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Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 379 records · Page 21Linked to original sources

[In vitro effects of free fatty acids on water content and osmotic fragility of erythrocytes in rabbits].

The effects of free fatty acids in the blood on osmotic fragility and water content of erythrocytes when combined with hyperthermia were investigated. The isotonic buffer, containing the fatty acid, was added to the erythrocyte suspension to a final concentration of 200 microM/l. The samples were kept for one hour in an incubator at 37 or 42 degrees C. The osmotic fragility of erythrocytes was determined by Coil Planet Centrifuge System and intracellular water content was measured by gas-liquid chromatography. A high concentration of linoleic acid and hyperthermia caused the increase in intracellular water and the decrease in osmotic resistance of the red blood cells. The present experiment demonstrated that unsaturated fatty acid was one of the principal chemical and metabolic factors which cause sports anemia.

Animals↗

Mouse bone marrow stromal cell line MC3T3-G2/PA6 with hematopoietic-supporting activity expresses high levels of stem cell antigen Sca-1.

The murine clonal preadipose cell line, MC3T3-G2/PA6 (PA6), has the ability to support in vitro proliferation of hematopoietic stem cells defined as colony-forming units in spleen (CFU-S). In order to ascertain the relationship between the hematopoietic-supporting activity of PA6 cells and their expression, we cultured a number of these cells for over 45 weeks and investigated the level at which they expressed several cell surface markers and membrane-bound growth factors. Besides expressing stem cell factor (SCF) and macrophage colony-stimulating factor (M-CSF), PA6 cells were found by flow cytometry analysis to express high levels of stem cell antigen-1 (Sca-1). The expression level of Sca-1 in PA6 cells correlated with the ability of the latter to support hematopoiesis, whereas no such correlation was observed in the case of SCF and M-CSF expression. A cDNA clone encoding the protein recognized by anti-Sca-1 antibody was isolated from PA6 cells by expression cloning, so that its nucleotide sequence encoded the protein identical to mouse alloantigen Ly-6A.2. Genetically engineered COS-7 cells, transformed by the expression vector carrying the Ly-6A.2 gene, suppressed proliferation of murine lineage marker-negative (Lin) bone marrow cells by themselves and synergistically augmented proliferation of these cells in the presence of SCF. These results suggest that Ly-6A.2 regulates the proliferation of hematopoietic progenitor cells, and is one of the molecules organizing the hematopoietic microenvironment provided by stromal cells.

Animals↗

Oncogenic transformation and inhibition of adipocytic conversion of preadipocytes by TLS/FUS-CHOP type II chimeric protein.

Myxoid liposarcomas are characterized by t(12; 16)(q13;p11) translocation and expression of TLS/ FUS-CHOP chimeric transcripts (types I to III). Among these, the type II transcript is expressed in the majority of cases of myxoid and round cell liposarcoma. To investigate the function of the type II chimeric protein, we obtained stable transformants of ST-13, a murine preadipocytic cell line, which express TLS/FUS-CHOP type II protein (ST-TC) or CHOP protein (ST-C) as well as vector-transfected controls (ST-V). ST-TC and ST-C cells showed almost complete or partial resistance to adipogenic conversion by insulin and thiazolidinedione, respectively. Induction by adipogenic stimulation of the adipocytic genes such as C/EBP alpha, aP2, and adipsin was almost totally suppressed in the ST-TC cells, whereas in ST-C cells C/EBP alpha alone was induced without induction of aP2 and adipsin. Transcriptional suppression of the C/EBP alpha gene in ST-TC cells was suggested by the results of chloramphenicol acetyltransferase (CAT) assay showing a significantly lower C/EBP alpha promoter activity compared with findings in ST-C and ST-V cells. Failure to rescue adipogenic conversion by ectopic expression of C/EBP alpha in ST-TC cells suggested a functional impairment of C/EBP alpha to induce expression of downstream genes. TLS/FUS-CHOP type II protein showed transforming activity, as evidenced by loss of contact inhibition of growth, anchorage-independent growth in soft agar, and tumor formation in nude mice, showing typical histological features of myxoid liposarcoma seen in humans. These findings suggest important roles for TLS/FUS-CHOP type II protein in the oncogenesis of myxoid liposarcoma.

Adipocytes↗

Effect of gentamycin on the melanosomes in the stria vascularis of the pigmented guinea pig: an ultrastructural study.

Melanosomes of the stria vascularis in gentamycin (GM)-intoxicated guinea pigs were examined ultrastructurally. Experimental animals were given GM sulfate intramuscularly in a daily adjusted dose of 100 mg/kg for 15 consecutive days (group A), and 150 mg/kg for 5 consecutive days (group B). Melanosomes of the intermediate cells in group B significantly increased in number in comparison with those in group A and the control group. Melanosomes in the apical turn outnumbered those in the basal turn in all three groups. Cytochemically, Na+, K(+)-ATPase activity was also demonstrated in the marginal cells. There was little difference in the degree of enzyme activity between groups A, B and the control group. The role and significance of melanosomes of the stria vascularis are discussed.

Animals↗

Sensitivity to radiation treatment and changes in metallothionein synthesis in a transplanted murine tumor.

A protective role for metallothionein (MT) in cellular injury caused by ionizing radiation has been proposed. To elucidate the role of MT in the sensitivity of tumors to radiation, we examined the effectiveness of radiation treatment of tumors with altered synthesis of MT after injection of tumor-bearing mice with zinc and/or propargyl glycine (PPG). The mice were inoculated with Meth-A fibrosarcoma cells and the antitumor activity of X radiation was tested in mice with and without induced synthesis of MT. Exposure to X radiation decreased the tumor weight markedly. In mice pretreated with zinc to induce MT, the tumor weight did not change compared to the controls. However, injection of PPG, an inhibitor of cystathionase, decreased the zinc-induced MT synthesis in the tumors and also decreased the tumor weight after exposure to X radiation. These results suggest that in radiation therapy one of the factors involved in radiosensitivity may be the expression of MT in certain tumors.

Alkynes↗

[Suitable and successful management in preoperative deposit of autologous blood transfusion in cases of orthopedic elective surgeries].

To reveal the suitable and successful management in preoperative deposit of autologous blood, the 307 cases who had autologous blood transfusion during orthopedic elective surgery were studied retrospectively. Light body weight(less than 43 kg), predonative anemic condition(less than 11.3 g/dl in Hb concentration), and the aged(older than 68 yrs) were the main factors causing less deposit than scheduled amount. Less deposit (< 766 ml in THA), when preoperative low Hb concentration and unexpectedly massive bleeding added to it, was responsible for necessity of homologous blood transfusion. Combination of 400 ml-donation with 200 ml-donation, and gradual increase of rhEPO administration, are effective to prevent from unexpectedly less deposit.

Blood Transfusion↗

[Metamorphopsia and transient increase in the cerebral blood flow of the left occipital pole on 123I-IMP SPECT: a case report].

A 55-year-old right-handed man suddenly developed unformed visual hallucination of rainbow-colored balls coming out from the lower quadrant of the right visual field. Visual field examination revealed a right lower quadrant homonymous hemianopia. Metamorphopsia of the hand or face appeared 6 days later when he looked at his hands or at the face in the mirror, and persisted for about 10 minutes. 123I-IMP SPECT demonstrated a marked increase in CBF of the left occipital pole while the patient realized the visual symptoms, and a marked decrease in CBF after the symptoms disappeared. T1 and T2-weighted MRIs of the brain were unremarkable, but the Gd-DTPA-enhanced T1-weighted MRI showed high signal in the subcortical white matter of the left occipital pole. The metamorphopsia was induced probably by the activation of the left occipital lesion by the epileptogenic mechanism although the nature of the lesion remained unclarified.

Amphetamines↗

Enhanced renal toxicity by inorganic mercury in metallothionein-null mice.

To elucidate a protective role of metallothionein (MT) in the manifestation of inorganic mercury toxicity, we studied the susceptibility of MT-null mice to the renal toxicity of mercuric chloride. Because the MT-null (J) mice are a genetic background of 129/Sv strain, the 129/Sv mice were used as wild-type controls. Nine-week-old male MT-null (J) and 129/Sv mice were given subcutaneous injections of mercuric chloride at doses of 10 to 40 micromol/kg. The basal MT level in the kidney of MT-null (J) mice was undetectable (<0.2 microg/g of tissue) and approximately 2.5 microg/g of tissue in 129/Sv mice. The sensitivity to the renal toxicity of mercuric chloride was markedly enhanced in the MT-null (J) mice compared with the 129/Sv mice. The renal mercury level was similar for the MT-null (J) and 129/Sv mice at 4 hr after the injection of mercuric chloride (20 micromol/kg) but became significantly lower in MT-null (J) mice than in 129/Sv mice at 24 and 72 hr. Based on the present results, we conclude that MT is an important protective factor against the renal toxicity caused by inorganic mercury and that it may play a major role in the retention of mercury in the kidney.

Animals↗

P21waf-1/cip-1/sdi-1 is expressed at G1 phase in primary culture of hepatocytes from old rats, presumably preventing the cells from entering the S phase of the cell cycle.

To elucidate whether p21waf-1/cip-1/sdi-1 expression is associated with loss of growth potential of hepatocytes of old rats, we determined p21waf-1/cip-1/sdi-1 expression of hepatocytes from old (30 months) rats during the cell cycle in primary culture. A high level of expression of p21waf-1/cip-1/sdi-1 was detected at the G1 phase in old-rat hepatocytes, but after the S phase in young-rat hepatocytes. Consistently, the incidence of the cells positive for p21waf-1/cip-1/sdi-1 in nuclei before entering the S phase was significantly higher in old-rat hepatocytes than in young-rat hepatocytes. These results account for the loss of growth potential of old-rat hepatocytes in vitro and the marked retardation of regeneration of liver in old rats in vivo.

Animals↗

Cytotoxic gammadelta or alphabeta T cells with a natural killer cell marker, CD56, induced from human peripheral blood lymphocytes by a combination of IL-12 and IL-2.

Populations of cytotoxic CD3+CD56+ cells were selectively expanded when monocyte-depleted human PBL (M(-) PBL) were cultured with 20 U/ml IL-12 and 100 U/ml IL-2. In a majority of cases, CD4-CD8- as well as CD8+ gammadelta T cells with CD56 Ag were induced, but in some cases CD4+CD56+ alphabeta T cells were selectively increased. Determination of which will increase, gammadelta or alphabeta T cells, apparently is dependent upon individuals. When M(-) PBL were stimulated with IL-12 and IL-2 in the presence of immobilized anti-CD3 Ab, CD8+CD56+ alphabeta T cells increased exclusively. When M(-) PBL were cultured by IL-2 alone, CD3+CD56- cell expansion was predominant while CD3+CD56+ cells remained a minor population. Cytotoxic activity of M(-) PBL cultured with a combination of IL-12 and IL-2 is much greater than when cultured with IL-2 alone. The cytotoxicity of activated M(-) PBL was abrogated by the depletion of either CD3+ or CD56+ cells irrespective of their gammadelta or alphabeta phenotypes. These types of cells are preferentially present in the livers of humans. The results revealed that, under certain conditions, IL-12 synergizes with IL-2 to induce potent cytotoxic T cells with CD56 Ag of humans, and suggest that these cells in the human liver are functionally similar to NK1+ alphabeta T cells in murine liver.

Biomarkers↗

Growth of the neopulmonary valve annulus after arterial switch operation in transposition of the great arteries.

BACKGROUND: It is known that supravalvular pulmonary artery stenosis can occur in patients with d-transposition of the great arteries (TGA) after arterial switch operation (ASO). However, little is known about the growth of the neopulmonary valve annulus after the ASO. This study investigated the growth potential of the neopulmonary (old aortic) valve annulus. METHODS AND RESULTS: Annular diameters of the old aortic and neopulmonary valve were measured from cineangiograms in patients who underwent cardiac catheterizations both before and > 1 year after the ASO. Of 71 patients, 13 (18%) had either a small annulus (< 70% of the expected normal value) or no significant growth of the neopulmonary annulus after the ASO, and 4 (6%) had a pressure gradient of > 30 mm Hg across the valve. The small annulus or no growth of the neopulmonary valve was more frequent in patients with a history of pulmonary artery banding. After the ASO, the valve diameter in patients with a ventricular septal defect was 80 +/- 15% of normal (n = 24), and the value was significantly less than in patients with an intact ventricular septum (91 +/- 11%, n = 47). In all patients with an intact ventricular septum who underwent the one-stage ASO, the valve diameters before and after the ASO were within normal limits, and a significant increase in the pulmonary valve annulus was observed. CONCLUSIONS: These data indicate that not only supravalvular pulmonary stenosis but also pulmonary valvular stenosis due to a small annulus can occur in TGA, especially in patients with a history of pulmonary artery banding and in patients with ventricular septal defect.

Humans↗

Cyclic AMP-dependent modulation of N- and Q-type Ca2+ channels expressed in Xenopus oocytes.

Xenopus oocytes were used for investigating the cAMP-dependent modulation of N- and Q-type Ca2+ channels. Treatments to increase intracellular cAMP concentration with forskolin (FK) and 3-isobutyl-1-methylxanthine (IBMX) markedly potentiated Q-type Ca2+ channel current in oocytes coexpressing alpha 1A and beta subunits, and the enhancement was reversed by protein kinase A inhibitors. Moderate enhancement was observed by FK+IBMX in N-type channel current, of which potentiation was equivalent to that of endogenous Ca2+ channel current being activated by exogenously-expressed beta subunits. No potentiation was observed in the oocyte-native Ca2+ channel current. These results suggest that Q-type Ca2+ channels are more susceptible to the protein kinase A-mediated facilitation than N-type channels. A significant role of Ca2+ channel beta subunits for the cAMP-dependent positive modulation was also suggested.

1-Methyl-3-isobutylxanthine↗

Pharmacological characterization of KT-90 using cloned mu-, delta- and kappa-opioid receptors.

We analyzed the pharmacological characteristics of (-)-3-acetyl-6 beta-acetylthio-N-cyclopropylmethyl-normorphine (KT-90) using Chinese hamster ovary (CHO) cells expressing cloned rat mu-, delta- and kappa-opioid receptors. KT-90 displaced the specific binding of the following radiolabeled ligands selective to the mu-, delta- and kappa-opioid receptors, [3H][D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO), [3H][D-Pen2,D-Pen5]enkephalin (DPDPE), [3H] (+)-(5 alpha, 7 alpha, 8 beta)-N-methyl-N-[7-(1-pyrrolidinyl) l-oxaspiro-(4,5)dec-8-yl]benzeneacetamide (U69,593), with Ki values of 3.3 +/- 0.7, 22.8 +/- 1.5 and 1.9 +/- 0.3 nM, respectively In CHO cells expressing the mu-, delta- and kappa-opioid receptors, KT-90 inhibited forskolin (10 microM)-induced cyclic AMP accumulation in a concentration-dependent manner with IC50 values of 2337 +/- 750, 17.3 +/- 4.6 and 2.0 +/- 0.1 nM, respectively. The maximal inhibitory effects of KT-90 in the cells expressing mu-, delta- and kappa-opioid receptors were significantly lower than those of the type-selective agonists DAMGO, DPDPE and U69,593, respectively. These results indicated that KT-90 acts as a partial agonist on mu-, delta- and kappa-opioid receptors. KT-90 (10 and 100 nM), when added with morphine, produced a rightward shift of the concentration-response curve of morphine to inhibit the cyclic AMP accumulation in CHO cells expressing mu-, but not delta- or kappa-, opioid receptors. This finding is consistent with the findings that lower doses of KT-90 antagonize morphine analgesia in vivo.

Animals↗

A unique human gene that spans over 230 kb in the human chromosome 8p11-12 and codes multiple family proteins sharing RNA-binding motifs.

A unique gene, RBP-MS, spanning over 230 kb in the human chromosome 8p11-12 near the Werner syndrome gene locus is described. The single-copy RBP-MS gene is alternatively spliced, resulting in a family of at least 12 transcripts (average length of 1.5 kb). Nine different types of cDNAs that encode an RNa-binding motif at the N terminus and helix-rich sequences at the C terminus have been identified thus far. Among the 16 exons identified, four 5'-proximal exons contained sequences homologous to the RNA-binding domain of Drosophila couch potato gene. Northern blot analysis showed that the RBP-MS gene was expressed strongly in the heart, prostate, intestine, and ovary, and poorly in the skeletal muscle, spleen, thymus, brain, and peripheral leukocytes. The possible role of this gene in RNA metabolism is discussed.

Alternative Splicing↗

Autoantibodies to ribosomal P antigens with immune complex glomerulonephritis in SJL mice treated with pristane.

BALB/c ByJ mice develop a lupus-like syndrome characterized by anti-nRNP/Sm and Su autoantibodies and immune complex glomerulonephritis after a single i.p. pristane injection. In contrast, mercuric chloride induces anti-fibrillarin Abs only in SJL and other H-2s mice, and not in BALB/c (H-2d) mice. In the present study, the specificities of autoantibodies induced by pristane and HgCl2 were compared in SJL and BALB/c mice to examine whether these strains are "programmed" to make different sets of autoantibodies in response to nonspecific immune stimulation. Unexpectedly, the predominant autoantibodies induced by pristane in SJL mice were neither those characteristic of HgCl2-treated SJL mice nor those associated with pristane-induced disease in BALB/c mice but, rather, anti-ribosomal P, another lupus-related specificity. The autoantibodies were strongly reactive with the C-terminal 22 amino acids of the ribosomal P2 protein, indicating that they exhibited similar fine specificities to anti-P Abs in human SLE and MRL/Ipr mice. Like BALB/c mice, pristane-treated SJL mice developed severe glomerulonephritis characterized by proteinuria, mesangial proliferation, and glomerular immune complex deposits. This is the first evidence that the induction of a lupus-like syndrome by pristane is not restricted to BALB/c mice. The predominance of anti-P Abs in SJL mice contrasts sharply with the predominance of anti-nRNP/Sm and Su, in pristane-treated BALB/c mice, even though the renal lesions were similar in both strains. The data suggest that H-2s does not program mice to produce anti-fibrillarin Abs in response to nonspecific immune stimulation, arguing that autoantibody induction by pristane involves Ag-specific mechanisms.

Animals↗

Co-localization of mu opioid receptor is greater with dynorphin than enkephalin in rat striatum.

Using a combination of radioactive and non-radioactive in situ hybridization, the mu opioid receptor mRNA was localized in enkephalin as well as dynorphin neurones of the rat striatum. The proportion of enkephalin neurones showing co-localized mu opioid receptor mRNA was dependent on the rostrocaudal level (17-39% in rostral/intermediate levels vs 0.4-5% caudally) but did not differ between striatal subregions. For dynorphin neurones the reverse was true, with consistently higher levels of co-localization in the caudate-putamen (56-77%) than the nucleus accumbens (15-43%), but no differences along the rostrocaudal axis. Furthermore, the degree of enkephalin/mu co-localization was significantly lower than that of dynorphin/mu. These results suggest a fine-grained topological differentiation of mu receptor modulation of striatal opioid systems.

Animals↗

Pharmacological characterization of 5-hydroxytryptamine-induced motor activity (in vitro) in the guinea pig gastric antrum and corpus.

In order to characterize the receptor subtypes involved in 5-hydroxytryptamine (5-HT)-induced circular muscle motor responses of the guinea pig gastric antrum and corpus, we examined the effects of several antagonists in vitro. 5-HT evoked concentration-dependent contractions of the gastric antrum and relaxations of the corpus. 5-HT induced antral contractions were abolished by pretreatment with atropine and tetrodotoxin. Methysergide, ketanserin, granisetron and [1-[2-(methylsulphonylamino)ethyl]-4-piperidinyl]methyl 1-methyl-1 H-indole-3-carboxylate maleate salt (GRl13808A), but neither 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190) nor N2-[(4R)-4-hydroxy-1-(1-methyl-1 H-indol-3-yl)carbonyl-L-prolyl]-N- methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide (FK888), inhibited 5-HT (3 x 10(-6) M: submaximal concentration)-induced antral contractions concentration dependently and shifted the 5-HT concentration-response curve to the right. 5-HT (3 x 10(-6) M)-induced corporal relaxation was not affected by tetrodotoxin, ketanserin, granisetron or GR113808A. At 10(-7) M, neither methysergide nor NAN-190 affected corporal relaxation, but at a high concentration (10(-6) M) they both inhibited it and shifted the 5-HT concentration-response curve to the right. We conclude that 5-HT-induced antral contraction is mediated by cholinergic neurons via 5-HT2A, 5-HT3 and 5-HT4 receptors, whereas corporal relaxation is mediated via 5-HT1-like receptors on smooth muscle that are sensitive to methysergide and NAN-190.

Animals↗