Search PubMed⌕ Search

Biomedical subjects

Y Ohmori

Publications and source records attributed to Y Ohmori.

At least 91 records · Page 5Linked to original sources
PubMed1995

Rapid incorporation of carbon-11-labeled diacylglycerol as a probe of signal transduction in glioma.

We have synthesized and characterized a positron-emitting carbon-11-labeled 1,2-diacylglycerol to study phosphoinositide turnover in tumor cells. Rapid incorporation of the 1,2-diacylglycerol was observed in the C6 glioma cell line. The incorporated lipid fraction consisted chiefly of phosphoinositide pool and another phospholipid pool in the proliferative state. When the state was inhibited by (-)-3D-3-deoxy-3-fluoro-myo-inositol, incorporation into the phosphoinositide pool decreased selectively. This suggested that phosphoinositide turnover is the leading regulator of tumor proliferation potential. On the basis of the concept of carbon-11-labeled 1,2-diacylglycerol as a specific probe for visualizing the tumor signal transduction in vivo, we obtained proliferating images of implanted C6 glioma cells in the rat brain by autoradiography and visualized the proliferation signal in human glioma by positron emission tomography.

Animals↗
PubMed1995

The interferon-stimulated response element and a kappa B site mediate synergistic induction of murine IP-10 gene transcription by IFN-gamma and TNF-alpha.

The present study investigates mechanisms involved in cooperation between IFN-gamma and TNF-alpha to promote transcription from the IP-10 gene in NIH 3T3 cells. IFN-gamma synergistically enhanced TNF-alpha-induced levels of IP-10 mRNA, whereas levels of JE (MCP-1) or KC (GRO/MGSA) mRNA induced by TNF-alpha were unaffected by IFN-gamma. The cooperation between IFN-gamma and TNF-alpha for induction of IP-10 mRNA was independent of de novo protein synthesis and mediated at least in part by increased transcription. Transient transfection analysis with a 243-bp fragment flanking the transcription start site of the murine IP-10 gene indicated that synergy between the two stimuli was dependent upon occupancy of at least two of three critical regulatory sequence elements: an IFN-stimulated response element (ISRE) and one of two kappa B sites. IFN-gamma and TNF-alpha independently activated nuclear factors capable of specific interaction with the ISRE and kappa B sites, respectively. IFN-gamma induced two ISRE binding complexes, one of which was protein synthesis independent, appeared within 15 min of stimulation, and contained p91 or signal transducer and activator of transcription (STAT) 1. TNF-alpha induced only one ISRE binding activity, which was dependent upon protein synthesis. TNF-alpha also induced kappa B binding activity that was composed of NF-kappa B1 (p50) and RelA (p65) whereas IFN-gamma had no detectable effect on kappa B binding activity. Together these results indicate that the highly synergistic transcriptional activation of the IP-10 gene by IFN-gamma and TNF-alpha involves the cooperation between factors that are independently activated by the two stimuli and that bind to independent sites.

3T3 Cells↗
PubMed1995

A case of advanced male breast cancer successfully treated by 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy combined with tamoxifen.

A 79-year old male advanced breast cancer patient with metastases in lymph nodes, bones and anterior chest wall was effectively treated by a combination of chemotherapy (5-fluorouracil, epirubicin and cyclophosphamide), tamoxifen and minor surgery. Two months after five cycles of chemotherapy, all lymph node swellings disappeared. The main breast cancer and the chest wall metastatic nodule were resected under local anesthesia. He was maintained on tamoxifen alone and showed no lymph node recurrence during the follow up period of 20 months, suggesting good control of bone metastatic lesions.

Aged↗
PubMed1995

Central projections of primary afferents from the interosseous nerve in the pigeon.

The interosseous nerve in the pigeon's leg innervates a string of Herbst corpuscles. Because Herbst corpuscles are vibration-sensitive, this study, using neuronal tracing methods, was expected to show the central representation of vibration sense. After application of a mixture of free and lectin-conjugated horseradish peroxidase to the interosseous nerve, labeled cell bodies of sensory and postganglionic neurons were mainly located in the dorsal root ganglia and paravertebral sympathetic ganglia L3/L4. In spinal segments L3/L4 fibers and terminals were mainly distributed at the lateral border of the head of the dorsal horn. In more cranial or caudal segments terminal fields were at intermediate parts of laminae I/II and laminae IV/V. Some labeled fibers entered the dorsal horn from medial to terminate in lamina IV. Primary afferents of the interosseous nerve projected directly to the gracile nucleus in the brainstem and distributed all along its rostrocaudal extent. Because the main terminal fields in the spinal cord are typical for the projection of small afferent fibers, vibration information seems to reach the brainstem via the dorsal column primary afferents.

Afferent Pathways↗
PubMed1995

Antiallergic constituents from oolong tea stem.

The antiallergic constituents of oolong tea stem were examined. The stem extracts inhibited the 48 h homologous passive cutaneous anaphylaxis (PCA) reactions or rats in a dose-dependent manner and showed the same extent of inhibitory activity as ketotifen. All antiallergic constituents from the stem were concentrated into chloroform and ethyl acetate fractions, when extracted by various solvents. These fractions were treated with polyvinylpolypyrrolidone (PVPP), which resulted in the elimination of antiallergic activity in the ethyl acetate fraction, suggesting that one of the antiallergic constituents may be tea catechins. Then, six kinds of catechins, (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), -epicatechin (EC), (+)-catechin (C) and (-)-gallocatechin gallate (GCG), were isolated from the ethyl acetate fraction, and the inhibitory activity of these catechins on histamine release from rat peritoneal mast cells passively sensitized with anti-egg albumin (EA) IgE antibody was investigated. Among these catechins, significant inhibitory activity was observed in all the catechins except for EC. In addition, the inhibitory activity of GCG was greater than that of EGCG, which is well known to be an antiallergic constituent in tea. These results suggest that GCG may be a novel antiallergic constituent among tea catechins, and also the most potent.

Animals↗
PubMed1995

Organization of the sources of reticulospinal projections in the chicken by means of a confocal laser scanning microscope.

To investigate the manner of reticulospinal projections in chickens, two different fluorescent dyes (Fast-Blue and Diamidino-Yellow) were injected into the lumbar and sacral segments. Results showed that the main projections to the spinal segments are clearly different for the pons and medulla. The main source of the medulospinal projections was in the ventral reticular formation, and the projections from the dorsal reticular formation were sporadic. On the other hand, the main pontine projections arose from the dorsolateral tegmentum and they projected to the sacral segments. In contrast, projections to the lumbar segments were somewhat more dominant in the ventromedial tegmentum than in the dorsolateral tegmentum. Double projection neurons were observed in the ventrolateral reticular formation and dorsolateral tegmentum where there were many cells of origin of the spinal descending projections. The reticulospinal projections manner of birds was organized dorsoventrally, and it was comparable with that of mammals.

Amidines↗
PubMed1995

[Carbon-11 labeled diacylglycerol for signal transduction imaging by positron CT: evaluation of the quality and safety for clinical use].

To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol: 11C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of 11C-DAG as the solution for injection. As a result, 11C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of 11C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, 11C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of 11C-DAG and 100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found in any organ 24 hours after administration. These findings indicated the safety of 11C-DAG solution. Clinical application of 11C-DAG using positron emission tomography may be useful to elucidate the dysfunction of intracellular signaling in disorders of higher cortical function such as Alzheimer disease.

Animals↗
PubMed1995

Clinical effect of the anti-platelet drug, dilazep dihydrochloride, in patients at the microalbuminuric stage of diabetic nephropathy--a multi-center study.

Clinical effects of an anti-platelet drug (dilazep dihydrochloride) in the microalbuminuric stage of diabetic nephropathy were investigated in a multi-center study. Thirty-seven patients with at the microalbuminuric stage of diabetic nephropathy were examined in the present study. They were administered 300 mg/day of dilazep dihydrochloride (Comelian-Kowa) orally for 6 months. Mean values of albuminuria after the administration of dilazep dihydrochloride were significantly decreased compared with the pre-administration values. Urinary NAG activity was improved after this treatment in the microalbuminuric stage of diabetic nephropathy. Furthermore, impairment of renal function was not observed at that stage. It appears that administration of dilazep dihydrochloride from the early stage of diabetic nephropathy may be useful for the improvement of albuminuria and prevention of renal dysfunction.

Adult↗
PubMed1994

Murine inhibitory protein-kappa B alpha negatively regulates kappa B-dependent transcription in lipopolysaccharide-stimulated RAW 264.7 macrophages.

The potential role of the inhibitory protein (I)-kappa B alpha gene in control of LPS-dependent transcription has been investigated in the murine macrophage cell line RAW 264.7. LPS-induced transcription in macrophages is believed to involve activation of members of the Rel homology family of transcription factors, and may be negatively regulated by cytoplasmic inhibitor proteins collectively termed I-kappa Bs. To evaluate the role of I-kappa Bs in LPS-stimulated macrophages, murine I-kappa B alpha (ml-kappa B alpha) has been expressed as a glutathione-S-transferase (GST) fusion protein and examined for its ability to control kappa B binding activities in nuclear extracts from LPS-treated RAW 264.7 macrophages. ml-kappa B alpha-GST inhibited LPS-induced kappa B binding activity from RAW 264.7 cells in a phosphorylation-dependent fashion, but did not affect IFN-alpha-induced IFN stimulus response element binding. Recombinant I-kappa B alpha inhibited kappa B motif binding by nuclear factor-kappa B1, RelA, and c-Rel as indicated by studies using UV radiation-induced covalent cross-linking to a bromodeoxyuridine-substituted kappa B oligonucleotide. Transfection of macrophages with an expression vector encoding ml-kappa B alpha inhibited LPS-stimulated transcription driven by a 243-bp promoter sequence obtained from the 5' flanking region of the murine IP-10 gene. This promoter sequence contains two kappa B motifs that have been shown to be critical to LPS-dependent reporter gene transcription. The kappa B sites seem to be the specific target of I-kappa B alpha function, as reporter gene transcription driven by these motifs in the context of a heterologous thymidine-kinase promoter (TK) also was inhibited by co-transfection with ml-kappa B alpha. These observations indicate that ml-kappa B alpha is capable of controlling kappa B-dependent transcription in LPS-stimulated murine macrophages.

Animals↗
PubMed1994

Mechanisms of IL-4-mediated suppression of IP-10 gene expression in murine macrophages.

The mechanisms involved in negative regulation of IFN-gamma-induced IP-10 mRNA expression by IL-4 have been examined in an immortalized murine macrophage cell line (ANA-1). As in primary peritoneal macrophages, IL-4 selectively inhibits the production of IP-10 mRNA by IFN-gamma-treated ANA-1 cells. Expression of another IFN-gamma-inducible gene (D3) was not affected by co-treatment with IL-4. Suppression of IFN-gamma-induced IP-10 mRNA expression by IL-4 is mediated at the level of transcription. IFN-gamma-induced transcription of CAT expression driven by a 243-bp IP-10 promoter fragment was also sensitive to the suppressive effects of IL-4. In contrast, LPS-induced CAT expression was unaffected under identical experimental conditions. The positive transcriptional response to IFN-gamma required an interferon stimulus response element (ISRE) sequence motif located approximately 230 bp upstream from the transcription start site of the IP-10 gene. That this site is the target of the suppressive action of IL-4 is indicated by the ability of IL-4 to inhibit IFN-gamma-mediated transcription from this ISRE sequence in the context of a heterologous promoter. Finally, both IFN-gamma and IL-4 can enhance or induce expression of distinct nuclear factors that exhibit ISRE-specific binding activity. IL-4 does not suppress the IFN-gamma-induced ISRE binding activity. Together, these findings demonstrate that IL-4 inhibits IP-10 mRNA production in murine macrophages by suppressing the formation of new transcripts. Both positive and negative transcriptional activity appears dependent on activation of factors that recognize the ISRE.

Animals↗
PubMed1994

IFN-gamma selectively inhibits lipopolysaccharide-inducible JE/monocyte chemoattractant protein-1 and KC/GRO/melanoma growth-stimulating activity gene expression in mouse peritoneal macrophages.

IFN-gamma and LPS have both been shown to stimulate enhanced chemoattractant cytokine gene expression in mononuclear phagocytes. In this report, IFN-gamma was found to suppress LPS-induced chemokine mRNA expression in a cell type- and gene-specific fashion. Expression of JE (monocyte chemoattractant protein-1) and KC (GRO/melanoma growth-stimulating activity) mRNA in macrophages stimulated with LPS was markedly suppressed by IFN-gamma in a dose- and time-dependent fashion. LPS-induced IP-10 mRNA was unaffected by IFN-gamma under identical experimental conditions. This effect was cell type-specific because JE and KC mRNA expression in LPS-stimulated murine endothelial cells, TNF-alpha-stimulated endothelial cells, and NIH-3T3 cells were unaffected by IFN-gamma. The IFN-gamma-mediated suppression of LPS-stimulated KC mRNA expression was independent of protein synthesis and mediated at the transcriptional level. These observations indicate that IFN-gamma may function as a negative regulatory signal for the expression of some proinflammatory cytokines in macrophages. The cell type-dependent differential behavior of individual members of the chemokine family may be an important determinant of the cellular composition and outcome of an inflammatory response.

Animals↗
PubMed1994

Kappa B binding activity in a murine macrophage-like cell line. Sequence-specific differences in kappa B binding and transcriptional activation functions.

The role of two distinct kappa B sequence motifs found in the promotor of the murine IP-10 gene was studied in the transcriptional response of macrophages to lipopolysaccharides (LPS). When the murine macrophage cell line RAW 264.7 was stimulated with LPS, at least three different kappa B sequence-specific complex-forming activities were observed in nuclear extracts as assayed by electrophoretic mobility shift assay (EMSA). These three complexes were distinguished from one another in terms of time of appearance following stimulation and selectivity for one of the two different kappa B sequence motifs. The participation of individual members of the Rel homology family of kappa B sequence binding factors was assessed by use of specific antibodies in combination with either EMSA or UV-cross-linking to radiolabeled, BrdUrd-substituted oligonucleotide probes. The C1 complex contained predominantly NF kappa B1 (p50). The C2 complex contained NF kappa B1, RelA (p65), and perhaps other factors. The C3 complex contained predominantly c-Rel. Both kappa B sequences were able to mediate reporter gene transcription in LPS-stimulated macrophages, but the sites behaved differentially in cells co-transfected with expression vectors encoding different members of the Rel homology family. The results indicate that LPS activates several different forms of kappa B binding activity in murine macrophages which are composed of at least three different members of the Rel homology family. These binding activities exhibit differential recognition of and functional activation through the two distinct kappa B sequence motifs.

Animals↗
PubMed1994

Preparation of fibre-entrapped enzyme using cellulose acetate-titanium-iso-propoxide composite as gel matrix.

Enzyme (uricase or invertase) was entrap-immobilized in gel fibre of cellulose acetate-TiO2 by using a gel formation of cellulose acetate and titanium iso-propoxide. The fibre is stable in common solvents, phosphate solution and electrolyte solution over a wide range of pH 4-10. The pH maximum of activity shifts to a more alkaline side compared to free enzyme, reflecting an amphoteric property of TiO2.

Cellulose↗
PubMed1994

Cell type and stimulus specific regulation of chemokine gene expression.

The pattern of chemoattractant cytokine gene (IP-10, JE, KC) expression has been examined in BALB/c 3T3 fibroblasts and MC3T3-E1 osteoblasts in response to a variety of different inflammatory stimuli, including IFN gamma, TNF alpha, IL-1 alpha, and IL-6. Both cell types expressed JE and IP-10 mRNAs but the response pattern varied in a stimulus- and gene-dependent fashion. KC mRNA was only expressed in BALB/c 3T3 cells stimulated by IL-1 alpha. The time dependence for expression was distinctive for each gene but was comparable despite different forms of stimulation. Nevertheless, the mechanisms involved in the induction of each gene varied with the stimulus and involved both transcriptional and post-transcriptional components. These findings reflect the diversity of chemokine gene expression in vivo and may be important in mechanistic understanding of the diversity of inflammatory response patterns.

3T3 Cells↗
PubMed1994

Idiopathic portal hypertension in renal transplant recipients: report of two cases.

We present herein the cases of two patients who developed idiopathic portal hypertension (IPH) following renal transplantation. Both patients had been treated with azathioprine and prednisolone for 6 years and 4 months and for 4 years and 7 months, respectively, and presented with splenomegaly and thrombocytopenia suggesting hypersplenism. Celiac angiography showed a dilated splenic artery and vein in both patients. When the splenic artery was obliterated with a balloon catheter in case 1, the portal venous pressure decreased from 51 cmH2O to 36 cmH2O, and the direction of the superiomesenteric venous blood flow became hepatopetal rather than hepatofugal. These results suggested that the spleen might have played an important role in the development of IPH in these two patients. A splenectomy was therefore performed, immediately following which the portal venous pressure decreased remarkably, and the esophageal varices disappeared during the postoperative follow-up period. Microscopic examination of liver biopsies taken at the operation revealed lymphoplasmacytic infiltration with bile duct hyperplasia but no evidence of periportal fibrosis, and electron microscopy demonstrated very mild perisinusoidal fibrosis. Thus, the histological changes seen in the livers of these patients seemed not to have caused the portal hypertension. In conclusion, although few patients develop IPH after renal transplantation, we should be aware of its possibility and consider splenectomy as the treatment of choice.

Adult↗
PubMed1994

Regulation of macrophage gene expression by T-cell-derived lymphokines.

Cytokines secreted from antigen-specific T lymphocytes provide important positive and negative control of inflammation through their effects on non-antigen-specific inflammatory leukocytes. These effects often involve modulation of gene expression. Lymphokine-inducible macrophage gene expression is largely controlled at the level of transcription. Multiple cis-acting sequence motifs cooperate with one another to produce patterns of expression that are relatively unique to individual genes. Members of trans-acting transcription factor families, which recognize related regulatory sequence elements, participate frequently in complex protein-protein interactions that generate remarkable complexity in terms of the number of potential combinations and the consequential functional differences exhibited by each combination. Thus, the remarkable plasticity of immune-mediated inflammation derives from combinations of finite numbers of options at several points in the cellular and molecular sequence.

Animals↗