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Biomedical subjects

K Oda

Publications and source records attributed to K Oda.

At least 109 records · Page 6Linked to original sources
PubMed1999

The adenovirus E1A domains required for induction of DNA rereplication in G2/M arrested cells coincide with those required for apoptosis.

Induction of apoptosis by adenovirus E1A in rodent cells is stimulated by wild type (wt) p53 but completely suppressed by mutated p53. The suppression is overcome by coexpression with Id proteins (Ids). The cells expressing E1A and Ids undergo apoptosis after accumulation in S phase, suggesting that S phase events are perturbed by E1A and Ids. The E1A domains required for induction of apoptosis, analysed by transfection with expression vectors for E1A, Ids and their mutants, followed by flow cytometry, reside in N-terminal (positions 17 - 38), CR1 and CR2 regions. Interaction of E1A with Ids requires the N-terminal and CR1 regions. The cyclin D1 promoter activity in S phase was reduced severely by E1A and this reduction is caused through CR1 and CR2 regions required for interaction with pRB. Analysis of DNA synthesis in G2/M arrested cells indicated that E1A is capable of inducing >4 N cells and this E1A-mediated DNA rereplication is enhanced by coexpression with Id-1H. The E1A domains required for induction of DNA rereplication coincide with those required for apoptosis.

Adenovirus E1A Proteins↗
PubMed1999

Synthesis of taxoids 5. Synthesis and evaluation of novel water-soluble prodrugs of a 3'-desphenyl-3'-cyclopropyl analogue of docetaxel.

A novel 3'-desphenyl-3'-cyclopropyl analogue of docetaxel was synthesized from 10-deacetyl-baccatin III. The cytotoxicity of the new taxoid was evaluated against several human tumor cell lines, and it had ca. 20 times stronger activity against human colon cancer cell lines (WiDr and Colon 320) than that of docetaxel. This taxoid was converted to its water-soluble prodrugs that have 2'-substituted amino acid derivatives with spacer. The prodrugs had good solubility in saline and showed more potent antitumor activity against B 16 melanoma in mice than that of docetaxel.

Animals↗
PubMed1999

Influence of antigenic forms and adjuvants on the IgG subclass antibody response to Aujeszky's disease virus in mice.

The influence of antigenic forms of Aujeszky's disease virus (ADV) and adjuvant types on the production of IgG subclass antibodies in mice was investigated. Particulate antigen, inactivated ADV, alone induced IgG1 and lower IgG2a antibody production, while the antigen adsorbed onto aluminum phosphate gel (alum) enhanced IgG1 antibody production but suppressed IgG2a antibody production as well as solubilized ADV antigen adsorbed onto alum. QS21 saponin purified from Quillaja saponaria promoted the production of IgG1 and IgG2a antibodies in a large extent against the both particulate and soluble antigens, while this saponin has strong hemolytic activity. Lablaboside F saponin isolated from Dolichos lablab without hemolytic activity, also induced the production of large IgG1 and little IgG2a antibody against both antigens. Oil-based adjuvant, ISA70 of water-in-oil type and ISA25 of oil-in-water type, increased IgG1 and IgG2a antibodies against the both soluble and particulate antigens, whereas a combination of ISA25 and soluble antigen reduced IgG2a antibody response. These results indicate that IgG1 antibody production was not suppressed by a combination of antigenic form and adjuvant type, however, IgG2a antibody production was influenced.

Adjuvants, Immunologic↗
PubMed1999

Angiotensin II-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms.

The signaling cascade elicited by angiotensin II (Ang II) resembles that characteristic of a growth factor, and recent evidence indicates transactivation of epidermal growth factor receptor (EGF-R) by G protein-coupled receptors. Here, we report the involvement of EGF-R in Ang II-induced synthesis of fibronectin and transforming growth factor-beta (TGF-beta) in cardiac fibroblasts. Ang II stimulated fibronectin mRNA levels dose dependently, with a maximal increase (approximately 5-fold) observed after 12 hours of incubation. Fibronectin synthesis induced by Ang II or calcium ionophore was completely abolished by tyrosine kinase inhibitors and intracellular Ca2+ chelating agents. Ang II-induced fibronectin mRNA was not affected by protein kinase C inhibitors or protein kinase C depletion, whereas specific inhibition of EGF-R function by a dominant negative EGF-R mutant and tyrphostin AG1478 abolished induction of fibronectin mRNA. We isolated the rat fibronectin gene, including the 5'-flanking region, and found that the activator protein-1 (AP-1) binding site present in the promoter region was responsible for the Ang II responsiveness of this gene. A gel retardation assay revealed the binding of nuclear protein to the AP-1 site, which was supershifted with anti-c-fos and anti-c-jun but not anti-activating transcription factor (ATF)-2 antibodies. Conditioned medium from Ang II-treated cells contained TGF-beta bioactivity, and addition of neutralizing TGF-beta antibody modestly (46%) inhibited induction of fibronectin. Ang II-induced synthesis of TGF-beta was also abolished by inhibition of EGF-R function. The effect of TGF-beta was exerted by stabilizing fibronectin mRNA without affecting the promoter activity and required de novo protein synthesis. We concluded that Ang II-induced expression of fibronectin and TGF-beta is mediated by downstream signaling of EGF-R transactivated by Ca2+-dependent tyrosine kinase and that Ang II-induced fibronectin mRNA expression is regulated by 2 different mechanisms, which are transcriptional control by binding of the c-fos/c-jun complex to the AP-1 site and posttranscriptional control by mRNA stabilization due to autocrine or paracrine effects of TGF-beta. Thus, this study suggests that the action of Ang II on extracellular matrix formation should be interpreted in association with the EGF-R signaling cascade.

Angiotensin II↗
PubMed1999

Effects of wild-type and mutated p53 and Id proteins on the induction of apoptosis by adenovirus E1A, c-Myc, Bax, and Nip3 in p53 null mouse cerebellum cells.

The sensitivities of apoptosis induced by E1A, c-Myc, Bax, and Nip3 to wild-type (wt) and mutated p53 and Id proteins were analyzed by transient transfection followed by flow cytometry with p53 null mouse cerebellum cell lines W7 and M13 that express wt and mutated p53 in response to dexamethasone, respectively. Apoptosis induced by c-Myc was stimulated weakly by wt p53, strongly by Ids, but suppressed completely by mutated p53 irrespective of coexpression with Ids, while apoptosis induced by E1A was suppressed by mutated p53 but stimulated when coexpressed with Ids. Apoptosis induced by Bax was little affected by wt and mutated p53, but inhibited by Ids, while apoptosis induced by Nip3 was inhibited by both wt and mutated p53 and inhibition was stimulated by Ids. Caspase-1 was activated only by Bax significantly when coexpressed with mutated p53 but not with wt p53. These results indicate that the apoptotic processes elicited by these inducers are different and differently affected by wt and mutated p53 and by Ids.

Adenovirus E1A Proteins↗
PubMed1999

Adoptive immunotherapy for advanced cancer patients using in vitro activated cytotoxic T lymphocytes.

BACKGROUND AND OBJECTIVES: We evaluated the clinical efficacy of adoptive immunotherapy using in vitro activated cytotoxic T lymphocytes (CTL) in the treatment of patients with advanced cancer. METHODS: CTL were induced with the mixed lymphocyte and tumor cell culture method, in which lymphocytes isolated from patient peripheral blood mononuclear cells were mixed with inactivated autologous tumor cells. Activated lymphocytes were administered intravenously to 11 patients once every 2 weeks for 10 weeks (i.e., 5 doses). RESULTS: Tumor reduction and decreased tumor marker were observed in 4 patients. Notably, successful CTL induction was identified in all of these patients. In patients who did not show induction of CTL response, a decreased proportion of lymphocytes, especially CD8(+) cells, and increased levels of CD14(+) cells were frequently observed. Fluorescence-activated cell sorter analysis indicated that expression of HLA class I and costimulatory factor B7-1 molecules was diminished on tumor cells. This was partly recovered with interferon-gamma, which resulted in successful induction of a CTL response. CONCLUSIONS: It was suggested that in vitro CTL induction is difficult in patients with advanced cancer. However, once the cells were induced successfully, some favorable clinical effects were seen by the adoptive transfer of such cell populations.

Aged↗
PubMed1999

Comparison of three PET dopamine D2-like receptor ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, in rats.

We studied the tracer kinetics of three dopamine D2-like receptor ligands, [11C]raclopride ([11C]RAC), [11C]nemonapride ([11C]NEM) and [11C]N-methylspiperone ([11C]MSP), in anesthetized rats by tissue dissection, ex vivo ARG and PET in order to clarify their characteristics for PET imaging. The in vivo affinity of the three ligands for the striatum ([11C]MSP > [11C]NEM > [11C]RAC) obeyed the in vitro affinity for dopamine D2 receptors. The affinity of [11C]RAC and [11C]MSP for the cerebellum was very low, but the affinity of [11C]NEM for the cerebellum was compatible to that for the cortex and was not to be ignored. Also the affinity of [11C]MSP for the cortex was relatively high. [11C]RAC showed the highest selectivity. The striatal PET image with [11C]RAC was clearer than that with [11C]NEM or [11C]MSP, but the activity decreased much faster than that measured by tissue dissection because of the partial volume effect. The striatal activity with [11C]NEM remained high and that with [11C]MSP gradually increased. [11C]RAC and [11C]MSP, but not [11C]NEM, showed a high accumulation in the periorbital region.

Animals↗
PubMed1999

Preserved benzodiazepine receptors in Alzheimer's disease measured with C-11 flumazenil PET and I-123 iomazenil SPECT in comparison with CBF.

This study evaluates the regional cerebral blood flow (CBF) with H2(15)O-PET and the distribution of central benzodiazepine receptor (BZR) with C-11 flumazenil (FMZ) by PET and I-123 iomazenil (IMZ) by SPECT in Alzheimer's disease (AD). In AD, whereas the CBF was diminished in the frontal, temporal, parietal, and occipital cortex, the distribution volume of FMZ and delayed activity of IMZ were relatively preserved in these cortices, suggesting that the BZR reduction, reflecting neuronal loss, is less prominent than the CBF suppression. The mini-mental state examination score (MMS) was weakly correlated with the CBF in the parietal cortex but not with BZR. It is speculated that the neuronal density reflected by BZR is less impaired than the neuronal function assessed with blood flow in the association cortex of AD. High correlation was found between the uptake of FMZ and the delayed activity of IMZ. The delayed image of IMZ-SPECT is clinically useful to evaluate the preservation of neuronal density in the affected temoporoparietal association cortex in AD.

Aged↗
PubMed1999

Fontan with pedicled pericardium.

Pedicled pericardium is a useful viable material for cardiac surgery. In an adolescent case, the extracardiac lateral tunnel of a Fontan connection was successfully constructed with pedicled pericardium. This procedure is expected to allow the growth of the tunnel and to need no anti-coagulant therapy, while careful long-term follow-up is necessary.

Child↗
PubMed1999

A subclavian artery aneurysm associated with aortitis syndrome.

We performed surgery on a 61-year-old woman who had increasingly severe right shoulder pain and paresthesia in her right upper extremity as a result of a large right subclavian artery aneurysm. She had suffered from aortitis syndrome for 10 years for which she was treated with steroids and had multiple arterial lesions, including bilateral subclavian artery aneurysms, abdominal aortic aneurysm and obstruction of bilateral superficial femoral arteries. The right subclavian artery aneurysm measured 4 cm in diameter and rupture appeared imminent, prompting surgical therapy. Via the supraclavicular incision approach and additional partial sternotomy, the aneurysm was excluded and the brachiocephalic to right axillar arterial bypass was set up using an extended polytetrafluoroethylene graft. The patient recovered without complications and a subclavian artery aneurysm demonstrated by computed tomography was thrombosed 1 month after surgery. In conclusion, we recommend the exclusion technique to treat subclavian artery aneurysms in cases in which aneurysmectomy is likely to injure adjacent veins and nerves.

Aneurysm↗
PubMed1999

Effects of dopamine agonists and antagonists on optical responses evoked in rat frontal cortex slices after stimulation of the subcortical white matter.

Effects of dopamine agonists and antagonists on the optical response of frontal cortical slices to stimulation of the subcortical white matter were examined using a voltage-sensitive dye and a high-speed image sensor. In the slices treated with bicuculline, stimulation of the white matter evoked optical responses propagating to the overlaying cortex. Bath application of the D1 agonist, chloro-APB (1 microM), consistently decreased the intensity of the early part of the response but increased the duration of the response occurring at the superficial layers of the cortex. Application of the D1 antagonist, SCH 23390 (1 microM), resulted in a small increase in both the intensity and the duration of the response. Bath application of the D2 agonist, quinpirole (1-10 microM), reduced the response occurring after 10 ms from stimulation. The effects of chloro-APB and quinpirole were additive. Application of the D2 antagonist, eticlopride, did not cause a significant change in the response but effectively blocked the quinpirole effects. This study suggests that although both D1 and D2 agonists reduced the peak optical response evoked in the slices of the frontal cortex, the two agonists exerted different temporal and spatial effects.

2-Amino-5-phosphonovalerate↗
PubMed1999

Nerve-sparing surgery for advanced rectal cancer patients: special reference to Dukes C patients.

Several nerve-sparing operations for advanced rectal cancer that aim to preserve genitourinary function without compromising tumor clearance have been developed in Japan. The aim of this study was to evaluate the survival and local recurrence of these procedures in Dukes B and C patients. A total of 177 patients with advanced rectal cancer underwent curative nerve-sparing surgery (NSS) over the last 11 years; 52 were Dukes B patients and 54 were Dukes C. Altogether 36 had Dukes C1 and 18 had Dukes C2 tumors, 13 with lateral lymph node metastases, designated lateral LN(+). The 5-year survival rate was 92% for Dukes B, 67% for Dukes C1, and 39% for Dukes C2 patients: 11% for Dukes C2 patients with lateral LN(+). The local recurrence rate was 6% for Dukes B, 11% for Dukes C1, and 33% for Dukes C2 patients: 20% for the lateral LN(-) group and 39% for the lateral LN(+) group. Almost all of the patients undergoing NSS could micturate spontaneously, but preservation of sexual function was not as successful. Although there is no guarantee of preserving satisfactory sexual function, our NSS is an acceptable procedure for Dukes B, C1, and C2 patients without lateral lymph node metastases.

Adult↗
PubMed1999

A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria.

Alkaptonuria is a rare autosomal recessive disorder characterized by homogentisic aciduria, ochronosis, and arthritis. Although a deficiency of homogentisic acid 1,2-dioxygenase has recently been confirmed at the molecular level, no effective treatment regimen has yet been developed for this disorder. In the present study, 2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of p-hydroxyphenylpyruvate dioxygenase (which catalyzes the formation of homogentisic acid from p-hydroxyphenylpyruvic acid) was adopted as a possible therapeutic agent for alkaptonuria. NTBC dose-dependently reduced the urinary output of homogentisic acid in a murine model of alkaptonuria that had been created with ethylnitrosourea. These findings suggest that NTBC may be the first potent pharmacotherapeutic agent for alkaptonuria.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1999

Intraoperative detection of embedded coronary arteries in MIDCAB using a color Doppler microprobe.

Intraoperative detection of deeply embedded coronary arteries is difficult, especially in minimally invasive coronary artery bypass grafts. This report describes an effective method to identify embedded coronary arteries by using a color Doppler microprobe. Five embedded left anterior descending coronary arteries were successfully identified by intraoperative ultrasonography. We believe that the color Doppler microprobe is helpful for surgeons in this difficult situation.

Coronary Artery Bypass↗
PubMed1999

Increased serum and urinary neopterin in nephrotic syndrome indicate cell-mediated immune dysfunction.

T-cell-mediated immune disturbances are likely but not certain to cause the nephrotic syndrome. Because neopterin (NP) production is closely related to activation of cell-mediated immunity, we addressed the question by measuring serum NP concentrations and urinary NP/creatinine (Cr) ratios, as well as by assessing interstitial lymphocyte and monocyte infiltration in the kidney and activation of the same cell types in peripheral blood. Finally, we observed whether urinary NP/Cr ratios in nephrotic syndrome are changed by steroid therapy. Seventy-four patients with primary glomerulonephritis were divided into 4 groups based on presence or absence of nephrotic syndrome and presence or absence of mesangial proliferation and expansion. Serum and urinary NP concentrations were measured chromatographically. Infiltrating cells in the kidney were identified by immunohistochemistry, and activation of peripheral blood cells was examined by fluorescent surface marker antibodies and flow cytometry. Irrespective of the pathohistology of glomeruli, nephrotic groups showed significantly higher urinary NP/Cr ratios and serum NP concentrations. Nephrotic groups also exhibited more activation of T cells in peripheral blood than did nonnephrotic groups or a healthy control group. Serum NP did not correlate with extent of interstitial renal infiltrates. Steroid therapy decreased urinary NP/Cr ratios in steroid-responsive patients, but not in steroid-resistant patients. Increased serum NP concentrations and urinary NP/Cr ratios may reflect disordered cell-mediated immunity in the nephrotic syndrome, irrespective of glomerular histology or interstitial cell infiltration.

Adult↗
PubMed1999

A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region.

The adenovirus E1B19K protein inhibits apoptosis induced by E1A and other divergent signals. The cellular proteins that interact with E1B19K have been analyzed by isolating cDNA clones by the yeast two hybrid system. One of these clones encodes B5 which consists of 219 amino acid residues and contains the putative BH3 and transmembrane regions. B5 binds strongly to Nip3 and itself, weakly to E1B19K, but not to Bcl-2 and localizes in nuclear envelope, endoplasmic reticulum and mitochondria. B5 has sequence homology with Nip3 in the middle and C-terminal regions, but not in the N-terminal region. Unlike other E1B19K binding BH3 proteins so far characterized, B5 does not induce apoptosis, but inhibits apoptosis induced by Nip3. However the deletion mutant B5Delta1-31 lacking the N-terminus does induce apoptosis, although weaker than does Nip3, suggesting that the N-terminal region is masking the apoptosis-inducing capacity of B5.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Enhancer and silencer binding proteins involved in the rat cdc2 promoter activation at the G1/S boundary.

BACKGROUND: Expression of the rat cdc2 gene during G1-S phase progression is negatively and positively regulated by the silencer and enhancer elements located upstream of the basal promoter. The silencer and enhancer sequences resemble each other, but the silencer contains extra internal AG residues. RESULTS: The cDNA clones encoding the enhancer binding proteins cdc2E1 and cdc2E2 were isolated by South-Western blotting. cdc2E1 and cdc2E2 comprise 436 and 256 amino acids and have two RNA binding domains which contain an RNP1 octamer and an RNP 2 hexamer. Both cdc2E1 and cdc2E2 bind to the double-stranded and single-stranded silencer and enhancer sequences, but their binding affinity to the enhancer was stronger than that to the silencer. Transfection of quiescent 3Y1 cells with the cdc2 promoter-luciferase constructs, followed by serum stimulation, showed that the promoter activation at the G1-S phase boundary was reduced greatly by base substitutions within the enhancer, but not within the silencer. Gel shift assays with oligonucleotides containing both the silencer and enhancer showed that formation of the large complex was greatly reduced if base-substitutions were introduced into the enhancer, but not within the silencer. The complex was supershifted completely by anti-cdc2E1 antibody and partially by anti-cdc2E2 antibody. CONCLUSION: These results suggest that cdc2E1 and cdc2E2 preferentially form the multimeric complex at the enhancer site after the late G1 phase for activation of the cdc2 promoter.

Amino Acid Sequence↗