Endothelin-3 frameshift mutation in congenital central hypoventilation syndrome.
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Base Sequence↗
Biomedical subjects
J Xie
Publications and source records attributed to J Xie.
Ethanol suppresses endotoxin but not platelet activating factor-induced hypotension and nitric oxide.
Ethanol (ETOH) inhibits the immune response to endotoxemia. The early stage of endotoxin (LPS)-induced shock is associated with an acute phase cardiovascular depression (APCD). Release of platelet activating factor (PAF) and tumor necrosis factor alpha (TNF alpha) with upregulation of nitric oxide (NO) production may initiate the APCD. Since ETOH inhibits induction of NO synthase (iNOS) mNRA by LPS, we postulate that ETOH may mask the APCD associated with endotoxemia. To test this, Sprague-Dawley rats (280-320 g, n = 5-6/group) were given LPS [0.75 mg/kg, intravenously (i.v.)] or PAF (10 to 150 micrograms/kg, i.v.) 30 min after administration of sterile saline (PBS), BN-5073 a mixed PAF antagonist (0.50 microgram/kg, i.v.), or ETOH [2.2-5.5 g/kg, intraperitoneally (i.p.)]. Cardiovascular parameters and plasma concentrations of nitrate and nitrite (RNI), ETOH, TNF alpha, and neutrophil (PMN) generation of RNI were measured. LPS and PAF both produced APCD. LPS-induced APCD was associated with tachycardia, elevated plasma TNF alpha and RNI, and ex vivo generation of RNI by PMNs. ETOH and BN-50730 prevented LPS-induced APCD and increases in RNI and TNF alpha. ETOH, however, increased the mortality associated with APCD. PAF produced only hypotension, bradycardia and elevated plasma levels of TNF alpha. ETOH and LNMMA did not affect PAF-induced APCD. BN-50730 inhibited PAF-induced APCD and plasma TNF alpha. We conclude that 1) ETOH inhibits the APCD and induction of NO characteristic of endotoxemia and 2) ETOH-induced suppression of LPS-mediated APCD may be mediated in part by suppression of release of intracellular PAF. Ethanol may increase the morbidity and mortality of endotoxemia by masking the hypotension and humoral changes characteristic of early endotoxemia thereby delaying appropriate therapy and by diminution of the protective effects of endogenous NO.
Alcohol Drinking↗
Participation of the yeast activator Abf1 in meiosis-specific expression of the HOP1 gene.
The meiosis-specific gene HOP1, which encodes a component of the synaptonemal complex, is controlled through two regulatory elements, UASH and URS1H. Sites similar to URS1H have been identified in the promoter region of virtually every early meiosis-specific gene, as well as in many promoters of nonmeiotic genes, and it has been shown that the proteins that bind to this site function to regulate meiotic and nonmeiotic transcription. Sites similar to the UASH site have been found in a number of meiotic and nonmeiotic genes as well. Since it has been shown that UASH functions as an activator site in vegetative haploid cells, it seemed likely that the factors binding to this site regulate both meiotic and nonmeiotic transcription. We purified the factor binding to the UASH element of the HOP1 promoter. Sequence analysis identified the protein as Abf1 (autonomously replicating sequence-binding factor 1), a multifunctional protein involved in DNA replication, silencing, and transcriptional regulation. We show by mutational analysis of the UASH site, that positions outside of the proposed UASH consensus sequence (TNTGN[A/T]GT) are required for DNA binding in vitro and transcriptional activation in vivo. A new UASH consensus sequence derived from this mutational analysis closely matches a consensus Abf1 binding site. We also show that an Abf1 site from a nonmeiotic gene can replace the function of the UASH site in the HOP1 promoter. Taken together, these results show that Abf1 functions to regulate meiotic gene expression.
Base Sequence↗
Open trial of intravenous tissue plasminogen activator in acute carotid territory stroke. Correlations of outcome with clinical and radiological data.
BACKGROUND AND PURPOSE: Pilot studies using early thrombolytic therapy in stroke have suggested that recombinant tissue plasminogen activator (rTPA) might be effective. While large, double-blind, randomized studies are needed, open trials could generate hypotheses concerning (1) the clinical correlations of outcome, (2) the significance of CT scan data during the first week, and (3) the use of adjunctive therapies. METHODS: We performed an open trial of intravenous rTPA on patients referred to our emergency service with all types of ischemic stroke in the carotid territory. All patients between 20 and 81 years hospitalized during 1994 with completed stroke in the internal carotid artery territory and a baseline Scandinavian Stroke Scale score lower than 48, even with severe disturbances of consciousness, were included. The inclusion time was within 7 hours after stroke onset. A 0.8-mg/kg dose of rTPA was infused for 90 minutes. Intravenous heparin was given either immediately at efficient dosage or after 24 hours. Mannitol was used in patients with severe presentation. The Scandinavian Stroke Scale evaluation was done at baseline, 3 hours, and 1, 7, 30, and 90 days. The CT scan was performed before the treatment and at days 1 (24 +/- 6 hours) and 7. RESULTS: Forty-three consecutive patients met the criteria of the protocol. The mean age at inclusion was 65 +/- 10.4 years, and the mean interval to treatment was 232 +/- 79 minutes. At day 90, 25 patients (58.1%) exhibited a complete regression of symptoms, and 3 had moderate neurological sequelae. Thirteen patients had severe neurological sequelae, 11 with infarcts and 2 with secondary parenchymal hematomas. Two patients died (4.6%), 1 with hematoma. The overall hematoma rate was 6.9%. Excellent outcome at day 90 was significantly correlated with major neurological improvement at day 1. Intravenous immediate heparin versus delayed heparin after 24 hours improved the ischemic outcome but not the overall outcome. Reinfarction syndromes after major neurological improvement, likely to be rethrombosis syndromes, were observed in 3 patients (6.9%). For the day 1 CT scan, poor outcome was associated with the presence of structured and homogeneous hypodensities likely to represent classic infarcts, as confirmed by day 7 CT scan. Conversely, total recovery was significantly associated with the absence of any image or with unstructured hypodensities, a particular type of image characterized by its heterogeneous darkness and often polylobar shape. This type of image disappeared at day 7 in 17.6% of the cases and is likely to represent reperfusion images and/or incomplete ischemic damage. CONCLUSIONS: The results obtained in this open, small study suggest safety and effectiveness of rTPA thrombolysis at the dose of 0.8 mg/kg within 7 hours in acute strokes of the carotid territory, including highly serious baseline neurological presentations, until age 81 years and under special therapeutic conditions. Complete recovery is significantly associated with major neurological improvement during the first 24 hours and the presence of a particular type of image at day 1 CT scan characterized by an unstructured hypodensity, often polylobar and heterogeneous, which is likely to correspond to reperfusion images.
Adult↗
Bond strength of composite to sound and artificial carious dentin.
PURPOSE: To determine the in vitro bond strength of a composite (Herculite XRV) to sound dentin and artificial carious lesions in dentin. MATERIALS AND METHODS: Buccal and lingual surfaces from extracted human molar teeth were ground to expose sound dentin surfaces. The buccal surface was maintained as sound dentin, while an artificial carious lesion was created in the lingual surface using an acidified gelatin gel. A bonding agent (Optibond) was applied to both buccal and lingual surfaces with and without prior etching with 37.5% phosphoric acid. The composite was applied and debonded under tension after 24 hours in water at 37 degrees C. RESULTS: Both sound dentin (23.1 MPa) and etched sound dentin (22.2 MPa) had similar bond strengths, whereas artificial carious lesions in dentin that had been etched (11.8 MPa) and non-etched dentin lesions (8.8 MPa) had significantly lower bond strengths. Adhesive failures were greatest for dentin lesions (60-95%) and least for sound dentin(40-50%). Etching with phosphoric acid did not improve the bond strength of composite to sound dentin or artificial carious lesions in dentin.
Acid Etching, Dental↗
[Interaction of human serum albumin with berberine hydrochloride by fluorescence method].
Fluorescence method has been used to observe the fluorescence quenching of human serum albumin (HSA) by its interaction with berberine hydrochloride (BH). The interaction dissociation constants of HSA and BH have been determined from a double reciprocal Lineweaver-Burk plot (Kd = 1.73 x 10(5) mol/L).
Berberine↗
Effects of chelating agents on testicular toxicity in mice caused by acute exposure to nickel.
N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), dihydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetraacetic acid (CDTA), and meso-2,3-dimercaptosuccinic acid (DMSA) were studied for their protective effects against the testicular toxicity in mice induced by acute exposure to nickel (Ni). Mice were injected intraperitoneally with NiCl2 (5 mgNi/kg) and 30 min or 24 h later, they were injected intraperitoneally with chelating agents (400 mumol/kg). Ni injection increased lipid peroxidation and concentrations of Ca and Fe in the testes, liver, and kidney, and decreased the testicular weight and the fertility rate. At 30 min after Ni treatment, the chelating agents other than CDTA effectively depressed Ni concentration in the testes. At 24 h after Ni treatment, DMSA, BGD, and DDTC were effective in mobilizing Ni from the testes. DMSA, BGD, and CDTA significantly prevented the increase in the lipid peroxidation, the increase in the concentrations of Ca and Fe in the testes, liver, and kidney, and the decrease in the fertility rate caused by Ni injection. Treatment with DMSA or BGD was more effective than that with the others in decreasing the testicular Ni concentration, resulting in effective protection against Ni-induced testicular damage.
Animals↗
Intracellular loop between transmembrane segments IV and V of cystic fibrosis transmembrane conductance regulator is involved in regulation of chloride channel conductance state.
The cystic fibrosis transmembrane conductance regulator (CFTR) contains two membrane-spanning domains; each consists of six transmembrane segments joined by three extracellular and two intracellular loops of different length. To examine the role of intracellular loops in CFTR channel function, we studied a deletion mutant of CFTR (delta 19 CFTR) in which 19 amino acids were removed from the intracellular loop joining transmembrane segments IV and V. This mutant protein was expressed in a human embryonic kidney cell line (293 HEK). Fully mature glycosylated CFTR (approximately 170 kDa) was immunoprecipitated from cells transfected with wild-type CFTR cDNA, while cells transfected with the mutant gene expressed only a core-glycosylated form (approximately 140 kDa). The chloride efflux rate (measured by 6-methoxyl-N-(3-sulfopropyl) quinolinium SPQ fluorescence) from cells expressing wild-type CFTR increased 600% in response to forskolin. In contrast, delta 19 CFTR-expressing cells had no significant response to forskolin. Western blotting performed on subcellular membrane fractions showed that delta 19 CFTR was located in the same fractions as delta F508 CFTR, a processing mutant of CFTR. These results suggest that delta 19 CFTR is located in the intracellular membranes, without reaching the cell surface. Upon reconstitution into lipid bilayer membranes, delta 19 CFTR formed a functional Cl- channel with gating properties nearly identical to those of the wild-type CFTR channel. However, delta 19 CFTR channels exhibited frequent transitions to a 6-picosiemens subconductance state, whereas wild-type CFTR channels rarely exist in this subconductance state. These data suggest that the intracellular loop is involved in stabilizing the full conductance state of the CFTR Cl- channel.
Amino Acid Sequence↗
Computerized microimage analysis of age-related changes of the human sinoatrial node.
This paper reports the age-related changes in the histological features of the sinoatrial node (SAN). The hearts of 106 persons dying at different ages (2 days-83 years), without clinical or pathological evidence of cardiac disease, were taken and divided into seven age-groups. Serial sections with a thickness of 2 microns, parallel to the long axis of the SAN, were prepared. Sections with the maximal area of the SAN were stained with hematoxylin/eosin (H & E) and Betty's method. The largest area of SAN were calculated by a computerized microimage analysis system. The age-related changes of the human SAN were discussed.
Adolescent↗
Intercellular adhesion molecule-2 (CD102) binds to the leukocyte integrin CD11b/CD18 through the A domain.
The interactions between the leukocyte-specific beta 2-integrins cluster of differentiation (CD) Ag CD11/CD18 and their ligands, the intercellular adhesion molecules (ICAMs), play important roles in many adhesion-dependent leukocyte functions. ICAM-1 is known to be a ligand for both CD11a/CD18 and CD11b/CD18. ICAM-2, whose two extracellular Ig domains show the highest homology to the two NH2-terminal domains of ICAM-1, has been previously shown to be a ligand for CD11a/CD18. We recently found that a 22-amino acid CD11a/CD18-binding peptide, P1, derived from the first domain of ICAM-2, also binds to purified CD11b/CD18. In the present study, we demonstrate that the ICAM-2 protein interacts with CD11b/CD18, and the binding is through the CD11b A domain.
Animals↗
Two closely linked but separable promoters for human neuronal nitric oxide synthase gene transcription.
In this report we demonstrate that the human cerebellum contains neuronal nitric oxide synthase (nNOS) mRNAs with two distinct 5'-untranslated regions that are encoded through use of closely linked but separate promoters. nNOS cDNA clones were shown to contain different 5' terminal exons spliced to a common exon 2. Genomic cloning and sequence analysis demonstrate that the unique exons are positioned within 300 bp of each other but separated from exon 2 by an intron that is at least 20 kb in length. A CpG island engulfs the downstream 5'-terminal exon. In contrast, most of the upstream exon resides outside of this CpG island. Interestingly, the upstream exon includes a GT dinucleotide repeat. A fusion gene with a 414-bp nNOS genomic fragment that includes a portion of the upstream 5'-terminal exon and its immediate 5'-flanking DNA is expressed in transfected HeLa cells. Also expressed is a fusion gene that contains the luciferase reporter under transcriptional control by a 308-bp genomic fragment that includes the region separating both 5'-terminal exons. These results indicate that expression of these exons is subject to transcriptional control by separate promoters. However, the proximity of these promoters raise the possibility that complex interactions may be involved in regulating nNOS gene expression at these sites.
Amino Acid Oxidoreductases↗
High-performance liquid chromatography of amino acids, peptides and proteins. CXXXVIII. Adsorption of horse heart cytochrome c onto a tentacle-type cation exchanger.
Determination of the change in the Gibb's free energy from the adsorption isotherm associated with the interaction between a biomolecule and an ion-exchange resin is often achieved by assuming that a Langmuirean model prevails. However, the adsorption of horse heart cytochrome c onto the tentacle-type cation exchanger LiChrospher 1000 SO3- at pH 4.00 showed an isotherm of rectangular form. In this case the Langmuirean model is not applicable. In this paper, we propose an alternative way to deal with this situation, whereby the adsorption capacity of the adsorbent with a defined protein sample is studied as a function of displacing-ion concentration. The experimental conditions over defined ranges are then selected in order to relate this function to the change in the Gibb's free energy for the interaction between the protein and the ion exchanger. Additional comments about the general utility of the on-line adsorption vessel system employed to determine the adsorption isotherms are also made.
Adsorption↗
Human myeloid cell nuclear differentiation antigen binds specifically to nucleolin.
The human myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed specifically in cells of the myelomonocytic lineage and regulated by interferon alpha in a cell-specific fashion. MNDA is also a member of a family of interferon-regulated genes of unknown function. In an effort to elucidate the function of MNDA, three techniques (affinity purification, coimmunoprecipitation, and protein blot assay) were used to characterize its specific protein binding activities. Microsequence analysis showed that MNDA bound the 100 kDa nucleolin protein. The identification of nucleolin was confirmed by immunoreaction with specific antibodies. MNDA contains motifs which could account for specific binding to nucleolin. Nucleolin binds other macromolecules and exhibits features consistent with roles in signal transduction, production of ribosomes, nuclear matrix structure, and regulation of transcription. The present results indicate that the function of MNDA is most likely related to interactions with other proteins. Through these associations, MNDA could contribute cell/lineage- and differentiation-specific limits to the function of ubiquitous proteins such as nucleolin. Further analysis of MNDA protein binding could be critical to elucidating the function of MNDA and could contribute to understanding the function of the products of other members of this interferon-inducible family of genes.
Amino Acid Sequence↗
Nitric oxide production in experimental alcoholic liver disease in the rat: role in protection from injury.
BACKGROUND & AIMS: Regulation of blood flow and oxygen supply are important pathogenetic factors in alcoholic liver disease. Because nitric oxide may have an important role, its effects on alcoholic liver injury were investigated. METHODS: Rats were fed ethanol intragastrically with either saturated fat or corn oil. Spontaneous production of NO by liver nonparenchymal cells was compared in the two dietary groups. Two additional groups of rats fed corn oil and ethanol were treated with either an NO inhibitor (L-NAME) or supplemented with L-arginine. Liver pathology and plasma NO production were evaluated. RESULTS: In the corn oil and ethanol group, a progressive decrease in liver nonparenchymal cell NO production and increased plasma NO levels were associated with liver injury. Reduced nicotinamide adenine dinucleotide phosphate diaphorase staining showed increased centrilobular staining of hepatocytes in the corn oil and ethanol group and L-NAME-treated group. Moreover, L-NAME increased the severity, whereas L-arginine supplementation completely prevented liver injury. In the saturated fat and ethanol group, in which there was no liver injury, the levels of NO2- in nonparenchymal supernatant were 5-10-fold higher than in the corn oil and ethanol group. CONCLUSIONS: Decreased NO production by nonparenchymal cells may contribute to liver injury in ethanol-fed rats, and the compensatory increase in hepatocyte NO production may contribute to centrilobular liver injury.
Analysis of Variance↗
Nitro containing L-arginine analogs interfere with assays for nitrate and nitrite.
We evaluated the effect of in vivo and in vitro administration of nitro-containing and nitro-deficient L-arginine-derived nitric oxide (NO) synthase inhibitors on the measurement of NO in plasma, urine and HEPES buffered physiologic salt solution (PSS) by ozone chemiluminescence and by the modified Griess reaction. In vivo administration of 1, 5, 25, 40 or 50 mg/kg of NG-nitro-L-or D-arginine methyl ester (LNAME, DNAME), NG-nitro-L-arginine (LNA) or aminoguanidine (AG) to rats and mice increased NO in urine and plasma as determined by chemiluminescence using 2.3% vanadium chloride in 2N HCI at 100 degrees C as the redox reagent. In vivo administration of 1 and 10 mg/kg/day of NG-imino-ethyl-L-ornithine (LNIO) or 3 amino-1,2,4 triazine (AT) reduced plasma and urine NO. Addition of LNAME, DNAME and LNA (100 nM to 1 mM) to the redox solution produced a concentration response curve for NO in the chemiluminescence assay similar to that produced by standard solutions of sodium nitrite and nitrate. LNMMA produced a small NO signal but only at concentrations equal to or exceeding 0.1 mM. LNIO, AT and AG did not give any NO signal even at concentrations exceeding 1 mM. Conversion of plasma or urine nitrate to nitrite with cadmium gave elevated values of plasma nitrite by the Greiss assay when LNAME or LNA was the NO synthase inhibitor. We conclude that in vivo and in vitro use of LNAME and LNA and in vivo use of high doses of aminoguanidine interfere with the assay of NO2- and NO3- with the modified Griess reaction and with chemiluminescence. We suggest that LNAME and LNA not be used in vivo or in vitro when total RNI is measured with these assays.
Animals↗
Synthesis, characterization and antibacterial activity of novel Fe(III), Co(II), and Zn(II) complexes with norfloxacin.
Three novel complexes of norfloxacin (abbreviated as NFL), [M(NFL)2(H2O)2]Cl3.6H2O, (M = Fe, Co), and [Zn(NFL)2]Cl2.7H2O, have been prepared. The compounds were characterized by IR, UV-Vis, NMR spectra, molar conductivity, and elemental analyses. In all of the complexes, the ligand NFL was coordinated through two carboxyl oxygen atoms. Octahedral and tetrahegon geometries have been proposed for Fe(III)-, Co(II)-complexes and Zn(II)-complex, respectively. In vitro test of susceptibility of Fe(III)- and Zn(II)-complexes showed stronger activity than that of norfloxacin against G(-) E.Coli and Bacillus dysenteriae bacteria.
Anti-Infective Agents↗
Transcription of the human neuronal nitric oxide synthase gene in the central nervous system is mediated by multiple promoters.
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Base Sequence↗
A peptide derived from the intercellular adhesion molecule-2 regulates the avidity of the leukocyte integrins CD11b/CD18 and CD11c/CD18.
beta 2 integrin (CD11a,b,c/CD18)-mediated cell adhesion is required for many leukocyte functions. Under normal circumstances, the integrins are nonadhesive, and become adhesive for their cell surface ligands, the intercellular adhesion molecules (ICAMs), or soluble ligands such as fibrinogen and iC3b, when leukocytes are activated. Recently, we defined a peptide derived from ICAM-2, which specifically binds to purified CD11a/CD18. Furthermore, this peptide strongly induces T cell aggregation mainly mediated by CD11a/CD18-ICAM-1 interaction, and natural killer cell cytotoxicity. In the present study, we show that the same ICAM-2 peptide also avidly binds to purified CD11b/CD18, but not to CD11c/CD18. This binding can be blocked by the CD11b antibody OKM10. The peptide strongly stimulates CD11b/CD18-ICAM-1-mediated cell aggregations of the monocytic cell lines THP-1 and U937. The aggregations are energy and divalent cation-dependent. The ICAM-2 peptide also induces CD11b/CD18 and CD11c/CD18-mediated binding of THP-1 cells to fibrinogen and iC3b coated on plastic. These findings indicate that in addition to induction of CD11a/CD18-mediated cell adhesion, the ICAM-2 peptide may also serve as a "trigger" for high avidity ligand binding of other beta 2 integrins.
Actin Cytoskeleton↗