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T Oda

Publications and source records attributed to T Oda.

At least 379 records · Page 21Linked to original sources
PubMed1993

Neoplasia of the ampulla of Vater. Ki-ras and p53 mutations.

Eleven tumors of the ampulla of Vater (5 stage IV and 2 stage II adenocarcinomas, 1 stage II papillary carcinoma, 1 neuroendocrine carcinoma, and 2 adenomas, one with foci of carcinoma) were examined for Ki-ras and p53 gene mutations by single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA fragments. Ki-ras mutations were found in one adenocarcinoma and in the adenoma with foci of carcinoma, both involving mainly the intraduodenal bile duct component of the ampulla. Seven cases showed p53 gene mutations: four advanced-stage adenocarcinomas, the papillary carcinoma, the neuroendocrine carcinoma, and the adenoma with foci of carcinoma. Nuclear accumulation of p53 protein was immunohistochemically detected in the morphologically high-grade areas of the five cancers harboring a p53 gene missense point mutation. The adenomas, the two frame shift-mutated cancers, and the adenomatous and low-grade cancer areas of mutated carcinomas were immunohistochemically negative. Our data suggest that in ampullary neoplasia 1) p53 mutations are common abnormalities associated with the transformation of adenomas and low-grade cancers into morphologically high-grade carcinomas, and 2) Ki-ras mutations are relatively less frequent and might be restricted to tumors originating from the bile duct component of the ampulla.

Aged↗
PubMed1993

[A new skeletal muscle powered ventricle (SMPV) designed to work under physiologic preload].

To maximize pumping function the SMPV has been highly preloaded (over 30 mmHg); but the effects of pump size and configuration on the required preload have never been determined. A new double barrel dual chamber single layered (DCSL) SMPV having two SL small pumps in parallel was compared with a single chamber double layered small pump (SCDL). Stroke volume (SV) and stroke work (SW) were determined in acutely constructed SMPV using mongrel dog untrained latissimus dorsi: 10 DCSL and 12 SCDL. Under physiologic afterload (120 mmHg) and preload (15 mmHg), the DCSL displayed a significantly (p < 0.05) larger SV (9.9 +/- 1.2 ml) and SW (0.84 +/- 0.15 x 10(6) ergs) than the SCDL pumps (SV = 6.9 +/- 0.6 ml, and SW = 0.55 +/- 0.07 x 10(6) ergs). The DCSL pumps, requiring less muscle mass for its construction, indicated better performance under physiologic pre and afterload conditions than SCDL pumps.

Animals↗
PubMed1993

Pancreatic adenocarcinomas frequently show p53 gene mutations.

Thirty-four pancreatic adenocarcinomas were studied for the presence of p53 gene mutations by the single-strand conformation polymorphism method and by direct sequencing of PCR-amplified fragments. p53 protein expression was immunohistochemically evaluated using monoclonal PAb1801 and polyclonal CM1 antibodies. Mutations were detected in 14 cases. The transitions were six G to A and two A to G; the transversions were one C to G and two A to C; the remaining three were frameshift mutations. Immunostaining results were identical with both antibodies. Nuclear immunohistochemical p53-positive cells were found in nine p53 mutated cases and in 12 cases in which no mutation was detected. In most of these latter cases only a minority of cancer cells showed immunohistochemical positivity. Twenty-nine cases, including all p53 mutated cancers, were known to contain codon 12 Ki-ras gene mutations. Also in the light of the demonstrated cooperation of ras and p53 gene alterations in the transformation of cultured cells, our data suggest that p53 mutation is one of the genetic defects that may have a role in the pathogenesis of a proportion of pancreatic cancers.

Adenocarcinoma↗
PubMed1993

Alterations of retinoblastoma susceptible gene accompanied by c-myc amplification in human bone and soft tissue tumors.

The present study was undertaken to examine oncogene abnormalities in human bone and soft tissue tumors. Twenty four tumor tissues and one human cell strain established from an osteosarcoma were examined by Southern blot analysis using a recessive oncogene (p0.9R and p3.8R derived from a cDNA of the Rb gene) and eight dominant oncogenes (c-myc, c-K-ras, c-fos, c-raf-1, c-fms, c-sis, N-myc, and c-erb B) as probes. Homozygous deletions or other alterations within the Rb locus were found in 3 of 6 osteosarcomas, 1 osteosarcoma cell line, 1 of 3 malignant fibrous histiocytomas and 1 of 2 Ewing's sarcomas. On the other hand, amplification of c-myc was found in 2 osteosarcomas and 1 osteosarcoma cell line. All cases with c-myc amplification had alterations in the structure of the Rb locus, and these patients showed rapid clinical malignancy progression and a probable tendency to bone metastases. Results of this study suggest that structural alterations of the Rb gene and amplification of c-myc might play an important role in the clinical course and pathogenesis of osteosarcoma.

Adolescent↗
PubMed1992

p53 gene mutation spectrum in hepatocellular carcinoma.

In order to clarify the significance of mutation of the p53 tumor suppressor gene in the genesis and development of human hepatocellular carcinoma (HCC) in an aflatoxin B1 low-exposure area, the spectrum, i.e., incidence, type, and site, of p53 gene mutations was examined in 169 tissue samples resected mainly from Japanese patients using single-strand conformation polymorphism analysis and direct sequencing. Forty-nine tumors (29%) showed a p53 mutation (39 point mutations and 10 frameshifts). The point mutations comprised 18 transitions, only 4 of which occurred at CpG sites, and 21 transversions. Two evolutionarily conserved domains, IV and V, contained 65% of all mutations and codon 249 was the most frequent mutation site (7/49). The spectrum of p53 mutation did not differ among HCCs in relation to the type of hepatitis virus infection, sex, age, and background liver disease of patients, tumor size, or presence of metastasis, but incidence and site were significantly associated with the degree of differentiation of cancer cells. In poorly differentiated HCC, p53 mutation was frequent (54%) and clustered on domains IV and V, whereas in well or moderately differentiated HCC, the mutation was less frequent (21%) and equally distributed on domains II to V. Restriction fragment length polymorphism analysis revealed loss of heterozygosity on chromosome 17p in 55 (69%) of 80 informative cases and in 34 (95%) of 36 cases with p53 mutation. Therefore, p53 gene mutation is suggested to occur independently of the type of viral infection or status of preexisting liver disease and to occur preferentially in moderately and poorly differentiated HCCs in association with or after loss of another p53 allele as a late event of HCC progression.

Adult↗
PubMed1992

Mutation pattern of the p53 gene as a diagnostic marker for multiple hepatocellular carcinoma.

Hepatocellular carcinoma, sometimes shows multiple tumor nodules, therefore poses a problem of differential diagnosis between cancers of multifocal and those of metastatic origin. Conventionally, pathological criteria have been used for this purpose, but these are largely subjective. In order to facilitate more objective differential diagnosis of multiple hepatocellular carcinoma, we used the pattern of mutation of the p53 gene as a marker for each tumor nodule. We studied 58 nodules from 26 cases of multiple hepatocellular carcinoma using polymerase chain reaction-single strand conformation polymorphism analysis, a simple method for detecting mutations. p53 gene mutations were detected in 65% (17 of 26) of cases. The internodule mutation patterns were heterogeneous in 11 cases and homogeneous in 6, enabling a multifocal origin to be diagnosed in the former and a metastatic origin in the latter at the genetic level. Moreover, the origin of recurrent tumors was determined from the mutation pattern. It is concluded that analysis of p53 mutations seems to be useful for differentiating the origin of multiple cancers, since the information it yields is essentially objective.

Base Sequence↗
PubMed1992

Different pattern of chromosomal allele loss in multiple hepatocellular carcinomas as evidence of their multifocal origin.

One of the most problematic aspects of surgery for hepatocellular carcinoma (HCC) is the frequent development of multiple tumors. Determination of the origin of multiple tumors, i.e., multifocal or metastatic, is important for predicting the clinical course of the disease after surgery. In order to clarify the origin of multiple tumors of HCC genetically, we examined patterns of loss of heterozygosity (LOH) on chromosome 16 for DNA isolated from 43 HCCs resected from 19 patients by analysis of restriction fragment length polymorphism. The cases were classified macro- and microscopically into 3 groups: multifocal origin; metastatic origin; and undetermined. Classification based on morphological features was shown to be well correlated with patterns of LOH in multiple tumors of HCC. Different patterns of LOH on chromosome 16 were detected in 8 of 11 patients with tumors of morphologically multifocal origin, whereas they were detected in none of 5 patients with tumors of morphologically metastatic origin. Among five patients with tumors of morphologically undetermined origin, a difference of LOH pattern among the tumors was detected in two, whereas in the other three, the pattern was identical between the tumors. A different pattern of LOH among HCCs arising in situ showed that they were composed of different clones, strongly suggesting their independent clonal origin and multifocal development. These results show that not only appropriate morphological observation but also examination of the LOH pattern on a particular chromosome is useful in diagnosis of multifocal HCC.

Alleles↗
PubMed1992

Inhibition site of dexamethasone on extravasation of polymorphonuclear leukocytes in the hamster cheek pouch microcirculation.

A video system was used to investigate the inhibitory effect(s) of the glucocorticoid dexamethasone (DEX) on polymorphonuclear leukocyte (PMN) extravasation in the microcirculation of hamster cheek pouch. DEX was given intraperitoneally at 0.1 or 0.3 mg/kg body weight 2 h before induction of extravasation by topical application of leukotriene B4 (LTB4) or formyl-methionyl-leucyl-phenylalanine (fMLP) on the microvasculature. The number, time course, and behavior of PMNs were examined in the following five steps of extravasation: (1) rolling on the venular endothelium, (2) adhesion on the endothelium, (3) passage between the endothelial cells, (4) staying in the venular wall, and (5) migration from the venular wall into the interstitial space. In either the presence or absence of DEX, topical application of LTB4 (15 pmol/50 microliters) or fMLP (10 nmol/50 microliters) caused an increase in the number of PMNs that adhered to the venules. Thus, DEX did not inhibit the adhesion of PMNs on the endothelial cells. The adhered PMNs induced by these chemoattractants became gradually smaller, finally disappearing in the vascular lumen, as observed on the monitor screen. The whole process took about 10 min. This passage of PMNs between the endothelial cells was also not inhibited by DEX, as over 90% of the adhered PMNs passed through the endothelial cells and advanced to the next step of extravasation in the presence or absence of DEX. When these chemoattractants were applied to DEX-untreated animals, the PMNs that passed through the endothelial cells stayed for about 30 min in the venular wall. Thereafter, PMNs migrated into the interstitial space. The numbers of PMNs in the interstitial space were counted at 30, 60, and 90 min after the application of chemoattractants. In the DEX-untreated animals, PMNs in the interstitial space started to appear by 30 min, and thereafter the number further increased. However, in the DEX-treated animals, the number of PMNs at 60 and 90 min was significantly suppressed. Since DEX may inhibit the synthesis and/or release of a proteinase(s) in the PMN granules, which would normally degrade the basement membrane, this inhibition may be due to the inability of PMNs to penetrate the basement membrane.

Animals↗
PubMed1992

Variability of respiratory system compliance in mechanically ventilated infants.

We measured respiratory flow, volume by integrated flow, and airway pressure in four mechanically ventilated infants. Compliance of the respiratory system (Crs) was measured by the multiple occlusion method. Airway occlusion and release were achieved by a balloon in an occlusion valve between the endotracheal tube and a pneumotachometer, all connected in series with the respirator circuit. Values of Crs varied greatly due to changes in mean airway pressure (MAP). The Crs increased with the elevation of MAP on some occasions and decreased on others. Values of Crs also varied corresponding to different occlusion pressures for individual levels of MAP. Thus Crs changed continuously, even within a single respiratory cycle. The observed variability in Crs was explained by the following mechanism: a pressure-volume (P-V) loop of tidal ventilation moves its position within the pressure-volume diagram and changes shape due to variations of the ventilator settings. In some infants the lungs were ventilated in the range of the linear portion of the P-V diagram while in others they may have been ventilated on the flattened portion. Some patients had convex expiratory P-V curves even with low pressure swings during tidal ventilation.

Airway Resistance↗
PubMed1992

Hydroxyl radical generation by red tide algae.

The unicellular marine phytoplankton Chattonella marina is known to have toxic effects against various living marine organisms, especially fishes. However, details of the mechanism of the toxicity of this plankton remain obscure. Here we demonstrate the generation of superoxide and hydroxyl radicals from a red tide unicellular organism, C. marina, by using ESR spectroscopy with the spin traps 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and N-t-butyl-alpha-phenylnitrone (PBN), and by using the luminol-enhanced chemiluminescence response. The spin-trapping assay revealed productions of spin adduct of superoxide anion (O2-) (DMPO-OOH) and that of hydroxyl radical (.OH) (DMPO-OH) in the algal suspension, which was not observed in the ultrasonic-ruptured suspension. The addition of superoxide dismutase (500 U/ml) almost completely inhibited the formation of both DMPO-OOH and DMPO-OH, and carbon-centered radicals were generated with the disappearance of DMPO-OH after addition of 5% dimethyl sulfoxide (Me2SO) and 5% ethanol. Furthermore, the generation of methyl and methoxyl radicals, which are thought to be produced by the reaction of hydroxyl radical and Me2SO under aerobic condition, was identified using spin trapping with a combination of PBN and Me2SO. Luminol-enhanced chemiluminescence assay also supported the above observations. These results clearly indicate that C. marina generates and releases the superoxide radical followed by the production of hydroxyl radical to the surrounding environment. The velocity of superoxide generation by C. marina was about 100 times faster than that by mammalian phagocytes per cell basis. The generation of oxygen radical is suggested to be a pathogenic principle in the toxication of red tide to susceptible aquaculture fishes and may be directly correlated with the coastal pollution by red tide.

Cyclic N-Oxides↗
PubMed1992

A single serine:pyruvate aminotransferase gene on rat chromosome 9q34-q36.

It was found in our previous study (Oda et al., 1990. J. Biol. Chem. 265: 7513-7519) that in the rat two mRNAs encoding mitochondrial and peroxisomal serine:pyruvate aminotransferase (SPT/AGT) are formed from a single SPT/AGT gene through alternative transcription initiation in exon 1. In an attempt to analyze the mechanisms underlying this unique phenomenon, we have isolated genomic clones harboring the entire rat SPT/AGT gene. In the present study, the location of the rat SPT/AGT gene was determined to be in the q34-q36 region of chromosome 9 by fluorescence in situ hybridization. Southern blot analysis of rat genomic DNA revealed an allelic BamHI restriction fragment length polymorphism among three different inbred rat strains. These results indicated that a single copy SPT/AGT gene is located on chromosome 9q34-q36 in the rat genome. This locus has been assigned the gene symbol Spat.

Animals↗
PubMed1992

Induction of protective immunity to Brugia pahangi in jirds by drug-abbreviated infection.

Protective immunity of homologous challenge infection was examined in jirds after drug-abbreviated infection with Brugia pahangi. Mebendazole (MBZ) treatment at the early prepatent (5-7 weeks of post infection) or the late prepatent (7-9 weeks of post infection) period was highly effective in causing almost complete eradication of the primary infection. After challenge infection, the worm burden was significantly reduced 19% (31.1 in average) and 77% (9.5) to that of the controls (38.8 and 41.7), respectively. The magnitude of eosinophil response paralleled the degree of protection. No or only a few microfilariae were seen after challenge infection in jirds treated during the prepatent periods. They were also resistant to intravenous challenge with the microfilariae of B. pahangi. MBZ treatment at the patent period was, on the contrary, incomplete against primarily infected adult worms, and was not able to induce either significant protection (30.1 vs 33.1 in control) or eosinophil response to the challenge infection.

Animals↗
PubMed1992

Determination of transcriptional activities of typical gene promoters in HL-60 cells.

We developed a highly sensitive procedure for assaying chloramphenicol acetyltransferase (CAT) enzyme activity in extracts of eukaryotic cells transfected with the CAT gene expression vector, by modification of the partition extraction procedure described by Sleigh [Anal. Biochem. 156, 251-256 (1986)]. The sensitivity of the new method was improved 100-fold on commercial purified enzyme. In routine measurements with cell extracts a CAT activity as low as 1.3 x 10(-4) unit could be measured within an error of less than 30%. The CAT enzyme expressions in undifferentiated human promyelocytic leukemic cell line HL-60 from typical gene promoters could be measured by the new method and compared to select a stronger promoter. Similar measurements were made with more mature monocytic THP-1 cells to evaluate the change in the promoter activity with cell maturation. Differentiation induction with 12-O-tetradecanoylphorbol-13-acetate (TPA) activated transcription from the human immunodeficiency virus (HIV) promoter about 10-fold in HL-60 cells, as expected, but the level was less than that in untreated THP-1 cells. In addition, a similar activation was observed in THP-1 cells as well.

Cell Differentiation↗
PubMed1992

A gene coding for a zinc finger protein is induced during 12-O-tetradecanoylphorbol-13-acetate-stimulated HL-60 cell differentiation.

ETR103 cDNA was cloned as an immediate early gene in the course of macrophagic differentiation of HL-60 cells stimulated by TPA (12-O-tetradecanoylphorbol-13-acetate). The induction by TPA was immediate-early (within 30 min) and transient. This gene was not induced by vitamin D3 or by retinoic acid, which stimulates differentiation of HL-60 cells to the monocytic or granulocytic lineage, respectively. The ETR103 mRNA was induced by TPA in lymphoid or myeloid leukemia cell lines of several maturation stages. The induction by TPA seems to proceed by a protein kinase C-mediated mechanism, on the basis of the results obtained by using protein kinase C inhibitor (H-7), protein kinase C activator (diC8), and an activator of protein kinase A (dibutyryl cAMP). Okadaic acid, an inhibitor of protein phosphatases, also induced the ETR103 mRNA expression. The nucleotide sequence of the ETR103 cDNA reveals that ETR103 encodes a human zinc finger-containing transcription factor identical to Egr-1 and 225, which is homologous to mouse Egr-1, Zif/268, Krox-24, and TIS8, or to rat NGFI-A.

Amino Acid Sequence↗
PubMed1992

Effects of prolactin on ovarian plasmin generation in the process of ovulation.

The present study was undertaken to assess the effects of prolactin (PRL) on gonadotropin-induced plasmin generation in the in vitro-perfused rabbit ovary. The ovarian plasmin activity was determined by measuring plasmin bound to its major inhibitor, alpha 2-plasmin inhibitor (alpha 2 PI-Plm). In the first experiment, exposure to hCG enhanced ovarian alpha 2 PI-Plm generation from 1.2 +/- 0.3 ng/min/ovary in unstimulated ovaries to 2.9 +/- 0.3 ng within 2 h. The concentration of alpha 2 PI-Plm reached a maximum at 4 h and then declined. A second peak occurred 8 h after hCG administration; however, the ovarian alpha 2 PI-Plm generation without hCG was very low throughout the entire perfusion period. In the subsequent experiment, the addition of PRL(10-10(3) ng/ml) to the perfusate inhibited hCG-induced ovulation in a dose-dependent manner. Exposure to PRL at 10(3) ng/ml significantly (p less than 0.05) inhibited hCG-induced alpha 2 PI-Plm generation in ovaries throughout the entire perfusion period. Furthermore, PRL inhibited hCG-stimulated alpha 2 PI-Plm generation at 4 h after hCG administration in the perfused rabbit ovaries in a dose-dependent manner. In conclusion, PRL directly inhibits hCG-induced ovulation in rabbit ovary, at least in part, by a mechanism depending upon inhibition of the plasmin-generating system in the preovulatory follicles.

Animals↗
PubMed1992

Protein kinase C mediates gonadotropin-releasing hormone agonist-induced meiotic maturation of follicle-enclosed rabbit oocytes.

The present study was undertaken to determine the effects of a protein kinase C inhibitor, staurosporine, on gonadotropin-releasing hormone agonist (GnRHa)-induced oocyte maturation and follicular prostaglandin (PG) production, and the response to direct activators of protein kinase C using rabbit mature follicle culture. Treatment of mature follicles with GnRHa (buserelin and leuprolide acetate) neither stimulated nor inhibited cAMP accumulation in both the follicle and oocyte. Exposure to staurosporine at 10(-6) M 60 or 15 min before GnRHa (buserelin) administration reduced significantly the meiotic maturation of follicle-enclosed oocytes induced by GnRHa at 10(-7) M. However, staurosporine addition coincident with the agonist or thereafter did not inhibit meiotic maturation. Staurosporine suppressed GnRHa-induced meiotic maturation in a dose-dependent manner, whereas hCG-stimulated oocyte maturation was not inhibited. Similarly, staurosporine administered 60 min before exposure to GnRHa suppressed GnRHa-stimulated PG production by mature follicles. The active phorbol esters, 10(-6) M 12-0-tetra-decanoyl phorbol 13-acetate (TPA) and 10(-6) M 4 beta-phorbol 12,13-didecanoate (4 beta-PDD) stimulated meiotic maturation whereas the biological inactive isomer, 4 alpha-PDD, did not. The kinetics of germinal versicle breakdown of follicle-enclosed oocytes in the presence of active phorbol esters paralleled that of GnRHa-treated oocytes. Furthermore, the concomitant addition of staurosporine at 10(-6) M to the culture medium inhibited significantly (p less than 0.05) TPA-induced meiotic maturation. These data demonstrate that GnRHa stimulated both the meiotic maturation of follicle-enclosed oocytes and follicular PG formation via a mechanism other than the cAMP-mediated process.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1992

Multidirectional instabilities of experimental burst fractures of the atlas.

For the purpose of understanding the acute instability of a burst (Jefferson) fracture of the atlas, the authors produced the fractures experimentally and measured multidirectional flexibilities in seven cadaveric C0-C3 specimens. The flexibilities were measured by the authors' standardized method: they applied six types of physiologically pure moments (up to 1.5 Nm) and recorded the ensuing C0-C2 motions by stereophotogrammetry. The flexibility tests were performed before and after the production of the fracture. The greatest increase in flexibility due to the injury was in flexion-extension (+22.0 degrees, 41.7%). In lateral bending, the increase was 7.7 degrees, or 23.9%. The flexibility was mostly maintained in axial rotation (+4.8 degrees, 5.4%). The increase in motion was due to an increase in neutral zone in flexion-extension, and an increase in the elastic zone in lateral bending. These flexibility results of experimentally produced fractures reflect quite well the acute instabilities seen clinically.

Cervical Atlas↗