[Case of neoplastic angioendotheliosis (angiotrophic B cell lymphoma)].
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Aged↗
Biomedical subjects
M Yoshida
Publications and source records attributed to M Yoshida.
Stimulation of DNA-dependent protein kinase activity by high mobility group proteins 1 and 2.
After incubation of high mobility group (HMG) proteins 1 and 2 with DNA-dependent protein kinase (DNA-PK) and [gamma-32P]ATP in the presence of double-stranded DNA, not only phosphorylation of HMG proteins but also enhancement of autophosphorylation of the catalytic polypeptide of 350 kDa in DNA-PK was observed. DNA-PK activity determined with a synthetic peptide and alpha-casein as substrates was stimulated several-fold by HMG1, HMG2, and the DNA-binding domains. The stimulation was decreased at higher concentrations of HMG proteins, and DNA-PK activity was inhibited by histone H1. Electrophoretic mobility shift analysis suggests that HMG proteins facilitate the binding of DNA-PK to DNA.
Adenosine Triphosphate↗
Therapeutic effects of imidazolineoxyl N-oxide against endotoxin shock through its direct nitric oxide-scavenging activity.
We recently found a new class of nitric oxide (NO) antidote, i.e., 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide derivatives (PTIOs). It has a potent inhibitory action against endothelium-derived relaxing factor. Here, we report the effect of a water-soluble carboxy derivative of PTIO (carboxy-PTIO) on endotoxin shock. Endotoxin [lipopolysaccharide (LPS)] (10 mg/kg) was injected into Wistar rats, and the mean arterial blood pressure (MABP), heart rate and urinary parameters were continuously measured. The MABP and urine volume gradually decreased during 1 hr after LPS injection, and within 4 hr, both values decreased to 50-70%. When carboxy-PTIO at 0.056-1.70 mg/kg/min was infused for 1 hr beginning 90 min after the LPS injection, the hypotension, renal dysfunction and survival rate were much improved and the state of shock was avoided. Carboxy-PTIO administered to normal rats did not affect each parameter. Measurement of urinary output of carboxy-PTIO and carboxy-2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl (carboxy-PTI), which is a reaction product of carboxy-PTIO and NO, showed that conversion of carboxy-PTIO to carboxy-PTI was augmented by LPS treatment due to the increased production of NO, and that the enhanced conversion (PTIO-->PTI) was significantly inhibited by administration of N omega-monomethyl-L-arginine. This indicates that carboxy-PTIO exhibits a potent therapeutic value in endotoxin shock through the direct scavenging action against NO.
Animals↗
Syosaiko-to and saiboku-to (Chinese-Japanese herbal medicine) suppress the release of arachidonic acid metabolites from cultured porcine pulmonary artery endothelial cells.
The influences of Syosaiko-to and Saiboku-to, traditional Chinese-Japanese medicines, on the arachidonic acid metabolism of porcine pulmonary artery endothelial cells (PPAEC) in culture were investigated. 6-keto-PGF1 alpha, a stable end product of prostacyclin, released by PPAEC during a 48 h incubation period with 1000 micrograms/ml of Syosaiko-to or Saiboku-to was significantly decreased. Analysis of the eicosanoid profile by high performance liquid chromatography revealed that both cyclooxygenase and lipoxygenase derivatives were released in smaller than usual proportions from PPAEC during 24 h incubation periods with 500 micrograms/ml of Syosaiko-to or Saiboku-to. Clinically, Syosaiko-to is used for chronic hepatitis and Saiboku-to is prescribed for bronchial asthma. The experimental findings could explain the anti-inflammatory effect of Syosaiko-to and Saiboku-to from the perspective of their influences on arachidonic acid metabolic activity associated with PPAEC.
Animals↗
Tetracycline/H+ antiporter was degraded rapidly in Escherichia coli cells when truncated at last transmembrane helix and this degradation was protected by overproduced GroEL/ES.
The in vivo degradation of the plasmid-encoded tetracycline/H+ antiporter (TET) in Escherichia coli cells was studied using three mutants with carboxyl-terminal truncation at the positions in the hydrophilic carboxyl-terminal tail (TET388), in the last putative transmembrane helix XII (TET382), and immediately before the helix XII (TET365). All the mutant TET proteins were localized in the membrane. Expressed TET388 was active in transport and stable against proteolysis. However, TET382 and TET365 were inactive and proteolyzed rapidly. Thus, the importance of the helix XII for protease-resistant proper folding of TET is obvious. Interestingly, overproduced chaperonin (GroEL and GroES) partly prevented degradation of TET365.
Amino Acid Sequence↗
Spatial precision of a catalytic carboxylate of F1-ATPase beta subunit probed by introducing different carboxylate-containing side chains.
Combining mutation and chemical modification, we have introduced Asp, Gln, Cys, S-carboxymethylcysteine (Cax) and S-carbamoylmethylcysteine (Cam) into the positions of Glu190 and Glu201 of the beta subunit of F1-ATPase from the thermophilic Bacillus PS3. The steady-state ATPase activities of alpha 3 beta 3 gamma complexes containing these changed beta subunits were 12% (E190Cax), 7% (E190D), 3% (E190Cam), < 1% (E190C), < 1% (E190Q), and 73% (E201D), 40% (E201Cax), 25% (E201C), 20% (E201Q), 4% (E201Cam), of that of that of the wild-type alpha 3 beta 3 gamma complex. For the complexes containing E190C or E190Q, even the ability of single-site catalysis was lost. Thus, the presence of a carboxylate at 190 (but not at 201) is absolutely required for catalysis and its spatial precision is very strict. Analysis of inactivation of the complexes by dicyclohexylcarbodiimide suggests that Glu190 and Glu201 are interacting in the F1-ATPase.
Amides↗
Biochemical pharmacology of homologous alicyclic mixed amine platinum(II) complexes in sensitive and resistant tumor cell lines.
Three homologous alicyclic mixed amine cis-(NH3)(R-NH2)Cl2Pt(II) complexes, in which R = C3H5, C6H11, and C8H15 (complexes abbreviated C3, C6, and C8, respectively), were evaluated with reference compounds cisplatin and tetraplatin for antitumor activities and biochemical pharmacology in wild-type (murine leukemia L1210/0 and human ovarian A2780) and corresponding variant cell lines resistant to cisplatin (L1210/DDP and 2780CP) and tetraplatin (L1210/DACH and 2780TP). Cytotoxicities, measured by either a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or a clonogenic assay, were maximal for the C6 complex, which was up to 12-, 40-, and 6-fold more potent than C3 against wild-type, cisplatin-resistant, and tetraplatin-resistant models, respectively, and up to 2-fold more potent than C8 against these cell lines. In general, cross-resistance to mixed amine analogues was partial in cisplatin- and tetraplatin-resistant cells and decreased (in L1210/DDP and 2780CP) or increased (in L1210/DACH and 2780TP) with increase in the alicyclic ring size. The increase in ring size resulted in a corresponding increase in partition coefficient, which correlated directly with intracellular accumulations of mixed amine analogues in all cell lines. However, the intracellular DNA-platinum adducts, and not cellular platinum content, was the pharmacological entity that corresponded closely to potencies of the molecules. DNA adduct formation was disproportionate to the level of cellular drug accumulation. For instance, complex C8, which accumulated to the greatest extent in any given cell line, produced adduct levels that were similar to or lower than those produced by C6. A partial explanation for this observation was the demonstrated reduced rate of binding of C8 to DNA. This study has highlighted the significance of alicyclic ring size in modulating the potency, cross-resistance profile, and biochemical pharmacology of mixed amine platinum(II) complexes in sensitive and cisplatin- or tetraplatin-resistant tumor cells.
Animals↗
Dissociation of the complex of dystrophin and its associated proteins into several unique groups by n-octyl beta-D-glucoside.
Dystrophin is purified as a complex with several proteins from the digitonin-solubilized muscle cell membrane. Most of dystrophin-associated proteins (DAPs) are assumed to form a large oligomeric transmembranous glycoprotein complex on the sarcolemma and link dystrophin with a basement membrane protein, laminin. In the present study, we found that the purified dystrophin-DAP complex was dissociated into several groups by n-octyl-beta-D-glucoside treatment. In particular, we found that the glycoprotein complex stated above was dissociated into two distinct groups: one composed of 156DAG and 43DAG (A3a) and the other composed of 50DAG, 35DAG and A3b. We confirmed by crosslinking and immunoaffinity chromatography that these two groups existed in a complexes. We thus concluded that the glycoprotein complex consists of these two subcomplexes. Furthermore, A3b and 43DAG, which had been formerly treated simply as the 43DAG doublets due to their similar electrophoretic mobilities in SDS/PAGE, were shown to be present in two different subcomplexes. Based on the analyses by two-dimensional gel electrophoresis, peptide mapping and immunoblotting, we concluded that A3b is a novel DAP different from 43DAG.
Amino Acid Sequence↗
Effects of ageing on microglia in the normal rat brain: immunohistochemical observations.
The numbers of ramified microglia stained by mouse monoclonal antibodies (OX-6 and X-42) in various regions of the brain were compared in the young (8 weeks) and aged (12 months) rats. OX-6-positive microglia increased in number with ageing, but OX-42-positive microglia did not. In both young and aged rats, the number of OX-6-positive microglia in white matter was higher than that in grey matter, but the number of OX-42-positive microglia in white matter was the same as that in grey matter. OX-42 stains microglia in both activated and resting states, whereas OX-6 stains mainly microglia in the activated state. Our findings suggest that microglia become activated with age-related changes, especially in white matter.
Aging↗
Mechanisms of vasoconstriction induced by endothelin-1 in smooth muscle of rabbit mesenteric artery.
1. The mechanism underlying the vasoconstriction induced by endothelin-1 (ET-1) was investigated by measuring the intracellular concentration of Ca2+ ([Ca2+]i), isometric force and phosphorylation of the myosin light chain (MLC) in endothelium-denuded unskinned and beta-escin-treated skinned smooth muscle from resistance vessels of the rabbit mesentery. The role of protein kinase C (PKC) in the action of ET-1 was studied in skinned smooth muscle using a synthetic peptide, PKC19-36, which corresponds to the autoinhibitory domain of PKC. 2. ET-1 (> 0.1 nM) induced slowly developing, maintained increases in [Ca2+]i and force. Nicardipine completely blocked the ET-1-induced increase in [Ca2+]i. BQ-123 (an inhibitor of the ETA receptor) blocked the ET-1-induced contraction but IRL 1620 (Suc-[Glu9,Ala11,15]-ET-1(8-21), an agonist of the ETB receptor) failed to induce contraction. 3. In ionomycin- and 70 mM K(+)-treated strips, ET-1 shifted the [Ca2+]i-force relationship to the left and enhanced the maximum amplitude of contraction induced by 2.6 mM Ca2+. In skinned smooth muscle treated with ionomycin, Ca2+ (0.1-3 microM) increased both force and MLC phosphorylation, in a concentration-dependent manner. ET-1 with GTP shifted both the Ca(2+)-force and Ca(2+)-MLC phosphorylation relationships to the left without significant changes in the maximum responses. ET-1 with GTP did not change the relationship between force and MLC phosphorylation. Similar effects were observed with phorbol 12,13-dibutyrate (PDBu, an activator of PKC). These results indicate that the sensitivity of MLC phosphorylation to Ca2+ is enhanced both by ET-1 with GTP and by PDBu. 4. PKC19-36 (an inhibitor of PKC) modified neither the contraction nor MLC phosphorylation induced by 0.3 microM Ca2+ but blocked the PDBu-induced enhancement of both these Ca(2+)-induced responses. However, PKC19-36 only partly inhibited the enhancement produced by ET-1 with GTP on the Ca(2+)-induced responses. PKC19-36 did not modify the relationship between force and MLC phosphorylation in the presence either of ET-1 with GTP or of PDBu. By contrast, BQ-123, neomycin and guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) each abolished the ET-1-induced enhancement of the contraction induced by 0.3 microM Ca2+. 5. These results suggest that ET-1 acts on the ETA receptor and increases Ca2+ influxes through an activation of the dihydropyridine-sensitive Ca2+ channel, causing a long-lasting and maintained contraction in resistance vessels of the rabbit mesentery.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Establishment of new SCID and nude mouse models of human B leukemia/lymphoma and effective therapy of the tumors with immunotoxin and monoclonal antibody: marked difference between the SCID and nude mouse models in the antitumor efficacy of monoclonal antibody.
BALL-1, a human B leukemia/lymphoma cell line, was transplanted into nude and SCID mice under various conditions. The transplantation was substantially improved by preadaptation of BALL-1 by serial passages in newborn and young nude mice. We were able to establish the desirable conditions where 100% of SCID and nude mice that were inoculated i.p. with various doses of the adapted BALL-1 (termed BALL-1a) developed tumors. Tumors in SCID mice were disseminated to various tissues in a manner analogous to tumors in patients with B leukemia/lymphoma, whereas tumors in nude mice were not as widely disseminated and grew mainly as ascites. Flow cytometric analyses showed that all of the 11 tested cell surface markers of the parental BALL-1 were well maintained on the tumor cells recovered from the SCID and nude mice. The utility of the developed tumor models for the therapeutic studies was investigated by i.p. or i.v. administration of an anti-B leukemia/lymphoma monoclonal antibody, termed SN7 (IgG1 kappa), and SN7 immunotoxin (IT) that was prepared by conjugating SN7 to ricin A chain (RA) or deglycosylated RA (dgRA). In the nude mouse model study, SN7-RA that had been administered i.p. suppressed the tumor growth completely in all of the treated mice (n = 5) without any sign of tumor or undesirable side effects for as long as followed (i.e., 350 days), whereas unconjugated SN7 showed only a slight therapeutic effect. A control RA conjugate was not effective. In the SCID mouse model studies, several sets of experiments were carried out by i.p. or i.v. administration of IT, monoclonal antibody, or control IT. In the first three sets of experiments, SCID mice inoculated with 1.1 x 10(6) BALL-1a cells received an i.p. administration of phosphate-buffered saline or three different doses (i.e., 4 x 10 micrograms, 4 x 20 micrograms, and 4 x 30 micrograms) of therapeutic agents (SN7-RA and SN7). Virtually an identical result was obtained from the three experiments. All of the phosphate-buffered saline control group mice (n = 15) died within 35 days post tumor inoculation. In contrast, all of the mice that were treated with SN7-RA (n = 19) or with SN7 (n = 15) survived for as long as followed (i.e., 250 days). However, the unconjugated SN7 was less effective than SN7 IT for tumor suppression in SCID mice that were inoculated with a larger tumor burden (i.e., 4 x 10(7) BALL-1a cells).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24.
Duchenne and Becker muscular dystrophies are caused by defects of dystrophin, which forms a part of the membrane cytoskeleton of specialized cells such as muscle. It has been previously shown that the dystrophin-associated protein A1 (59-kDa DAP) is actually a heterogeneous group of phosphorylated proteins consisting of an acidic (alpha-A1) and a distinct basic (beta-A1) component. Partial peptide sequence of the A1 complex purified from rabbit muscle permitted the design of oligonucleotide probes that were used to isolate a cDNA for one human isoform of A1. This cDNA encodes a basic A1 isoform that is distinct from the recently described syntrophins in Torpedo and mouse and is expressed in many tissues with at least five distinct mRNA species of 5.9, 4.8, 4.3, 3.1, and 1.5 kb. A comparison of our human cDNA sequence with the GenBank expressed sequence tag (EST) data base has identified a relative from human skeletal muscle, EST25263, which is probably a human homologue of the published mouse syntrophin 2. We have mapped the human basic component of A1 and EST25263 genes to chromosomes 8q23-24 and 16, respectively.
Amino Acid Sequence↗
Effect of opioid peptides on dopamine release from nucleus accumbens after repeated treatment with methamphetamine.
The effect of opioid peptides on extracellular dopamine levels in the nucleus accumbens was compared between rats treated with methamphetamine and saline repeatedly (for 9 days) by using microdialysis. After the period of repeated treatment, the rats in both groups were kept for an additional 9 days without further treatment. Repeated administration of methamphetamine reduced the decreasing effect of dynorphin (10 microM), applied locally in the perfusate, and enhanced the increasing effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 10 microM) on the extracellular dopamine levels in the nucleus accumbens. It is possible that repeated treatment with methamphetamine leads to attenuation of the inhibition and enhancement of the stimulation of dopamine release from the nucleus accumbens via presynaptic dynorphin- and enkephalin-sensitive receptors, respectively.
Analgesics↗
Comparison of the ATPase activities of bovine heart and liver mitochondrial ATP synthases with different tissue-specific gamma subunit isoforms.
The kinetics of heart and liver mitochondrial ATPase (FoF1) were examined using submitochondrial particles (SMPs) purified from the two tissues to obtain information on the role of gamma subunit isoforms. The F1 portion is mainly composed of the catalytic, common alpha beta subunits and tissue-specific gamma subunits. In contrast to the previous reports on the kinetics and crystallography of various F1's, the Vmax and Km of the two isoforms of FoF1 were identical although the SMPs were prepared from different tissues. Moreover sodium azide inhibited the two equally. The ATPase activity of liver SMP showed slightly steeper pH-dependency than that of heart SMP but the pH optima of the two were the same (pH 8).
Animals↗
Tax protein of human T-cell leukemia virus type I binds to the ankyrin motifs of inhibitory factor kappa B and induces nuclear translocation of transcription factor NF-kappa B proteins for transcriptional activation.
Human T-cell leukemia virus type I causes adult T-cell leukemia and tropical spastic paraparesis, and its regulator protein Tax has been implicated in the pathogenic activity of human T-cell leukemia virus type I. Tax activates transcription of viral and cellular genes through specific enhancers: the 21-bp enhancer of human T-cell leukemia virus type I, the nuclear factor kappa B (NF-kappa B)-binding site of the interleukin 2 receptor alpha gene, and the serum-responsive element of c-fos. Tax binds to enhancer-binding proteins including cAMP-responsive element-binding protein, cAMP-responsive element modulator, transcription factor NF-kappa B p50 and p67SRF, and associates with each enhancer DNA indirectly. In addition to this mechanism, we report here that Tax binds to inhibitory factor kappa B gamma (I-kappa B) gamma, which forms a complex with NF-kappa B protein heterodimer p50-p65 or homodimer p50-p50 and retains them in the cytoplasm. Tax binding to I-kappa B gamma induces nuclear translocation of NF-kappa B p65. In association with this nuclear translocation of p65, transcription directed by the kappa B enhancer is strongly activated. Tax binds to the ankyrin motifs of I-kappa B gamma, suggesting its possible interaction with many other proteins carrying ankyrin motifs contributing to various regulatory processes. This is a different mechanism of transcriptional activation by the oncoprotein Tax and seems to be independent from the trans-activation through indirect binding to enhancer DNAs.
Animals↗
Isolation of prokaryotic V0V1-ATPase from a thermophilic eubacterium Thermus thermophilus.
The soluble ATPase purified from an aerobic thermophilic eubacterium, Thermus thermophilus, was not a usual F1-ATPase but a V1-ATPase, a peripheral section of plasma membrane V-type ATPase (Yokoyama, K., Oshima, T., and Yoshida, M. (1990) J. Biol. Chem. 265, 21946-21950). Here, we report the purification of V-type ATPase from the same bacterium (V0V1-ATPase) which consists of V1-ATPase and a membrane-integrated section, V0. The V0V1-ATPase, either in the Triton X-100-solubilized membrane fraction or in the purified state, migrates as a single band in a non-denaturing polyacrylamide gel electrophoresis for membrane protein complexes, and eight kinds of polypeptides are found when this band is developed in a second dimension denaturing gel electrophoresis in the presence of sodium dodecyl sulfate. The 66-, 56-, 30-, and 12-kDa polypeptides are the subunits of V1-ATPase and the 100-, 38-, 24-, and 13-kDa polypeptides are candidates for V0 (or V0-associated) subunits. The amino-terminal amino acid sequences of the 38- and 24-kDa subunits do not show obvious similarity to any subunits of eukaryotic V0V1-ATPases. The kinetic properties of the purified V0V1-ATPase are very similar to those of V1-ATPase: a very low ATPase activity, stimulation by bisulfite, inhibition by nitrate, and resistance against inhibitors of eukaryotic V-type ATPases, Bafilomycin A1 and N-ethylmaleimide. The V0 vesicles prepared from reconstituted V0V1-ATPase vesicles by 6 M urea treatment show the H+ channel activity. This H+ channel activity is abolished either by treatment of vesicles with dicyclohexylcarbodiimide or by the back addition of V1-ATPase. These results indicate that the coupling ion of this V0V1-ATPase is H+.
Amino Acid Sequence↗
Characterization of a 60-kilodalton substrate of the insulin receptor kinase.
A 60-kDa tyrosine-phosphorylated protein has been observed after insulin treatment of cells in immunoprecipitations of the GTPase-activating protein of Ras (called GAP) as well as the phosphatidylinositol 3-kinase. In the present studies, these two 60-kDa proteins have been shown to differ by limited proteolytic digestions as well as by immunoprecipitation with a monoclonal antibody. This monoclonal antibody was also utilized to show that the 60-kDa GAP-associated protein was rapidly phosphorylated in intact cells after insulin stimulation and to associate with GAP only after insulin treatment of the cells. In addition, the 60-kDa protein was found to be phosphorylated in vitro by the insulin receptor. Finally, the 60-kDa protein immunoprecipitated by this antibody was found not to react with a polyclonal antibody directed against a 62-kDa tyrosine-phosphorylated GAP-associated protein previously observed in src-transformed cells. These studies indicate that insulin stimulates the tyrosine phosphorylation of at least two distinct 60-kDa proteins, one that becomes associated with GAP and appears to be a direct substrate of the insulin receptor kinase and another that associates with the phosphatidylinositol 3-kinase.
Animals↗
A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group.
We conducted a prospective, double-blind controlled study to determine the efficacy of a recombinant granulocyte colony-stimulating factor (G-CSF, 200 microgram/m2) starting daily from 2 days before an induction therapy until neutrophils recovered to above 1,500/microL or until 35 days after the therapy in 58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty-eight patients in the G-CSF group showed significantly faster recovery of neutrophils (P < .001) than 30 patients in the placebo group. The incidence of febrile episodes and of documented infections was almost the same in both groups. However, among 39 patients who did not show any infectious episodes during the 2-week period after the start of chemotherapy, the incidence of documented infections after the third week tended to be lower in the G-CSF group, but not statistically significantly. There was no evidence that G-CSF stimulated the growth of AML cells in the bone marrow during the 2-day period before the chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5-week period after the therapy. Fifty percent of patients in the G-CSF group and 37% in the placebo group had complete remission (CR). Although the rate was higher in the G-CSF group, the difference was not statistically significant (P = .306). There was no difference between the two groups in event-free survival of all patients and in disease-free survival of patients who had achieved CR.
Adolescent↗