[IFAP syndrome(ichthyosis follicularis, alopecia, and photophobia syndrome)].
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Alopecia↗
Biomedical subjects
K C Kim
Publications and source records attributed to K C Kim.
Taming superacids: stabilization of the fullerene cations HC60+ and C60.+.
A new superacid, H(CB11H6X6) (where X = chlorine or bromine), whose conjugate base is the exceptionally inert CB11H6X6- carborane anion, separates Bronsted acidity from oxidizing capacity and anion nucleophilicity in a manner not previously achieved. Reaction of this superacid with C60 gives HC60+ as a stable ion in solution and in the solid state. In a separate experiment, an oxidant was developed such that the long-sought C60.+ ion can be synthesized in solution. The preparation of these two fullerene carbocations is a notable departure from the prevalent chemistry of C60, which is dominated by the formation of anions or the addition of nucleophiles. The H(CB11H6X6) superacid overcomes the major limitations of presently known superacids and has potentially wide application.
Acids↗
Squamous differentiation downregulates Muc1 mucin in hamster tracheal surface epithelial cell.
To investigate whether the squamous differentiation of primary hamster tracheal epithelial cell, which is induced by retinoic acid deficiency or chronic PMA treatment, regulates Muc1 expression, we first produced and characterized a monoclonal antibody against hamster tracheal Muc1 mucin using pGEX-Muc1 fusion protein as an antigen and the changes of Muc1 mucin expression was determined by Western blot. Squamous differentiation downregulated the expression of Muc1 mucin from HTSE cells. The decrease in the immunoreactivity of Muc1 mucin was parallel to the decrease in the immunoreactivity of high molecular weight mucin, which is secreted from HTSE cells. The data from the present study implicate a possible role of Muc1 mucin in squamous differentiation of HTSE cells.
Animals↗
Androgen receptor gene mutation identified by PCR-SSCP and sequencing in 4 patients with complete androgen insensitivity syndrome.
To study the genetic defect of the human androgen receptor (hAR) gene in the complete androgen insensitivity syndrome (CAIS), we amplified each of the eight exons by PCR in genomic DNA extracted from the paraffin blocks of the resected gonads. We analyzed using SSCP, and directly sequenced the abnormally shifted bands. Mutations were found in 4 cases of CAIS. Patient 1 carried a point mutation; a G to A transition in exon 7 resulted in a change from arginine to glutamine at codon 831. Patient 2 carried a point mutation; a C to T transition in exon 7 resulted in a change from arginine to stop at codon 831. Patient 3 carried a point mutation and deletion in exon 7. A point mutation was an A to G transition that caused a glutamine to be substituted for the asparagine present at codon 819. A deletion of a G at codon 820 resulted in a frameshift and consequently in the introduction of a premature stop at codon 821. Patient 4 carried a mutation in 5' splice donor site of intron 7; a G to T transition might have caused an abnormal splicing of the exon 7. All of the mutations were found in exon 7. These mutations of hAR gene might be related to the pathogenesis of CAIS.
Adolescent↗
Construction and characterization of a chimeric receptor containing the cytoplasmic domain of MUC1 mucin.
MUC1 mucin is a transmembrane glycoprotein that is highly expressed in various cancer cell lines and is also present in most of the glandular epithelial cells including the airway. Although the presence of numerous phosphorylation sites in its cytoplasmic domain suggests its potential role as a receptor, the unavailability of a ligand for MUC1 mucin has limited our understanding of its function. In this paper, we tried to circumvent this problem by constructing a chimeric receptor containing the cytoplasmic domain of MUC1 mucin, which can be phosphorylated on activation. To this end, we constructed a chimeric plasmid vector (pCD8/MUC1) by replacing the extracellular and transmembrane domains of human MUC1 mucin with those of human CD8. Transient transfection of the vector into COS-7 cells resulted in expression of the chimeric receptor on the surface of the COS-7 cells as judged by immunologic assays with various antibodies as well as by fluorescence-activated cell-sorting analysis. Treatment of the transfected COS-7 cells with an anti-CD8 antibody resulted in a significant increase in phosphorylation of tyrosine moieties of the chimeric receptor. This chimeric receptor will serve as a powerful tool in elucidating the signaling mechanism as well as the functional role of MUC1 mucin in the airway.
Amino Acid Sequence↗
Organo-axial volvulus of the stomach with diaphragmatic eventration.
Gastric volvulus occurs when the stomach rotates about its longitudinal axis (organo-axial volvulus), or about an axis joining the lesser and greater curvatures (mesentero-axial volvulus). Primary gastric volvulus, making up one third of cases, occurs when the stabilizing ligaments are too lax as a result of congenital or acquired causes. Secondary gastric volvulus, making up the remainder of cases, occurs in association with a paraesophageal hernia or other congenital or acquired diaphragmatic defects. While gastric volvulus may occur acutely, especially in children, it may not be clinically apparent and discovered incidentally. The authors present a case of chronic organo-axial volvulus of the stomach secondary to left hemidiaphragmatic eventration with a review of the relevant literature.
Adult↗
FGFR3 gene mutation (Gly380Arg) with achondroplasia and i(21q) Down syndrome: phenotype-genotype correlation.
We report the case of a boy with achondroplasia and i(21q) Down syndrome. Besides craniofacial features typical in Down syndrome, the skeletal findings of achondroplasia dominate the clinical picture. The diagnosis of Down syndrome was based on clinical features and the cytogenetic finding of i(21q) trisomy 21. The diagnosis of achondroplasia was based on the presence of clinical and radiographic findings and confirmed by the presence of a common FGFR3 gene mutation (Gly380Arg) detected by restriction enzyme analysis and sequencing of the polymerase chain reaction products. This is the first report of achondroplasia associated with i(21q) Down syndrome.
Achondroplasia↗
Noradrenaline synchronizes evoked quantal release at frog neuromuscular junctions.
1. Noradrenaline (NA) increases synaptic efficacy at the frog neuromuscular junction. To test the hypothesis that one of the actions of NA is to shorten the period over which evoked quanta are released, we measured the latencies of focally recorded uniquantal endplate currents (EPCs). 2. NA shortened the release period for evoked quantal release. The interval between the time when responses with minimal delay appeared and the point at which 90 % of all latencies had occurred was shortened in the presence of 1 x 10-5 M NA by about 35 % at 20 C and by about 45 % at 8 C. Inhibitor and agonist experiments showed that NA acts on a beta-adrenoreceptor. 3. The better synchronization of release significantly increased the size of reconstructed multi- quantal EPCs. This suggests that NA facilitates synaptic transmission by making the release of quanta more synchronous. 4. The synchronizing action of NA might potentiate neuromuscular transmission during nerve regeneration, transmitter exhaustion and other extreme physiological states where the quantal content is reduced, such as survival in cold and hibernation.
Adrenergic alpha-Agonists↗
Two eosinophil granule proteins, eosinophil peroxidase and major basic protein, inhibit mucin release from hamster tracheal surface epithelial cells in primary culture.
OBJECTIVES AND DESIGN: Effects of eosinophil proteins on airway goblet cell mucin release were investigated using primary hamster tracheal surface epithelial (HTSE) cell cultures. MATERIALS AND METHODS: HTSE cells were metabolically labeled using 3H-glucosamine and chased in the presence of varying concentrations of eosinophil proteins. The amount of 3H-mucin in the spent media was measured by Sepharose CL-4B gel-filtration column chromatography. Possible cytotoxicity by the eosinophil proteins was assessed by measurements of both lactic dehydrogenase and mucin release during as well as after the treatment period. RESULTS: (1) Neither eosinophil cationic protein nor eosinophil-derived neurotoxin affected mucin release at concentrations up to 10(-6) M; (2) both major basic protein (MBP) and eosinophil peroxidase (EPO) inhibited mucin release in a dose-dependent fashion, and the inhibitory effect by these proteins appeared to be reversible; (3) neither MBP nor EPO caused any apparent cytotoxicity at concentrations up to 10(-6) M. CONCLUSION: Eosinophil proteins such as MBP and EPO inhibit mucin release from primary HTSE cells without causing any apparent cytotoxicity.
Animals↗
Clinical characteristics of Angelman syndrome patients with a non-IC-deleted imprinting mutation.
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Angelman Syndrome↗
Visual impairment and REP-1 gene mutations in Japanese choroideremia patients.
Choroideremia (CHM), an X-linked recessive hereditary disease, is an intractable chorioretinal dystrophy. The rate of disease progression of CHM reportedly shows considerable variability. A number of mutations involving the gene that codes for Rab escort protein-1 (REP-1) have been detected in CHM patients. We have analyzed REP-1 gene mutations of Japanese CHM patients. The present study was designed to investigate the clinical variability and the genotype to phenotype relationship in 15 Japanese CHM patients referred to the Department of Ophthalmology of Juntendo University Hospital. The clinical investigation of visual acuity, visual field, color vision and refraction revealed inter-individual variability. Mutation analyses of the REP-1 gene revealed 10 types of mutations in 13 patients from 11 families, including an insertion, small deletions, nonsense mutations and an A to CC mutation. In 13 CHM patients with detectable REP-1 gene mutations, no relationship of genotype to phenotype was detected. At present, we consider the REP-1 genotype to be an unreliable prognostic factor for counseling of CHM patients. In two patients from one family, no mutations were detected in coding regions of the REP-1 gene. These patients may have intron mutations of the REP-1 gene, not detectable by the techniques employed in this study, or other causative genes. Both were observed to have somewhat slower disease progression than the other 13 patients. More advanced analyses are necessary to answer questions regarding the genotype-phenotype relationship in CHM patients.
Adaptor Proteins, Signal Transducing↗
A monoclonal antibody against hamster tracheal mucin, which recognizes N-acetyl-galactosamine containing carbohydrate chains as an epitope.
Airway mucin that is present in airway secretion, plays an important role in host-defense by trapping airborne particles and removing them by mucociliary transport system. For the study of mucin, it is crucially important to have antibodies specific against mucin because other commonly used methods such as histologic stain for the detection of mucin usually suffer from varying levels of nonspecificity. In this study, we produced a monoclonal antibody (MAb) against hamster airway mucin, which is one of the most commonly used animal species for the study of mucin in vitro, and characterized its immunological properties along with the determination of the epitope it recognizes. The MAb, which was named MAb HTA, was IgM isotype and specific against mucin from both in vitro cell culture and in vivo airway secretion. In Western blot, MAb HTA specifically recognized high molecular weight airway mucin, which was also confirmed by the appearance of peak profile of immunological signal only on void volume fraction in Sepharose CL-4B gel filtration chromatography. It also immunoprecipitated high molecular weight hamster airway mucin with the aid of antimouse IgM agarose. In immunohistochemical stain of hamster trachea, it showed strong signal on airway epithelium and also on the mucin secreting goblet cell granules. The immunological signal was greatly increased by the treatment of endotoxin, which has been reported to cause airway secretory cell metaplasia. The MAb HTA recognized carbohydrate chains containing N-acetyl-galactosamine, one of the linking sugars of airway mucin, as an epitope. Treatment of mucin with N-acetyl-galactosaminidase caused great reduction of immunological signal. To the best of our knowledge, this is the first to report a MAb that recognizes N-acetylgalactosamine, a linking sugar of airway mucin. The specificity of MAb HTA against airway mucin and the clear demonstration of the epitope it recognizes should greatly aid the pharmacological and biochemical study of mucin in various physiological and pathological situations.
Acetylgalactosamine↗
Inhibition of mucin release from airway goblet cells by polycationic peptides.
In the present study, we investigated whether polycationic peptides affect mucin release from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled with [(3)H]glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of either poly-L-arginine (PLA) or poly-L-lysine (PLL) to assess the effects on [(3)H]mucin release. Possible cytotoxicity by the polycations was assessed by measuring lactate dehydrogenase release, (51)Cr release, and cell exfoliation. The results were as follows: 1) both PLA and PLL inhibited mucin release in a dose-dependent fashion; 2) there was no significant difference in either lactate dehydrogenase release, (51)Cr release, or the number of floating cells between control and treatment groups; 3) the effects of both PLA and PLL on mucin release were completely blocked by neutralizing the positive charges either by pretreatment with heparin or by N-acetylation of the polycations; and 4) both PLA and PLL completely masked the stimulatory effect of ATP on mucin release. We conclude that these polycationic peptides can inhibit mucin release from airway goblet cells without any apparent cytotoxicity, and the inhibitory effect seems to be attributable to their positive charges. These are the first nonsteroidal agents, to the best of our knowledge, that have been shown to inhibit mucin release from airway goblet cells.
Acetylation↗
Nucleotide-induced PMN adhesion to cultured epithelial cells: possible role of MUC1 mucin.
Accumulation of intraluminal polymorphonuclear leukocytes (PMN) is a hallmark of inflammatory diseases of the airways. Extracellular nucleotides stimulate PMN adhesion to human main pulmonary artery endothelial cells (HPAEC) by a purinoceptor-mediated mechanism. We investigated the effects of nucleotides on adhesion of freshly isolated human PMN to cultured human tracheobronchial epithelial cells (HBEC). We found that extracellular ATP and UTP were much less effective in stimulating PMN adhesion to HBEC compared with HPAEC, whereas the bacterial chemotactic peptide N-formyl-Met-Leu-Phe stimulated PMN adhesion to both cell types to an equal degree. We investigated several mechanisms that might account for decreased nucleotide-induced PMN adhesion to HBEC. The ectonucleotidase-resistant ATP analog adenosine 5'-O-(3-thiotriphosphate) was also ineffective in stimulating PMN adhesion to HBEC, indicating that degradation of ATP by ectonucleotidase(s) was not responsible for altered PMN adhesion. HBEC responded to ATP and UTP with increased intracellular calcium, indicating that these cells are capable of purinoceptor-mediated responses. We found that ATP and UTP also did not stimulate PMN adhesion to Chinese hamster ovary (CHO) cells, which had been stably transfected with the gene for hamster Muc1, a cell-associated mucin. However, ATP and UTP did stimulate adhesion of PMN to nontransfected CHO cells. These results suggested that MUC1 mucin modulates PMN adhesion to epithelium. We found that cultured HBEC expressed more mRNA and protein for MUC1 mucin than did HPAEC. We conclude that extracellular nucleotides are less effective in stimulating PMN adhesion to epithelial cells than to endothelial cells and that overexpression of hamster Muc1 mucin inhibits nucleotide-induced PMN adhesion to CHO cells.
Adenosine Triphosphate↗
Ganoderma lucidum extract protects DNA from strand breakage caused by hydroxyl radical and UV irradiation.
The fruit bodies of Ganoderma lucidum have been used for the prevention and treatment of various diseases in the Orient. Its antitumor and immune enhancing properties, along with no cytotoxicity, raise the possibility that it could be effective in preventing oxidative damage and resulting disease. Using agarose gel electrophoresis, we have evaluated the potential of Ganoderma lucidum extract as a radioprotector and antioxidant defense against oxygen radical-mediated damage. Although the evidence presented here is based on in vitro using isolated DNA, the results clearly demonstrate that the hot-water extract of Ganoderma lucidum shows good radioprotective ability, as well as protection against DNA damage induced by metal-catalyzed Fenton reactions and UV irradiation. We also found that the water-soluble polysaccharide isolated from the fruit body of Ganoderma lucidum was as effective as the hot-water extract in protecting against hydroxyl radical-induced DNA strand breaks, indicating that the polysaccharide compound is associated with the protective properties. Our data suggest that Ganoderma mushroom merits investigation as a potential preventive agent in humans.
Ascorbic Acid↗
Thiol-linked peroxidase activity of human ceruloplasmin.
Human ceruloplasmin exhibited different antioxidant effects according to the electron donors in a metal-catalyzed oxidation system. Purified ceruloplasmin did not play a significant role in the protection of DNA strand breaks in the ascorbate/Fe3+/O2 system. However, when ascorbates were replaced with a thiol-reducing equivalent such as dithiothreitol, DNA strand breaks were significantly prevented by the same amount of ceruloplasmin. Ceruloplasmin did not catalyze the decomposition of H2O2 in the absence of reduced glutathione. On the contrary, ceruloplasmin showed a potent peroxidase ability to destroy H2O2 in the presence of reduced glutathione. In conclusion, the removal of H2O2 by human ceruloplasmin is not simply stoichiometric but thiol-dependent.
Antioxidants↗
Syntheses of two enantiomeric pairs of myo-inositol(1,2,4,5,6) and -(1,2,3,4,5) pentakisphosphate.
Two enantiomeric pairs of myo-inositol(1,2,4,5,6)P5 and -(1,2,3,4,5)P5 have efficiently been synthesized by means of the lipase catalyzed acetylation of 1,2:5,6-di-O-isopropylidene-myo-inositol and the benzoyl migration procedure.
Inositol Phosphates↗
Comparison between ELISA and gel-filtration assay for the quantitation of airway mucins.
In this study, we developed immunoassay methods for the more convenient and effective detection of rat tracheal mucin and the results were compared with those of [3H]glucosamine based gel-filtration method. A monoclonal anti-rat tracheal mucin antibody, mAbRT03, which specifically recognizes rat tracheal mucins, was used throughout in this study. To induce mucin secretion, varying concentrations of ATP (0-2 mM) were applied to the primary rat tracheal surface epithelial (RTSE) cell culture which had been metabolically radiolabeled with [3H]glucosamine and the secretion of mucin was analyzed both by the immunoassay and the gel-filtration chromatography methods. For the immunoassay, the following two procedures were employed. 1) Simple ELISA; the culture spent media were directly coated onto the assay plate and the immunoreactivity with mAbRT03 was assessed from the standard curve generated with the purified rat mucin. 2) Inhibition ELISA; A known amount of the purified rat mucin was coated onto the assay plate and then ATP-stimulated culture spent media were added to inhibit the immunoreactivity with mAbRT03. The contents of mucin in the sample were calculated from the standard inhibition curve which was generated with the purified rat mucin. The assay results obtained from the immunoassays were identical with those from the gel-filtration methods. The present result indicates that ELISA can be substituted for the laborious, time-consuming gel-filtration assay in studying the regulation of airway mucin release from cultured airway epithelial cells.
Adenosine Triphosphate↗