What is proper treatment for Wegener granulomatosis?
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Adult↗
Biomedical subjects
K Inoue
Publications and source records attributed to K Inoue.
Very-long-chain fatty acid-containing phospholipids accumulate in fatty acid synthase temperature-sensitive mutant strains of the fission yeast Schizosaccharomyces pombe fas2/lsd1.
Fission yeast lsd1 strains show aberrant mitosis with a lsd phenotype, large and small daughter nuclei, and a very thick septum, the phenotypic expression being temperature-sensitive. The lsd1(+) gene is the homologue of the budding yeast FAS2 gene encoding the fatty acid synthase alpha-subunit as reported previously (S. Saitoh, K. Takahashi, K. Nabeshima, Y. Yamashita, Y. Nakaseko, A. Hirata, M. Yanagida, J. Cell Biol. 134 (1996) 949--961). In this paper, lsd1 is considered to represent fas2. Here, three fas2 strains were investigated and found to have missense point mutations at different sites in the gene encoding the alpha-subunit of fatty acid synthase. The mutation affected only slightly the enzymatic activities monitored in vitro. Unexpectedly, abnormal phospholipids, phosphatidylcholine and phosphatidylethanolamine, both of which contain a very-long-chain fatty acyl residue (1-melissoyl-2-oleolyl-sn-glycero-3-phosphocholine and 1-melissoyl-2-oleolyl-sn-glycero-3-phosphoethanolamine), accumulated in fas2 strains in a temperature-sensitive manner. Rescue of the fas2 strains by addition of palmitate to the medium at restrictive temperature was accompanied by disappearance of these abnormal phospholipids. Accumulation of these lipids in membranes may cause alteration of various cellular functions.
Carbon Radioisotopes↗
Requirements of basic amino acid residues within the lectin-like domain of LOX-1 for the binding of oxidized low-density lipoprotein.
Lectin-like OxLDL receptor-1 (LOX-1) was identified as the major receptor for oxidized low-density lipoprotein (OxLDL) in aortic endothelial cells. LOX-1 is a type II membrane protein that structurally belongs to the C-type lectin family. Here, we found that the lectin-like domain of LOX-1 is essential for ligand binding, but the neck domain is not. In particular, the large loop between the third and fourth cysteine of the lectin-like domain plays a critical role for OxLDL binding as well as C-terminal end residues. Alanine-directed mutagenesis of the basic amino acid residues around this region revealed that all of the basic residues are involved in OxLDL binding. Simultaneous mutations of these basic residues almost abolished the OxLDL-binding activity of LOX-1. Electrostatic interaction between basic residues in the lectin-like domain of LOX-1 and negatively charged OxLDL is critical for the binding activity of LOX-1.
Alanine↗
Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.
Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0 MeV. The measured solar neutrino flux is 2.32+/-0.03(stat)+0.08-0.07(syst)x10(6) cm(-2) x s(-1), which is 45.1+/-0.5(stat)+1.6-1.4(syst)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry (Phi(n)-Phi(d))/Phi(average) is 0.033+/-0.022(stat)+0.013-0.012(syst). The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L. upper limit of 40x10(3) cm(-2) x s(-1), which is 4.3 times the BP2000 SSM prediction.
Journal Article↗
Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.
We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.
Journal Article↗
A new locus for a dominant form of multinodular goiter on 3q26.1-q26.3.
A mass screening program for congenital hypothyroidism has markedly improved prognosis of children with congenital hypothyroidism and also revealed several cases with unknown pathogenesis. We here report two independent Japanese multigeneration families with multinodular goiter (MNG) with euthyroidism and with high TSH. The propositi, 3- and 8-year-old girls in two families, were found during a mass screening. An autosomal dominant pattern of inheritance was suggested in both families. The clinical examinations suggested impaired hormonogenesis but discarded known defects in iodine transport, organification, deficiency of hydrogen peroxide, and thyroid peroxidase. Linkage analysis of the two families including 10 members each using 343 microsatellite markers mapped a single locus independently at D3S1618 (theta = 0) on 3q26.1-q26.3 with a two-point LOD score 3.62 (1.81 for each family) and multipoint LOD score of 3.61 (1.80 for each family). Haplotype inspection delimited an 18-cM interval between D3S1565 and D3S3686.
Adult↗
Role of endogenous ATP at the incision area in a rat model of postoperative pain.
The aim of the present study is to characterize the role of endogenous ATP leaked from damaged cells in a rat model of postoperative pain using behavioural and immunocytochemical approaches. We found that systemic (i.v.) and local (incision area) administration of a P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) before surgery significantly attenuated mechanical allodynia caused by an incision of the plantar surface of the hindpaw. Furthermore, PPADS significantly reduced the incision-evoked c-Fos protein expression, a marker of neuronal activity, in the dorsal horn of the spinal cord. The present findings suggest that excitatory signaling by endogenous ATP leaked from damaged cells via PPADS-sensitive P2 receptors is necessary for the induction of the postoperative pain characterized by mechanical allodynia.
Adenosine Triphosphate↗
Homozygosity mapping to chromosome 5p15 of a gene responsible for Hartnup disorder.
Hartnup disorder is an autosomal recessive phenotype involving a transporter for monoamino-monocarboxylic acids. Genetic analysis of the mouse model mapped its locus to human chromosome 11q13 (8). We report here the results of linkage analysis in two Japanese first cousin-marriage families. In the first family, the proband had Hartnup disorder and his deceased older brother was reported to have had typical Hartnup symptoms. The younger brother of the proband was shown to have decreased tryptophan absorption by oral loading test. In the second family, a 6-year-old girl, the proband, had specific hyperaminoaciduria. DNA was isolated from either blood samples or umbilical cord stumps. Genome-wide screening by homozygosity mapping was conducted. Taking into account that the older brother was affected and the younger brother was a carrier in the first family, homozygosity mapping (LOD score = 3.55) and GENEHUNTER (LOD score = 3.28) locates the locus of the Hartnup disorder on 5p15.
Child↗
Phosphatidylserine-specific phospholipase A1 stimulates histamine release from rat peritoneal mast cells through production of 2-acyl-1-lysophosphatidylserine.
Lysophosphatidylserine (1-acyl-2-lyso-PS) has been shown to stimulate histamine release from rat peritoneal mast cells (RPMC) triggered by FcepsilonRI (high affinity receptor for IgE) cross-linking, although the precise mechanism of lyso-PS production has been obscure. In the present study we show that phosphatidylserine-specific phospholipase A(1), PS-PLA(1), stimulates histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of FcepsilonRI cross-linker. The potency of 2-acyl-1-lyso-PS was almost equal to that of 1-acyl-2-lyso-PS. A catalytically inactive PS-PLA(1), in which an active serine residue (Ser(166)) was replaced with an alanine residue did not show such activity. sPLA(2)-IIA, another secretory PLA(2) that is capable of producing lyso-PS in vitro, was also a poor histamine inducer against RPMC. PS-PLA(1) significantly stimulated histamine release from crude RPMC, indicating that lyso-PS is mainly derived from cells other than mast cells. In agreement with this phenomenon, the enzyme stimulated the histamine release more efficiently when RPMC were mixed with apoptotic Jurkat cells. Under these conditions, lyso-PS with unsaturated fatty acid was released from the apoptotic cells treated with PS-PLA(1). Finally, heparin, which has affinity for PS-PLA(1), completely blocked the stimulatory effect of the enzyme. In conclusion, PS-PLA(1) may bind to heparan sulfate proteoglycan, efficiently hydrolyze PS appearing on plasma membranes of apoptotic cells, and stimulate mast cell activation mediated by 2-acyl-1-lyso-PS.
Animals↗
Skin surface electric potential induced by ion-flux through epidermal cell layers.
The skin surface electric potential has been widely used for psychological studies because it is sensitive to emotional conditions. We measured the electric potential on the surface of hairless mice skin in organ culture with several physiological factors. Disruption of mitochondrial function and inhibition of ATPase reduced the skin surface potential 50-70%. Calcium, potassium, and sodium channel blockers also reduced the potential. A calcium-specific and potassium ionophore reduced the potential, but the calcium and magnesium ionophore increased it. EDTA decreased the potential but EGTA had no effect. Skin surface barrier disruption reduced the potential and calcium and potassium channel blockers partially prevented the decrease. Substance P and corticotropin-releasing factor decreased the potential, and antagonists blocked the decreases. These results suggest that the ion flux in the nucleated layer of the epidermis induce the skin surface potential and it is influenced by environmental and neuroendocrinological factors.
4-Aminopyridine↗
Leukaemia inhibitory factor and interleukin 6 inhibit secretion of prolactin and growth hormone by rat pituitary MtT/SM cells.
The rat pituitary cell line, MtT/SM, has the characteristics of somatomammotrophs. The cells secrete both prolactin (PRL) and growth hormone (GH). We examined the effects of cytokines such as leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), oncostatin M and interleukin 11 on the secretion of these hormones by the cells. These cytokines stimulate proliferation of the cells and inhibit the secretion of PRL by 70-80% and that of GH by 50%. They induce tyrosine phosphorylation of STAT3 in the cells. The cells containing PRL or GH decreased at 48 h after treatment of the cells with LIF or IL-6. These results suggest that the LIF/IL-6 family of cytokines inhibits the functions of mammotrophs and somatotrophs in the pituitary gland.
Animals↗
Feedback control of the arachidonate cascade in rheumatoid synoviocytes by 15-deoxy-Delta(12,14)-prostaglandin J2.
Rheumatoid arthritis (RA) is a chronic polyarticular joint disease associated with massive synovial proliferation, inflammation, and angiogenesis. PPAR-gamma ligands, both 15-deoxy-Delta(12,14)-prostaglandin J2 (15d- PGJ2) and troglitazone (TRO), can inhibit the growth of RA synoviocytes in vitro, and suppress the chronic inflammation of adjuvant-induced arthritis in rats, but the potency of 15d-PGJ2 is higher than TRO. Prostaglandin (PG) E2 plays important roles in joint erosion and synovial inflammation. In the present study, 15d-PGJ2, but not TRO and other prostanoids, suppressed interleukin (IL)-1beta-induced PGE2 synthesis in rheumatoid synovial fibroblasts (RSFs) through the inhibition of cyclooxygenase (COX-2) and cytosolic phospholipase A2 (cPLA2) expression. Furthermore, the inhibition was not affected by pretreatment with anti-PPAR-gamma antibody. It means that this anti-inflammatory effect of 15d-PGJ2 for PG synthesis may be independent of PPAR-gamma and 15d-PGJ2 is a key regulator of negative feedback of the arachidonate cascade on the COX pathway. These findings provide new insight into the feedback mechanism of the arachidonate cascade.
Arachidonic Acid↗
Peribronchiolar accumulation of dendritic cells and their close association with CD4(+) T cells in the murine lung hypersensitivity.
In order to understand the interaction between dendritic cells (DCs) and helper T (Th) cells in the region exposed to antigens during pulmonary delayed-type hypersensitivity (DTH), which is considered to be mediated by Th1 cells, we immunohistochemically investigated their spatial relationship in the cellular infiltrate. At 24 hours after intratracheal instillation of hapten in sensitized mice, DCs were preferentially accumulated around the bronchioles, whereas macrophages were more abundant around the accompanying arteries. DCs often formed a cluster, in which they were interconnected with each other by projections. Serial section analysis revealed that clustered DCs made a close apposition to Th cells but much less frequently to cytotoxic T cells and B cells. Immunoelectron microscopy demonstrated that lymphocytes extravasated the capillaries in the peribronchiolar interstitium and made conjugation with DCs. In the interstitial tissue, DCs often adhered to the fibroblasts, suggesting the supportive role of the latter cells in DC migration. Eosinophils were also frequent around the arteries, representing the possible involvement of Th2 cytokines. By contrast, in a chronic type of airway inflammation induced by repeated challenges of aerosolized ovalbumin, DCs were densely and diffusely accumulated around the arteries in the same way as macrophages. The present study demonstrated a close association of DCs with Th cells around the bronchioles during pulmonary DTH, suggesting that local interaction between them in the lung may play important roles in the development of this disorder.
Animals↗
Platelet-activating factor acetylhydrolases: broad substrate specificity and lipoprotein binding does not modulate the catalytic properties of the plasma enzyme.
Platelet-activating factor acetylhydrolases (PAF-AHs) are a group of enzymes that hydrolyze the sn-2 acetyl ester of PAF (phospholipase A(2) activity) but not phospholipids with two long fatty acyl groups. Our previous studies showed that membrane-bound human plasma PAF-AH (pPAF-AH) accesses its substrate only from the aqueous phase, which raises the possibility that this enzyme can hydrolyze a variety of lipid esters that are partially soluble in the aqueous phase. Here we show that pPAF-AH has broad substrate specificity in that it hydrolyzes short-chain diacylglycerols, triacylglycerols, and acetylated alkanols, and displays phospholipase A(1) activity. On the basis of all of the substrate specificity results, it appears that the minimal structural requirement for a good pPAF-AH substrate is the portion of a glyceride derivative that includes an sn-2 ester and a reasonably hydrophobic chain in the position occupied by the sn-1 chain. In vivo, pPAF-AH is bound to high and low density lipoproteins, and we show that the apparent maximal velocity for this enzyme is not influenced by lipoprotein binding and that the enzyme hydrolyzes tributyroylglycerol as well as the recombinant pPAF-AH does. Broad substrate specificity is also observed for the structurally homologous PAF-AH which occurs intracellularly [PAF-AH(II)] as well as for the PAF-AH from the lower eukaryote Physarum polycephalum although pPAF-AH and PAF-AH(II) tolerate the removal of the sn-3 headgroup better than the PAF-AH from P. polycephalum does. In contrast, the intracellular PAF-AH found in mammalian brain [PAF-AH(Ib) alpha 1/alpha 1 and alpha 2/alpha 2 homodimers] is more selectively operative on compounds with a short acetyl chain although this enzyme also displays significant phospholipase A(1) activity.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Diagnostic value of bone-turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma.
BACKGROUND: Several biochemical markers of bone formation and bone resorption have been developed recently. The authors evaluated the usefulness of new biomarkers, such as urinary deoxypyridinoline (D-PYD), serum pyridinoline cross-linked C-telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), in the assessment of bone metastases in patients with lung carcinoma. METHODS: The serum concentrations of 1CTP and the urinary concentrations of D-PYD and NTx were measured in 100 lung carcinoma patients, of whom 20 patients had bone metastases and 80 patients did not. Receiver operating characteristic (ROC) curves were drawn for these markers to compare their usefulness in detecting bone metastases originating in lung carcinoma. RESULTS: Urinary concentrations of NTx in patients with bone metastases were significantly greater than in patients without bone metastases (147.1 +/- 129.3 pmol bone collagen equivalents [BCE]/micromol Cr vs. 47.2 +/- 29.9 pmol BCE/micromol Cr; P < 0.0001). Urinary concentrations of D-PYD in patients with bone metastases also were significantly greater than in patients without bone metastases (10.0 +/- 3.6 BCE/micromol Cr vs. 6.6 +/- 2.2 pmol BCE/micromol Cr; P = 0.0001). No significant difference was observed in serum concentrations of 1CTP between patients with and without bone metastases. A moderate but significant correlation was seen between NTx and D-PYD (correlation coefficient [R] = 0.435; P < 0.0001) and between D-PYD and 1CTP (R = 0.525; P < 0.0001). NTx had a better ROC curve than D-PYD and 1CTP (the areas under the ROC curve were 0.84, 0.79, and 0.62, respectively). Using the threshold of 62.5 pmol BCE/micromol Cr for NTx, sensitivity, specificity, and accuracy were 0.800, 0.737, and 0.750, respectively. CONCLUSIONS: In the current study, the measurement of NTx appeared to be most useful as a marker of bone metastases in patients with lung carcinoma.
Adult↗
Biochemical identification of Xenopus Pumilio as a sequence-specific cyclin B1 mRNA-binding protein that physically interacts with a Nanos homolog, Xcat-2, and a cytoplasmic polyadenylation element-binding protein.
Translational activation of dormant cyclin B1 mRNA stored in oocytes is a prerequisite for the initiation or promotion of oocyte maturation in many vertebrates. Using a monoclonal antibody against the domain highly homologous to that of Drosophila Pumilio, we have shown for the first time in any vertebrate that a homolog of Pumilio is expressed in Xenopus oocytes. This 137-kDa protein binds to the region including the sequence UGUA at nucleotides 1335-1338 in the 3'-untranslated region of cyclin B1 mRNA, which is close to but does not overlap the cytoplasmic polyadenylation elements (CPEs). Physical in vitro association of Xenopus Pumilio with a Xenopus homolog of Nanos (Xcat-2) was demonstrated by a protein pull-down assay. The results of immunoprecipitation experiments showed in vivo interaction between Xenopus Pumilio and CPE-binding protein (CPEB), a key regulator of translational repression and activation of mRNAs stored in oocytes. This evidence provides a new insight into the mechanism of translational regulation through the 3'-end of mRNA during oocyte maturation. These results also suggest the generality of the function of Pumilio as a translational regulator of dormant mRNAs in both invertebrates and vertebrates.
3' Untranslated Regions↗
Adhesion of adenosine diphosphate-activated platelets to human brain microvascular endothelial cells under flow in vitro is mediated via GPIIb/IIIa.
Employing video-enhanced contrast (VEC) microscopy, we examined whether TAK-029 (GPIIb/IIIa antagonist) inhibits the adhesion of activated platelets to human brain microvascular endothelial cells (HBEC) in vitro. HBECs were cultured on a coverglass and put in the observation chamber of VEC microscopy. Then, activated platelets by adenosine diphosphate (ADP) (2 microM) were perfused over HBEC at a low shear rate of 10 s(-1) for 30 min and washed out. Platelets adhered directly to HBEC. However, platelet adhesion to HBEC was suppressed when platelet rich plasma with ADP (2 microM) plus TAK-029 (GPIIb/IIIa antagonist; 1 microM) was perfused over HBEC for 30 min and washed out. Anti-GPIbalpha antibody (GUR20-5) did not inhibit adhesion of ADP-activated platelets to HBEC. The above results showed adhesion of ADP-activated platelets to HBEC under flow in vitro is mediated via GPIIb/IIIa
Adenosine Diphosphate↗
Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors.
The initial microglial responses that occur after brain injury and in various neurological diseases are characterized by microglial accumulation in the affected sites of brain that results from the migration and proliferation of these cells. The early-phase signal responsible for this accumulation is likely to be transduced by rapidly diffusible factors. In this study, the possibility of ATP released from injured neurons and nerve terminals affecting cell motility was determined in rat primary cultured microglia. Extracellular ATP and ADP induced membrane ruffling and markedly enhanced chemokinesis in Boyden chamber assay. Further analyses using the Dunn chemotaxis chamber assay, which allows direct observation of cell movement, revealed that both ATP and ADP induced chemotaxis of microglia. The elimination of extracellular calcium or treatment with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, suramin, or adenosine-3'-phosphate-5'-phosphosulfate did not inhibit ATP- or ADP-induced membrane ruffling, whereas AR-C69931MX or pertussis toxin treatments clearly did so. As an intracellular signaling molecule underlying these phenomena, the small G-protein Rac was activated by ATP and ADP stimulation, and its activation was also inhibited by pretreatment with pertussis toxin. These results strongly suggest that membrane ruffling and chemotaxis of microglia induced by ATP or ADP are mediated by G(i/o)-coupled P2Y receptors.
Adenosine Diphosphate↗