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Biomedical subjects

Y Ohmori

Publications and source records attributed to Y Ohmori.

At least 145 records · Page 8Linked to original sources

cAMP differentially regulates expression of mRNA encoding IL-1 alpha and IL-1 beta in murine peritoneal macrophages.

The influence of PGE2 and the consequent rise in intracellular cAMP on LPS-induced IL-1 alpha and IL-1 beta mRNA levels has been examined in murine peritoneal macrophages. As has been previously reported, neither PGE2 nor dibutyryl cAMP modulated the levels of LPS-induced IL-1 alpha mRNA. In contrast, the levels of IL-1 beta mRNA were markedly potentiated (greater than 10 fold) under the same experimental conditions. This effect was due to elevation of intracellular cAMP because other agents known to elevate cAMP levels (e.g., cholera toxin, forskolin, 1-isomethyl-3-isobutylxanthine) had the same selective effect on IL-1 beta mRNA levels. PGE2 and dBcAMP not only potentiated LPS-induced IL-1 beta mRNA levels but were also able to stimulate modest accumulation of IL-1 beta mRNA in the absence of LPS. Although measurement of IL-1 activity by bioassay suggested that dBcAMP and PGE2 could suppress LPS-induced IL-1 expression, levels of IL-1 protein, determined by radioreceptor assay, were markedly elevated. cAMP did not appreciably alter the stability of either IL-1 alpha or IL-1 beta mRNA. Instead dBcAMP independently stimulated the transcriptional activity of the IL-1 beta gene. In concert the results demonstrate that cAMP can modulate the response of mononuclear phagocytes to LPS in a complex pattern; gene expression may be unaltered, suppressed, or potentiated and will thereby affect both the quality and magnitude of the ensuing inflammatory response.

Animals↗

Solubilization and partial purification of GABAB receptor from bovine brain.

gamma-Aminobutyric acid (GABA)B receptor has been solubilized and partially purified by an affinity column chromatography. GABAB receptor was solubilized by 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) in the presence of asolectin. The solubilized GABAB receptor was adsorbed on baclofen-coupled epoxy-activated Sepharose 6B. The affinity matrix adsorbed 80% of the solubilized [3H]GABA binding activity to GABAB receptor, and approximately 75% of the adsorbed activity could be eluted with 1 M KC1. GABAB receptor binding in the fraction eluted from affinity column was displaced by GABA, baclofen and 2-hydroxy saclofen in a dose-dependent manner. Furthermore, the purified GABAB receptor showed approximately 2800-fold purification as compared with the original solubilized fraction and possessed the specific binding activity of 17.68 p mol/mg of protein. This binding consisted of a single binding site with a dissociation constant of 64.4 nM. The present results indicate that affinity column chromatographic procedures using baclofen-coupled epoxy-activated Sepharose 6B are suitable for the partial purification of GABAB receptor from cerebral tissues.

Animals↗

A macrophage LPS-inducible early gene encodes the murine homologue of IP-10.

Recently, we have isolated and characterized a set of cDNA clones which encode lipopolysaccharide-inducible proteins in murine peritoneal macrophages. Here, we report the sequence and identification of one of these cDNAs previously termed C7. Nucleotide sequence analysis revealed an open reading frame encoding a predicted polypeptide composed of 98 amino acids, which contained a 21 amino acid residue signal peptide, indicating approximately 9 kDa of mature protein. The deduced protein sequence showed homology (67% identity, 77% considering conservative amino acid changes) with the human INF gamma-inducible gene IP-10, a member of the recently described superfamily of chemotactic and mitogenic proteins which includes platelet factor 4, monocyte-derived neutrophil chemotactic factor (NAF, NAP-1, IL-8), and MGSA/gro/KC. Thus C7 would appear to represent the murine homologue of the human IP-10 gene or a very closely related gene.

Amino Acid Sequence↗

Functional coupling of the gamma-aminobutyric acidB receptor with calcium ion channel and GTP-binding protein and its alteration following solubilization of the gamma-aminobutyric acidB receptor.

The coupling mechanism of the gamma-aminobutyric acid (GABA)B receptor, one of the subtypes of GABA receptors, with calcium ion channel and GTP-binding protein was examined using a crude synaptic membrane (P2) fraction from the bovine cerebral cortex and a fraction solubilized with sodium deoxycholate. In the P2 fraction, [3H]GABA binding to the GABAB receptor was increased significantly by the addition of calcium ion, and this enhancement was accentuated further by calcium ion channel blockers such as nicardipine and diltiazem. In contrast, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, did not affect on the calcium ion-induced enhancement of GABAB receptor binding. These results suggest that the GABAB receptor may be functionally coupled with the calcium ion channel, which exhibits an inhibitory modulation against the receptor. On the other hand, GABAB receptor binding, which was noncompetitively inhibited by guanine nucleotides such as GTP, guanosine 5'-(3-O-thio)triphosphate (GTP gamma S), guanosine 5'-(beta, gamma-imido)triphosphate [Gpp(NH)p], and GDP, was competitively inhibited by (-)-baclofen. Although the affinity of (-)-baclofen for the GABAB receptor was decreased in the presence of GTP, pretreatment of the P2 fraction with islet-activating protein (IAP) eliminated the effect of GTP. In addition, GABA and (-)-baclofen induced an increase of GTPase activity in the P2 fraction, and this increase was also eliminated by treatment with IAP. These results suggest that the GABAB receptor may also be functionally coupled with IAP-sensitive GTP-binding protein. Treatment of the P2 fraction with sodium deoxycholate resulted in the highest solubilization of GABAB receptor among various detergents examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Two cases of rectal carcinoma that developed as a late complication of pelvic radiotherapy].

Two cases of a pelvic evisceration have been performed, due to an irradiation-induced rectal cancer. Described are the cases of two women who had been treated with irradiation for a cervical cancer following a hysterectomy, one patient being 65 years old and the other 67. After a latent period that lasted for 12 and 24 years, respectively, each had developed a rectal cancer. In each case, case excised specimen showed diffuse fibrosis and a hyaline change, reflecting the effect of radiation on the tumoral tissue. Cases of an irradiation-induced rectal cancer are uncommon, and the symptoms of enterocolitis caused by irradiation are similar to those of a colorectal cancer. The authors therefore suggest careful and long-term follow-up of patients that have received pelvic radiation.

Adenocarcinoma↗

Location of motoneurons innervating the musculus sphincter cloacae in the domestic fowl.

Horseradish peroxidase was injected into the musculus (m.) sphincter cloacae through the mucosa from the lumen side of the cloaca in the domestic fowl. Labeled neurons were found in the ventrolateral area of the ventral horn from the lumbosacral segments 7-9. The craniocaudal distribution of labeled neurons overlapped with that of hindlimb motoneurons. The m. sphincter cloacae is innervated by motoneurons sending axons to the sphincter cloacae either through the connexus caudalis branching from the caudal coxal nerve of the sacral plexus or through the lateral caudal nerve arising from the pudendal plexus.

Animals↗

Immunohistochemical studies on distribution of GABAA receptor complex in the rat brain using antibody against purified GABAA receptor complex.

The distribution of the gamma-aminobutyric acid (GABA)A receptor/benzodiazepine receptor/Cl- channel complex in the rat brain was examined immunohistochemically using the specific antibody against purified GABAA receptor complex. The immunization of white albino rabbit with purified GABAA receptor complex resulted in the formation of specific antibody as indicated by the immunoprecipitation test. Immunohistochemical examinations using the antiserum on rat brain slices by the peroxidase-antiperoxidase method revealed the presence of the following immunoreactive sites which coincided with a previous report using antibody against L-glutamic acid decarboxylase; ventromedial nucleus of hypothalamus, red nucleus, globus pallidus, zona compacta and zona reticulata of substantia nigra, layers of Purkinje cells and granular cells of cerebellum, layers III-V of cerebral cortex and stratum radiatum of hippocampus. These results strongly suggest that immunohistochemical application of the antibody against the purified GABAA receptor complex is a useful tool for identifying GABAergic neurons having GABAA receptor complex-mediated synapses.

Animals↗

IFN-gamma and IFN-beta independently stimulate the expression of lipopolysaccharide-inducible genes in murine peritoneal macrophages.

We have recently described the isolation and characterization of a set of cDNA encoding genes whose expression is induced or enhanced in murine peritoneal macrophages by treatment with LPS. In the present report we have analyzed the expression of the mRNA which hybridize with these cDNA probes in macrophages treated with other cytokines known to modulate functional activity. Three distinct patterns of expression have been documented. Two genes (D3 and C7) are inducible by LPS, IFN-gamma, and IFN-beta; D3 is comparably sensitive to all three, whereas C7 is more sensitive to LPS and IFN-gamma than to IFN-beta. The mRNA encoded by D8 is expressed in response to LPS and IFN-beta but not in response to IFN-gamma. Finally the gene encoded by D5 is inducible only in cells treated with LPS. The expression of all three cytokine-inducible mRNA was both dose and time dependent and was mediated by increased transcriptional activity of the genes. As with stimulation by LPS, the expression induced by IFN was independent of protein synthesis and occurred in a rapid and transient fashion. TNF-alpha had little or no detectable effect on any of the genes by themselves. The expression of C7, however, could be induced synergistically by treatment with a combination of TNF-alpha and either IFN-gamma of IFN-beta. The expression of these genes was not specific for macrophages as both IFN were able to induce a comparable pattern of gene expression in BALB/c 3T3 cells. Treatment of macrophages with dexamethasone inhibited LPS-induced C7 and D8 expression but did not affect that seen in response to IFN-gamma or IFN-beta, respectively. The results suggest that IFN and LPS act to modulate early gene expression by the generation of at least three overlapping but distinct signaling pathways. In some cases the pathway(s) which mediate response to LPS appear to be mechanistically distinct from those which mediate response to IFN-beta or IFN-gamma. The spectrum of stimuli and cell types which express these and other early genes suggest that they may play an important role in orchestration of the inflammatory response.

Animals↗

Long-term prognosis of surgical patients with hepatocellular carcinoma.

We reviewed 139 resected patients with hepatocellular carcinoma at our clinic between 1963 and 1987, and using the 118 cases for the period between 1963 and 1986, we analyzed the prognostic factors that influenced the long-term prognosis by comparing the survival curves. Significant differences in the survival patterns were noted when analysed on the basis of the preoperative indocyanine green maximal removal rate (greater than 0.4 mg kg-1 min-1 versus less than 0.4 mg kg-1 min-1), tumor size (greater than 5 cm versus less than 5 cm, etc.) and the existence of tumor capsule. The recurrence of carcinoma was the main cause of death of 32 patients (56%), who died after being discharged from hospital. To improve the prognosis of patients with surgically treated hepatocellular carcinoma, postoperative multidisciplinary treatment is mandatory.

Carcinoma, Hepatocellular↗

Breast cancer arising de novo in recipients of kidney allograft.

Immunosuppressive therapy is not only an etiologic factor of de novo malignant disease but is also accelerates progression of the already developed malignant disease in immunosuppressed recipients. Two cases of de novo breast cancer arising in kidney transplant recipients are reported herein. A 25 year-old woman, transplanted one haploidentical kidney transplant 4 years and 9 months ago, developed a left breast tumor. Within one month the tumor had rapidly enlarged from 3.5 cm to 8 cm in diameter by the time she underwent a radical mastectomy. Nine axillary lymph nodes were positive for metastasis. Although her graft function had been poor due to chronic rejection, she was treated with standard immunosuppressive therapy, but not adjuvant therapy. Since local recurrent disease appeared two months postoperatively, the immunosuppressive therapy was ceased and 60Co therapy started. Recurrent disease progressed rapidly, however, and she died 7 months after her operation. A 27 year-old woman, having allograft from an identical sibling, noted a right breast tumor, 8 years and 7 months later. Again the tumor had grown rapidly from 1.8 cm to 3 cm in diameter within one month. She underwent a standard radical mastectomy. One axillary lymph nodes was positive for metastasis. She has been treated with standard immunosuppressive therapy and adjuvant endocrinochemotherapy. Presently, she is alive with a well functioning graft and no disease.

Adult↗

The successful outcome of second kidney transplantation and its contributing factors.

Fourteen out of 301 patients who underwent allogeneic kidney transplantations, between April, 1970 and December, 1987, received second kidney allografts, including 4 living and 10 cadaveric grafts. The survival of the second grafts transplanted in those 14 recipients was superior to that of the first grafts transplanted in the other 287 recipients. Furthermore, the survival of the second grafts from 4 years onwards was significantly higher than that of the first grafts, in spite of a higher population of cadaveric grafts used in the second transplantation than in the first. Although it was impossible to determine the main factor which induced the improved survival of the second grafts when compared with that of the first, a combination of beneficial factors, such as a high rate of living related transplantation resulting in long-term graft survival of the first transplantation, the administration of immunosuppressive drugs during the period of re-hemodialysis and blood transfusion prior to the second transplantation, was considered to be the reason why successful second graft survival was achieved.

Cyclosporins↗

Cyclosporine-associated microangiopathic hemolytic anemia in a renal transplant recipient.

A case of microangiopathic hemolytic anemia (MHA) associated with the immunosuppressive agent, cyclosporine, is reported herein. The patient manifested anemia with red blood cell fragmentation, hypertension, thrombocytopenia, elevation of serum LDH levels and glomerular capillary thromboses within a few days of his transplantation. Extensive treatments with urokinase and heparin proved ineffective and graftectomy was performed 7 days after his transplantation. Immunofluorescent staining failed to show immunoglobulin (IgG or IgM) or complement (C3) deposition within the glomeruli, which discriminated MHA from acute humoral-vascular rejection.

Adult↗

An autopsy case of breast carcinoma with prominent lipid-secretions in the metastatic foci.

A 70-year-old woman was treated with a simple mastectomy followed by a course of 5000 rad to the breast and chemotherapy with 5-fluorouracil for breast cancer. About 15 months later, the patient died of widespread metastases. An autopsy revealed no recurrent cancer in the breast. The metastases were seen in bones (sternum, ribs and spine), pleura, spleen, uterus, ovaries, small intestine, adrenal glands, and lymph nodes (hilar, periaortic and mesenteric). Histologically, the resected tumor was a solid-tubular carcinoma with an infiltrative growth pattern. At autopsy, the tumor cells in the metastatic foci contained an abundance of lipids in the cytoplasm, while the tumor cells in the primary tumor contained small amounts of lipids.

Adenocarcinoma↗