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Biomedical subjects

Y Oda

Publications and source records attributed to Y Oda.

At least 379 records · Page 21Linked to original sources
PubMed1994

Tumour necrosis factor-alpha induces an increase in susceptibility of human glioblastoma U87-MG cells to natural killer cell-mediated lysis.

The mechanism by which tumour necrosis factor (TNF)-alpha increases the susceptibility of U87-MG human glioblastoma cells to lysis by natural killer (NK) cells was studied. Treatment with TNF-alpha (100 units ml-1) for 48 h enhanced the susceptibility of tumour cells to lysis by NK cells. Increased susceptibility to lysis was associated with enhanced expression of intercellular adhesion molecule 1 (ICAM-1) and HLA class I antigen. Antisense ICAM-1 oligonucleotide inhibited lysis by NK cells of TNF-alpha-treated tumour cells. In contrast, acid treatment following TNF-alpha treatment increased lysis by NK cells. These findings indicate that TNF-alpha treatment of glioblastoma cells increased their susceptibility to lysis by NK cells, since ICAM-1 up-regulation would have more profound effects on NK susceptibility than would HLA class I antigen up-regulation.

Antigens, Neoplasm↗
PubMed1994

Assessment of the proliferative activity and radiosensitivity of human tumours using the cytokinesis-block micronucleus assay.

We established an in vitro cytokinesis-block micronucleus assay of human tumours for estimation of the proportion of cells undergoing mitosis (the dividing fraction, DF), the time for the number of nuclei to double and the radiosensitivity in terms of the micronucleus frequency, based on a concept described previously. Under certain conditions, the nuclear number doubling time (NNDT) was considered to represent the potential doubling time. Tumour specimens obtained at surgery were disaggregated into single-cell suspensions and were directly cultured in the presence of cytochalasin B with or without irradiation. At various intervals, the percentage of multinucleate cells (the plateau value represented the DF), the average number of nuclei per cell and the number of micronuclei in binucleate cells were determined. DF and NNDT values were obtained in 58 of the 73 tumours investigated, and the micronucleus frequency was obtained in 54 of these 58 tumours. The DF ranged from 4.1% to 71% and the NNDT ranged from 3.1 to 83 days. A DF > or = 20% was associated with a higher recurrence rate in patients undergoing curative operation. A correlation was found between the NNDT and the time to relapse in patients with recurrent disease. The average number of micronuclei per binucleate cell at 2 Gy of irradiation (after subtraction of the value at 0 Gy) ranged from 0.052 to 0.35. Tumours which produced more micronuclei after irradiation showed a better response to radiotherapy. This assay can be readily performed on human tumours and appears to have promise as a predictive assay for radiation therapy.

Adenocarcinoma↗
PubMed1994

bcl-2 gene enables rescue from in vitro myelosuppression (bone marrow cell death) induced by chemotherapy.

Recent studies have shown that the use of cytokines such as granulocyte colony-stimulating factor (G-CSF) to ameliorate chemotherapy-induced myelosuppression may enhance the viability of tumour cells with functional receptors for these cytokines. In this study, therefore, we used murine bone marrow (BM) cells in an in vitro model in an attempt to determine whether topoisomerase inhibitors (camptothecin, etoposide and doxorubicin) induce myelosuppression (BM cell death) and whether novel treatments other than the administration of G-CSF can be used for rescue from myelosuppression. DNA fragmentation assay, ultrastructural analysis and cell cycle analysis demonstrated that these chemotherapeutic agents induced apoptosis in BM cells. We demonstrated in addition that enforced expression of the bcl-2 gene in BM cells by MPZenNeo (bcl-2) retroviral gene transfer increased resistance to the apoptosis induced by these agents. These findings suggest the possibility that enforced expression of the bcl-2 gene in BM cells using gene transfer techniques may enable rescue from chemotherapy-induced myelosuppression.

Animals↗
PubMed1994

Detection of human cytomegalovirus, Epstein-Barr virus, and herpes simplex virus in diffuse interstitial pneumonia by polymerase chain reaction and immunohistochemistry.

Using formalin-fixed and paraffin-embedded tissues from autopsy, the authors examined infection by human cytomegalovirus, Epstein-Barr virus, and herpes simplex virus in 54 patients with primary or secondary diffuse interstitial pneumonia (DIP) by polymerase chain reaction and immunohistochemistry and compared it with that in 32 persons without lung complications. Polymerase chain reaction and immunohistochemistry demonstrated that approximately 40% and 30% of DIP were positive for human cytomegalovirus and Epstein-Barr virus, respectively, but none of 32 controls had evidence of infection by human cytomegalovirus and Epstein-Barr virus. The polymerase chain reaction was more sensitive than the immunohistochemical technique for detection of herpes simplex virus. The former technique revealed herpes simplex virus infection in approximately 90% of DIP and controls and the latter in approximately 50% of each group. However, immunohistochemistry had the advantage of demonstrating the morphologic location of infected cells and of allowing their semiquantitative evaluation. Herpes simplex virus was more extensively distributed in the lungs of several DIP cases than in those of controls, suggesting the reactivation of herpes simplex virus. Only DIP patients (31 cases [57.4%]) were infected by two or three kinds of herpesviruses. The combination of polymerase chain reaction and immunohistochemistry revealed that these herpesviruses proliferated in many cases of DIP.

Base Sequence↗
PubMed1994

Activation of trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene to genotoxic metabolites by rat and human cytochromes P450.

In order to address the hypothesis that 6-aminochrysene (6-AC) is converted to genotoxic products by cytochrome P450 enzymes via two activation pathways (N-hydroxylation and epoxidation), the activation of 6-AC and trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene (6-AC-diol) to genotoxic metabolites was examined in rat and human liver microsomal cytochrome P450 enzymes using Salmonella typhimurium TA1535/pSK1002 and TA1535/pSK1002/pNM12 (NM2009) as tester strains. The latter bacteria, an O-acetyltransferase-overexpressing strain, was highly sensitive to metabolites derived from activation of 6-AC, but not those from 6-AC-diol, using liver microsomes from phenobarbital-treated rats or a reconstituted monooxygenase system containing P4502B1 or -2B2, thus suggesting the roles of P450 and acetyltransferase systems in the activation process. 6-AC-diol, on the other hand, was activated very efficiently by liver microsomes prepared from beta-naphthoflavone-treated rats or a reconstituted system containing P4501A1 or -1A2; the activation reaction is considered to proceed through diol-epoxide formation. The contribution of rat P4501A enzymes towards activation of 6-AC-diol was confirmed by the inhibitory effects on the activation process of alpha-naphthoflavone, a specific inhibitor of P4501A-related activities, and antibodies raised against purified P4501A1 and -1A2. In humans, P4501A2 was found to be the major enzyme involved in the activation of 6-AC-diol to genotoxic metabolites while the parent compound 6-AC was activated mainly by P4503A4. Experiments using recombinant P450 proteins expressed in human lymphoblastoid cell lines showed that human P4501A1 could also activate 6-AC-diol to reactive metabolites at almost the same rate measured with P4501A2. In addition, P4502B6 was found to efficiently catalyze the activation of 6-AC to genotoxic metabolites, and P4503A4 was active in the activation of 6-AC-diol as well as 6-AC. Addition of purified rat epoxide hydrolase to the incubation mixture containing purified rat P4501A1 or microsomes expressing human P4501A1 caused inhibition of activation of 6-AC-diol. These results suggest the existence of different enzymatic activation pathways for 6-AC and 6-AC-diol. The former carcinogen may be N-hydroxylated principally by P4502B enzymes in rats and P4503A4 and -2B6 in humans and activation to its ultimate metabolites may proceed through esterification of the N-hydroxy metabolites by an N-acetyltransferase. The 6-AC-diol is metabolized to its ultimate diolepoxide product by P4501A enzymes in rat and human liver microsomes. P4503A4 (humans) and P4503A2 (rats) may also contribute to some extent in the activation of 6-AC-diol, albeit at lower rates than those of P4501A enzymes.

Animals↗
PubMed1994

Relation between the occurrence of K-ras gene point mutations and genotypes of polymorphic N-acetyltransferase in human colorectal carcinomas.

We examined the point mutations of codons 12, 13 and 61 in K-ras gene by slot blot hybridization analysis following polymerase chain reaction and genotypes of polymorphic N-acetyltransferase (NAT) by Southern blot analysis in 36 colorectal carcinoma tissues obtained at surgery. NAT genotypes of 36 autopsied livers from patients without colorectal carcinoma were also determined to compare the populations of each polymorphic NAT genotype in the patients with or without the neoplasm. Genetically, 44.4% (16 cases), 47.2% (17 cases) and 8.3% (3 cases) of patients with colorectal carcinoma were classified as rapid, intermediate and slow acetylators, respectively. Point mutations of K-ras gene were detected in eight carcinomas out of 16 rapid acetylators, two out of 17 intermediate acetylators and one out of three slow acetylators. In control livers, 52.8% (19 cases), 38.9% (14 cases) and 8.3% (3 cases) were classified as rapid, intermediate and slow acetylators, respectively. The occurrence of K-ras gene point mutations was closely linked to rapid acetylator genotype, although there was no statistical difference of NAT genotypes between the group of patients with colorectal carcinoma and the group of controls.

Adult↗
PubMed1994

A major glucocorticoid-inducible P450 in rat liver is not P450 3A1.

A new P450 3A cDNA (RL33) has been cloned from a liver cDNA library of untreated male rat. RL33 is 2032 nucleotides in length and has an open reading frame of 502 amino acid residues. The nucleotide sequence of its 5'-noncoding region is completely identical with that of a genomic clone of P450 3A1 isolated by Burger et al. [Proc. Natl. Acad. Sci. USA 89, 2145-2149 (1992)]. Compared with rat P450 3A1, P450 RL33 showed 98 and 97% identities in the nucleotide and deduced amino acid sequences, respectively, with the deletion of 2 amino acids and substitution of 12 amino acids. These residues were localized around amino acids 107-230. Recently Kirita and Matsubara have isolated the same P450 3A cDNA (cDEX) from dexamethasone (DEX)-treated rat liver [Arch. Biochem. Biophys. 307, 253-258 (1993)]. Northern blot analysis using an oligonucleotide probe specific for P450 RL33/cDEX revealed that P450 RL33/cDEX mRNA was induced strongly by pregnenolone 16 alpha-carbonitrile and DEX and weakly by phenobarbital (PB) and triacetyloleandomycin. We constructed a P450 3A cDNA library by the reverse transcriptase-polymerase chain reaction using common primers to P450 RL33/cDEX, 3A1, and 3A2, and subcloned the cDNAs into pUC119. The expression level of P450 RL33/cDEX mRNA was investigated by identifying each clone with the above oligonucleotide probe. P450 RL33/cDEX mRNA represented over 70% of the total P450 3A mRNA from untreated, PB-, and DEX-treated rat liver. These results indicated that the major DEX-inducible form of P450 3A is P450 RL33/cDEX and not P450 3A1.

Amino Acid Sequence↗
PubMed1994

An autopsy case of hepatic sarcomatoid tumor: immunohistochemical comparison with a sarcomatous component of hepatocellular carcinoma.

A case of primary hepatic tumor exclusively composed of malignant cells with sarcomatous features is described and compared immunohistochemically with two cases of hepatocellular carcinoma (HCC) with a sarcomatous component. More than 30% of HCC cells were positively stained with anti-cytokeratin (CAM5.2), anti-albumin, anti-fibrinogen and anti-alpha 1-antitrypsin antibodies, and some with anti-epithelial membrane antigen. The present sarcomatoid tumor and the sarcomatous component with HCC showed similar immunohistochemistry; many tumor cells were strongly immunoreactive for vimentin and some positive for cytokeratin, albumin, fibrinogen and alpha 1-antitrypsin. Other immunohistochemical markers, indicating specific differentiations to lineage of macrophages, muscle cells, glial cells, endothelial cells and so forth, were not detected in sarcomatous tumor cells of all cases. These findings suggest that the present sarcomatoid tumor would belong to an anaplastic sarcomatous variant of HCC.

Aged↗
PubMed1994

Kabuki make-up syndrome associated with chronic idiopathic thrombocytopenic purpura.

Although susceptibility to infections in Kabuki make-up syndrome (KMS) has frequently been reported, there have been few immunological studies. We describe a 14 year old girl with KMS exhibiting chronic idiopathic thrombocytopenic purpura (chronic ITP), including immunological studies. Corticosteroid therapy was not effective therefore splenectomy was performed. The patient's platelet count increased transiently. Immunological studies revealed normal T cell functions and low serum immunoglobulin A (IgA) levels. Because of the abnormalities of B cell functions in chronic ITP and low serum IgA levels in our patient, we speculate that there may be some abnormalities of humoral immunity in KMS.

Adolescent↗
PubMed1994

Right atrial pressure and ANP release during prolonged exercise in a hot environment.

To investigate the relationship between right atrial pressure (RAP) and atrial natriuretic peptide (ANP) release during prolonged exercise in a hot environment (30 degrees C, 20% relative humidity), we studied with a Swan-Ganz catheter five male volunteers exercising on a cycle ergometer at 60% of peak aerobic power for 50 min. The ANP level increased from 14 +/- 3 (SE) to 69 +/- 10 pg/ml (P < 0.001) during the first 10 min of exercise as RAP rose from 4.3 +/- 0.8 to 6.9 +/- 1.1 mmHg (P < 0.001). The 10-min ANP level was significantly correlated with RAP (r = 0.88, P < 0.05) but not with heart rate, pulmonary arterial blood temperature, plasma norepinephrine, or plasma epinephrine. The 10-min RAP value was inversely correlated with blood volume (r = -0.98, P < 0.01) and also with stroke volume (r = -0.96, P < 0.01). In the next 20 min of exercise, ANP continued to increase to 101 +/- 12 pg/ml (P < 0.02 vs. 10 min) and remained at this level until 50 min of exercise, whereas RAP decreased and reached a level not significantly different from baseline at 50 min (5.7 +/- 1.0 mmHg; P < 0.01 vs. 10 min). This dissociation of ANP and RAP may have been related to the significant increases from the 10-min values of heart rate, blood temperature, norepinephrine (all P < 0.01), and epinephrine (P < 0.02) during the same period. These results suggest that ANP release is primarily controlled by atrial distension at the onset of exercise but that other stimulators may be involved thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Prevention of arterial reocclusion after thrombolysis with activated protein C. Comparison with heparin in a canine model of coronary artery thrombosis.

BACKGROUND: Reocclusion of recanalized coronary arteries often limits the efficacy of coronary thrombolytic therapy in patients with acute myocardial infarction. Activated protein C (APC) is an important regulatory enzyme in hemostasis. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the effect of APC on thrombolysis with recombinant tissue-type plasminogen activator (rTPA) was studied in a canine model of coronary artery thrombosis. METHODS AND RESULTS: Continuous artery flow monitoring in the left anterior descending coronary artery of 30 anesthetized adult beagles was performed by a magnetic flowmeter. Localized thrombosis was produced in the left anterior descending coronary artery and administration of rTPA (alteplase, 0.45 mg/kg IV) was done for 30 minutes. The dogs were randomly assigned to receive one of the following intravenous adjunctive therapies: (1) control group (n = 10): human albumin at a rate of 0.83 mL/min; (2) APC group (n = 10): human plasma-derived APC (0.6 mg/kg) with human albumin as a vehicle at a rate of 0.83 mL/min; and (3) heparin group (n = 10): heparin (200 U/kg) with saline at a rate of 0.83 mL/min. Each adjunctive therapy was started simultaneously with rTPA and lasted for 60 minutes. Coronary recanalization occurred in all dogs of each adjunctive treatment group in 19.1 +/- 1.9 minutes (mean +/- SEM). In a 120-minute observation after the termination of rTPA, reocclusion developed in all the dogs in the control and heparin groups but in only 3 of the 10 dogs in the APC group (P < .002 versus control and heparin). Time from recanalization to reocclusion (minutes, mean +/- SEM) was prolonged in the APC group (103.2 +/- 14.2) as compared with the control (10.2 +/- 2.3, P < .001) and heparin (30.3 +/- 11.8, P < .002) groups. Activated partial thromboplastin time was prolonged similarly in each group after thrombolytic therapy. On the other hand, bleeding time was prolonged in only the heparin group after the treatment. Serious hemorrhagic side effects were not observed in all three groups. CONCLUSIONS: APC prevents coronary artery reocclusion after recanalization with rTPA in a canine model of coronary artery thrombosis. This finding suggests that APC may be useful as an adjunctive treatment to enhance the effects of thrombolytic therapy in patients with acute myocardial infarction.

Animals↗
PubMed1994

Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus.

Novel mutations in the V2 vasopressin receptor gene were identified in two Japanese pedigrees with X-linked congenital nephrogenic diabetes insipidus. The V2 receptor belongs to the family of G-protein-coupled receptors that contain seven distinct transmembrane domains, and the V2 receptor gene is encoded by three exons. The coding regions amplified by polymerase chain reaction were directly sequenced. In a pedigree, one of four consecutive guanine sequences (nucleotides 528-531) in the second exon was deleted (528delG). This deletion mutation results in a frame shift beginning at codon 154 in the second intracellular domain and a premature termination at codon 161. In another pedigree, a missense mutation (A-->G) was identified at nucleotide position 310 in the second exon. This point mutation, H80R, changes a histidine at codon 80 in the second transmembrane domain to an arginine that is more positively charged than histidine under the neutral environment. Each mutation cosegregated with the phenotype of diabetes insipidus and supposed to be a cause for resistance to arginine vasopressin.

Adolescent↗
PubMed1994

Expression of fibroblast growth factor receptor-1 in human glioma and meningioma tissues.

We examined the expression of fibroblast growth factor receptor-1 (FGFR-1), namely FLG, in tissues of 18 human gliomas, 10 human meningiomas, 3 human metastatic brain tumors, and 2 normal human brains by means of immunohistochemistry. All tissues were positively stained for FGFR-1. Primary brain tumors were more abundantly immunoreactive than normal brain tissues (Mann-Whitney U test, P < 0.05). There was significant correlation between the expression level of basic fibroblast growth factor (basic FGF) and that of FGFR-1 in tissues of human glioma (Spearman's test, P < 0.05). The expression level of FGFR-1 of tumor cells increased in correlation with that of endothelial cells in glioma tissues (Spearman's test, P < 0.001). We previously reported that basic FGF is produced in more than 90% of human glioma and meningioma tissues. Together with these data, it is suggested that basic FGF is involved in autonomous cell growth and tumorigenesis of gliomas and meningiomas as an autocrine growth factor in vivo.

Adenocarcinoma↗
PubMed1994

Interferon-gamma induces a decrease in the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells.

We studied the effect that treating two types of glioblastoma cell lines, U-87 MG and U-251 MG, with interferon (IFN)-gamma had on their susceptibility to lysis by lymphokine-activated killer (LAK) cells. We also examined the participation of cell-adhesion molecules and major histocompatibility complex (MHC) class I and II antigens present on the target cells in lysis by LAK cells. Treatment with IFN-gamma (1000 U/ml) for 48 hours resulted in the increased expression of both intercellular-adhesion molecule 1 and MHC class I antigens on tumor cells. In addition, untreated tumor cells expressed neural-cell-adhesion molecules and MHC class II antigens highly, but their expression was not affected by IFN-gamma treatment. These changes in expression were accompanied by a decreased susceptibility to lysis by LAK cells. Treatment with antisense-intercellular-adhesion molecule-1 oligonucleotide further inhibited LAK lysis of target cells, following treatment with IFN-gamma. In contrast, acid treatment of tumor cells after treatment with IFN-gamma increased their susceptibility to lysis by LAK cells. These findings suggest that treatment of glioblastoma cells with IFN-gamma decreased their susceptibility to lysis by LAK cells, and that this decrease in susceptibility is attributable principally to the increased expression of MHC class I antigen on target cells.

Base Sequence↗
PubMed1994

Correlation of octanol-water partition coefficients with capacity factors measured by micellar electrokinetic chromatography.

Micellar electrokinetic chromatography (MEKC) was used to measure hydrophobicity of 18 aromatic compounds. The capacity factors, which are proportional to the micelle-water distribution coefficients, were closely correlated with the octanol-water partition coefficients. The addition of Brij 35 to the charged micelle was effective in improving the correlation because the surface charges of the micelle were shielded.

Chromatography↗
PubMed1994

Evidence for sympathetic, purinergic transmission in the iris dilator muscle of the rabbit.

Electrical transmural stimulation of isolated iris dilator muscle of the rabbit produced a transient contraction that consisted of adrenergic and nonadrenergic components. In contrast to the adrenergic component, the nonadrenergic component was resistant to prazosin and other adrenoceptor antagonists. However, both components were completely blocked by guanethidine or tetrodotoxin. Among some tested compounds including neuropeptide Y, both ATP and 2-methylthio ATP produced a transient contraction in the dilator muscle and the sustained treatment with each markedly attenuated the nonadrenergic responses to electrical stimulation and to ATP. Suramin had no effect on and alpha,beta-methylene ATP potentiated the responses to electrical stimulation and to ATP. These results suggest that the nonadrenergic contraction induced by electrical transmural stimulation is a sympathetic purinergic response that may be mediated through unique purinoceptors.

Adenosine Triphosphate↗