[Adult-onset Still's disease].
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
M Yamaguchi
Publications and source records attributed to M Yamaguchi.
Regucalcin modulates hormonal effect on (Ca(2+)-Mg2+)-ATPase activity in rat liver plasma membranes.
The interaction of various hormones and regucalcin on (Ca(2+)-Mg2+)-ATPase activity in rat liver plasma membranes was investigated. The presence of epinephrine (10(-6)-10(-4) M), phenylephrine (10(-6)-10(-4) M), and insulin (10(-8)-10(-7) M) in the reaction mixture produced a significant increase in (Ca(2+)-Mg7+)-ATPase activity, while the enzyme activity was decreased significantly by calcitonin (3 x 10(-8)-3 x 10(-6) M). These hormonal effects, except for calcitonin, were clearly inhibited by the presence of vanadate (10(-4) M) which can inhibit the Ca(2+)-dependent phosphorylation of enzyme. Meanwhile, regucalcin (0.25 and 0.50 microM), isolated from rat liver cytosol, elevated significantly (Ca(2+)-Mg2+)-ATPase activity in the plasma membranes, although this elevation was not inhibited by vanadate (10(-4) M). The epinephrine (10(-5) M) or phenylephrine (10(-4) M)-induced increase in (Ca(2+)-Mg2+)-ATPase activity was disappeared in the presence of regucalcin; in this case the effect of regucalcin was also weakened. However, the inhibitory effect of calcitonin (3 x 10(-6) M) was not weakened by the presence of regucalcin (0.5 microM). Moreover, GTP (10(-5) and 10(-4) M)-induced increase in (Ca(2+)-Mg2+)-ATPase activity was not seen in the presence of regucalcin (0.25 microM). The present finding suggests that the activating mechanism of regucalcin on (Ca(2+)-Mg2+)-ATPase is not involved on GTP-binding protein which modulates the receptor-mediated hormonal effect in rat liver plasma membranes.
Animals↗
Energy-transducing nicotinamide nucleotide transhydrogenase. Nucleotide binding properties of the purified enzyme and proteolytic fragments.
The mitochondrial energy-transducing nicotinamide nucleotide transhydrogenase is a homodimer of monomer M(r) = 109,065. It is composed of a 430-residue-long N-terminal hydrophilic domain, a 400-residue-long central hydrophobic domain, and a 200-residue-long C-terminal hydrophilic domain. The N- and the C-terminal hydrophilic domains extend into the mitochondrial matrix, and the central hydrophobic domain intercalates into the inner membrane. Equilibrium binding of [14C]NADH and [14C]NADPH was carried out to the purified transhydrogenase, transhydrogenase modified with N,N'-dicyclohexylcarbodiimide (DCCD) at the NADH-protectable Glu257, and to proteolytic fragments corresponding to dimers of the N-terminal and the C-terminal hydrophilic domains. The intact enzyme bound 1 mol of [14C]NADH or [14C]NADPH per dimer with Kd values of 9.5 and 5.7 microM, respectively. The 90% DCCD-inhibited enzyme bound [14C]NADPH with undiminished capacity and [14C]NADH with 10% capacity as compared with unmodified enzyme. The Kd values were unaltered. The N-terminal fragment bound [14C]NADH at 0.76 mol/dimer with unaltered Kd but did not bind [14C]NADPH. The C-terminal fragment bound 0.32 mol of [14C]NADPH/dimer with unaltered Kd but did not bind [14C]NADH. These results are consistent with our previous assignment of the NAD(H) and the NADP(H) binding sites to the N- and the C-terminal hydrophilic domains, respectively. The binding stoichiometries of 1 mol each of [14C]NADH and [14C]NADPH/dimeric transhydrogenase suggest half-of-the-sites reactivity, which is consistent with our previous findings that 100% inhibition by either p-[3H]fluorosulfonylbenzoyl-5'-adenosine or [14C]DCCD involved the incorporation of 1 mol of inhibitor/dimeric enzyme. We had shown earlier that N-(ethoxycarbonyl)2-ethoxy-1,2-dihydroquinoline (EEDQ) inhibits the transhydrogenase, apparently at the NAD binding site, but differently from DCCD. The enzyme was protected by 5'-AMP strongly against DCCD and weakly against EEDQ, whereas it was protected by NMNH strongly against EEDQ and not at all against DCCD. We have now determined the EEDQ binding sites to be Glu232 and Glu880. The different mononucleotide protections against DCCD and EEDQ suggest that the AMP moiety of NAD binds near Glu257 and its NMN portion near Glu232. They also suggest that the NMN moiety of NADP may bind near Glu880.
Amino Acid Sequence↗
Characterization of Ca(2+)-stimulated adenosine 5'-triphosphatase and Ca2+ sequestering in rat liver nuclei.
The role of Ca(2+)-stimulated adenosine 5'-triphosphatase (Ca(2+)-ATPase) in Ca2+ sequestering of rat liver nuclei was investigated. Ca(2+)-ATPase activity was calculated by subtracting Mg(2+)-ATPase activity from (Ca(2+)-Mg2+)-ATPase activity. Ca2+ uptake and release were determined with a Ca2+ electrode. Nuclear Ca(2+)-ATPase activity increased linearly in the range of 10-40 microM Ca2+ addition. With those concentrations, Ca2+ was completely taken up by the nuclei dependently on ATP (2 mM). Nuclear Ca(2+)-ATPase activity was decreased significantly by the presence of arachidonic acid (25 and 50 microM), nicotinamide-adenine dinucleotide (NAD+; 2 mM) and zinc sulfate (2.5 and 5.0 microM). These reagents caused a significant decrease in the nuclear Ca2+ uptake and a corresponding elevation in Ca2+ release from the nuclei. Moreover, calmodulin (10 micrograms/ml) increased significantly nuclear Ca(2+)-ATPase activity, and this increase was not seen in the presence of trifluoperazine (10 microM), an antagonist of calmodulin. The present findings suggest that Ca(2+)-ATPase plays a role in Ca2+ sequestering by rat liver nuclei, and that calmodulin is an activator. Moreover, the inhibition of Ca(2+)-ATPase may evoke Ca2+ release from the Ca(2+)-loaded nuclei.
Animals↗
Molecular cloning and sequencing of the cDNA coding for a calcium-binding protein regucalcin from rat liver.
The cDNA of a Ca(2+)-binding protein regucalcin was cloned from a rat liver cDNA library which was constructed in lambda ZAPII by immunoscreening. Positive clones were obtained from which spanned the region of interest, and they gave a sequence of 1.7 kb by sequencing with the dideoxynucleotide method. Analysis of the sequence of the cloned cDNA showed that the cDNA encoded the complete amino acid sequence of the regucalcin molecule. Regucalcin was composed of 299 amino acid residues and its molecular weight was estimated to be 33,388 Da. The hydropathy profile of regucalcin showed a highly hydrophilic character. The nucleotide and amino acid sequences of regucalcin did not have statistically significant homology, as compared with the registered sequences which are found in the EMBL and GenBank databases containing several other Ca(2+)-binding proteins (calmodulin, calbindin-D28k and S-100 beta). The regucalcin molecule did not contain the EF-hand motif as a Ca(2+)-binding domain. The present study demonstrates that regucalcin is a unique Ca(2+)-binding protein in the liver of rats.
Amino Acid Sequence↗
Spontaneous regression in adult T-cell leukemia/lymphoma.
BACKGROUND: Spontaneous regression of adult T-cell leukemia/lymphoma (ATL) is considered to be extremely unusual. Of the 82 patients with ATL who the authors saw between 1981 and 1991, spontaneous regression occurred in 3 (3.7%), 2 of whom were previously untreated and one who had been previously treated. Surgical excisional biopsy triggered the spontaneous regression in these patients. METHODS: In two of these patients with spontaneous regression, gene analysis studies of human T-cell leukemia virus type I (HTLV-I) proviral DNA, and T-cell receptor (TCR) were carried out by Southern blot analysis in lymph node cells or peripheral lymphocytes before regression and after recurrence. RESULTS: One patient exhibited monoclonal integration of HTLV-I proviral DNA and the rearranged band of the TCR-beta gene at the same positions both before regression and after recurrence. The other patient showed them at the different positions before regression and after recurrence. CONCLUSIONS: The authors' studies indicated heterogeneity in ATL patients with spontaneous regression. Temporary spontaneous regression could occur in typical ATL and might be associated with a longer survival time than that for prototypic ATL.
Blotting, Southern↗
Regulatory effect of regucalcin on (Ca(2+)-Mg2+)-ATPase in rat liver plasma membranes: comparison with the activation by Mn2+ and Co2+.
The effect of various metals and regucalcin, a calcium-binding protein isolated from rat liver cytosol, on (Ca(2+)-Mg2+)-ATPase activity in the plasma membranes of rat liver was investigated. Of various metals (Zn2+, Cu2+, Ni2+, Mn2+, Co2+ and Al3+; 100 microM as a final concentration), Mn2+ and Co2+ increased markedly (Ca(2+)-Mg2+)-ATPase activity, while other metals had no effect. When Ca2+ was not added into enzyme reaction mixture, Mn2+ and Co2+ (25-100 microM) did not significantly increase the enzyme activity, indicating that heavy metals act on Ca(2+)-stimulated phosphorylation of the enzyme. Meanwhile, regucalcin (0.25-1.0 microM) caused a remarkable elevation of (Ca(2+)-Mg2+)-ATPase activity. This increase was not inhibited by the presence of 100 microM vanadate, although the effects of Mn2+ and Co2+ (100 microM) were inhibited by vanadate. Also, the inhibition of the Mn2+ and Co2+ effects by vanadate was not seen in the presence of regucalcin. Moreover, regucalcin (0.5 microM) increased significantly the enzyme activity in the absence of Ca2+. This effect of regulcalcin was not altered by increasing concentrations of Ca2+ added, indicating that the regucalcin effect does not depend on Ca2+. The present results suggest that regucalcin activates directly (Ca(2+)-Mg2+)-ATPase in liver plasma membranes, and that the activation is not involved in the Ca(2+)-dependent phosphorylation of the enzyme.
Animals↗
Induction of stress proteins in mouse peritoneal macrophages by oxidized low-density lipoprotein.
The synthesis of 23-kDa and 34-kDa proteins in mouse peritoneal macrophages was enhanced when they were incubated with oxidatively modified low-density lipoprotein (LDL). This response required the oxidation of the lipid of the LDL, because native LDL had little effect and acetylated LDL enhanced the synthesis of 34-kDa protein only slightly. Since macrophages can bind and sequester oxidized LDL, they are subjected to an oxidative stress. The results suggest that the 34-kDa protein, which is identical with heme oxygenase, and the 23-kDa protein serve as stress protein that might afford protection against the oxidative stress.
Animals↗
Granulocyte colony-stimulating factor-dependent leukemic cell proliferation in vivo in acute promyelocytic leukemia.
Explore the source record for details and available documents.
Adult↗
Stimulatory effect of beta-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells.
The effect of beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism was investigated in osteoblastic MC3T3-E1 cells. Cells were cultured for 3 days at 37 degrees C in a CO2 incubator in plastic dishes containing alpha-modified minimum essential medium supplemented with 10% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1% bovine serum albumin plus various concentrations of AHZ or other reagents, and the cells were cultured further for appropriate periods of time. The presence of AHZ (10(-7)-10(-5) M) stimulated the proliferation of cells. AHZ (10(-6) and 10(-5) M) increased deoxyribonucleic acid (DNA) content in the cells with 48 hr-culture. This increase was completely blocked by the presence of cycloheximide (10(-6) M) or hydroxyurea (10(-3) M). Also, the presence of cycloheximide (10(-6) M) completely inhibited the AHZ (10(-5) M)-induced increase in the proliferation of cells. Meanwhile, parathyroid hormone (10(-7) M), estrogen (10(-9) M) and insulin (10(-8) M) significantly increased cellular DNA content. However, these hormonal effects clearly lowered in comparison with that of AHZ (10(-5) M). Dibutyryl cyclic AMP (10(-4) M) and zinc sulfate (10(-5) M) did not cause a significant increase in cellular DNA content. The present results support the view that AHZ has a direct specific proliferative effect on osteoblastic cells in vitro and that this effect is dependent on protein synthesis.
Carnosine↗
Tissue concentration of calcium-binding protein regucalcin in rats by enzyme-linked immunoadsorbent assay.
The concentration of calcium-binding protein regucalcin in the tissues of rats was estimated by enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG. In male rats (5 weeks old), regucalcin was most pronounced in the liver. Liver regulcalcin concentration was about 0.1 microM, when it was calculated with regucalcin molecular weight of 28,800. The relatively higher level of regucalcin was also found in the kidney as compared with that of the skeletal muscle, duodenum, testis, lung, heart, spleen, cerebral cortex and hippocampus. Similarly in female rats, regucalcin was remarkable in the liver, and appeared only slightly in the kidney. Thus, the tissue distribution of regucalcin in rats was specific in the liver. The concentration of regucalcin in the liver was altered with increasing age of rats; liver regucalcin level linearly increased during 5 weeks old after birth of male rats, and then began to decrease gradually. The results coincided with the previous observation of Northern blot analyses by using liver regucalcin cDNA as a probe. The present finding clearly demonstrates that regucalcin is specifically synthesized in the liver of rats.
Aging↗
Effect of nicotinamide-adenine dinucleotides on Ca2+ transport system in rat liver nuclei: stimulation of Ca2+ release by NAD+.
The effect of nicotinamide-adenine dinucleotides (NAD+ and NADP+) on Ca2+ transport in rat liver nuclei was investigated. Ca2+ uptake and release were determined with a Ca2+ electrode. Ca2+ uptake was dependent on adenosine triphosphate (ATP; 2 mM). The presence of NAD+ (2 mM) or NADP+ (1 and 2 mM) caused a significant inhibition of Ca2+ uptake following addition of 2 mM ATP. Ca2+, which accumulated in the nuclei during 6 min after ATP addition, was significantly released by the addition of NAD+ (0.5-2 mM) or NADP+ (0.1-2 mM). However, the effect of NADH (2 mM) or NADPH (2 mM) on Ca2+ uptake and release clearly weakened in comparison with the effects of NAD+ and NADP+. Meanwhile, ryanodine (10 microM), thapsigargin (10 microM) or oxalate (0.5 mM) had no effect on Ca2+ uptake and release in rat liver nuclei. These reagents did not significantly alter the effects of 2 mM NAD+ on Ca2+ uptake and release. Thus, NAD+ and NADP+ had a potent effect on Ca2+ transport in rat liver nuclei. The present findings suggest that the liver cytosolic NAD+ (NADP+) is a factor in the regulation of the nuclear Ca2+ concentration.
Animals↗
Regulatory effect of arachidonic acid on the calcium transport system in rat liver nuclei.
The effect of arachidonic acid (AA) on Ca2+ transport in rat liver nuclei was investigated. Ca2+ uptake and release were determined with a Ca2+ electrode. Ca2+ uptake increased dependent on ATP (0.5-2.0 mM), while uptake was negligible in the presence of 2.0 mM ADP or AMP. AA (10-100 microM) caused a marked inhibition of Ca2+ uptake following the addition of 2.0 mM ATP. Also, Ca2+, which accumulated in the nuclei during 6 min after ATP addition, was clearly released by the addition of AA (10-100 microM). The alterations were concentration dependent. The nuclear Ca2+ uptake and release were not altered significantly by the presence of prostaglandin E2 (10 and 20 microM), prostaglandin H2 (1 and 4 microM), thromboxane B2 (1 and 4 microM), leukotriene A4 (1 and 4 microM), Ins(1,4,5)P3 (1 and 10 microM) or dibutyryl cAMP (10 and 50 microM). Only, 5-hydroxy-eicosatetraenoic acid (5-HETE) at 4 microM caused a significant inhibition of nuclear Ca2+ uptake and an appreciable increase in Ca2+ release; the 1 microM concentration had no effect. These results indicate that AA, one of the prostanoids, has a unique effect on Ca2+ uptake and release in rat liver nuclei. The finding suggests that AA has a regulatory effect on the Ca2+ transport system in liver nuclei.
Animals↗
Mitochondrial NADH:ubiquinone oxidoreductase (complex I): proximity of the subunits of the flavoprotein and the iron-sulfur protein subcomplexes.
The proximities of the three subunits (51, 24, and 9 kDa) of the flavoprotein subcomplex (FP) and five subunits (75, 49, 30, 18, and 13) of the iron-sulfur protein subcomplex (IP) of the bovine NADH: ubiquinone oxidoreductase (complex I) were investigated by cross-linking studies. The cross-linking reagents used were disuccinimidyl tartrate and ethylene glycol bis(succinimidyl succinate). The cross-linked products were identified by sodium dodecyl sulfate gel electrophoresis and immunoblotting with antibodies specific for each subunit. Results showed that the three FP subunits are juxtaposed to one another, and only the 51 kDa subunit of FP is in close proximity to only the 75-kDa subunit of IP. The 75-kDa subunit cross-linked to the 30- and the 13-kDa subunits, the 49-kDa subunit cross-linked to the 30-, 18-, and 13-kDa subunits, and the 30-kDa subunit cross-linked to the 18- and the 13-kDa subunits. No cross-linked products of 75+49-, 75+18-, or 18+13-kDa subunits were detected. These results are consistent with the occurrence of potential electron carriers in FP and IP subunits. These electron carriers are FMN and one iron-sulfur cluster in the 51-kDa subunit, one iron-sulfur cluster in the 24-kDa subunit, and apparently two iron-sulfur clusters in the 75-kDa subunit.
Animals↗
[Radiation stenosis and fistula formation developed after iridium-192 high-dose-rate intracavitary radiation boost therapy for carcinoma of the esophagus].
Intracavitary irradiation using a high-dose-rate Ir-192 remote after-loading system was applied to 14 advanced or inoperable patients with esophageal carcinoma as a boost therapy. The total dose of external irradiation was 45-70 Gy/15-35 fractions and that of intracavitary irradiation was 11.6-34.0 Gy/2-4 fractions at a point 5 mm deep from the inner surface of the esophageal mucosa. The time-dose-fractionation factor (TDF) of the whole treatment was 116-186 (mean, 146). Six patients (43%) had complete response (CR), three (21%) had partial response and five (36%) had no response. Esophageal carcinoma that showed exophytic growth, was less than 5 cm ling, and showed favorable response to external irradiation was likely to be a good candidate for intracavitary radiation boost therapy. Fistula formation was produced in five patients (36%), four of whom were irradiated at more than 140 TDF. All six CR patients were free from esophageal tumors, but severe esophageal stenosis due to radiation injury developed in five (83%) of them. They were irradiated at more than 135 TDF. One- and two-year survival rates were 28.6% and 14.3%, respectively. The poor prognosis was ascribed to the frequent occurrence of fatal radiation stenosis and fistula formation. An appropriate therapeutic dose for esophageal carcinoma that does not cause severe radiation stenosis was estimated to be under 120 TDF.
Aged↗
Regulatory effects of zinc and copper on the calcium transport system in rat liver nuclei. Relation to SH groups in the releasing mechanism.
In isolated hepatic nuclei, the heavy metals Zn2+ and Cu2+ (10 microM) inhibited Ca2+ uptake and caused a prompt release of Ca2+ from preloaded nuclei in a concentration-dependent manner, with Zn2+ being more effective than Cu2+. The sulfhydryl group reducing agent dithiothreitol (DTT) protected the nuclei from the effects of heavy metals; DDT (1 mM) almost completely blocked Zn(2+)- or Cu(2+)-induced Ca2+ release and inhibition of Ca2+ uptake. The sulfhydryl modifying reagent N-ethylmaleimide (NEM; 0.2 mM) also caused Ca2+ release, but it did not have an appreciable effect on Ca2+ uptake. Furthermore, in the presence of NEM heavy metals did not evoke Ca2+ release. The present study demonstrates that Zn2+ and Cu2+ have a stimulatory effect on Ca2+ release from isolated rat liver nuclei, and that the SH group may play an important role in the Ca(2+)-releasing mechanism in liver nuclei.
Adenosine Triphosphate↗
Modulation of human basophil histamine release by insulin-like growth factors.
Several lines of evidence indicate that basophils play an active pathogenic role in the late-phase reaction. Inasmuch as various cytokines are produced locally by activated cells of the immune system during late-phase reaction, "priming" of basophils by cytokines has become an area of active study over the last few years. We studied the effect of insulin-like growth factor (IGF)-I, shown to be active on immature and mature hemopoietic cells, on histamine release from human basophils. IGF-I enhanced histamine release initiated by anti-IgE, calcium ionophore A23187, and phorbol ester in a dose-dependent fashion (ED50: 300-600 pM), although IGF-I had little or no effect on the release caused by FMLP and C5a. The priming effect of IGF-I took place rapidly and reached plateau levels in 15 min. IGF-II and insulin, both of which have high amino acid sequence homology with IGF-I, also primed basophils. The order of enhancing potencies was IGF-I > IGF-II > insulin; IGF-I was 10-fold more potent than IGF-II and 250-fold more potent than insulin. Although specific receptors for each factor have been identified, blocking experiments using a mAb against IGF-I receptor showed almost complete abolishment of the enhancing effect of these factors, indicating that the enhancing effect is exhibited via the IGF-I receptor. Inasmuch as IGF-I has been shown to be produced by alveolar macrophages, fibroblasts, and nasal polyps, these results indicate that IGF may regulate allergic reactions in vivo by enhancing histamine release from basophils.
Basophils↗
Novel 8-base pair sequence (Drosophila DNA replication-related element) and specific binding factor involved in the expression of Drosophila genes for DNA polymerase alpha and proliferating cell nuclear antigen.
Upstream regions containing a novel common 8-base pair (bp) palindromic sequence, 5'-TATCGATA (Drosophila DNA replication-related element (DRE)), are required for the high expression of Drosophila genes for DNA polymerase alpha and the proliferating cell nuclear antigen (PCNA) (an auxiliary protein for DNA polymerase delta). Three DREs and one DRE are present in the DNA polymerase alpha gene (nucleotides-217, -83, and -30 with respect to the transcription initiation site) and in the PCNA gene (nucleotide-100), respectively. Deletions or 2-bp insertional mutations of DRE sequences led to an extensive reduction of promoter activities of both genes. Chemically synthesized oligonucleotides containing DRE sequences greatly stimulated the activity of the heterologous promoter of the Drosophila metallothionein gene, in addition to the promoter of the PCNA gene, when they were placed upstream from these promoters in a normal or a reverse orientation. The stimulatory effect increased synergistically and depended on the number of DREs. DRE activated the promoter when placed within 1.4 kilobases upstream from the promoter, but was much less active when placed 2.5 kilobases or more apart from the promoter. Using a gel mobility shift assay method, we obtained evidence for a protein factor (DREF) in the nuclear extract of cultured Drosophila cells (Kc cells), and this factor specifically binds to DREs of both genes. DNase I footprinting analysis indicated that DREF binds to the 24-bp DRE region of the DNA polymerase alpha gene in which 8-bp palindromic sequences are centered. A UV cross-linking experiment revealed that a polypeptide of approximately 90 kDa in the nuclear extract interacts directly with the DRE sequence. Using DRE-conjugated latex particles, DREF was affinity-purified from the Kc cell nuclear extract. By comparing results obtained by SDS-polyacrylamide gel electrophoresis and gel mobility shift experiments, we concluded that DREF is associated with the 86-kDa polypeptide. On gel filtration chromatography, a single peak of DREF activity was recovered in fractions corresponding to a molecular mass of 170 kDa, and the 86-kDa polypeptide was detected only in the corresponding fractions; thus, active DREF is probably a homodimeric form of the 86-kDa polypeptide. DREF may play important roles in coordinating expressions of Drosophila DNA replication-related genes.
Animals↗