Bronchoscopic diagnosis in patients with small cell lung cancer.
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Biopsy, Needle↗
Biomedical subjects
H Satoh
Publications and source records attributed to H Satoh.
Post-irradiation erythroderma.
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Administration, Topical↗
Increased cytosolic Ca(2+) concentration in endothelial cells by calmodulin antagonists.
Many functions of endothelial cells are Ca(2+)/calmodulin dependent, whereas the role of calmodulin in the regulation of cytosolic Ca(2+) ([Ca(2+)](i)) remains largely unexplained. In the present study, effects of various calmodulin antagonists on [Ca(2+)](i) were investigated in cultured aortic endothelial cells loaded with the Ca(2+)-sensitive dye fura-2/AM, and were compared with those of calmodulin-dependent protein kinase II (CaM kinase II) inhibitors. The calmodulin antagonists W-7, calmidazolium and fendiline provoked dose-dependent increases in [Ca(2+)](i). However, the CaM kinase II inhibitors KN-93 and lavendustin C had no effect on [Ca(2+)](i). In the absence of extracellular Ca(2+), pretreatment of cells with bradykinin (BK) and thapsigargin completely prevented W-7-stimulated increase in [Ca(2+)](i). Alternatively, pretreatment with W-7 also completely blocked BK- and thapsigargin-stimulated increases in [Ca(2+)](i). The time course of the Ca(2+)-response in W-7 treated cells was identical to that in thapsigargin-treated cells, but not that in BK-stimulated cells, suggesting that calmodulin antagonists could share a common signaling pathway with thapsigargin to increase [Ca(2+)](i) in endothelial cells. These findings indicate that calmodulin is involved in the regulation of [Ca(2+)](i), and may play an important role in the uptake of Ca(2+) to intracellular stores.
Animals↗
Comparison of 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine with gemcitabine in its antitumor activity.
The antitumor activity of a novel nucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D arabinofuranosyl)cytosine (4'-thio-FAC) was compared with that of 2'-deoxy-2',2'-difluorocytidine (gemcitabine). 4'-Thio-FAC showed potent antitumor effects against various solid cancer cell lines in vitro. Also, gemcitabine showed remarkable in vitro antitumor effects, even more potent than 4'-thio-FAC. However, 4'-thio-FAC inhibited tumor growth more strongly than gemcitabine did at the same dose against human cancer cells implanted s.c. in nude mice. In addition, 4'-thio-FAC suppressed the tumor growth by oral administration. The toxicity of 4'-thio-FAC was weaker than that of gemcitabine in nude mice in both consecutive and intermittent administration. Accordingly, clinical usefulness of 4'-thio-FAC is expected.
Animals↗
Peflin, a novel member of the five-EF-hand-protein family, is similar to the apoptosis-linked gene 2 (ALG-2) protein but possesses nonapeptide repeats in the N-terminal hydrophobic region.
The calpain small subunits of sorcin, grancalcin, and ALG-2 constitute a family of the Ca(2+)-binding proteins with five EF-hand-like motifs (penta-EF-hand domain or PEF domain) in their C-terminal regions and hydrophobic domains with variable lengths in their N-terminal regions. Searching the human DNA data base of expressed sequence tags (EST) revealed novel partial sequences similar to, but distinct from, the sequences of the previously known PEF proteins. We isolated a cDNA clone of near full length by 5'- and 3'-RACE (rapid amplification of cDNA end) methods and compared the predicted amino acid sequence (284 residues) of the novel EF-hand protein, named peflin, with those of known PEF proteins. The PEF domain of peflin is most similar to ALG-2 (40.9% identity) among the family, particularly in EF-1 (46.2%) and EF-3 (57.1%) regions. Peflin has a longer N-terminal hydrophobic domain than any other member of the family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. Western blot analysis demonstrated that peflin (30 kDa) was expressed in various nonadherent and adherent cultured human cell lines, including Jurkat, HL60, HeLa, and HT1080. Peflin may play basic roles in Ca(2+) signaling irrespective of cell types.
Amino Acid Sequence↗
The small GTP-binding protein rac is a regulator of cell death in plants.
Cell death plays important roles in the development and defense of plants as in other multicellular organisms. Rapid production of reactive oxygen species often is associated with plant defense against pathogens, but their molecular mechanisms are not known. We introduced the constitutively active and the dominant negative forms of the small GTP-binding protein OsRac1, a rice homolog of human Rac, into the wild type and a lesion mimic mutant of rice and analyzed H(2)O(2) production and cell death in transformed cell cultures and plants. The results indicate that Rac is a regulator of reactive oxygen species production as well as cell death in rice.
Amino Acid Sequence↗
Tumor necrosis factor-alpha-converting enzyme and tumor necrosis factor-alpha in human dilated cardiomyopathy.
BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). TNF-alpha-converting enzyme (TACE) has recently been purified and its complementary DNA cloned. The expression of TACE results in the production of a functional enzyme that has precursor TNF-alpha in the mature form. The aim of this study was to determine whether TACE is expressed with TNF-alpha in myocardium and whether levels of TACE and TNF-alpha are related to clinical severity of DCM. METHODS AND RESULTS: Endomyocardial tissues were obtained from 30 patients with DCM and 5 control subjects. TNF-alpha and TACE mRNA levels were measured by a novel real-time quantitative reverse transcriptase-polymerase chain reaction method. Expression of TNF-alpha and TACE proteins was determined by immunohistochemical analysis. TNF-alpha mRNA was expressed in DCM patients (TNF-alpha/GAPDH ratio 0.85+/-0.24) but not in control subjects. TACE mRNA expression was significantly greater in DCM patients than in control subjects (TACE/GAPDH ratio 2.52+/-0.59 vs 0.03+/-0.02, P<0.05). A positive correlation was found between TNF-alpha and TACE mRNA levels (r=0.779, P<0.001). TACE and TNF-alpha immunostaining was observed in myocytes in patients with DCM. When 2 subgroups of DCM were divided on the basis of left ventricular end-systolic diameter (LVESD) of 45 mm and left ventricular ejection fraction (LVEF) of 40%, the DCM subgroup with high LVESD (>/=45 mm) showed significantly greater expression of TACE (P=0.02) and TNF-alpha (P=0. 001) than did the low LVESD subgroup (<45 mm). In addition, the DCM subgroup with lower LVEF (<40%) showed higher expression of TACE (P=0.006) and TNF-alpha (P=0.01) than did the subgroup with high LVEF (>/=40%). CONCLUSIONS: This study has shown that increased myocardial TACE expression is associated with elevated myocardial TNF-alpha expression in both mRNA and protein levels in clinically advanced DCM.
ADAM Proteins↗
Relationship between levels of leptin and hemoglobin in Japanese men.
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Adult↗
Thiazolidinediones down-regulate plasminogen activator inhibitor type 1 expression in human vascular endothelial cells: A possible role for PPARgamma in endothelial function.
The effect of peroxisome proliferator-activated receptor (PPAR) gamma activators, thiazolidinediones, on plasminogen activator type 1 (PAI-1) was examined in cultured human umbilical vein endothelial cells (HUVEC). Tumor necrosis factor alpha (TNF-alpha) enhanced PAI-1 secretion and mRNA expression by approximately 2-fold. The thiazolidinediones, troglitazone and pioglitazone, decreased basal and TNF-alpha-stimulated PAI-1 secretion and mRNA expression in HUVEC in a dose-dependent fashion. PPARgamma mRNA in HUVEC could be detected by reverse transcriptase-polymerase chain reaction using specific primers. These results suggest that PPARgamma may regulate PAI-1 expression in HUVEC and that thiazolidinediones have a therapeutic potential for improving endothelial dysfunction observed in insulin resistance.
Base Sequence↗
Lewy body-type degeneration in cardiac plexus in Parkinson's and incidental Lewy body diseases.
Heart tissues of patients with PD or incidental Lewy body (LB) disease (ILBD) were examined by light and electron microscopy. LBs and alpha-synuclein-positive neurites were identified in the hearts from 9 of 11 patients with PD and from 7 of 7 patients with ILBD. LBs were present in both tyrosine hydroxylase-positive and -negative nerve processes, which are nerves of extrinsic sympathetic and intrinsic origin, respectively. These findings provide histologic evidence that the postganglionic sympathetic and intrinsic neurons in the heart are involved in the PD disease process.
Aged↗
Molecular cloning and characterization of two sets of alpha-theta genes in the rat alpha-like globin gene cluster.
The highly heterogeneous rat hemoglobin system was investigated at the gene level. Two regions of the alpha-like globin gene cluster from a Wistar rat were isolated. Four lambda Dash recombinant clones carrying rat alpha-like globin genes were localized on two distinct gene regions. A region of approximately 16kb was found to contain the 5'-IIalpha1-psi theta 1-3' loci, and another of approximately 24kb the 5'-IIalpha2-psi theta2-psiI alpha3-3' loci. Both IIalpha1 and IIalpha2 are considered to be active, coding the IIalpha-globin chain. The nt sequences of IIalpha1 and IIalpha2 are identical except for six nt in the non-coding region. The psiI alpha3 locus is a truncated pseudogene. The putative promoter region of an alpha-like globin gene is joined directly to the third exon, homologous to that of Ialpha-globin cDNA. psi theta1 and psi theta2 are also pseudogenes, as evidenced by several deletions located in the protein-coding regions of these loci. The psi theta1 and psi theta2 loci exhibit extensive homology, but the restriction maps of these genes and their flanking regions differ considerably. Genomic Southern blot analyses of the total liver DNA from six rats showed the existence of three theta-globin-related genes, including psi theta1 and psi theta2. These results indicate that the two gene regions investigated are not allelic variants, but may be generated by block duplication. This is the first report of the existence of rodent theta-globin genes.
Animals↗
(3-substituted benzyl)thiazolidine-2,4-diones as structurally new antihyperglycemic agents.
A series of 3-[(2,4-dioxothiazolidin-5-yl)methyl]benzamide derivatives was prepared as part of a search for antidiabetic agents. A structure-activity relationship study of these compounds led to the identification of 5-[(2,4-dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[4-(trifluorome thyl)-phenyl]methyl]benzamide (KRP-297) as a candidate drug for the treatment of diabetes mellitus.
Animals↗
Separation of selenium-containing proteins in human and mouse plasma using tandem high-performance liquid chromatography columns coupled with inductively coupled plasma-mass spectrometry.
An analytical method that uses two different high-performance liquid chromatography (HPLC) columns in tandem has been developed that separates three major selenium-containing proteins (albumin, glutathione peroxidase, and selenoprotein P) found in human blood plasma. The first column was a heparin affinity column and the second was a gel filtration column whose outlet was directly connected to an inductively coupled plasma-mass spectrometer. The method successfully separated plasma selenium into the three selenium-containing proteins and revealed the preferential retention of selenium in the form of selenoprotein P in a selenium-deficient human and in selenium-deficient mice. Our results also confirm the results of previous studies that showed a preference for supplemented selenium to be taken up as selenoprotein P in rats. Advantages of the tandem column method are that it allows rapid and convenient analyses of the distribution of plasma selenium, and that it is suitable for stable isotope tracer studies and metal interaction studies.
Adult↗
Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: a new possible role of PPARgamma on vascular endothelial function.
We examined the effect of troglitazone on immunoreactive endothelin-1 (ET-1) secretion from cultured bovine vascular endothelial cells (bVECs). Insulin (10(-9)-10(-7) M) stimulated ET-1 secretion in a dose-dependent fashion without any kinetic change. Troglitazone (1-20 microM) dose-dependently inhibited both spontaneous and insulin-stimulated ET-1 secretion. This inhibitory effect of troglitazone was associated with reduced ET-1 mRNA levels. Addition of indomethacin (100 microM) or Nw-nitro-l-arginine methyl ester (1 mM) and downregulation of protein kinase C by prolonged pretreatment of the cells with a phorbol ester, 12-O-tetradecanoylphorbol 13-acetate, did not affect the inhibitory effect of troglitazone at concentrations up to 10 microM. Troglitazone did not change the intracellular Ca2+ concentration stimulated by angiotensin II (10 microM). Other PPARgamma ligands, pioglitazone (1-10 microM) and 15-deoxy-delta 12, 14-prostaglandin J2 (1-10 microM), but not a PPARalpha ligand, bezafibrate (1-10 microM), dose-dependently suppressed spontaneous ET-1 secretion from bVECs. These results, taken together, suggest that troglitazone inhibits ET-1 mRNA expression and secretion in bVECs possibly through activation of PPARgamma. This inhibition may contribute to the hypotensive effect of troglitazone in insulin-resistant subjects.
Animals↗
Augmented proliferation of human alveolar macrophages after allogeneic bone marrow transplantation.
After allogeneic bone marrow transplantation (allo-BMT), recipient alveolar macrophages (AM) are gradually replaced by AM of the donor origin. An influx of mononuclear phagocytes of donor origin to the lung is responsible for the repopulation, but the detailed kinetics remain unclear. We therefore studied 24 BMT recipients who underwent bronchoalveolar lavage (BAL) from 24 to 83 days after BMT. AM cell number, size, morphology, proliferating ability, and genotype of AM were measured. Before day 50, the number and size of AM in BAL fluid were similar to those of normal nonsmokers. However, after day 50, the mean number of AM increased threefold and the mean cell size decreased due to the increase of small AM. These small cells are presumably of donor origin based on DNA fingerprinting analysis and based on fluorescence in situ hybridization for the Y chromosome in a sex-mismatched case. Immunohistochemistry and cell cycle analysis demonstrated that the increase in AM number coincided with a remarkable increase of AM expressing proliferating cell nuclear antigen, suggesting that small AM are proliferating. This is the first report representing that augmented proliferation of donor AM in situ may contribute to the reconstitution of AM population after BMT.
Adolescent↗
Lack of class II transactivator causes severe deficiency of HLA-DR expression in small cell lung cancer.
Small cell lung cancer (SCLC) is characteristically not associated with tumour-infiltrating lymphocytes. Since SCLC has been reported to show marked reduction of class I HLA, the reduced expression has been considered a means of escaping anti-cancer immunity. However, HLA-DR expressed in cancer cells is now known to contribute to anti-cancer immunity. To clarify the difference in HLA-DR expression between SCLC and non-small cell lung cancer (NSCLC), and the mechanism, the expression and the cis- and trans-acting factors involved were investigated. HLA-DR was not immunohistochemically detected in any SCLC and could not be induced by interferon gamma (IFN-gamma) in any SCLC cell line, whereas HLA-DR was expressed to varying degrees and was easily induced in NSCLC. SCLC cell lines lacked class II transactivator (CIITA) even after IFN-gamma induction, whereas NSCLC cell lines expressed CIITA. The other class II HLA-specific transcription factors were expressed and genomic DNA of HLA-DR, including the promoter, was conserved well both in SCLC and in NSCLC cell lines. CIITA transfection improved the expression of HLA-DR in SCLC. In conclusion, the lack of CIITA results in severe deficiency of HLA-DR expression in SCLC. Since CIITA has also been reported to induce class I HLA, CIITA transfection might make it possible to establish effective anti-cancer immunotherapy against SCLC through the up-regulation of class I and class II HLA.
Blotting, Northern↗
The three copies of the ATP1 gene are arranged in tandem on chromosome II of Saccharomyces cerevisiae S288C.
In the yeast Saccharomyces cerevisiae there are three copies of the F(1)F(0)-ATPase alpha-subunit gene ATP1 on chromosome II (Takeda et al., 1995). However, after genome analysis using S. cerevisiae strain S288C, only one ATP1 gene sequence was observed (Feldman et al., 1994; Obermaier et al., 1995). To check whether the number of copies of ATP1 is strain-dependent or not, we carried out three different experiments: (a) long-PCR analyses of total DNAs isolated from several reference strains, carried out by preparing 29-mer oligonucleotides based on the 5'- and 3'- up- and downstream regions of the ATP1 nucleotide sequence using the data from the genome project to synthesize primers; (b) restriction analyses of chromosome II from the reference strains with SplI; and (c) long-PCR analyses of prime clones 70113 and 70804, both of which contained two ATP1 gene copies, ATP1a and ATP1b, and ATP1b and ATP1c, respectively, using 30 nucleotides just inside the 3'-end (sense) and 5'-end (antisense) of the ATP1-coding region as primers. In the case of the long-PCR experiments, the reference strains DC5, SEY2102, W303-1A, W303-1B, LL20 and DBY746, as well as strain S288C, generated a DNA fragment of approximately 32 kb, which hybridized with ATP1. During SplI digestion, a DNA fragment of more than 50 kb which hybridized with ATP1, was obtained from all reference strains. In the case of prime clone analyses using the long-PCR experiments, the distance between ATP1a and ATP1b or ATP1b and ATP1c was approximately 10 kb or 7 kb, respectively. The S288C strain generated these two DNA fragments, as do the other strains. These results showed that all these strains contained three copies of ATP1 on chromosome II.
Base Sequence↗
In utero methylmercury exposure differentially affects the activities of selenoenzymes in the fetal mouse brain.
Pregnant ICR mice were subcutaneously injected with 0,5, or 3x3 mg Hg/kg of methylmercury (MeHg) on days 12,13, and 14(G12-14) of gestation and were sacrificed on G17. Activity of selenoenzymes, including glutathione peroxidase (GPx) and 5'- or 5-iodothyronine deiodinases (5'-DI, 5-DI), was determined in fetal brain and placenta. MeHg did not affect the concentration of Se in these tissues, while it significantly inhibited the activity of GPx in the fetal brain and placenta, but not in the maternal brain. Although the levels of thyroid hormones in the maternal and fetal plasma were not affected by MeHg, 5-DI decreased and 5'-DI increased in the fetal brain, as if they had responded to hypothyroidism. Because the level of T4 in the fetal plasma was not affected by MeHg, these changes in enzymatic activities may result in a harmful excess of T3 in the fetal brain. In addition, 5-DI activity was increased in the placenta of MeHg-treated mice. These effects of prenatal MeHg exposure on fetal and placental DIs differed from those of dietary-induced Se deficiency, where the activities of DIs were decreased or not affected. Further evaluation of the effect of MeHg on selenoenzymes, especially 5-DIs, is warranted.
Animals↗