Regulation of glutathione transferase P gene during hepatocarcinogenesis of the rat.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
A Okuda
Publications and source records attributed to A Okuda.
Case report: diagnosis of cavo-portal shunt in inferior vena cava obstruction: comparison between venography and dynamic scintigraphy.
A cavo-portal shunt is a rare complication of inferior vena cava obstruction. A patient is described who had complete obstruction of the inferior vena cava (IVC) due to extension of tumour thrombus from a left renal cell carcinoma. Venocavography clearly showed many collateral veins but not a cavo-portal shunt. Dynamic scintigraphy, however, distinctively showed a draining vein and subsequent homogeneous radionuclide uptake of the liver, which indicates a cavo-portal shunt.
Carcinoma, Renal Cell↗
[A successful case of concomitant operation for coronary artery disease and rectal cancer in elderly patient].
We report a successful case of 75-year-old man who was simultaneously undertaken CABG for coronary artery disease and Miles' operation for rectal cancer. A concomitant cardiac and rectal operation involves serious problems, such as increasing operative risk, bleeding tendency after cardiopulmonary bypass, infection and radicality against malignancy, however, it should be a definitive method for the selective case.
Adenocarcinoma↗
[A case report on a double chambered right ventricle (DCRV)--pre- and postoperative responses of the right ventricle to atrial pacing and the isoproterenol tolerance test].
To evaluate the development of an anomalous muscle bandle of the right ventricle (RV) and results of surgical intervention, responses of the RV to atrial pacing and the isoproterenol tests were examined in both the pre- and postoperative periods. Although cardiac output did not increase in proportion to the rate of atrial pacing or the dose of isoproterenol, the pressure gradient through the RV increased abnormally from 38 mmHg to 59 mmHg (atrial pacing) and 116 mmHg (isoproterenol). On the other hand, postoperative evaluation showed normal RV responses in these tests. Since the response of the right ventricle to these tolerance tests in patients with DCRV in pre- and postoperative periods has not been well elucidated, a precise evaluation is reported in this paper.
Cardiac Output↗
The yeast heat shock transcription factor contains a transcriptional activation domain whose activity is repressed under nonshock conditions.
Transcription of heat shock genes is induced by exposure of cells to elevated temperatures or other stress conditions. In yeast, it is thought that induction of transcription is mediated by conversion of a DNA-bound transcriptionally inactive form of the heat shock transcription factor (HSTF) to a DNA-bound transcriptionally active form. We have identified domains in HSTF involved in transcriptional activation and in repression of transcriptional activation at non-shock temperatures. We present evidence that a temperature-regulated transcriptional activation domain exists in HSTF and that this domain is essential for survival of yeast cells at heat shock temperatures. We propose a model for temperature-regulated transcriptional activation by a derepression mechanism.
Amino Acid Sequence↗
A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells.
We have identified a novel octamer binding factor (Oct-3) in P19 embryonal carcinoma cells. Oct-3, which recognizes the typical octamer motif (ATTTGCAT) as well as the AT-rich sequence TTAAAATTCA, is present in P19 stem cells but disappears when the cells are induced to differentiate by retinoic acid (RA). Cloned cDNA corresponding to Oct-3 encodes a protein of 377 amino acids. Oct-3 has a conserved POU domain, but the remaining part is distinct from other POU domain-containing proteins such as Oct-1 and Oct-2. mRNA of 1.5 kb coding for Oct-3 is abundant in P19 stem cells but is dramatically repressed during RA-induced differentiation. Repression of the 1.5 kb mRNA is rapid and specific to RA. In mouse, oct-3 mRNA is undetectable in all the adult organs examined. The N-terminal proline-rich region of Oct-3, when fused to the DNA binding domain of c-Jun, functions as a transcriptional activating domain. We suggest that Oct-3 is a novel octamer binding transcription factor that is developmentally regulated during mouse embryogenesis.
Amino Acid Sequence↗
Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonic stem cells.
We have recently identified an enhancer, termed GPEI, in the 5'-flanking region of the rat glutathione transferase P gene, that is composed of two imperfect TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive elements (TREs). Unlike other TRE-containing enhancers, GPEI exhibits a strong transcriptional enhancing activity in F9 embryonic stem cells. Mutational analyses have revealed that the high activity of GPEI is mediated by two imperfect TREs. Each TRE-like sequence has no activity by itself but acts synergistically to form a strong enhancer which is active even in the very low level of AP-1 activity in F9 cells. Furthermore, we show that synthetic DNAs containing two perfect TREs in certain arrangements have strong transcriptional enhancing activities in F9 cells and the activity is greatly influenced by the relative orientation and the distance of two TREs.
Animals↗
The effects of sodium fluoride on the resorptive activity of isolated osteoclasts.
It is not clear to what extent the increased bone mass observed in vertebral trabecular bone of fluoride-treated mammals is a consequence of effects of fluoride on the number and activity of osteoclasts or of osteoblasts. In the present communication, we have analyzed the effects of NaF on the activity of isolated rabbit osteoclasts cultured on thin slices of devitalized compact bovine bone. Osteoclastic resorption was quantitated by counting the number of resorption lacunae and measuring their surface area and their depth using scanning electron microscopy. Our results show that NaF in concentrations of 0.5-1.0 mM decreased the number of resorption lacunae made by individual osteoclasts and decreased the resorbed area per osteoclast. We argue that the concentration of fluoride in these experiments may be within the range "seen" by osteoclasts in mammals treated for prolonged periods with approximately 1 mg of NaF/kg body weight (bw) per day.
Acid Phosphatase↗
Cell-cycle independent increase in heat production in response to growth factors in cultured rat fibroblasts: interpretation by continuum model.
We measured the heat output from rat 3Y1 fibroblastic cells by stopped-flow method using a flow microcalorimeter. When the resting cells were stimulated to initiate DNA synthesis with growth factors, the heat output increased. Although cells normally progressed through S and G2 phases in the absence of any growth factor, cells increased the heat output in response to the growth factors during the progression through these phases. These results are consistent with the continuum model in which the preparation for the initiation of S phase occurs continuously and cumulatively between adjacent S phases not restricted in G1 phase.
Animals↗
Transformation by v-H-ras does not restore proliferation of a set of temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts.
Three temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts (3Y1tsD123, 3Y1tsG125, and 3Y1tsH203, each belonging to distinct complementation groups) were transformed with plasmid DNA carrying Harvey murine sarcoma virus cDNA. The criteria for transformation were increase in saturation cell density, capability to clone in soft agar, and alteration in the cellular morphology. At 39.8 degrees C (restrictive temperature of the parental cell lines), all the transformed sublines of each mutant ceased to proliferate and were arrested reversibly in the G1 phase of the cell cycle like the parental lines. At both 39.8 degrees C and 33.8 degrees C (permissive temperature for the parental lines), all the untransformed parental lines synthesized p21ras at low rate. At 33.8 degrees C, all the transformed sublines synthesized p21ras at much higher rate and expressed the morphological phenotype characteristic to v-H-ras-induced transformation. At 39.8 degrees C, the rate of p21ras synthesis was not changed in the transformed sublines of 3Y1tsD123 and 3Y1tsG125, and the morphology of transformed phenotype also remained intact. In the transformed subline of 3Y1tsH203, the rate of p21ras synthesis was lowered at 39.8 degrees C to that seen in the untransformed parental line, and the transformed phenotype in morphology disappeared. In all of the transformed sublines, the amount of v-H-ras mRNA markedly expressed at both 33.8 degrees C and 39.8 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of surface substances of untransformed fibroblastic cells on the adhesion and proliferation of neighboring cells: a study using fixed confluent cell sheets.
To study the effects of surface materials of cells on the behavior of other neighboring cells in a crowded culture, confluent sheets of rat 3Y1 fibroblasts were fixed and then 3Y1 cells were seeded on to them. Among confluent sheets unfixed, fixed with formalin and fixed with ethanol and an empty plastic dish surface, the substrate activity to permit cell adhesion was compared. After confluent 3Y1 cells (mainly composed of cells with a G1-DNA content) were reseeded with fresh medium on to these substrates, the capacity to initiate DNA synthesis per attached cell was also compared. The substrate activity of the ethanol-fixed cell sheet to permit cell adhesion was as high as that of the empty dish surface, whereas that of the unfixed cell sheet and that of the formalin-fixed cell sheet were low. When the ethanol-fixed cell sheet and the empty dish surface were coated with the ethanol extract of the unfixed cell sheet, the substrate activity diminished, indicating that during the fixation process with ethanol an adhesion-inhibitory factor (s) was removed. The capacity to initiate DNA synthesis of each cell that had completed adhesion and spreading on the cell sheets unfixed, fixed with formalin, and fixed with ethanol was lower compared to the cell that had adhered to the empty dish surface. We conclude that factors over the 3Y1 cell surface inhibit the overlapping cell adhesion and the proliferation of cells contacting each other, resulting in the ordered cell configuration in the confluent culture.
Animals↗
Contribution of growth factors to heat production by cultured rat fibroblasts.
The heat released from rat 3Y1 fibroblasts was measured by the stopped-flow method using a flow microcalorimeter. The heat output from a monolayer culture is defined as the maximum heat output from the cell suspension, after dispersion of the monolayer. The heat output per cell was not significantly changed when exponentially proliferating cells ceased dividing, with a G1 DNA content, at confluent cell density. When the growth-arrested (resting) cells were exposed to fresh medium containing various combinations of growth factors, heat output increased in parallel with the fraction of the cells that entered S phase of the cell cycle. The increase in heat output was correlated with the increase in cell volume. We infer from these findings that the resumption of cell proliferation stimulated by growth factors involves an increase in cell volume and a concomitant increase in heat production, but that entry into the resting state does not involve abrupt decreases in cell volume and heat production.
Animals↗
Mechanism of specific expression of glutathione transferase P gene during hepatocarcinogenesis.
The mechanism of specific expression of glutathione transferase P gene during hepatocarcinogenesis of the rat has been investigated by cloning the gene and determining the upstream regulatory sequences. Two enhancers and a silencer are located within 3 kb upstream of the promoter. The stronger enhancer designated GPEI has two TPA (12-O-tetradecanoyl phorbol 13-acetate)-response element (TRE)-like sequences arranged in a palindrome at a 3 base pairs spacing. This special combination was found to form a very strong enhancer which could act efficiently even in F9 cells where the collagenase enhancer with a singlet TRE cannot work due to the low c-jun content. Whether this structure is operating with a very low concentration of c-jun/c-fos heterodimer or with any other proteins remains to be determined. These findings suggest that new and more efficient enhancers evolve by a combination of basic enhancer elements. The silencer region consists of several sequences that can bind specific protein(s) and works cooperatively.
Animals↗
[Stratification of the experimental incipient caries (polarized light microscopy and microradiography)].
The enamel caries establishes when at least a part of enamel dissolves by the action of cariogenic bacteria which produce insoluble glucan and lactic acid. The experimental caries should be prepared at the condition which simulates the natural environment. The author made 1 mm thick sections from 29 teeth extracted for convenience of orthodontic reason. The surface was covered except the "window" which will be exposed to the acid milieu. The samples were immersed for 4 to 120 days in the gelatin added lactate buffer of pH 4.5, pH 5.0, and pH 5.5. Ground sections were made after the experiment. The structure of the experimental incipient caries was described after Darling (1963); surface layer, body of the lesion, dark zone, and translucent zone. When the section was immersed for shorter period in the buffer of pH 4.5, the lesion was made up only two layers, namely, the surface layer and the body of the lesion. This type of lesion will be called Type I, hereafter. When the action of acid was more intense, only one layer, the body of the lesion remained after the dissolution of the surface layer. This type of lesion will be called Type II. The lesion which provided with all 4 layers will be called as Type III, and the lesion which was made up of 3 layers which remained after dissolved surface layer, will be called as Type IV. Both Type III and Type IV were established after immersing for longer period in pH 5.5, although they could be observed in groups which immersed in lower pH. Of the samples examined, a few example showed a five-layered structure; the surface layer, the first body of lesion, the first dark zone, the second body of lesion, the second dark zone, and the translucent zone. This phenomenon suggests that the speed of caries development was not uniform throughout the experiment. The relationship between the depth of the lesion, and the pH and the duration of acid action was studied. In the pH 5.0 group, the development of caries lesion was temporarily arrested between 30 and 60 days. This phenomenon would be an explanation to the formation of five-layered lesion.
Dental Caries↗
[Double chambered right ventricle: surgical experience in a 60-year-old woman].
The patients reported as double chambered right ventricle are mainly children. A 60-year-old woman had been pointed out for her systolic cardiac murmur without any symptom. She was admitted to our hospital for her gradual onset of fatigue, lassitude. Cardiac catheterization data revealed a 105 mmHg peak-to-peak gradient within the right ventricular cavity with normal pulmonary pressures [20/5 (12) mmHg]. Right ventricular end-diastolic pressure was 4 mmHg. Right ventriculogram demonstrated double chambered right ventricle. Electrocardiogram showed neither right ventricular hypertrophy nor upright T wave in V3R. In order to release intraventricular pressure gradient and her symptom, the anomalous muscle bundles were resected through both the right atrium and the pulmonary artery. Surgical repair without right ventriculotomy is suitable for such an elder patient with double chambered right ventricle whose ventricular function may decrease.
Age Factors↗
[Flow cytometric DNA analysis of papillary carcinoma of the thyroid using paraffin-embedded specimens].
A flow cytometric DNA analysis of papillary thyroid carcinomas has been performed on paraffin-embedded specimens, in order to determine the clinical usefulness of this method by defining the degree of the biological malignancy. Fifty-eight patients with papillary carcinomas were followed from 2 to 8 years. They were classified according to their prognosis into three groups: non-recurrent (47 patients), recurrent (5 patients), and a deceased group (6 patients). Aneuploidy was found in 6 (10.3%) of the total 58 patients. It was more frequently detected in the recurrent (40%) and in the deceased (33.3%) groups than in the non-recurrent group (4.3%). Higher proliferating index values were observed in the deceased group than in the recurrent and non-recurrent groups. These results indicate that a DNA analysis, using routine paraffin-embedded materials, is a useful adjunct in the determination of the degree of the biological malignancy of a papillary carcinoma.
Adult↗
Regulation of glutathione transferase P (GST-P) gene expression during chemical hepatocarcinogenesis.
Glutathione transferase P gene becomes highly and constitutively expressed in the course of chemical hepatocarcinogenesis of the rat. To understand the mechanism of this specific gene activation and also to obtain an insight into the general mechanism of tumor marker expression, we have been studying the regulation of a cloned gene of this enzyme. Analysis of the GST-P cDNA clone revealed that this enzyme consists of 209 amino acid residues and that homologies with other isozymes, Ya and Yc, were both about 32%. The rat GST-P gene consists of seven exons and six introns. Multiple regulatory elements were found in the 5' flanking region including two TPA responsive elements (TRE), a GC box, viral enhancer, core-like elements, and a silencer. This gene was activated by a tumor promoter TPA in certain cell lines. The rat cDNA clone or a TRE binding protein, c-jun oncogene, was isolated and characterized. Analysis of the tissue distribution and expression during chemical hepatocarcinogenesis of the c-jun mRNA suggests that the GST-P gene is regulated, at least in part, by the c-jun product. Further investigation of the mechanism of expression of GST-P, particularly in terms of the interaction with c-jun products, is now underway.
Amino Acid Sequence↗
Structure and expression of the rat c-jun messenger RNA: tissue distribution and increase during chemical hepatocarcinogenesis.
c-jun is the cellular homologue of the recently isolated nuclear oncogene v-jun. This protooncogene encodes the cellular transcription factor AP-1. We have isolated the complementary DNA clone of rat c-jun mRNA. The rat c-jun complementary DNA clone encodes 334 amino acid residues, the sequence of which shows about 98, 96, and 81% homologies with mouse, human, and chicken c-jun products, respectively. The c-jun mRNA is highly expressed in the lung and slightly expressed in the brain. The amount of mRNA is even smaller in the liver and is not detected in the spleen. We have also determined c-jun expression during chemical hepatocarcinogenesis and demonstrated increased expression of mRNA in the precancerous lesion, hyperplastic nodules, as well as in the primary hepatocellular carcinomas.
Amino Acid Sequence↗