[A follow-up study of the prognosis and eradication after endoscopic injection sclerotherapy in esophageal varices].
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Esophageal and Gastric Varices↗
Biomedical subjects
M Sakai
Publications and source records attributed to M Sakai.
[Adverse effect of sclerosants on the liver, kidney and lung].
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Esophageal and Gastric Varices↗
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↗
Increased expression of glutathione S-transferase gene in cis-diamminedichloroplatinum(II)-resistant variants of a Chinese hamster ovary cell line.
We have isolated cis-diamminedichloroplatinum(II) (CDDP)-resistant variants, C/CDP-1 and C/CDP-2, from a Chinese hamster ovary (CHO) cell line after a stepwise exposure to increasing concentrations of CDDP, and a CDDP-sensitive revertant, R-1, from C/CDP-2 after continuous incubation for 5 months in the absence of CDDP, C/CDP-1 and C/CDP-2 showed 7- and 10-fold higher resistance to CDDP, respectively, compared to CHO cells. C/CDP-2 was cross-resistant to carboplatin, L-phenylalanine mustard (melphalan), and CdSO4, but not to other anticancer agents. Alkaline elution of DNA showed an increased amount of DNA interstrand cross-linking formation in CHO cells, but not in C/CDP-2 cells, when CHO and C/CDP-2 cells were cultured with CDDP. By contrast, alkaline elution of DNA showed increased formation of DNA cross-links when nuclei of C/CDP-2 cells were treated with CDDP. The activity of glutathione S-transferase (GST) of C/CDP-1 and C/CDP-2 was 4- and 6-fold higher than that of CHO cells, respectively. The cellular level of GST activity of R-1 was almost similar to that of CHO cells. Northern blotting analysis revealed that GST-pi mRNA in both C/CDP-1 and C/CDP-2 cell lines was increased more than 5-fold over that of CHO and R-1 cells. There is no apparent gene amplification of GST-pi gene in CDDP-resistant cell lines. Immunoblot assays showed a specific increase of GST-pi in C/CDP-1 and C/CDP-2, but no increase in GST-mu and GST-alpha. We also compared CDDP-resistant properties of a resistant variant, P/CDP-5, derived from human prostate cancer PC-3 cell line, with those of C/CDP-1 and C/CDP-2 cells and found no increased GST activity in P/CDP-5 cells. Multiple mechanisms might be considered for acquisition of CDDP resistance in various cell lines in culture.
Animals↗
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↗
Structural and functional analysis of an enhancer GPEI having a phorbol 12-O-tetradecanoate 13-acetate responsive element-like sequence found in the rat glutathione transferase P gene.
We have recently identified a typical enhancer, termed GPEI, located about 2.5 kilobases upstream from the transcription initiation site of the rat glutathione transferase P gene. Analyses of 5' and 3' deletion mutants revealed that the cis-acting sequence of GPEI contained the phorbol 12-O-tetradecanoate 13-acetate responsive element (TRE)-like sequence in it. For the maximal activity, however, GPEI required an adjacent upstream sequence of about 19 base pairs in addition to the TRE-like sequence. With the DNA binding gel-shift assay, we could detect protein(s) that specifically binds to the TRE-like sequence of GPEI fragment, which was possibly c-jun.c-fos complex or a similar protein complex. The sequence immediately upstream of the TRE-like sequence did not have any activity by itself, but augmented the latter activity by about 5-fold.
Animals↗
Optical studies of the quasi-one-dimensional charge-density-wave state in
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Journal Article↗
Fructose-related glycation.
We investigated in vitro the effect of the polyol pathway on the formation of advanced Maillard reaction products which have fluorescence and cross-links. Bovine serum albumin supplemented with various concentrations of glucose, fructose or sorbitol was incubated for 14 days. The fluorescence intensity was higher after incubation with fructose than after incubation with glucose. However, no significant increase in fluorescence intensity was found after incubation with sorbitol. These results suggest that in the polyol pathway fructose plays an important role in the formation of advanced Maillard products.
Fructose↗
Mechanism of fibrin-specific fibrinolysis by staphylokinase: participation of alpha 2-plasmin inhibitor.
When the extent of plasminogen activation by staphylokinase (SAK) or streptokinase (SK) was measured in human plasma, SAK barely induced plasminogen activation, whereas SK activated plasminogen significantly. When the plasma was clotted with thrombin, the plasminogen activation by SAK was markedly enhanced, but that of SK was little enhanced. Similarly, in a purified system composed of plasminogen, fibrinogen and alpha 2-plasmin inhibitor (alpha 2-PI, alpha 2-antiplasmin), such a fibrin clot increased the activity of SAK significantly. However, when alpha 2-PI was removed from the reaction system, enhancement of the SAK reaction was not observed. In addition, SAK as distinct from SK, showed very little interference with the action of alpha 2-PI. Plasminogen activation by SAK is thus essentially inhibited by alpha 2-PI, but this reaction is not inhibited in fibrin clots. These results suggest that SAK forms a complex with plasminogen, which binds to fibrin and induces fibrinolysis.
Blood Coagulation↗
Electron and hole doping in Nd-based cuprates with single-layer CuO2 sheets: Role of doped Ce ions and 30-K superconductivity.
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Journal Article↗
Dopaminergic cells in the superior cervical ganglion of the rat: light and electron microscopic study using an antibody against dopamine.
So-called small intensely fluorescent (SIF) cells were visualized immunohistochemically using a newly developed anti-dopamine (DA) serum in the rat superior cervical ganglia (SCG), both light and electron microscopically. Specificity of the anti-DA serum was tested in a control test and enzyme-linked immunosorbent assay (ELISA). DA-immunoreactivity was found in a subpopulation of SIF cells, but not in principal neurons. Ultrastructurally, DA-immunoreactivity was noticed in the cytoplasmic matrix and vesicles of perikarya, dendritic processes and terminals of SIF cells. DA-labeled terminals made symmetrical synaptic contacts with unlabeled principal neurons. These findings provide a morphological basis for the role of dopaminergic SIF cells as interneurons.
Animals↗
Quantitative measurement of abdominal arterial blood flow using image-directed Doppler ultrasonography: superior mesenteric, splenic, and common hepatic arterial blood flow in normal adults.
To measure volume blood flow quantitatively in human abdominal arteries, we used an ultrasonic image-directed Doppler system and electromagnetic flowmeter to first measure volume flow in canine arteries. In dogs, there was a strong linear correlation (R = 0.98) between the product of the time average of the maximum blood flow velocity and the average cross-sectional area and the volume blood flow measured by an electromagnetic flowmeter. These results enabled measurement of volume blood flow in the human superior mesenteric (SMA), splenic (SPA), and common hepatic (CHA) arteries from the abdominal wall. Comparison of pulsatility index values indicated a larger vascular resistance in the SMA than in the SPA or CHA.
Adult↗
Lysosomal movements during heterophagy and autophagy: with special reference to nematolysosome and wrapping lysosome.
Recent studies on lysosomal movements during heterophagy and autophagy performed in our laboratory for the past several years were reviewed; methods for the investigation of lysosomes and the cytoskeleton in these studies mainly involved electron microscopic cytochemistry. Lysosomal movements during heterophagy were observed in cultured rat alveolar macrophages taking up horseradish peroxidase (HRP) and rat peroxidase-antiperoxidase (PAP) by fluid-phase pinocytosis and adsorptive pinocytosis, respectively. A characteristic lysosomal change which was induced by the pinocytosis was the appearance of long, threadlike lysosomes (nematolysosomes) in the cytoplasm. The effects of actin filament destabilizer and antimicrotubular drug on lysosomal changes revealed that the appearance of nematolysosomes was dependent on the presence of both actin filaments and microtubules. The close morphological relationship between lysosomes and cytoskeletal elements, such as actin filaments and microtubules in the alveolar macrophages, supports the participation of the cytoskeletal system in the regulatory mechanism of lysosomal movements. In the study of the lysosomal wrapping mechanism (LWM), which is one type of lysosomal movement that occurs during autophagy, it was found that the occurrence of LWM was dependent on energy--namely, the supply of ATP--and on the presence of actin filaments. However, deconstruction of microtubules induced or favored the occurrence of LWM. It is conceivable that the LWM is also related to the cytoskeletal system. We conclude that intracellular dynamics of lysosomes during heterophagy and autophagy are largely a consequence of complicated modulation by the cytoskeletal system.
Animals↗
Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse. An immunohistochemical study.
Immunohistochemical studies of monoamine neurons were performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with those of their offspring. Mice, 9-11 weeks old (C57BL/6J), injected subcutaneously with a large dose of MPTP (17 mg/kg per day) during pregnancy on Day 9 and 12 of gestation (G9 and G12) miscarried and were examined at 13 weeks of age. Conversely, mice treated during pregnancy with sequential low dose of MPTP (2.8 mg/kg per day at G9-G17 for 8 days) successfully delivered their babies and were examined at the age of 15 weeks. Baby mice were examined at 1 and 6 weeks of age. The tyrosine hydroxylase-, aromatic L-amino acid decarboxylase- and dopamine (DA)-immunoreactive density of caudoputamen was reduced in 13-week-old mice treated with high dose of MPTP but not in the 15-week-old mothers exposed to a low dose of MPTP as compared to their respective controls. The DA-immunoreactive density of the caudoputamen was the only staining that was reduced in both 1- and 6-week-old baby mice. In conclusion, these results demonstrate that MPTP injected to pregnant mice causes a DA depletion in the striatum of their offspring indicating a transplacental effect of MPTP. The findings also indicate that fetal brain is more susceptible to MPTP toxicity than the brain of young pregnant mice.
Animals↗
Distribution of electric charges and concanavalin A binding sites on autophagic vacuoles and lysosomes in mouse hepatocytes.
The distributions of electric charges and Concanavalin A binding sites in autophagic vacuoles and lysosomes in mouse hepatocytes were studied by utilizing a frozen ultrathin section labeling method with cationized ferritin (CF) or anionized ferritin and ferritin-conjugated Concanavalin A (Con A-F) as visual probes. Our observations revealed that the inner surface of the autophagic vacuole membrane has more anionic sites (CF binding) than other organelle membranes. This suggests that if the limiting membranes of autophagic vacuoles originate from preexisting membranes, such membranes must undergo structural and compositional alternation during the formation of the autophagic vacuoles. In contrast to CF, Con A-F showed no distinct binding to the membranes of autophagic vacuoles, but the contents of vacuoles displayed varying Con A-F binding, depending on the stage of the autophagic process. Increased binding was seen in more mature autophagic vacuoles. Since lysosomes showed a preferential accumulation of Con A-F particles, molecules with Con A-F binding sites in autophagic vacuoles may be of lysosomal origin. Con A-F distribution varied from lysosome to lysosome in the same cell, indicating heterogeneity of lysosomal contents. These results suggest that ferritin-conjugated lectin labeling methods applied to frozen, ultrathin section are a useful new approach in analyzing the natural history of autophagic vacuoles and the heterogeneity of lysosomes.
Animals↗
Parietal cell autoantigens involved in neonatal thymectomy-induced murine autoimmune gastritis. Studies using monoclonal autoantibodies.
Autoimmune gastritis accompanied by autoantibodies to parietal cells was induced in BALB/c nu/+ mice by neonatal thymectomy 2-4 days after birth. Three monoclonal autoantibodies, designated as 2B6 (IgG1), 2G10 (IgG2b), and 1H9 (IgG1), were obtained from one of these mice. All three reacted specifically with parietal cells, 2G10 recognizing species-specific antigenic determinants and 2B6 and 1H9 recognizing interspecies-specific antigenic determinants. All three recognized antigens on the membrane of intracellular secretory canaliculi and the cytoplasmic tubulovesicular system of parietal cells. At least two different molecular groups were recognized by these antibodies; 2B6 recognizing a 65,000-79,000-mol wt group and 1H9 recognizing a 92,000-120,000-mol wt group. Sera of most mice with autoimmune gastritis reacted with either or both groups. Both groups were consistently coprecipitated by any of the three antibodies when solubilized in NP-40. Sera, from patients with pernicious anemia, containing anti-parietal cell antibodies could also precipitate these two groups of antigens. Competition assay and physicochemical studies showed that the epitopes recognized by the three monoclonal antibodies are different.
Anemia, Pernicious↗
Decrease with senescence in the norepinephrine-induced phosphorylation of myofilament proteins in isolated rat cardiac myocytes.
(1) The effects of norepinephrine on protein phosphorylation in isolated rat cardiac ventricular myocytes were determined by autoradiography on 32P-labelled proteins separated by electrophoresis; (2) In cells from young adult rats (6 months old) there was a marked increase due to norepinephrine (10(-8) to 10(-4) M) in the incorporation of 32P into proteins identified on the grounds of molecular weight as troponin I and C-protein: in cells from senescent rats (24 months old) this increase was much attenuated. (3) Age-associated decrements in protein phosphorylation were much diminished when maximally effective concentrations of the adenylate cyclase-activator forskolin and the cyclic AMP analog 8(4-chlorophenylthio) cyclic AMP were used instead of norepinephrine. Moreover, age-associated differences were abolished if the phosphodiesterase inhibitor isobutylmethylxanthine was present in addition to norepinephrine, or alone. (4) Study of the rates of dephosphorylation of troponin I, as initiated with the beta-adrenergic antagonist propranolol, showed no change in half-time as a function of age: this indicates no change in protein phosphatase activity. (5) These results suggest that there is less active net formation of cyclic-AMP in senescent heart cells in response to the neurotransmitter norepinephrine, giving a lesser activation of c-AMP-dependent protein kinase and less phosphorylation of these target proteins.
Actin Cytoskeleton↗
Effects of delayed monocular enucleation after birth upon black-white discrimination learning in the albino rat.
Many investigators have demonstrated that enucleation of one eye in rats and hamsters soon after birth results in an increased number of uncrossed optic nerve terminals in the main visual centers, and that they are physiologically functional. Such changes, however, became less evident as the time of enucleation is delayed after birth. We also have found that rats with one eye removed at birth were able to relearn a black-white discrimination task faster than rats monocularly enucleated at maturity when relearning was conducted after destruction of the visual cortex contralateral to the remaining eye. This faster relearning phenomenon is considered to be a behavioral expression of such morphological and physiological changes. The present study was then undertaken to examine the question of how this faster relearning phenomenon is affected by the delay of enucleation time after birth. Two experiments were conducted. In Experiment 1 the effects of the removal of one eye at 0, 5, 10, 15, 20 days and at three months of age were compared, and in Experiment 2 those at 10, 11, 12, 13, 14 and 15 days of age were compared. Experiment 1 showed that enucleation at 0, 5 and 10 but not at 15, 20 days and at three months of age facilitated relearning, and that the degree of facilitation decreased as age increased. And, although the results were not unequivocal, Experiment 2 did suggest that the removal of one eye at and beyond 13 days of age was no longer able to facilitate relearning.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗