Biomedical subjects

Y Ohmori

Publications and source records attributed to Y Ohmori.

At least 127 records · Page 7Linked to original sources

PubMed1993

Functional domains of c-Myc involved in the commitment and differentiation of murine erythroleukemia cells.

In the early event of the induction of mouse erythroleukemia (MEL) cell differentiation, c-myc mRNA levels show a drastic change. The elevated expression of a transfected c-myc gene inhibits the commitment and differentiation of MEL cell transformants. In the present work, we have introduced human c-myc mutants into MEL cells under the inducible promoter to define the functional domains of c-Myc involved in erythroid differentiation. The c-Myc domains necessary for commitment and differentiation are not co-localized; almost entire regions are required for inhibition of commitment, whereas domains II and IV that are essential for co-transforming activity with ras are required for inhibition of differentiation. Interestingly, mutants that delete domains for c-Myc dimerization motifs enhanced differentiation. These results suggest that c-Myc may regulate commitment and differentiation by interacting with proteins through different domains.

Animals↗

PubMed1993

Protein kinase C imaging using carbon-11-labeled phorbol esters: 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate as the potential ligand for positron emission tomography.

Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-11C]butyrate, phorbol 12,13-[1-11C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate, were synthesized by using [11C]ethylketene with a high specific activity (186GBq/mumol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of this compound to protein kinase C were confirmed by in vivo displacement studies with unlabeled 12-deoxyphorbol 13-isobutyrate-20-butyrate and unlabeled phorbol 12,13-dibutyrate. This suggests that 12-deoxyphorbol 13-isobutyrate-20-[1-11C] butyrate has a specific binding affinity for protein kinase C.

Animals↗

PubMed1993

Tumor necrosis factor-alpha induces cell type and tissue-specific expression of chemoattractant cytokines in vivo.

Recombinant murine tumor necrosis factor-alpha (TNF-alpha) was shown to be a strong, systemic stimulus in vivo for members of the chemoattractant cytokine gene families (JE, KC, IP-10). The three genes showed differential sensitivity to TNF-alpha, and their expression demonstrated differential tissue specificity. IP-10 was the most strongly induced messenger RNA and was seen in the liver, kidney, and spleen but very poorly in the lung or skin. JE exhibited a similar pattern, though the magnitude of expression was markedly lower. KC expression was seen only in the liver of TNF-alpha-treated mice. The time course of expression for IP-10 was rapid and transient and showed strong dose dependence. In mice treated with TNF-alpha intravenously, messenger RNA was localized in the splenic stroma but not in adherent macrophages or nonadherent lymphocytes. In situ hybridization found the majority of intercrime expression in the splenic red pulp with little or no expression seen in the white pulp. In vitro, TNF-alpha was a potent stimulus of chemoattractant messenger RNA expression in fibroblasts but not in inflammatory peritoneal macrophages. These results indicate that TNF-alpha may be an important stimulus for chemoattractant cytokine gene expression in vivo, and the primary cell types responsible may be either stromal fibroblasts, microvascular endothelium, and/or a subset of anchored mononuclear phagocytes.

3T3 Cells↗

PubMed1992

Ca2+ and calmodulin selectively regulate lipopolysaccharide-inducible cytokine mRNA expression in murine peritoneal macrophages.

The role of Ca2+ and Calmodulin in regulating LPS-induced cytokine gene expression in murine peritoneal macrophages has been investigated. Treatment of macrophages with three structurally distinct antagonists of Calmodulin (Trifluoperazine, N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide, and 1,3-dihydro-1-(-((4-mentyl-4H,6H-pyrrolo(1,2-a) (4,1)-benzoxazepin-4-yl)methyl)-4-peperidinyl)-2H-benzimi dazol-2-one) resulted in a characteristic modulation of the expression of three LPS-inducible cytokine genes: IL-1 alpha mRNA levels were only modestly reduced, IL-1 beta mRNA levels were markedly suppressed and IP-10 mRNA levels were increased. The same pattern of modulation was seen when LPS-stimulated cells were also treated with two different Ca2+ antagonists (8-(diethylamono)-octyl-3,4,5-trimethoxybenzoate hydrochloride and bis-(o-amonophenoxy)-ethane-N,N,N'N'-tetraacetic acid). Although the suppression of IL-1 beta mRNA accumulation by N-(6-amonohexyl)-5-chloro-1-napthalene-sulfonamide or bis-(o-amonophenoxy)ethane-N,N,N'N'-tetraacetic acid occurred even if the antagonist was added after LPS, the potentiation of IP-10 mRNA levels required the use of the agent before or along with the LPS stimulus. Elevation of intracellular Ca2+ using ionomycin did not initaite cytokine gene expression and thus changes in Ca2+ cannot replace the LPS-initiated signal. Furthermore, removal of extracellular Ca2+ did not block the response to LPS. Calmodulin antagonists selectively increased the transcriptional activity of the IP-10 gene but decreased the stability of all three mRNA measured. Thus the mechanisms involved in Ca2+/Calmodulin control of macrophage gene expression are multifactorial and contribute to the diversity of macrophage inflammatory behavior. In concert with previous reports, the present results indicate that Ca2+, acting through Calmodulin may be a necessary but insufficient component of the signalling process that mediates intracellular response to LPS. Agents that alter intracellular Ca2+ levels without inducing cytokine gene expression may thereby indirectly regulate inflammation.

Animals↗

PubMed1992

Clinical factors which influence the long-term survival of kidney allografts donated from haploidentical donors.

All patients with renal transplants are very much concerned about their chance of long-term graft function. Chronic rejection is the most common cause of decline in function and graft failure, and after the first post-transplant year, 3-4% of recipients lose their graft every year. However, the cause, time of onset and mechanism of decline in graft function are not clear. Also unclear is whether clinical and laboratory parameters may predict patients who are at risk of developing chronic rejection. The aim of this study was to find the marker which may determine long-term graft survival in the azathioprine era and in the cyclosporine era.

Biomarkers↗

PubMed1992

Immunohistochemical studies on the intrinsic pancreatic nerves in the chicken.

A peroxidase anti-peroxidase method or an avidin-biotinylated complex method was used to visualize neural elements immunostained for several neuropeptides in the chicken pancreas. Pancreatic ganglion cells were only immunoreactive with vasoactive intestinal polypeptide (VIP), galanin and substance P (SP) antisera. VIP-immunoreactive (IR) ganglion cells were the most numerous, and most of them also showed the distinct immunoreaction with galanin. VIP- and galanin-IR nerve fibers were observed in the exocrine portion, the adventitia of the artery and the connective tissue of the ductal wall. The number and distribution of the VIP- and galanin-IR nerve fibers around the artery and duct were similar. SP-IR nerve fibers were found mainly close to the blood vessel. SP- and CGRP-IR nerve fibers were detected in the VIP-IR ganglion and extrapancreatic nerve bundle. Tyrosine hydroxylase (TH)- and aromatic L-amino acid decarboxylase (AADC)-IR nerve fibers were observed as nerve bundles in the interlobular space or extrapancreatic nerves. Consequently, VIP and galanin coexist in the intrinsic neural elements. SP is partially located in the intrinsic neural elements, but most of it seems likely to originate from the extrinsic ganglion. It is probable that calcitonin gene related peptide (CGRP)-, TH- and AADC-IR nerve fibers have an extrinsic origin.

Animals↗

PubMed1992

Sympathetic and sensory neurons projecting into the cervical sympathetic trunk in the chicken.

The cell bodies of the sensory and sympathetic pre- and postganglionic neurons projecting into the cervical sympathetic trunk were retrogradely labeled with horseradish peroxidase in the chicken. Preganglionic neurons were located in the spinal segments T1-T6 (maximum T2), postganglionic neurons in the paravertebral ganglia T1-T3 (maximum T1) and sensory neurons in the dorsal root ganglia T1-T4 (maximum T1). Labeled preganglionic neurons were widely distributed across the intermediate gray matter and lateral funiculus, but the majority of them were located in the intermediomedial area dorsolateral to the central canal. The short and long axis diameters of labeled preganglionic neurons in this area decreased caudally. From the data of the present study, it is estimated that about 4190 preganglionic, about 450 postganglionic and about 390 sensory neurons project into the cervical sympathetic trunk cranial to the paravertebral ganglion T1 in the chicken.

Animals↗

PubMed1992

The effects of pravastatin on hyperlipidemia in renal transplant recipients.

Hyperlipidemia may be one of the risk factors in the development of atherosclerotic disease in renal transplant recipients. In the present study, 24 kidney recipients with hyperlipidemia were treated with an HMG-CoA reductase inhibitor, pravastatin (10 mg/day). All recipients had been treated with cyclosporine (CsA), azathioprine (Az), and prednisolone (Pred). The mean total cholesterol (T-chol) level decreased from 323 +/- 7.4 to 261 +/- 7.9 mg/dl at one month after starting treatment (P less than 0.01) and this level did not change during treatment for further 6 months. The mean LDL cholesterol level was also decreased from 205.9 +/- 11.2 to 118.7 +/- 8.1 mg/dl at 3 months after starting treatment (P less than 0.01). On the other hand, pravastatin did not affect the levels of HDL-cholesterol and triglycerides. Pravastatin did not show any effects on the white blood cell, monocyte, and lymphocyte counts, or the hemoglobin concentration (NS). One patient displayed a slight elevation of aspartate aminotransferase and alanine aminotransferase levels, but this was not sufficient to cease treatment. Pravastatin did not adversely affect the renal function or creatinine phosphokinase (CPK) levels. Two recipients developed nausea and vomiting and their treatment was stopped. Pravastatin appears to be a safe and efficacious method of treating hyperlipidemia in renal transplant recipients.

Cholesterol↗

PubMed1992

c-Myc interferes with the commitment to differentiation of murine erythroleukemia cells at a reversible point.

When murine erythroleukemia (MEL) cells, containing the transferred rat c-myc gene under the control of human metallothionein II gene promoter, are induced to differentiate with dimethyl sulfoxide, the level of differentiation is dependent on the c-Myc level, which is modulated by the addition of Zn ions. In this work, we examined the point of inhibition of differentiation by elevated levels of c-Myc in one (clone 38-2) of the typical transformants. Commitment assay indicated that elevated levels of c-Myc interfere with entry of the transformant into the commitment event, but when c-myc expression was reduced by removing Zn ions from the medium, the cells could reenter the commitment program. However, once the cells were committed, such cells could not return to the uncommitted state. In addition, time-dependent expression of two erythroid specific genes was inhibited by elevated levels of c-Myc in time-dependent manner. These results suggest that c-Myc modulates MEL cell differentiation at a reversible point of commitment.

Animals↗

PubMed1992

Immunohistochemical morphometry of pancreatic islets in the cat.

The application of immunohistochemical technique with antisera for glucagon (Glu), insulin (Ins), somatostatin (Som) and pancreatic polypeptide (PP) to serial sections of the cat pancreas permitted the quantitative evaluation of the population of 4 endocrine cell types and that of the area, larger diameter and density of islets. The pancreas was divided macroscopically into the 4 portions, duodenal, gastric, anastomotic and splenic. The duodenal portion was characterized by the localization of PP-immunoreactive (IR) cell-rich islets, the dissemination of PP-IR cells in the exocrine parenchyma and the absence of Glu-IR cells. In the duodenal portion, the area, the larger diameter and the density of islets were significantly smaller than those in the other 3 portions. On the contrary, the other 3 portions were marked with the deficiency of PP-IR cells and the existence of Glu-IR cell-rich islets. Ins-IR cells, identified as compact cell masses without any other types of cells, occupied a major part of every islet, composing much the same population throughout the 4 portions. The Som-IR cell population appeared to be closely in parallel with the Glu-IR cell population in all of the portions. It is concluded that all islets are similar in the Ins-IR cell population, but different in the complementary arrangement of Glu- and PP-IR cells. Based on this difference, 2 types of islets can be classified.

Animals↗

PubMed1992

Role of c-Myc on erythroid differentiation.

In the early event of the induction of mouse erythroleukemia (MEL) cell differentiation, c-myc mRNA levels show a biphasic change. The elevated expression of a transfected c-myc gene inhibits the commitment and differentiation of MEL cell transformants. In the present work, we have introduced human c-myc mutants into MEL cells under the inducible promoter to define the functional domains of c-Myc involved in erythroid differentiation. The c-Myc domains necessary for commitment and differentiation are not colocalized; almost entire regions are required for inhibition of commitment, whereas domains II and IV that are essential for co-transforming activity with ras are required for inhibition of differentiation. Interestingly, mutants that delete domains for c-Myc dimerization motifs enhanced differentiation. Thus, c-Myc interferes with MEL cell differentiation by interacting with c-Myc partners and the induced protein(s) through dimerization domains. These results suggest that c-Myc may regulate commitment and differentiation by interacting with proteins through different domains.

Animals↗

PubMed1992

Positron emission tomographic measurement of acute hemodynamic changes in primate middle cerebral artery occlusion.

Specific hemodynamic changes in acute ischemia were investigated using a middle cerebral artery occlusion primate model and positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate for oxygen were measured 1, 3, and 9 hours after occlusion. OEF showed an increase in ischemic areas, and especially where CBF was below 18 ml/100 gm/min 1 hour after occlusion the OEF increased significantly (0.69 +/- 0.20, p < 0.05). Nine hours after occlusion, the OEF values were lower compared to those 1 and 3 hours after occlusion. Areas where CBF ranged from 18 to 31 ml/100 gm/min showed an increase in OEF at all times (p < 0.05). Clearly, OEF changes remarkably in the acute stage.

Animals↗

PubMed1991

Number and density of intrapancreatic ganglion cells in the chicken.

The avian pancreas contains numerous small ganglia in nerve bundles within the interlobular connective tissue. The present study assesses the number and density of intrapancreatic ganglion cells in the chicken. The number of ganglion cells in the pancreas was about 14,000 and the density was 18.0 cells/mm3. No ganglion cells were found in the pancreatic islet. The topographical distribution of ganglion cells suggests that they have a closer relationship with the acinus than with the pancreatic islet and, furthermore, closer with B-islets than with A-islets.

Acetylcholinesterase↗

PubMed1991

Modulation of Na+/K+ exchange potentiates lipopolysaccharide-induced gene expression in murine peritoneal macrophages.

The role of Na+/K+ exchange in regulating lipopolysaccharide (LPS)-mediated induction of cytokine gene expression has been examined in murine peritoneal macrophages. Depletion of K+ from the culture medium resulted in a three- to five-fold potentiation of tumor necrosis factor-alpha (TNF alpha), KC (gro), and IP-10 mRNA expression in LPS-treated macrophages. The potentiating effect was apparently the result of inhibition of Na+/K+ exchange through the Na+/K(+)-adenosine triphosphatase (ATPase) because ouabain-mediated inhibition of Na+/K(+)-ATPase was also able to potentiate cytokine mRNA expression as much or more than did K+ depletion. The effects of K+ depletion or ouabain treatment were not caused by depolarization of the macrophage membrane because depolarization mediated by elevating extracellular K+ levels was inhibitory to cytokine mRNA expression. Depletion of Na+ by substitution with choline in the culture medium also markedly potentiated LPS-induced gene expression. The Na+/H+ antiporter was not, however, involved in potentiating cytokine expression because treatment of macrophages with amiloride either had no effect on or was inhibitory to the LPS-induced changes in mRNA levels. The potentiation of gene expression was selective and was at least partially the result of increased transcriptional activity of each gene. Whereas Na+ depletion and ouabain both inhibited 86Rb+ uptake by macrophages, treatment with LPS had no effect either on Rb+ uptake or on efflux. Thus altered Na+/K+ exchange is not a component of the primary signalling pathway(s) mediating response to LPS. Nevertheless, modulation of macrophage Na+/K+ exchange by agents encountered during an inflammatory response may be an important determinant of the magnitude and quality of specific gene expression.

Animals↗

PubMed1991

Pharmacological and biochemical characteristics of partially purified GABAB receptor.

Pharmacological and biochemical characteristics of the partially purified gamma-aminobutyric acid (GABA)B receptor using baclofen affinity column chromatography have been examined. The Scatchard analysis of [3H]GABA binding to the purified GABAB receptor showed a linear relationship and the KD and Bmax values were 60 nM and 118 pmol/mg of protein, respectively. Although GTP and Mg2+ did not affect on the GABAB receptor binding, Ca2+ significantly increased [3H]GABA binding to the purified GABAB receptor in a dose-dependent manner and showed its maximum effect at 2 mM. The enhancement of the binding by Ca2+ was found to be due to the increase of Bmax by the Scatchard analysis. The treatments with pronase and trypsin significantly decreased the binding of [3H]GABA, but phospholipase A2 had no significant effect on the binding. In addition, treatment with glycosidases such as glycopeptidase A and beta-galactosidase significantly decreased the binding of [3H]GABA to the purified GABAB receptor. These results suggest that purification of the solubilized GABAB receptor by the affinity column chromatography may result in the functional uncoupling of GABAB receptor with GTP-binding protein. Furthermore, the present results suggest that cerebral GABAB receptor may be a glycoprotein and membrane phospholipids susceptible to phospholipase A2 treatment may not be involved in the exhibition of the binding activity.

Animals↗

PubMed1991

Bacteroides (Porphyromonas) gingivalis fimbriae activate mouse peritoneal macrophages and induce gene expression and production of interleukin-1.

The purpose of this study was to examine whether Bacteroides (Porphyromonas) gingivalis fimbriae, an important structure involved in attachment of the bacteria to periodontal tissues, activate macrophages and subsequently induce gene expression and production of interleukin-1 (IL-1) in the cells. The fimbriae increased glucose consumption and lysozyme activity in BALB/c macrophages, both criteria of macrophage activation of peritoneal macrophages, in a dose-dependent fashion. A marked increase in the mRNA level of the c-myc gene, an oncogene, in the cells was observed after a 1-h treatment with the fimbriae, and the level decreased rapidly after 3 h. The fimbriae (4 micrograms of protein per ml) markedly induced IL-1 alpha and IL-1 beta gene expression in the cells and IL-1 production. The expression of IL-1 alpha and IL-1 beta genes measured in terms of specific mRNA increased 1 h after the start of treatment and peaked at 6 h. Such increased expression of IL-1 beta was also observed in C3H/HeJ mice, a lipopolysaccharide low-responder strain. The fimbriae stimulated transcriptional activity of IL-1 beta in the cells, but not that of IL-1 alpha. We also observed that fimbriae-induced IL-1 gene expression was not regulated by endogenous prostaglandin triggered by the fimbriae. Therefore, these observations suggest that B. gingivalis fimbriae may be involved in the pathogenesis of adult periodontal disease via triggering of IL-1 production by monocytes/macrophages in periodontal diseases.

Animals↗

PubMed1991

[An evaluation of cerebral blood flow and metabolism of reconstructive vascular surgery using positron emission tomography--a report of 4 cases].

Changes in cerebral hemodynamics due to reconstructive cerebral vascular surgery were evaluated using positron emission tomography (PET). Three minor stroke cases and 1 TIA case, brought on by main trunk stenosis, were included. STA-MCA anastomoses was performed in two of the cases and carotid endarterectomy was performed in the remaining two cases. CBF, CBV, OEF, CMRO2 and CBF/CBV were investigated using PET with the ROIs fixed in both normal and stenosis areas. On the two cases of STA - MCA anastomosis, clear hemodynamic improvement was not demonstrated. On the two carotid endarterectomy cases, the hemodynamic factors showed improvement.

Aged↗

PubMed1991

[Intracranial fibrous xanthoma (xanthofibroma) in an infant: a case report].

A case of intracranial fibrous xanthoma (xanthofibroma) is reported. Intracranial fibrous xanthoma in infancy under the age of 1 year is extremely rare. This patient was a 8-month-old boy with a history of convulsive seizure. He had a previously known chest wall tumor which was diagnosed as fibrous xanthoma of the skin. Plain CT scan revealed a well defined high density area in the left temporal lobe. The area was well enhanced with contrast media. At operation, it was found that the tumor did not attach to dura mater and was almost well demarcated. Total removal of the tumor was performed. The patient has been doing well for these 6 months following craniotomy, with no sings of recurrence and no neurological deficits. Histologically, the tumor was composed of fibroblastic cells and foamy phagocytic cells in storiform pattern. Some multinucleated giant cells were found. Immunohistochemistry technique revealed that the tumor cells were negative for GFAP, positive for Vimentin, positive for S-100 protein and negative for EMA. Our studies support the diagnosis of intracranial fibrous xanthoma coexistent with the same tumor found in the subcutaneous space of the chest wall of a boy under 1 year of age. We regard it as a rare incidence. Differential diagnosis and the characteristics of fibrous xanthoma were discussed.

Brain Neoplasms↗