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Biomedical subjects

E Ogata

Publications and source records attributed to E Ogata.

At least 127 records · Page 7Linked to original sources
PubMed1992

Expression of activin A/erythroid differentiation factor in murine bone marrow stromal cells.

Accumulating evidence suggests that activin A/erythroid differentiation factor (EDF), a homodimer of beta A chain, is a physiologic hematopoietic factor, particularly of erythroid lineage. Media conditioned by phorbol myristate acetate (PMA)-stimulated murine bone marrow stromal cell lines, MC3T3-G2/PA6 and ST2, contained activin A/EDF, assayed as the activity inducing erythroid differentiation of an activin A/EDF-responsive murine erythroleukemia cell clone F5. Follistatin, a protein specifically binding to activin A/EDF, abolished this erythroid differentiation. Northern blot analysis showed that PMA rapidly increased beta A chain messenger RNA levels in MC3T3-G2/PA6 and ST2 cells. In a search for natural stimulators, we found that tumor necrosis factor-alpha, in itself and synergistically with interleukin-1 beta, induced activin A/EDF production in both cell lines. These results indicate that stromal cells produce activin A/EDF in bone marrow.

Activins↗
PubMed1992

Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells.

The present study was undertaken to clarify the relationship between c-fos and c-jun protooncogene expression and the differentiation and/or proliferation of osteoblasts, using osteoblast-like MC3T3-E1 (E1) cells. c-fos mRNA was barely detectable, whereas c-jun mRNA was constitutively expressed in E1 cells after serum deprivation for 24-72 h. When serum was added, a rapid and transient induction of c-fos and c-jun mRNAs was observed. The c-fos and c-jun mRNAs reached peak levels at 30 minutes, with a rapid disappearance of c-fos mRNA within 3 h and a much slower decrease in c-jun mRNA. The addition of serum together with cycloheximide, an inhibitor of protein synthesis, resulted in the superinduction of both c-fos and c-jun mRNAs. Among various growth factors, PDGF, EGF, and bFGF mimicked the serum effect, whereas IGF-I and TGF-beta failed to induce c-fos and c-jun mRNA. The effects of PDGF, EGF, and bFGF were completely abolished by pretreatment with actinomycin D, an inhibitor of RNA synthesis, suggesting a transcriptional mechanism. Nuclear runoff experiments showed that the transcription rate of c-fos and c-jun protooncogenes was increased by serum and growth factors. The effects of PDGF, EGF, and bFGF were inhibited by H-7 or staurosporine, inhibitors of protein kinase C (PKC), but not by HA1004 with a much weaker inhibitory activity, suggesting the involvement of PKC for the activation of the protooncogenes.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Vasodilating actions of calcitonin gene-related peptide in normal man: comparison with atrial natriuretic peptide.

To compare the vasodilator effect of calcitonin gene-related peptide (CGRP) with that of atrial natriuretic peptide (ANP), forearm blood flow (FBF) was measured by strain-gauge plethysmography during the continuous infusion of different doses of the peptides dissolved in 5% dextrose into the brachial artery in healthy subjects. Either CGRP or ANP increased FBF in a dose-dependent fashion. Although 100 ng/ml CGRP increased FBF from 3.27 +/- 0.41 to 10.70 +/- 1.77 ml/100 ml/min, the same dose of ANP increased FBF from 2.40 +/- 0.38 to 5.39 +/- 0.22 ml/100 ml/min, which was significantly lower than the increase in CGRP (p less than 0.01): Plasma concentration of peptides (on a molar basis) was positively correlated with FBF in CGRP (r = 0.820, p less than 0.01) or ANP (r = 0.722, p less than 0.01). However, the slope of the regression line between plasma level and FBF was significantly higher (p less than 0.01) in CGRP (12.88 +/- 0.99) than in ANP (2.10 +/- 0.27). Thus the vasodilator effect of CGRP was more potent than that of ANP. The present findings are compatible with functional involvement of CGRP in the regulation of forearm circulation.

Adult↗
PubMed1992

Tumor necrosis factor-alpha induces vascular hyporesponsiveness in Sprague-Dawley rats.

The cytokine tumor necrosis factor-alpha (TNF alpha) is one of the major mediators of septic shock. Because vasodilation is a hallmark of sepsis and decreased vascular responsiveness has been implicated in the pathogenesis of septic shock, we studied the effect of TNF alpha on the mean blood pressure in conscious rats and vascular responsiveness to vasoconstrictors ex vivo using the standard organ bath method. Intravenous infusion of TNF alpha (0.006 or 0.06 mg/kg/hr for 10 hours) decreased mean blood pressure in a dose-dependent fashion. Contractile responses to norepinephrine were depressed dose-dependently in the aortic rings both with and without its endothelium. Aortic contractions by potassium depolarization were also depressed. These results suggest that TNF alpha induces non-specific vascular hyporesponsiveness, which is independent of the presence of the endothelium. The TNF alpha-induced vascular hyporesponsiveness might contribute to the hypotensive action of TNF alpha.

Analysis of Variance↗
PubMed1992

Autocrine secretion of transforming growth factor-beta in cultured rat mesangial cells.

Transforming growth factor-beta (TGF-beta) recently has been shown to modulate mesangial cell growth and to stimulate mesangial matrix synthesis by mesangial cells. Here we examined whether mesangial cells expressed TGF-beta mRNA and secreted mature TGF-beta, and we investigated the role of TGF-beta in mesangial cell growth. Cultured rat mesangial cells expressed 2.5 kb TGF-beta mRNA, and removal of fetal calf serum (FCS) for two days decreased the TGF-beta mRNA level, which was then stimulated by re-addition of 17% FCS reaching the maximum at nine hours. 12-O-tetradecanoyl phorbol-13-acetate (TPA), one of the phorbol esters, markedly increased the mRNA level and reached the maximum at six or nine hours. Immunoblot analysis of the conditioned media using specific anti-TGF-beta 1 antibodies revealed single 12.5 kDa proteins, the size compatible with mature TGF-beta subunits. By means of bioassay using CCL-64 cell line, TGF-beta production rate by mesangial cells was estimated to be 22.1 +/- 6.5 (mean +/- SD) ng/10(6) cells/24 hours, 96% of which was in latent forms. Exogenously added TGF-beta inhibited mesangial cell growth at 10 pM or higher. Moreover, addition of anti-TGF-beta neutralizing antibodies augmented mesangial cell growth, indicating that the secreted TGF-beta actually exerted a growth-inhibitory action. In summary, mesangial cells produce and secrete substantial amounts of TGF-beta but mostly in latent forms, and the secreted TGF-beta may regulate mesangial cell growth and differentiation. We conclude that TGF-beta may function as an autocrine factor in mesangial cells.

Animals↗
PubMed1992

Immunohistochemical demonstration of bone morphogenetic protein-2 and transforming growth factor-beta in the ossification of the posterior longitudinal ligament of the cervical spine.

To clarify the mechanism of ossification of the posterior longitudinal ligament, immunohistochemical localization of bone morphogenetic protein-2 and transforming growth factor-beta was examined using surgical specimens of ligament tissues from an affected patient. Two polyclonal antibone morphogenetic protein-2 antibodies and an anti-human transforming growth factor-beta antibody were used as primary antibodies. Bone morphogenetic protein-2 and transforming growth factor-beta were present in ossified matrix and chondrocytes of adjacent cartilaginous areas of ossification of the posterior longitudinal ligament. Although immunostaining with antibone morphogenetic protein-2 antibodies also was observed in mesenchymal cells with fibroblastic features in the immediate vicinity of the cartilaginous areas, no staining could be detected with anti-human transforming growth factor-beta antibody in these cells. The presence of these factors were specific for the ossified ligament because no immunostaining was observed after using antibodies in the posterior longitudinal ligament at unossified levels from the same patient. It is suggested that bone morphogenetic protein-2 and transforming growth factor-beta play important roles in the development of ossification of the posterior longitudinal ligament and that bone morphogenetic protein-2 may act as an initiating factor in the development of ossification of the posterior longitudinal ligament by stimulating differentiation of mesenchymal progenitor cells. Transforming growth factor-beta may stimulate bone formation at a later stage of the process of ectopic ossification.

Aged↗
PubMed1992

Oscillation of cytoplasmic free calcium concentration induced by insulin-like growth factor I.

The effect of insulin-like growth factor I (IGF-I) on cytoplasmic free calcium concentration ([Ca2+]c) was studied in single BALB/c 3T3 cells by monitoring fura-2 fluorescence. In primed competent cells, IGF-I (1 nM) increased [Ca2+]c in approximately 60% of the cells tested. IGF-I-mediated elevation of [Ca2+]c was observed after a 4- to 17-min lag period. Elevation of [Ca2+]c was only transient but was followed by repetitive increases in [Ca2+]c. The interval between each peak was quite constant in each cell at a given concentration of IGF-I. When the concentration of IGF-I was reduced, both the latent period and interval of each peak were prolonged, whereas amplitude of the increase in [Ca2+]c was not altered. In medium containing 10 microM extracellular calcium, IGF-I did not cause any increase in [Ca2+]c. Likewise, blockade of IGF-induced calcium entry by either cobalt or tetramethrin abolished IGF-I action on [Ca2+]c. IGF-I-mediated oscillation was not affected by either ryanodine or caffeine, compounds that affect calcium-induced calcium release. In addition, pretreatment of the cell with neomycin did not affect IGF-I-mediated oscillation. In agreement with this, IGF-I did not augment production of [3H]inositol trisphosphate in cells prelabeled with [3H]inositol. These results indicate that IGF-I induces oscillation of [Ca2+]c in a single primed competent cell and that the oscillation is totally dependent on IGF-I-mediated calcium entry.

3T3 Cells↗
PubMed1992

Conserved mechanism of negative gene regulation by extracellular calcium. Parathyroid hormone gene versus atrial natriuretic polypeptide gene.

We found that a negative calcium-responsive element (nCaRE) originally reported in the human parathyroid hormone gene is conserved among several genes. The results of the present study show that expression of one of the genes, the rat atrial natriuretic polypeptide gene, was negatively regulated in the heart by extracellular calcium by using an in vivo infusion system. Moreover, transfection of the cultured cells revealed that this DNA element conferred negative regulation by extracellular calcium on the reporter gene. It is suggested that there is a gene family whose expression is negatively regulated by extracellular calcium through this conserved DNA motif, nCaRE.

Animals↗
PubMed1992

The role of renal hemodynamics in the antihypertensive action of mepirodipine, a new calcium antagonist.

To evaluate the role of regional hemodynamics in the anti-hypertensive effect of mepirodipine, a new dihydropyridine-derivative calcium antagonist, we measured systemic, renal, hepatic, and forearm hemodynamics in 10 patients with essential hypertension treated with mepirodipine (15 mg/day) for 4 weeks. After the administration of mepirodipine, a significant decline in mean blood pressure (-13.8 +/- 2.3%, p less than 0.01) accompanied by a decrease in systemic vascular resistance (-21.1 +/- 2.6%, p less than 0.01) was observed. Although forearm vascular resistance did not change significantly, both renal (-19.2 +/- 6.7%, p less than 0.01) and hepatic vascular resistance (-17.6 +/- 3.8%, p less than 0.01) decreased considerably. The decrements of mean blood pressure with mepirodipine did not correlate with those of hepatic or forearm vascular resistance but correlated positively with those of renal vascular resistance (r = 0.699, p less than 0.05). Moreover, the increment of renal blood flow with mepirodipine was negatively correlated with the pretreatment level of renal blood flow (r = -0.670, p less than 0.05); renal blood flow increased to a greater extent in patients with lower pretreatment renal blood flow. These findings suggest that the oral administration of mepirodipine in patients with essential hypertension can produce selective vasodilation in the renal vasculature, which may play an important role in the relatively long-term antihypertensive effect of this drug.

Adult↗
PubMed1992

Serum intact parathyroid hormone concentration measured by a two-site immunoradiometric assay in normal subjects and patients with various parathyroid disorders.

Serum intact parathyroid hormone (PTH) concentration was measured by a two-site immunoradiometric assay (IRMA) in normal subjects and patients with various parathyroid disorders. Serum intact PTH levels were all within the detection limit of the IRMA in normal subjects, and there was a significant negative correlation between serum calcium (Ca) and intact PTH levels. Although 3 out of 26 patients (11.5%) with primary hyperparathyroidism had a normal serum intact PTH concentration, these patients could be readily discriminated from normal subjects by plotting serum intact PTH against the serum Ca concentration. In contrast, serum intact PTH was undetectable in 16 out of 17 patients (94.1%) with idiopathic hypoparathyroidism. Patients with pseudohypoparathyroidism (PHP) type I, mostly under treatment with active vitamin D, exhibited wide distribution of serum intact PTH concentration, and appeared to belong to two distinct subgroups. One group of patients demonstrated a similar relationship between serum intact PTH and Ca levels to normal subjects. The other exhibited much higher serum intact PTH levels despite a normal serum Ca concentration, and no obvious relationship could be observed between the two parameters. These results demonstrate that an inverse relationship between serum Ca and intact PTH can be demonstrated in normal subjects with normocalcemia, that most of the parathyroid disorders can be diagnosed by measuring serum Ca and the intact PTH concentrations simultaneously, and that patients with PHP can be divided into two subgroups: one with a normal relationship between serum Ca and intact PTH, and the other with a high serum PTH level in the face of normocalcemia.

Adolescent↗
PubMed1992

Simultaneous measurement of changes in the membrane potential and the intracellular Ca2+ concentration caused by somatostatin in human GH-producing pituitary tumor cells.

Changes in the membrane potential and the intracellular Ca2+ concentration ([Ca2+]i) caused by somatostatin (SRIF) were simultaneously measured in human GH-producing pituitary tumor cells, by means of the nystatin-perforated whole cell clamp technique and Fura-2 AM. An application of 10(-8) M SRIF hyperpolarized the membrane and arrested Ca(2+)-dependent spontaneous action potentials. [Ca2+]i concurrently decreased during membrane hyperpolarization. When the membrane potential was clamped below the threshold for voltage-gated Ca2+ channels, [Ca2+]i decreased and SRIF did not further reduce [Ca2+]i. In cells which did not show spontaneous action potentials, SRIF hyperpolarized the membrane but it affected [Ca2+]i little. From these results it was concluded that the reduction in [Ca2+]i caused by SRIF was ascribed to the decrease in Ca2+ influx through voltage-gated channels during membrane hyperpolarization. The effect of SRIF on the voltage-gated Ca2+ channel current was also examined under the perforated whole cell clamp. SRIF (10(-8) M) inhibited the Ca2+ channel current to 80.8 +/- 15.4% (n = 5) of the control. Because SRIF-induced inhibition of the voltage-gated Ca2+ channel current was not prominent, it was considered that membrane hyperpolarization is the major cause of the reduction in [Ca2+]i in human GH-producing cells.

Adenoma↗
PubMed1992

A patient with protein-losing enteropathy associated with systemic lupus erythematosus.

A 46-year-old woman previously diagnosed as having systemic lupus erythematosus presented with severe hypoalbuminemia and anasarca. She was demonstrated to have protein-losing enteropathy without any other active symptoms of SLE. Her bowel habit was normal and endoscopic examination revealed non-specific colitis and a small ulcer in the duodenum. Serum biochemistry showed an abnormal profile of the serum protein, including severe hyperlipoproteinemia and hyperfibrinogenemia. The process of protein-losing was not selective in terms of the molecular size. All of these symptoms and the abnormalities in laboratory data were improved by corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMed1992

Hypomagnesemia with increased metabolism of parathyroid hormone and reduced responsiveness to calcitropic hormones.

A patient with severe hypomagnesemia due to chronic alcoholism is presented who repeatedly exhibited marked hypocalcemia with a dissociation between radioimmunoassay findings for mid region of parathyroid hormone (PTH-M) and immunoradiometric assay findings of serum intact PTH (PTH-intact). Serum PTH-M was moderately elevated whereas serum PTH-intact was in a low normal range every time when her serum magnesium (Mg) concentration was markedly reduced. There was also a marked reduction in serum osteocalcin concentration. Supplementation of Mg resulted in a sharp increase in serum PTH level with a rapid disappearance of the dissociation between the two immunoassays of PTH. Shortly after serum PTH and 1,25(OH)2D levels reached their peak, serum osteocalcin started to increase, and was elevated into a supranormal level with normalization of serum Ca concentration. Mg is thought to act as a mimic/antagonist of calcium (Ca), and high extracellular Ca is shown to cause an inhibition of secretion with a stimulation of degradation of PTH. Thus, these observations are consistent with the hypothesis that Mg deficiency causes an increase in the metabolism of PTH and a reduction in the secretion of bioactive intact PTH by increasing the sensitivity of parathyroid cells to Ca. In addition, the fact that hypocalcemia disappeared concomitant with a marked increase of serum osteocalcin from undetectable levels suggest that refractoriness of bone to calcitropic hormones is present which plays a significant role in the development of hypocalcemia under hypomagnesemia, and that serum osteocalcin can be a good marker for the assessment of the responsiveness of bone to calcitropic hormones in these patients.

Alcoholism↗
PubMed1992

Effect of 24,25-dihydroxyvitamin D3 in osteoclasts.

Previous results demonstrated that the administration of pharmacological doses of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) to animals reduces bone resorption and increases bone volume with a decrease in osteoclast number. In order to clarify whether 24,25(OH)2D3 has an effect to inhibit osteoclastic bone resorption, the effect of 24,25(OH)2D3 on the formation and function of osteoclastic cells was examined in vitro. Treatment of hemopoietic blast cells, which are progenitors of osteoclasts, with parathyroid hormone (PTH) or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulated the formation of osteoclast-like multinucleated cells in a dose-dependent manner. Although 24,25(OH)2D3 in itself had little effect on osteoclast-like multinucleated cells formation, it inhibited the stimulatory effect of PTH on the formation of osteoclastic cells. In addition, 24,25(OH)2D3 also inhibited the stimulation of resorption pit formation by osteoclasts under stimulation with PTH. In contrast, 1,25(OH)2D3 stimulated the formation and function of osteoclastic cells even at low concentrations, and the effect was additive to PTH. These results could not be explained by either an agonistic or antagonistic effect of 24,25(OH)2D3 on 1,25(OH)2D3, and are consistent with the assumption that 24,25(OH)2D3 has a unique inhibitory effect on the formation and function of osteoclasts. Because 24,25(OH)2D3 is shown to stimulate the degradation of 1,25(OH)2D3 and because the formation of 24,25(OH)2D3 is stimulated by 1,25(OH)2D3 not only in the kidney but also in many of its target tissues, including bone, the inhibitory effect of 24,25(OH)2D3 on osteoclastic bone resorption may play a role in the local modulation of the actions of osteotropic hormones in bone.

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Hemodynamic and endocrine changes associated with hypotensive action of amosulalol in essential hypertension.

To clarify the hemodynamic and endocrine mechanisms of the hypotensive effect of amosulalol, an alpha- and beta-adrenoceptor antagonist, 19 patients with essential hypertension received amosulalol (20-80 mg/day; average 48.4 mg/day) for 16 weeks. Mean blood pressure (MBP) was significantly decreased (105 +/- 1 vs. 120 +/- 1 mm Hg, p less than 0.001), associated with a decrement in heart rate (HR). Although both cardiac index (CI, 3.68 +/- 0.09 vs. 3.91 +/- 0.09 L/min/m2, p less than 0.001) and total peripheral resistance index (TPRI, 2,271 +/- 78 vs. 2,441 +/- 79 dynes.s.cm-5.m2, p less than 0.001) were reduced, changes in TPRI positively correlated with those of MBP (r = 0.9155, p less than 0.001) but the change in CI did not (r = 0.3568, NS). Plasma renin activity (PRA, 0.55 +/- 0.09 vs. 0.95 +/- 0.14 ng/ml/h, p less than 0.05) and aldosterone concentration (4.6 +/- 0.4 vs. 8.6 +/- 0.5 ng/dl, p less than 0.001) were also decreased with amosulalol. Thus, the hypotensive effect of amosulalol may be due mainly to vasodilation by alpha 1-blocking action. In addition, this hypotensive effect may be facilitated by either beta-blocking action such as decreased cardiac output (CO), with suppression of reflex tachycardia or of the renin-angiotensin-aldosterone system.

Adult↗