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Biomedical subjects

K Kume

Publications and source records attributed to K Kume.

At least 109 records · Page 6Linked to original sources

Positive and negative regulations of human platelet-activating factor receptor transcript 2 (tissue-type) by estrogen and TGF-beta 1.

We found that the expression of human platelet-activating factor receptor (PAFR) gene is differentially regulated by estrogen and TGF-beta 1. Primer extension analysis revealed that the levels of the PAFR transcript 2 were increased by estrogen, but decreased by TGF-beta 1 in the human stomach cancer cell line (JR-St cells) which expressed both functional endogenous PAFR transcript 1 (leukocyte-type) and transcript 2 (tissue-type). Both ligands did not affect the expression of intrinsic PAFR transcript 1. Furthermore, the response elements to estrogen and TGF-beta 1 in the PAFR promoter 2 were delineated by a transient expression assay using the chloramphenicol acetyltransferase (CAT) gene as a reporter in this cell line. A negative response element for TGF-beta 1 was mapped on the sequence from -90 bp to -81 bp, which has consensus sequence for TIE (TGF-beta 1 inhibitory element). Although consensus estrogen response element (AGGTCAnnnTGACCT) is not present in this promoter, the entire sequence comprising two AGGTCA half motifs spaced by 153 bp (from -257 bp to -93 bp) conferred weak but significant estrogen responsiveness. Thus, through these elements in the PAFR promoter 2, estrogen and TGF-beta 1 may regulate the PAFR gene to achieve a tissue-specific expression.

Base Composition↗

Wortmannin inhibits mitogen-activated protein kinase activation induced by platelet-activating factor in guinea pig neutrophils.

Stimulation of guinea pig neutrophils with platelet-activating factor (PAF) caused a rapid and transient activation of mitogen-activated protein kinase (MAPK). Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, partially (approximately 50%) inhibited PAF-induced MAPK activation. Half-maximal inhibition was observed with 200-300 nM wortmannin, while it did not inhibit phorbol ester-induced MAPK activation. Neutrophils preloaded with 1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM) failed to raise cytosolic Ca2+ concentrations toward PAF, while they still responded to PAF with a 40-50% activation of MAPK. However, when cells were treated with BAPTA/AM and wortmannin in combination, the MAPK activation was completely inhibited. These results suggest that PAF activates MAPK through two distinct pathways in guinea pig neutrophils, one Ca(2+)-dependent, and the other Ca(2+)-independent but wortmannin-sensitive.

Androstadienes↗

Activation of mitogen-activated protein kinase and arachidonate release via two G protein-coupled receptors expressed in the rat hippocampus.

Platelet-activating factor and somatostatin receptors, two G protein-coupled receptors expressed in the rat hippocampus, were analyzed for the downstream signaling pathways in Chinese hamster ovary cells stably expressing each receptor. Ligand stimulation to each CHO cell line induced (1) inhibition of forskolin-induced accumulation of cAMP, (2) arachidonate release, and (3) activation of mitogen-activated protein kinase and MAP kinase kinase. In contrast, inositol phosphate breakdown was seen only in the PAF-stimulated CHO cells. The induction of these signals accompanied no detectable Ras activation. Suppression of the signals by pertussis toxin was almost complete for the somatostatin receptor but partial for the PAF receptor, suggesting that the somatostatin receptor couples only with PTX-sensitive G protein, while the PAF receptor couples with both PTX-sensitive and -insensitive G proteins. A model of G protein-mediated signaling pathways was proposed in which the signals from Gi and those from Gq converge at MAP kinase kinase and lead to arachidonate release. The present system using CHO cells is useful for analyzing signaling pathways from G proteins to MAP kinase kinase and will thereby provide clues for understanding the mechanisms underlying the physiological and pathological events mediated by PAF, somatostatin, and other G protein-coupled receptors in the central nervous system and other tissues.

Amino Acid Sequence↗

The cell envelope structure of the lipopolysaccharide-lacking gram-negative bacterium Sphingomonas paucimobilis.

From the cell envelope preparation of Sphingomonas paucimobilis two membrane fractions with different densities were separated by sucrose density gradient ultracentrifugation. The high-density fraction contained several major proteins, phospholipids, and glycosphingolipids, which are the only glycolipids of this lipopolysaccharide-lacking gram-negative bacterium. The low-density fraction showed many minor bands of proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and NADH oxidase activity was localized in this fraction. Combined with morphological data of vesicles formed by these membrane fractions, the high-density and low-density fractions were proposed to be an outer membrane and a cytoplasmic membrane, respectively. The localization of the glycosphingolipid was investigated also by means of immunoelectron microscopic analysis using a glycosphingolipid-specific antibody. The glycosphingolipid was shown to localize at the cell envelope, and the antigenic sugar portion was exposed to the bacterial cell surface. From these results the glycosphingolipid was assumed to have a function similar to that of the lipopolysaccharide of other gram-negative bacteria.

Antibodies, Bacterial↗

Detection of coxsackie B4 virus RNA in infected mouse kidneys by in situ hybridization.

We describe a method for detecting virus-specific RNA sequences using a nonradioactive enzyme system, and analyze coxsackie B4 virus (cox.B4) RNA sequences in infected mouse kidney with pathological changes. Diffuse mesangial proliferation was observed transiently 24 h after inoculation of cox.B4 virus in glomeruli. OCT-treated thin sections of the same tissue were hybridized in situ using a digoxigenin-labeled oligonucleotide probe. The strongest signal was observed in the mesangial sample. These findings suggest that the transient proliferative mesangial changes were caused by direct injury following virus infection without immune complex.

Animals↗

[A stage IIIc ovarian cancer case of pathological CR after combination treatment with carboplatin and cisplatin].

Combination carboplatin and cisplatin (JP) is one of the new strategies for increasing dose intensity and total platinum dose in ovarian cancer chemotherapy. We treated a woman age 65, with stage IIIc ovarian cancer. At the first operation, the tumor size was 20 cm and could not be removed because of severe adhesion of intestine. After 4 courses of JP, she underwent second optimal surgery (total hysterectomy, bilateral salpingo-oophorectomy and omentectomy). There were no residual cancer cells microscopically in any specimen. Following 2 additional courses of JP, the patient is alive with no evidence of disease 18 months after the first operation. JP proved to be an efficacious strategy to increase platinum dose intensity for this advanced ovarian cancer.

Adenocarcinoma, Papillary↗

Protective effect of dihydroheptaprenol in combination with vaccine to experimental Actinobacillus pleuropneumoniae infection in guinea pigs and pigs.

We investigated the effects of dihydroheptaprenol (DHP) on resistance of guinea pigs and pigs inoculated with Actinobacillus pleuropneumoniae (Apn) vaccine to subsequent challenge with Apn. Guinea pigs with complement-fixation (CF) antibody titers of 1:8 and 1:16 after intramuscular (i.m.) inoculation with inactivated Apn vaccine showed enhanced resistance to intraperitoneal (i.p.) infection with a homologous Apn strain (5 x 10(10) CFU/animal) when injected with DHP (20 mg/kg, i.m.) on the day before infection. The survival rates of the control, vehicle (lecithin solution without DHP), and DHP groups were 33%, 37%, and 63%, respectively, and that of the DHP group was significantly higher than the rates of the other groups (P < 0.05). Pigs with CF antibody titers of 1:8 and 1:16 after i.m. inoculation with inactivated Apn vaccine showed enhanced resistance to intratracheal infection with 5 x 10(10) CFU of Apn when injected with DHP (1, 2.5, or 5 mg/kg, i.m.) on the day before infection. The survival rates of the control, vehicle, DHP 1 mg/kg, DHP 2.5 mg/kg, and DHP 5 mg/kg groups were 37%, 38%, 47%, 60%, and 73%, respectively, and pigs given DHP at a dose of 5 mg/kg showed a significantly higher survival rate than the vaccinated control pigs (P < 0.05). The protective effect of DHP in vaccinated guinea pigs and pigs suggests that phagocytosis and bactericidal activity may be enhanced by this agent, depending on some opsonification effect on Apn antibody.

Actinobacillus Infections↗

[An autopsy case of the sinus of Valsalva aneurysm involved with tuberculous inflammation, leading to complete heart block].

A case is presented of unruptured aneurysm of the non coronary sinus of Valsalva, causing involvement of A-V node and right coronary artery compression. The patient was a 68 year-old woman with a complaint of general fatigue. Electrocardiogram showed complete A-V block. Computed tomography showed an aneurysm of the non coronary sinus of Valsalva. A temporary pacemaker was implanted, but the patient developed respiratory failure and heart failure and died. At autopsy, macroscopically disseminated tuberculosis was noted in both lungs and kidneys. Microscopically a tuberculous inflammatory lesion extending into the A-V node was found. We report this rare case with some consideration of the literature.

Aged↗

[A case of giant advanced breast cancer responding remarkably to CEFT therapy].

A fifty-two-year-old female was admitted with unresectable advanced giant breast cancer, which was attached to the chest wall and had a bone metastasis to the thoracic vertebrae. At first, depression and fixation were performed for the bone metastasis, and 2 courses of CEFT therapy were administered. One course was intra-arterial chemotherapy. After 2 courses of treatment, the tumor size was not changed, but tumor marker, CT and physical findings showed a remarkable improvement, and mastectomy could be performed. It was suggested that this regimen is very effective for advanced giant breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Bordetella bronchiseptica dermonecrotizing toxin suppresses in vivo antibody responses in mice.

The effects of Bordetella bronchiseptica dermonecrotic toxin (DNT) on the in vivo antibody response of mice were investigated. Intravenous injection of DNT at doses of 0.5 and 2.0 ng resulted in a significant suppression of the antibody response both to sheep red blood cells and to Escherichia coli lipopolysaccharide as measured by plaque-forming cell and hemagglutination assays. Spleen weights of mice given the same doses of DNT were significantly reduced, while the weights of thymuses and mesenteric lymph nodes were not. Numbers of Thy-1,2+ T lymphocytes, L3T4+ T lymphocytes, Lyt-2+ T lymphocytes and surface-immunoglobulin-positive lymphocytes decreased in spleens of the DNT-treated mice. Since the ratio of each lymphocyte population to the total number of splenic lymphocytes was not significantly different between the DNT-treated and non-treated mice, it is unlikely that DNT has a cytotoxic activity or a mitogen activity to some specific population of lymphocytes. Thus, we considered that the immunosuppression was attributable to a dysfunction of the spleen atrophied by the DNT.

Animals↗

Clinicopathologic evaluation of recurrence in early gastric cancer.

Five hundred ninety-two patients with early gastric cancer underwent surgical resection from 1970 to 1986 in our hospital, and 13 died from a recurrence of their disease. A careful analysis of these 13 patients suggests that carcinomas which invaded to the submucosa tend to recur more often than those confined to the mucosa. Well differentiated and papillary adenocarcinomas characterized by protruded or elevated lesions tend to recur earlier than poorly differentiated or signet-ring cell carcinomas characterized by depressed or excavated lesions. However, both types recurred from hematogenous metastases, with the liver being the most common site. Therefore, the macroscopic and histological features presently used to characterize early gastric cancer do not provide sufficient information to accurately predict which patients are at most risk for recurrence.

Adenocarcinoma↗