Search PubMed⌕ Search

Biomedical subjects

T Oda

Publications and source records attributed to T Oda.

At least 307 records · Page 17Linked to original sources
PubMed1994

Loss of amplified c-myc genes in the spontaneously differentiated HL-60 cells.

Amplification of the c-myc gene in the human promyelocytic leukemia cell line HL-60 is considered to be one of the major causes of its malignant phenotype. It is also well known since the establishment of the cell line that a culture of HL-60 cells contains a small but fixed percentage of spontaneously differentiated cells. We show that the spontaneous differentiation could be a result of extensive losses of amplified c-myc genes by the findings: (a) the spontaneously differentiated HL-60 cells express Mac-1 (CR3, CD11b/CD18) antigen, irreversibly stop the uptake of [3H]thymidine, and die by apoptosis; (b) these cells, when isolated, and when the copy number of c-myc genes is precisely quantitated, show extensive losses of c-myc genes; and (c) low concentrations of hydroxyurea increase the percentage of spontaneously differentiated cells in which the number of c-myc genes is further decreased. A simple theoretical consideration suggests that an active elimination process(es) must be operating besides the stochastic losses of the extrachromosomally amplified c-myc genes by unequal partition at mitosis.

Base Sequence↗
PubMed1994

Argyrophilic thread-like structure in corticobasal degeneration and supranuclear palsy.

Massive argyrophilic thread-like structures (ATS) are observed in corticobasal degeneration and, in varied degrees, in some cases of progressive supranuclear palsy. Immunohistochemically, ATS has a full length of phosphorylated tau epitopes without ubiquitin. Gallyas- and immuno-electron microscopic observation revealed that ATS is a cytoskeletal abnormality occurred in both the inner and outer loop of the oligodendroglia. tau-Positive oligodendroglial tangles were distributed in the same region as ATS.

Aged↗
PubMed1994

Regulation by glucagon of serine: pyruvate/alanine: glyoxylate aminotransferase gene expression in cultured rat hepatocytes.

The effects of glucagon on serine: pyruvate/alanine: glyoxylate aminotransferase (SPT/AGT) gene expression were studied in primary cultured rat hepatocytes. When hepatocytes had been precultured for 16-18 h under serum- and hormone-free conditions, the addition of glucagon caused (after a lag period of about 2 h) a remarkable increase in the cellular level of SPT/AGT mRNA by 4 h in a time- and dose-dependent manner. The induced mRNA was that for mitochondrial SPT/AGT, as judged by ribonuclease protection analysis. A nuclear run-on assay revealed that activation of transcription is responsible for the increase in mitochondrial SPT/AGT mRNA and that the maximal rate of transcription occurs 1.5 h after glucagon addition. The effect of glucagon was mimicked by 8-bromo-cAMP and suppressed by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, an inhibitor of cAMP-dependent protein kinase (protein kinase A), while both 12-O-tetradecanoylphorbol-13-acetate and A23187 were without effect in elevating the SPT/AGT mRNA level, suggesting that the cAMP/protein kinase A system is involved in the regulation of SPT/AGT gene expression. In hepatocytes precultured for 16-18 h under serum- and hormone-free conditions, the glucagon-induced transcription was severely inhibited by cycloheximide. When the preculture was for 2 h, on the other hand, the activation of transcription by glucagon was more rapid, and the inhibition by cycloheximide was less than that observed with cells precultured for 16-18 h, suggesting that a short-lived protein factor is involved in the hormonal regulation. The glucagon-induced expression of the SPT/AGT gene was also turned off by dexamethasone.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

E-cadherin gene mutations in human gastric carcinoma cell lines.

Reduced expression of E-cadherin has been regarded as one of the main molecular events involved in dysfunction of the cell-cell adhesion system, triggering cancer invasion and metastasis. However, even with a sufficient amount of E-cadherin, cell-cell adhesion is sometimes lost in "diffusely invasive" human carcinomas. Ten human cancer cell lines, showing growth characterized morphologically by loose cell-cell adhesion, were analyzed for possible structural abnormalities of their expressed E-cadherin. Four of the cell lines showed strong mRNA and protein expression with no nucleotide sequence abnormalities, and mRNA was absent in four other cell lines. mRNA sequence was abnormal in the remaining two gastric carcinoma cell lines. In MKN45 (poorly differentiated adenocarcinoma), this involved a 12-bp in-frame deletion with strong expression of mRNA and protein. In KATO-III (signet ring cell carcinoma), there were four mRNA species with insertions of different sizes, among which the major transcripts (with a 7-bp insertion) caused a frameshift, and expression of both mRNA and protein was markedly reduced. In these two cell lines, DNA mutations were detected around exon-intron junctions, revealing that aberrant RNA splicing was the cause of the mRNA abnormalities. In addition, the wild-type allele of the E-cadherin locus was lost, suggesting that the E-cadherin gene had been inactivated by two hits (mutation and allele loss), similar to the mechanism for inactivation of tumor suppressor genes.

Amino Acid Sequence↗
PubMed1994

Clusterin (SGP-2): a multifunctional glycoprotein with regional expression in astrocytes and neurons of the adult rat brain.

Clusterin (SGP-2) is a newly described glycoprotein associated with several putative functions including responses to brain injury. This study reports the regional and cell type expression of clusterin mRNA and its encoded glycoprotein in the rat brain; a limited comparison was also done with the human brain. Using in situ hybridization combined with immunocytochemistry, we found that astrocytes and neurons may express clusterin mRNA in the normal adult brain. While astrocytes throughout the brain contained clusterin mRNA, there was regional selectivity for neuronal clusterin expression. In the striatum, clusterin mRNA was not detected in neurons. Only a subset of substantia nigra dopaminergic neurons or locus ceruleus noradrenergic neurons (tyrosine hydroxylase immunopositive) contained clusterin mRNA. However, neuronal clusterin mRNA was prevalent in pontine nuclei and in the red nucleus of the midbrain tegmentum. Similarly, clusterin mRNA was prevalent in both rat and human hippocampal neuron-specific enolase immunopositive pyramidal neurons, although rat CA1 neurons had less mRNA than CA2-CA3 neurons. Monotypic primary cell cultures from the neonatal rat showed clusterin mRNA in both neurons and astrocytes, but not in microglia. By immunocytochemistry, no clusterin immunopositive glia were observed in any region of the rat brain, confirming previous studies. However, clusterin immunopositive cells (putative neurons) were observed in the Purkinje cell layer of the cerebellum, medial and interposed cerebellar nuclei, trigeminal motor nucleus, and red nucleus. Finally, in vitro studies suggest that astrocytes, but not neurons, secrete clusterin, which is pertinent to clusterin immunodeposits found after experimental lesioning.

Alzheimer Disease↗
PubMed1994

Horseshoe crab (1,3)-beta-D-glucan-sensitive coagulation factor G. A serine protease zymogen heterodimer with similarities to beta-glucan-binding proteins.

Horseshoe crab factor G is an intracellular serine protease zymogen that initiates the (1,3)-beta-D-glucan-sensitive hemolymph clotting pathway. Unlike other known serine protease zymogens, which are composed of a single subunit, factor G consists of two distinct subunits, alpha and beta, which are autocatalytically converted to active factor G in the presence of (1,3)-beta-D-glucan. We have now cloned and sequenced cDNAs encoding both subunits of factor G. The subunits are derived from separate mRNA species and thus encoded by different genes. Subunit beta is a serine protease zymogen which consists of 278 residues with a calculated molecular mass of 30,846 Da; it exhibits homology to the serine protease domain of horseshoe crab factor B. Subunit alpha, on the other hand, is a new type of mosaic protein with intriguing features. The mature protein consists of 654 residues with a calculated molecular mass of 73,916 Da. The NH2-terminal portion of this subunit is similar to bacterial beta-1,3-glucanases. Its 126 amino acid COOH terminus exhibits a repetitive sequence having partial homology to xylanases. Between these regions are three repeating units of 47 amino acids, whose similarity to carbohydrate-binding proteins suggests that these may be the (1,3)-beta-D-glucan-binding domain(s) of factor G. Factor G, thus, is a structurally unique heterodimeric serine protease zymogen and as such may represent a new class of active defense proteins.

Amino Acid Sequence↗
PubMed1994

Effect of lovastatin on the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in brefeldin A-sensitive and -resistant cell lines.

Lovastatin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibits the biosynthesis of cholesterol and the prenylation of proteins. In this study, we have found that lovastatin inhibited the cytotoxicities of modeccin, ricin, Pseudomonas toxin, and diphtheria toxin in Vero and a brefeldin A (BFA)-resistant mutant of Vero cells (BER-40) to different extents. Among these toxins tested, the cytotoxicity of modeccin was most strongly inhibited by lovastatin in a dose-dependent manner. The protective effect of lovastatin was completely reversed by the addition of mevalonic acid, while the addition of cholesterol had no effect on the cytotoxicity of modeccin in lovastatin-treated cells. These results suggest that prenylated proteins are involved in the intoxication process of modeccin. The addition of cycloheximide to the growth medium also reversed the protective effect of lovastatin, suggesting a requirement of de novo protein synthesis for the protection by lovastatin against toxins. In contrast to Vero and BER-40 cells, no significant effect of lovastatin was observed in naturally BFA-resistant cell lines, PtK1 and MDCK cells, even though similar morphological changes and disassembly of the actin microfilaments were induced by lovastatin in these cell lines as observed in Vero and BER-40 cells. Lovastatin did not affect the binding and internalization of ricin and modeccin in Vero and BER-40 cells. Our results suggest that prenylated cellular proteins are involved in intracellular trafficking or processing of protein toxins, especially modeccin. In PtK1 and MDCK cells, such intracellular vesicle trafficking of protein toxins may be regulated by lovastatin-resistant mechanisms.

ADP Ribose Transferases↗
PubMed1994

Neutrophil activation after percutaneous transluminal coronary angioplasty.

We investigated whether percutaneous transluminal coronary angioplasty (PTCA) would induce neutrophil activation in patients with coronary artery disease. Blood samples were taken from the coronary sinus in 14 patients who underwent PTCA and in 9 control subjects who underwent coronary arteriography (CAG). Flow cytometry was used to measure membrane surface expression of beta 2 integrin (CD11b) and the generation of hydrogen peroxide in neutrophils after ex vivo phorbol myristate acetate stimulation by 2,'7'-dichlorofluorescein. Neutrophil elastase was measured by an immunoenzymatic method. Surface expression of CD11b increased significantly, approximately twofold, after PTCA but not after CAG. Mean fluorescence intensity of 2',7'-dichlorofluorescein in stimulated neutrophils decreased significantly after PTCA, suggesting a previous in vivo activation, but not after CAG. Neutrophil elastase increased significantly after PTCA but not after CAG. These data indicate that PTCA induces neutrophil activation and suggest that neutrophils may contribute to the ischemic injury.

Adult↗
PubMed1994

Emergency operation for thoracic aortic aneurysm caused by the Ehlers-Danlos syndrome.

Two patients were treated emergently for impending ruptured thoracic aortic aneurysms caused by type IV Ehlers-Danlos syndrome. One patient had typical physical evidence of type IV Ehlers-Danlos syndrome. The other patient had a normal phenotype. Type IV Ehlers-Danlos syndrome was diagnosed by electrophoresis of the collagen extracted from the skin. The clinician must be aware of the variations in presentation of type IV Ehlers-Danlos syndrome.

Adolescent↗
PubMed1994

Recovery of load-induced left ventricular diastolic dysfunction by coenzyme Q10: echocardiographic study.

UNLABELLED: Load-induced cardiac dysfunction (LCD), in which a supernormal left ventricular (LV) systolic performance at rest decreases due to an afterload challenge, usually occurs among children with mitral valve prolapse (MVP). However, diastolic performance is also important because relaxation, like contraction, is based on a process that requires energy. The aim of this study was to examine LV diastolic response patterns to stress in patients with LCD before and after coenzyme Q10 (CoQ) therapy and in controls. The D-E slope, E-F slope and maximal diastolic endocardial velocity were used as echographic diastolic indices. Thirty subjects, aged 9-16 years, were divided into four groups: group 1, 10 normals; group 2, 10 patients with LCD; group 3, the same 10 as in group 2, who recovered with CoQ, 3.0-3.4 mg/kg/day for 7 days; group 4, 10 asymptomatic children with MVP. The heart rate, both at rest and during handgrip (HG), showed little intergroup difference. Only in group 2, were the ejection fraction and all the diastolic indices greater than in the other groups, but these became subnormal with HG. In the other groups, these indices increased with HG to a similar extent, although resting values were smaller than in group 2. IN CONCLUSION: (1) in normal hearts and in hearts with LCD, diastolic performance mimicked systolic performance both in resting and loading conditions; (2) CoQ improved not only the load-induced systolic but also the diastolic dysfunctions in a similar time-course, and (3) mechanical stiffness of the cardiac tissue may not be a cause of load-induced diastolic dysfunction, because the dysfunction was quickly resolved with CoQ therapy. CoQ may be a key substance which affects a common bioenergetic process in contraction and relaxation, to keep these functions normal.

Adolescent↗
PubMed1994

Free oxygen radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries.

OBJECTIVES: The purpose of this study was to test the hypothesis that free oxygen radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured coronary arteries. BACKGROUND: Although free oxygen radicals, such as superoxide anion and hydrogen peroxide, have been shown to alter platelet function in vitro, the potential role of free oxygen radicals has not been fully described in an in vivo model of coronary artery thrombosis. METHODS: Cyclic flow variations were produced in dogs by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery was monitored by a pulsed Doppler flow probe. If cyclic flow variations were observed during postoperative days, dogs intravenously received superoxide dismutase plus catalase. In anesthetized dogs that did not develop an episode of cyclic flow variations, the effect of intracoronary infusion of xanthine plus xanthine oxidase or hydrogen peroxide on arterial blood flow velocity was studied. In platelet studies, the effect of free oxygen radicals and radical scavengers on platelet aggregation was examined. RESULTS: In conscious dogs with cyclic flow variations, superoxide dismutase plus catalase significantly reduced cyclic flow variations (n = 7), whereas saline infusion had no effect (n = 7). The infusion of xanthine plus xanthine oxidase or hydrogen peroxide significantly induced cyclic flow variations in four of six dogs or in five of seven dogs, respectively. In vitro platelet studies showed that xanthine plus xanthine oxidase or hydrogen peroxide significantly enhanced platelet aggregation, and superoxide dismutase or catalase significantly inhibited such aggregation. CONCLUSIONS: Reduction of free radical formation decreases platelet aggregation and may eliminate cyclic flow variations, whereas promotion of free radical generation enhances platelet aggregation and may induce cyclic flow variations. Thus, free oxygen radicals are an important mediator in this model.

Animals↗
PubMed1994

Variability in circadian activity patterns within the Culex pipiens complex (Diptera: Culicidae).

Circadian activity was compared among four strains of Culex pipiens molestus Forskal from Iran, Egypt, two localities (Ebira and Yanagawa) in Nagasaki, Japan, and one strain of Cx. p. pallens Coquillett from Japan. Under a 16:8 (L:D) h photoperiod, all the strains showed peaks of activity at lights on and off, with additional activity during both light and dark periods; Egyptian females and both sexes of Cx. p. pallens were inactive during the photophase. Under 0:24 (L:D) h, the length of the free-running activity period was significantly shorter in the "Iran" (21 h) than in the other three Cx. p. molestus strains (range, 21-23 h) and Cx. p. pallens (approximately 24 h). Under 24:0 (L:D) h, the activity rhythm was obscured. The length of the period was shorter in 24:0 (L:D) h than in 0:24 (L:D) h, violating Aschoff's circadian rule. Furthermore, the circadian peak did not always occur every day under 24:0 (L:D) h but rather exhibited "day-skipping."

Animals↗
PubMed1994

Prolactin inhibits ovulation by reducing ovarian plasmin generation.

The present study was undertaken to investigate the effects of prolactin (PRL) on gonadotropin-induced ovulation and the biosynthesis of prostaglandin (PG), leukotriene (LT), and plasmin in in vitro perfused rabbit ovaries. The addition of PRL to the perfusate inhibited hCG-induced ovulation in vitro in a dose-dependent manner. Although exposure to hCG significantly increased PGF2 alpha, PGE2, and LTB4 production by perfused rabbit ovaries, PRL did not affect the secretion rates of PGs and LTB4 stimulated by hCG administration. The ovarian plasmin generation was determined by measuring the amount of plasmin bound to its major inhibitor, alpha 2-plasmin inhibitor (alpha 2PI-Plm). Exposure to hCG enhanced biphasically the ovarian secretion rate of alpha 2 PI-Plm, while PRL at a dose of 10(3) ng/ml significantly inhibited the hCG-stimulated generation of alpha 2 PI-Plm in ovaries throughout the entire perfusion period. A significant correlation was observed between ovulatory efficiency and ovarian plasmin generation in the PRL-treated ovaries. Additionally, PRL inhibited intrafollicular concentrations of alpha 2 PI-Plm in hCG-treated ovaries in a dose-dependent manner. These observations substantiate an essential role for a plasma-generating system in the cascade of events leading to ovulation. In conclusion, PRL may act directly on the ovary and block ovulation, at least in part, via the inhibition of ovarian plasmin generation.

Animals↗
PubMed1994

Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast.

Reduced or heterogeneous expression of E-cadherin has been demonstrated immunohistochemically in poorly differentiated carcinoma, which frequently shows weak intercellular adhesiveness and marked invasiveness. In vitro, not only reduced expression but also structural abnormalities of E-cadherin have been observed in human carcinoma cell lines which grow in a loosely adhering manner. To clarify the participation of structural abnormalities of E-cadherin in cancer invasion in vivo, sequence abnormalities were examined in the cadherin domain (exons 5, 6, 7 and 8) including the region essential for E-cadherin specific binding, using the polymerase chain reaction-single-strand conformation polymorphism method and direct sequencing in invasive lobular carcinoma of the breast, in which cancer cells become detached from each other and invade the stroma in a particularly scattered pattern. In 2 (10%) of the 20 cases examined, an identical sequence abnormality was detected in E-cadherin exon 7, i.e. a point mutation of codon 315 (AAT to AGT) which resulted in a single amino acid substitution (asparagine to serine). This mutation may abolish the E-cadherin-mediated cell-cell adhesion and be at least partly responsible for the weak intercellular adhesiveness and scattered histological pattern of the tumor.

Base Sequence↗
PubMed1994

Human parvovirus B19-induced aplastic crisis in iron deficiency anemia.

Human parvovirus B19 (HPVB19) infects and replicates in erythroid progenitor cells. Its specific cytotoxic effect on these cells results in aplastic crises in patients with congenital hemolytic anemias. Aplastic crisis due to HPVB19 infection in a healthy girl revealed occult iron deficiency anemia. The condition is characterized by a high serum iron level in the aplastic phase and rapid recovery after administration of iron. Temporary HPVB19-induced red blood cell aplasia could occur in patients with other anemias, particularly those with non-inherited form of hemolysis.

Adolescent↗
PubMed1994

Recovery period from ureteral obstructions of different duration and severity in the rat kidney.

The relationship between the period for recovery from hydronephrosis and the characteristics of the obstruction still needs to be clarified. In rat kidney the left ureter was completely obstructed for 3, 7, 14 and 21 d and the renal function was measured by renal scintigraphy using 99mTC-dimercaptosuccinic acid 3, 7 and 14 d after the obstruction was removed. In addition, recovery from unilateral partial obstruction (PO) of different degrees of severity for 7 d was examined. The kidneys with very mild PO recovered within 3 d and those with a very long period of complete obstruction (CO) did not exhibit any significant recovery. However, most of the kidneys with CO of various durations and those with 7 days PO of various degrees of severity exhibited maximum recovery 7 d after the release of the obstruction. This study suggests that the period required for maximum recovery from hydronephrosis is usually constant, unless the obstruction is too mild to cause any damage or too long to permit any recovery.

Animals↗