metatropic dysplasia variants who manifest delayed carpal ossification. Another hallmark was congenital dislocation of the radial heads. A description of a patient with similar skeletal changes was found in the literature. CONCLUSION: These patients are considered to represent a distinct subgroup of metatropic dysplasia variants. It remains unknown whether the present siblings represent an autosomal recessive trait or an autosomal dominant trait with germinal mosaicism related to increased paternal age.

Abnormalities, Multiple↗

Solitary fibrous tumor of the parotid gland extending to the parapharyngeal space.

Solitary fibrous tumors (SFT) arise in the pleura and less commonly in extrapleural sites. Head and neck regions have included the nose and paranasal sinuses, soft palate, epiglottis, thyroid, parotid and submandibular glands, as well as the infratemporal fossa and parapharyngeal space. We report a case of SFT arising from the parotid gland and extending to the parapharyngeal space. To our knowledge, this is the fourth case of SFT originating from the parotid gland and is the largest of its kind among the extrapleural lesions described. The characteristics revealed by computed tomography and magnetic resonance imaging are presented.

Fibroma↗

Neuroendocrine carcinoma of the extrahepatic biliary tract with positive immunostaining for gastrin-releasing peptide: report of a case.

We report herein the first documented case of gastrin-releasing peptide-positive neuroendocrine (NE) carcinoma of the extrahepatic biliary tract. An invasive tumor measuring 2.5 x 1.5 cm was located in the confluence portion of the cystic duct in a 70-year-old Japanese man. Histologically, the tumor was found to be composed of small polygonal cells which formed a solid and trabecular structure, and the frequencies of both mitoses and small necrotic areas were dominant. The tumor cells were immunoreactive to the NE markers chromogranin-A and neuron-specific enolase, as well as to carcinoembryonic antigen and gastrin-releasing peptide. Although a few cases of gastrin-releasing peptide-positive small-cell lung carcinoma have been documented, there have been no reports of gastrin-releasing peptide-positive NE carcinoma occurring in the gastrointestinal tract. We consider our case not merely to be of pathological interest, but also to have clinical and therapeutic implications.

Aged↗

Differential regulation of N- and Q-type Ca2+ channels by cyclic nucleotides and G-proteins.

Voltage-dependent Ca2+ channels play a central role in controlling neurotransmitter release at the synapse. They can be inhibited by certain G-protein-coupled receptors, acting by a pathway delimited to the membrane. In addition, modulation of Ca2+ channel activity by protein kinases also contributes to the dynamic regulation of neuronal physiology. Recently, differences in these modulations between Ca2+ channel subtypes have been shown in several neuronal preparations. Here we show that two types of presynaptic Ca2+ channel (N-type and Q-type) are differentially regulated by cAMP and G-proteins using a Xenopus oocyte expression system. Treatment to increase cytosolic cAMP concentration with forskolin and 3-isobutyl-1-methylxanthine (IBMX) markedly potentiated Q-type channel current, and the enhancement was reversed by protein kinase A inhibitors. Much smaller enhancement was observed in N-type channel current after the cAMP elevation. When large depolarizing prepulse was applied to the oocytes for evaluation of the tonic inhibition of Ca2+ channels by intrinsic G-protein activity, N-type channel current elicited a large prepulse facilitation but Q-type channels did not. The tonic inhibition of N-type channels was abolished by an intracellular perfusion with a 'cut-open' recording configuration, or by co-expression with G(alpha o). When kappa opioid receptors were co-expressed and stimulated with agonists, depolarization-resistant inhibition was more apparent in Q-type channels than in N-type channels. These results suggest that Q-type channels are more susceptible to the protein kinase A-mediated facilitation than N-type channels, and that activity of N-type channels can be more highly regulated in a voltage-dependent manner by G(betagamma) than that of Q-type channels. These differences may account for the selective regulation of neurotransmitter release by these Ca2+ channels.

1-Methyl-3-isobutylxanthine↗

Laminin inhibits Cl- -secretion across canine tracheal epithelium.

We examined the effect of laminin (a major component of the basement membrane) on potential difference (PD) and short circuit current (SCC) in both posterior epithelial membranes (native tissue) and cultured epithelial cell layers from canine trachea using an Ussing chamber. Although laminin itself did not alter the baseline values of SCC or PD, it significantly inhibited in a dose-dependent manner the isoproterenol induced SCC and PD rises of the epithelial membrane. In the cultured epithelial layer treated with amiloride, laminin did not alter the baseline values of SCC, PD or resistance (R) but it significantly inhibited the isoproterenol induced SCC rises. However, laminin did not significantly inhibit the bradykinin induced SCC rise in the cultured epithelial layer treated with amiloride. These findings indicate that laminin is a determinant in ion transport (mainly Cl- secretion) across canine tracheal epithelium, inhibiting the beta-agonist induced Cl- transport.

Adrenergic beta-Agonists↗

Protein kinase C mediates increase of Ca2+ sensitivity for contraction by cholinoceptor partial agonist in ileal longitudinal muscle of guinea pig.

1. Experiments were designed to study the roles of protein kinase C in carbachol- and pilocarpine-induced contraction and the increase in cytosolic Ca2+ concentration ([Ca2+]i) in guinea pig ileal longitudinal muscle. 2. The protein kinase C inhibitors, GF 109203X (10 microM), calphostin C (10 microM) and H-7 (10 microM), reduced the maximum of the concentration response curve produced by pilocarpine more effectively than that produced by carbachol. 3. The slopes of the regression lines between [Ca2+]i and tension development for pilocarpine and carbachol in tissues treated with GF 109203X were significantly gentler than those for untreated tissues. 4. The protein kinase C alpha- and beta 1 selective inhibitor Goe 6976 (1 microM) decreased both [Ca2+]i and contraction, but did not affect the slopes of the regression lines for pilocarpine and carbachol. 5. These results suggest that protein kinase C (both n- and/or a-type) plays an important role in the increase of Ca2+ sensitivity of the contractile element, and that pilocarpine mainly activates the protein kinase C-dependent pathways for contractile mechanisms in guinea pig ileal longitudinal muscle.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

A T1083C polymorphism in the human adenosine A2a receptor gene is not associated with essential hypertension.

The adenosine A2a receptor (A2aAR) gene is thought to be involved in essential hypertension because adenosine elicits vasodilation and decreases arterial blood pressure via this receptor, and because disruption of the A2aAR gene increases blood pressure in mice. Therefore, using a restriction fragment length polymorphism (RFLP) of the A2aAR gene, we performed an association study in patients with essential hypertension. One hundred forty-two patients with essential hypertension and 142 age-matched subjects with normal blood pressure were studied. Polymerase chain reaction (PCR) was applied to amplify the T1083C polymorphic site in the A2aAR gene, and restriction analysis of the PCR product was employed to score the T and C alleles. Overall distributions of allele frequencies in the two groups were not significantly different. Thus, the alleles detected by this RFLP polymorphism in the A2aAR gene are not associated with essential hypertension.

Adult↗

Involvement of 5-hydroxytryptamine7 receptors in inhibition of porcine myometrial contractility by 5-hydroxytryptamine.

1 5-Hydroxytryptamine (5-HT; 1 nM - 100 microM) concentration-dependently inhibited the amplitude and frequency of spontaneous contractions in longitudinal and circular muscles of the porcine myometrium. The circular muscle (EC50; 68-84 nM) was more sensitive than the longitudinal muscle (EC50; 1.3-1.44 microM) to 5-HT. To characterize the 5-HT receptor subtype responsible for inhibition of myometrial contractility, the effects of 5-HT receptor agonists on spontaneous contractions and of 5-HT receptor antagonists on inhibition by 5-HT were examined in circular muscle preparations. 2 Pretreatment with tetrodotoxin (1 microM), propranolol (1 microM), atropine (1 microM), guanethidine (10 microM) or L-NAME (100 microM) failed to change the inhibition by 5-HT, indicating that the inhibition was due to a direct action of 5-HT on the smooth muscle cells. 3 5-CT, 5-MeOT and 8-OH-DPAT mimicked the inhibitory response of 5-HT, and the rank order of the potency was 5-CT>5-HT>5-MeOT>8-OH-DPAT. On the other hand, oxymethazoline, alpha-methyl-5-HT, 2-methyl-5-HT, cisapride, BIMU-1, BIMU-8, ergotamine and dihydroergotamine had almost no effect on spontaneous contractions, even at 10-100 microM. 4 Inhibition by 5-HT was not decreased by either pindolol (1 microM), ketanserin (1 microM), tropisetron (10 microM), MDL72222 (1 microM) or GR113808 (10 microM), but was antagonized by the following compounds in a competitive manner (with pA2 values in parentheses): methiothepin (8.05), methysergide (7.92), metergoline (7.4), mianserin (7.08), clozapine (7.06) and spiperone (6.86). 5 Ro 20-1724 (20 microM) and rolipram (10 microM) significantly enhanced the inhibitory response of 5-HT, but neither zaprinast (10 microM) nor dipyridamole (10 microM) altered the response of 5-HT. 6 5-HT (1 nM - 1 microM) caused a concentration-dependent accumulation of intracellular cyclic AMP in the circular muscle. 7 From the present results, the 5-HT receptor, which is functionally correlated with the 5-HT7 receptor, mediates the inhibitory effect of 5-HT on porcine myometrial contractility. This inhibitory response is probably due to an increase in intracellular cyclic AMP through the activation of adenylate cyclase that is positively coupled to 5-HT7 receptors.

Adenylyl Cyclases↗

Platelet-like particle formation in the human megakaryoblastic leukaemia cell lines, MEG-01 and MEG-01s.

The platelet-sized particle formation in the human megakaryoblastic leukaemia cell line MEG-01 and its subline MEG-01s was examined. MEG-01 and MEG-01s cells spontaneously released platelet-sized particles into the culture medium, in which the cells occasionally extended cytoplasmic processes similar to those of megakaryocyte proplatelets. Scanning electron microscopic images showed cytoplasmic processes elongated from blebs on the MEG-01 and MEG-01s cell surface and were constricted between segments of platelet size. Immunofluorescence staining with anti-tubulin antibody showed that the cytoplasmic processes contained microtubules that were organized into a ring, which is a characteristic of circulating platelets. Some platelet-sized particles, probably released by ruptures at the sites of the process constriction, were metabolically active in an MTT assay (about 50%). Some particles also expressed the platelet-specific glycoproteins GPIIb, IIIa and GMP-140. Rarely, in response to thrombin, particles underwent a shape change from spherical to a shape with irregular membrane protrusions and fine filopodia, and aggregating with one another. The particles also had increased GMP-140 (P-selectin) expression with the addition of thrombin. These results show the usefulness of the MEG-01 and MEG-01s cell lines for the study of thrombopoiesis.

Blood Platelets↗

A boy with fatal infectious mononucleosis suspected as the first Japanese case of X-linked lymphoproliferative syndrome.

We report a case of a 10-month-old boy who died of severe hepatic failure after a prolonged course of infectious mononucleosis. He also presented interstitial pneumonitis, meningoencephalitis and aplastic anaemia. Epstein-Barr virus (EBV)-specific cytotoxic T lymphocyte (CTL) activity had not been detected in his peripheral blood during the course of the illness. Studies of his mother revealed a severe reactivation pattern of anti-EBV antibodies and decreased EBV-specific CTL activity. An X-linked familial susceptibility to EBV infection such as X-linked lymphoproliferative syndrome (XLP) might be associated with his fatal EBV infection.

Cytotoxicity, Immunologic↗

Purification of recombinant human pepsinogens and their application as immunoassay standards.

Human pepsinogen (PG) A and C were cloned in Escherichia coli, but the levels of expression were low and unstable. When there were fused to maltose-binding protein (MBP), the fusion proteins (MBP-PGA and MBP-PGC) were expressed as the major products. Although these fused products were almost totally recovered from the insoluble fraction, the renaturation and purification procedures were easy and simple. MBP-PGA and the PGA segment obtained by factor Xa digestion (designated as r-PGA) possessed proteolytic activities equivalent to native PGA purified from gastric tissue (t-PGA). For PGCs (MBP-PGC, r-PGC and t-PGC) also, the specific activities were almost the same. However, the activities of PGCs were about 3- to 4-hold higher than those of PGAs. In PGA and PGC immunoassay systems, r-PGs (r-PGA and r-PGC) and the EIA kit standard PGs (gastric mucosal PGs) exhibited a good correlation. From these results, r-PGs would seem to be applicable as assay standards without compromising the sensitivity of the immunoassay systems.

ATP-Binding Cassette Transporters↗

Diagnosis and treatment of malignant lymphoma of the parotid gland.

BACKGROUND: To correlate the imaging and pathological features and to discuss therapeutic modalities and the prognosis of malignant lymphoma originating in the parotid gland, which is relatively rare. METHODS: The subjects were five patients with malignant lymphoma originating in the parotid gland. Three and two patients were stage I and stage II, respectively. CT examination was applied to all, whereas only one case was examined by MRI. All were treated with radiotherapy following surgery or chemotherapy. Three patients underwent combination chemotherapy, such as with MACOP-P or VEPA, following surgery. RESULTS: Although malignant lymphoma originating in the parotid gland is histologically described as low-grade non-Hodgkin's lymphoma, two and one of the cases were classified as intermediate and high grade in the present series, respectively. These three exhibited a tendency for infiltration into the adjacent tissue and tumor inhomogeneity in the imaging findings, suggesting a correlation with histologically intermediate or high-grade non-Hodgkin's lymphoma. It was successfully controlled by radiotherapy, with dosages ranging from 40 to 44 Gy. The patients were followed for 2-8 years. No relapse was found in the three patients with stage I. However, both stage II patients had relapses and were subjected to additional radiotherapy combined with chemotherapy. Since then, no tumor relapse has been noted at either this or other sites. CONCLUSIONS: Malignant lymphoma including intermediate or high grade originating in the parotid gland indicated satisfactory prognosis following radiotherapy and chemotherapy.

Aged↗

Mucoepidermoid carcinoma of the larynx: a case which responded completely to radiotherapy and a review of the literature.

Most laryngeal cancers are squamous cell carcinomas, and adenocarcinomas account for < 1% of cancers of the larynx. Among them, mucoepidermoid carcinoma is extremely rare and there is little agreement about the treatment of this carcinoma. We encountered one patient with mucoepidermoid carcinoma of the bilateral vocal cords (T1bN0M0, Stage 1). For this, most investigators recommended a surgical procedure. However, because of his old age, the early stage and low grade of histopathology, we treated this patient with radiotherapy alone, delivered by accelerated hyperfractionation, which is a more effective strategy for treating radioresistant tumors than conventional irradiation. Following radiotherapy, the tumor disappeared and the patient has been alive and well for more than six years. An old patient with mucoepidermoid carcinoma of the larynx was successfully treated with radiotherapy alone.

Aged↗