Trichostatin D, a new inducer of phenotypic reversion in transformed cells.
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3T3 Cells↗
Biomedical subjects
M Nakai
Publications and source records attributed to M Nakai.
Analysis of hepatocellular carcinoma fed by internal thoracic artery
Purpose: The purpose of this study was to elucidate the clinical features of hepatocellular carcinoma (HCC) fed by the internal thoracic artery (ITA). Methods: In seven patients HCC fed by the ITA was confirmed by digital subtraction angiography. The number of previous transcatheter arterial embolization (TAE), the period from the first TAE to TAE of the ITA, tumor location, tumor size, and occlusion of the hepatic artery (HA) and other collateral vessels were explored in each case. Results: The HCCs were located in S4 of the liver (n = 5) and in S8 (n = 1) and were fed by the right ITA and one nodule in S2-3 was fed by the left ITA. Tumor size was 3-10 cm. The number of previous TAE of the HA ranged from 2 to 12. The period from the first TAE to TAE of the ITA was 3-53 months. Angiography of these patients showed occlusion of the HA in six cases, and of the extrahepatic collaterals including the inferior phrenic artery (IPA) in five cases, intercostal artery (ICA) in one case, and epicholedocal artery (EPA) in one case. Conclusion: The ITA often supplies HCC located in the anterior superior region of the liver under the diaphragm; there can be long-term survival with repeated TAE and occlusion of HA.
Journal Article↗
[Progress of adenovirus vector development].
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Adenoviridae↗
[Paralytic ileus, pneumatosis cystoides intestinalis and pneumoperitoneum complicated with overlap syndrome (progressive systemic sclerosis and polymyositis): report of an autopsy case].
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Female↗
Did ossification of the posterior longitudinal ligament of the spine evolve in the modern period? A paleopathologic study of ancient human skeletons in Japan.
OBJECTIVE: To investigate the historical origins of ligamentous ossifications of the spine in Japan. METHODS: We studied skeletons of Jomonese of the period 5000-2300 years BP, of Japanese of the 17th-19th century Edo Period, and of Ainu of the 18th-20th century in Japan with special emphasis on spinal ligament ossifications as in the posterior longitudinal ligament. A comparison to our previous study on ancient Chinese skeletons was done. RESULTS: Cervical ossification of the posterior longitudinal ligament (OPLL) was the only ossification that increased significantly in prevalence in people of the near-modern period in comparison to the Neolithic gathering-hunting people. CONCLUSION: Socioeconomic changes from a subsistence gathering-hunting economy to the near-modern livelihood depending on rice-eating and a diet high in vegetable protein are speculated to be responsible for the prevalence increase of cervical OPLL.
Adult↗
Chloroplast chaperonins: evidence for heterogeneous assembly of alpha and beta Cpn60 polypeptides into a chaperonin oligomer.
Higher plant chloroplasts contain two chaperonin 60 family proteins, Cpn60alpha and Cpn60beta, which are known to have divergent amino acid sequences. Although Cpn60alpha and Cpn60beta are present in roughly equal amounts and copurify in their native states, a heterogeneous ensemble of the chaperonin oligomer has not yet been demonstrated. We separately purified Cpn60alpha and Cpn60beta proteins from spinach leaves as the monomeric form. Either antibody raised against one chaperonin 60 protein could coimmunoprecipitate the other chaperonin 60 protein in their oligomeric state but not in its monomeric state, suggesting that the chloroplast Cpn60alpha and Cpn60beta polypeptides actually reside in the same chaperonin oligomer in the stroma. Moreover, the chaperonin oligomers migrated as at least two distinct bands on the native gel electrophoresis, each of which contained both chaperonin 60 proteins. These results suggest that chloroplast chaperonin oligomers might be composed of at least two distinct sets of two chaperonin proteins.
Amino Acid Sequence↗
Scopolamine-sensitive and resistant components of increase in cerebral cortical blood flow elicited by periaqueductal gray matter of rats.
The present study attempted to evaluate the effects of inhibition of cortical muscarinic receptors on the increase in cortical blood flow (laser-Doppler flowmetry) elicited by chemical stimulation of the periaqueductal gray matter in 28 anesthetized rats with cervical cordotomy. A new device was introduced which allowed focal cortical superfusion with scopolamine, an antagonist for muscarinic receptors, without disturbing the temperature of an exposed cortical area under study. We found that although the flow increase was attenuated by scopolamine (31.6 micromol/l to 1 mmol/l) so applied, about one third of it was resistant to the treatment. Cortical muscarinic and non-muscarinic receptor mechanisms may thus subserve the mediation of the flow increase.
Animals↗
Nuclear factor kappaB nuclear translocation upregulates c-Myc and p53 expression during NMDA receptor-mediated apoptosis in rat striatum.
Nuclear factor kappaB (NF-kappaB) appears to participate in the excitotoxin-induced apoptosis of striatal medium spiny neurons. To elucidate molecular mechanisms by which this transcription factor contributes to NMDA receptor-triggered apoptotic cascades in vivo, rats were given the NMDA receptor agonist quinolinic acid (QA) by intrastriatal infusion, and the role of NF-kappaB in the induction of apoptosis-related genes and gene products was evaluated. QA administration induced time-dependent NF-kappaB nuclear translocation. The nuclear NF-kappaB protein after QA treatment was comprised mainly of p65 and c-Rel subunits as detected by gel supershift assay. Levels of c-Myc and p53 mRNA and protein were markedly increased at the time of QA-induced NF-kappaB nuclear translocation. Immunohistochemical analysis showed that c-Myc and p53 induction occurred in the excitotoxin-sensitive medium-sized striatal neurons. NF-kappaB nuclear translocation was blocked in a dose-dependent manner by the cell-permeable recombinant peptide NF-kappaB SN50, but not by the NF-kappaB SN50 control peptide. NF-kappaB SN50 significantly inhibited the QA-induced elevation in levels of c-Myc and p53 mRNA and protein. Pretreatment or posttreatment with NF-kappaB SN50, but not the control peptide, also substantially reduced the intensity of QA-induced internucleosomal DNA fragmentation. The results suggest that NF-kappaB may promote an apoptotic response in striatal medium-sized neurons to excitotoxic insult through upregulation of c-Myc and p53. This study also provides evidence indicating an unique signaling pathway from the cytoplasm to the nucleus, which regulates p53 and c-Myc levels in these neurons during apoptosis.
Animals↗
Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B.
Wilson's disease, an autosomal recessive disorder, is characterized by the excessive accumulation of hepatic copper that results from reduced biliary copper excretion and disturbed incorporation of copper into ceruloplasmin. The ATP7B gene, responsible for the disease, encodes a copper transporting P-type ATPase. We previously demonstrated the involvement of ATP7B in hepatic copper secretion into plasma after the introduction of ATP7B into the Long-Evans Cinnamon (LEC) rat, a rodent model of Wilson's disease. In this study we found the increased copper contents of the hepatic lysosomal fractions and bile in the LEC rats after ATP7B introduction, indicating the participation of ATP7B in the biliary excretory pathway for copper.
Adenosine Triphosphatases↗
Uncoupling of transfer of the presequence and unfolding of the mature domain in precursor translocation across the mitochondrial outer membrane.
Translocation of mitochondrial precursor proteins across the mitochondrial outer membrane is facilitated by the translocase of the outer membrane (TOM) complex. By using site-specific photocrosslinking, we have mapped interactions between TOM proteins and a mitochondrial precursor protein arrested at two distinct stages, stage A (accumulated at 0 degrees C) and stage B (accumulated at 30 degrees C), in the translocation across the outer membrane at high resolution not achieved previously. Although the stage A and stage B intermediates were assigned previously to the forms bound to the cis site and the trans site of the TOM complex, respectively, the results of crosslinking indicate that the presequence of the intermediates at both stage A and stage B is already on the trans side of the outer membrane. The mature domain is unfolded and bound to Tom40 at stage B whereas it remains folded at stage A. After dissociation from the TOM complex, translocation of the stage B intermediate, but not of the stage A intermediate, across the inner membrane was promoted by the intermembrane-space domain of Tom22. We propose a new model for protein translocation across the outer membrane, where translocation of the presequence and unfolding of the mature domain are not necessarily coupled.
Amino Acid Sequence↗
Involvement of a chloroplast homologue of the signal recognition particle receptor protein, FtsY, in protein targeting to thylakoids.
We isolated an Arabidopsis thaliana cDNA whose translated product shows sequence similarity to the FtsY, a bacterial homologue of SRP receptor protein. The Arabidopsis FtsY homologue contains a typical chloroplast transit peptide. The in vitro-synthesized 37 kDa FtsY homologue was imported into chloroplasts, and the processed 32 kDa polypeptide bound peripherally on the outer surface of thylakoids. Antibodies raised against the FtsY homologue also reacted with a thylakoid-bound 32 kDa protein. The antibodies inhibited the cpSRP-dependent insertion of the light-harvesting chlorophyll alb-binding protein into thylakoid membranes suggesting that the chloroplast FtsY homologue is involved in the cpSRP-dependent protein targeting to the thylakoid membranes.
Amino Acid Sequence↗
Two distinct mechanisms operate in the reactivation of heat-denatured proteins by the mitochondrial Hsp70/Mdj1p/Yge1p chaperone system.
The yeast mitochondrial Hsp70, Ssc1p, functions as a molecular chaperone with its partner proteins, Mdj1p (DnaJ homologue) and Yge1p (GrpE homologue). We have purified a mature form of Ssc1p from yeast mitochondria and those of Mdj1p and Yge1p from Escherichia coli overexpresser cells. With these purified components of the mitochondrial Hsp70 chaperone system, we have succeeded in reconstituting their chaperone functions in the protection of firefly luciferase against thermal damage in vitro. Heat-denatured luciferase is prevented from irreversible aggregation and is maintained in a refolding-competent state by Ssc1p and/or Mdj1p at 42 degreesC. Luciferase denatured at 42 degreesC is actively reactivated by Ssc1p, Mdj1p and/or Yge1p after lowering the temperature to 25 degreesC. The reactivation process of heat-denatured luciferase shows two-phase kinetics. The slow refolding process requires either Ssc1p or Mdj1p at 42 degreesC but the presence of Ssc1p, Mdj1p and Yge1p, and ATP hydrolysis, is essential at 25 degreesC. The slow refolding of luciferase involves multiple rounds of formation and dissociation of the complex between luciferase and Mdj1p/Ssc1p. On the other hand, the fast refolding process is most enhanced when luciferase is incubated with Ssc1p alone at 42 degreesC, and it requires neither the assistance of Mdj1p and Yge1p nor ATP hydrolysis. We have observed a similar two-pathway reactivation of heat-denatured luciferase by the bacterial Hsp70 and the yeast cytosolic Hsp70 systems.
Adenosine Triphosphate↗
Free radical scavenger OPC-14117 attenuates quinolinic acid-induced NF-kappaB activation and apoptosis in rat striatum.
Oxidative stress has long been implicated in the pathogenesis of both the acute and chronic neurotoxic effects of glutamate acting through ionotrophic receptors of the N-methyl-d-aspartate (NMDA) subtype. To evaluate the contribution of oxidative stress to the NMDA receptor-mediated apoptotic death of rat striatal neurons in vivo, the effects of a novel, orally administered free radical scavenger, OPC-14117, was studied following intrastriatal infusion of the NMDA receptor agonist quinolinic acid (QA). Receptor autoradiography and in situ hybridization histochemistry showed that pretreatment with OPC-14117 (600 mg/kg) reduced the QA (120 nmol)-induced loss of striatal D1 dopamine receptors by about 20% (p<0.01) and NMDA receptors by 15% (p<0.01) as well as 67 kDa glutamic acid decarboxylase mRNA (34%; p<0.01) and proenkephalin mRNA (36%; p<0.01). OPC-14117 also decreased the apomorphine-induced ipsilateral rotational response in unilaterally QA-lesioned animals by about 70% (p<0.05). In addition, OPC-14117 pretreatment inhibited QA-induced internucleosomal DNA fragmentation. Western blot analysis and electrophoresis mobility shift assay further revealed that the free radical scavenger (300 and 600 mg/kg) blunted the QA-induced degradation of IkappaBalpha (increased IkappaBalpha levels from about 15% to 33 and 62% of control, respectively; p<0.01) as well as the ensuing activation of NF-kappaB by 25 to 34%, respectively (p<0. 01) and the augmentation in c-Myc (35 to 70%, respectively) and p53 expression by 50-80%, respectively (both p<0.01). In contrast, OPC-14117 had no significant effect on the QA-induced increase in AP-1 binding activity. These results suggest that the NMDA receptor-mediated generation of reactive oxygen species contributes to the QA-induced activation of NF-kappaB and further that orally administered OPC-14117 partially protects against excitotoxin-induced apoptosis of striatal neurons through inhibition of the NF-kappaB apoptotic cascade.
Animals↗
Binding characteristics of dialkyl phthalates for the estrogen receptor.
Dialkyl phthalates have been suggested to function as xenoestrogen. To explore the structural essentials, a series of ring and alkyl-chain isomers of dialkyl phthalates C6H4(COOCnHm)2 were examined for their ability to displace [3H]17beta-estradiol in the recombinant human estrogen receptor expressed on Sf9 vaculovirus. Compounds with an alkyl chain of more than C3 (n = 3) exhibited a distinct full receptor binding in a dose-dependent manner. When the ring isomers of C3-diallyl (-CH2-CH=CH2) derivatives, namely diallyl phthalate, diallyl isophthalate, and diallyl terephthalate, were examined, the ortho isomer of diallyl phthalate was most potent to bind to the estrogen receptor. The interaction with the estrogen receptor was optimized with dibutyl phthalates of C4. The conformational studies by 1H-NMR measurements and ab initio molecular orbital calculations have suggested that the structure mimics the interface of steroid A and B/C rings of 17beta-estradiol. Dicyclohexyl phthalate bound to the estrogen receptor with a biphasic binding curve, suggesting the compound discriminates two different receptor conformations.
Binding, Competitive↗
cDNA sequence and overexpression of chloroplast chaperonin 21 from Arabidopsis thaliana.
Higher plant chloroplasts contain a 21-kDa protein, chaperonin 21 (Cpn21), that is a functional homolog of the chaperonin 10 (Cpn10). The chloroplast Cpn21 polypeptide consists of two Cpn10-like domains fused together in tandem. We describe here the cDNA sequence of the Cpn21 (AtCpn21) precursor protein from Arabidopsis thaliana. The deduced amino acid sequence of the AtCpn21 precursor protein, 253 amino acids long, shows 61% identity with the spinach Cpn21 protein. The AtCpn21 precursor protein contains the typical chloroplast transit peptide of 51 amino acids at its aminoterminus and the two Cpn10-like domains which exhibits 46% sequence identity to each other. The predicted mature-sized polypeptide of AtCpn21 was expressed in Escherichia coli as a soluble 21-kDa protein. Gel-filtration and chemical cross-linking analyses showed that the recombinant mature AtCpn21 protein forms a stable homo-oligomer composed of three or four polypeptides.
Amino Acid Sequence↗
Co-stimulation of cyclic-AMP-linked metabotropic glutamate receptors in rat striatum attenuates excitotoxin-induced nuclear factor-kappaB activation and apoptosis.
Interactions between glutamatergic mechanisms mediated by receptors of the ionotropic and metabotropic classes in the central nervous system are complex and incompletely understood. To explore the consequences of these interactions on excitotoxicity, we examined the influence of group II and group III selective metabotropic glutamate receptor agonists on the N-methyl-D-aspartate-induced apoptotic destruction of GABAergic neurons in rat striatum. The intrastriatal administration of a group III metabotropic glutamate receptor agonist (amino-4-phosphonobutyric acid, 900-1800 nmol), but not of a group II agonist [(2S,1'S,2'S)-(carboxycyclopropyl)glycine, 100-1800 nmol] produced internucleosomal DNA fragmentation. Similarly, amino-4-phosphonobutyric acid (600 nmol) but not (2S,1'S,2'S)-(carboxycyclopropyl)glycine (100-1800 nmol) destroyed some striatal neurons as indicated by a loss of D1 dopamine receptors and 67,000 mol. wt glutamate decarboxylase (glutamate decarboxylase-67) messenger RNA. On the other hand, the intensity of internucleosomal DNA fragmentation induced by N-methyl-D aspartate (150 nmol) was substantially decreased by the intrastriatal co-administration of either (2S,1'S,2'S)-(carboxycyclopropyl)glycine or amino-4-phosphonobutyric acid (100-600 nmol). Both (2S, 1'S,2'S)-(carboxycyclopropyl)glycine and amino-4-phosphonobutyric acid also reduced the N-methyl-D-aspartate-induced loss of striatal D1 dopamine receptors by 67% and 68% (both P < 0.001), and glutamate decarboxylase-67 messenger RNA by 68% and 61%, respectively. Furthermore, both (2S,1'S,2'S)-(carboxycyclopropyl)glycine and amino-4-phosphonobutyric acid also attenuated the N-methyl-D-aspartate-induced decline in striatal IKB-alpha protein levels by 62% and 37%, as well as the increase in nuclear transcription factor nuclear factor-kappaB binding activity by 135% and 94% (both P < 0.001), and the subsequent rise in p53 and c-Myc protein levels. These results suggest that stimulation of cyclic-AMP-linked metabotropic glutamate receptors inhibits ionotropic glutamate receptor-mediated activation of apoptotic cascades involving IkappaB-alpha degradation and nuclear factor-kappaB nuclear translocation, as well as p53 and c-Myc induction. Certain selective metabotropic glutamate receptor agonists might thus find utility as adjuncts to N-methyl-D-aspartate antagonists in the protection against the neurotoxicity initiated by excessive ionotropic glutamate receptor stimulation.
Amino Acids, Dicarboxylic↗
Bone mineral density in steroid-dependent asthma assessed by peripheral quantitative computed tomography.
Chronic use of systemic glucocorticoids results in progressive bone loss and pathologic fractures. This study identified the predictive variables for bone loss and used peripheral quantitative computed tomography (pQCT) to measure changes in cortical and trabecular bone in patients receiving systemic glucocorticoid therapy of prednisone 15.4 g. Eighty-four asthmatic patients were included in the study. Vertebral fractures were diagnosed via plain spinal radiograms. pQCT was used to measure cortical and trabecular bone mineral density. Multiple regression analysis identified variables with predictive value. The cumulative dose of glucocorticoid correlated with the bone mineral density (p<0.05) and the trabecular bone density (p<0.01). Among patients > or = 65 yrs of age, the cumulative dose of glucocorticoid correlated with the occurrence of vertebral fractures (p<0.05), total bone mineral density (p<0.01) and cortical bone mineral density (p<0.01). Bone mineral density in the distal radius measured by pQCT and the vertebral bodies by axis QCT were correlated, regardless of whether systemic glucocorticoids were administered. Glucocorticoid administration not only decreases trabecular but also cortical bone mineral density. Since cortical bone provides strength and stiffness, it appears that the loss of cortical bone is responsible for the increased incidence of fracture seen in patients receiving systemic glucocorticoid therapy.
Aged↗
A study of metabolites isolated from urine samples of pigs and calves administered orbifloxacin.
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Animals↗