Biomedical subjects

X Guo

Publications and source records attributed to X Guo.

At least 253 records · Page 14Linked to original sources

PubMed1998

Four distinct regions in the auxiliary domain of heterogeneous nuclear ribonucleoprotein C-related proteins.

A 306 amino acid sequence deduced from a rabbit bladder cDNA is 98% identical to the human heterogeneous nuclear ribonucleoprotein (hnRNP) C2. The sequence comparison of the hnRNP C-related proteins reveals four distinct regions in the C-terminal auxiliary domain. The region next to the N-terminal RNA-binding domain is variable in length. Following the variable region, a basic region and a leucine zipper are conserved in all hnRNP C-related proteins including mouse and human Raly. Several Lys-Ser-Gly repeats are present in the basic region of the hnRNP C proteins. The C-terminal region is more divergent between hnRNP C and Raly. Signature sequences and possible functions are proposed for the different regions of the hnRNP C proteins.

Amino Acid Sequence↗

PubMed1998

Synthesis and characterization of long chain alkyl acyl carnitine esters. Potentially biodegradable cationic lipids for use in gene delivery.

A series of alkyl acyl carnitine esters (alkyl 3-acyloxy-4-trimethylammonium butyrate chloride) were synthesized as potential biocompatible cationic lipids for use in gene transfer. The physicochemical properties of the lipids, liposomes prepared from them, and their complexes with DNA were characterized by differential scanning calorimetry (DSC), particle size, zeta potential, and surface monolayer measurements. The transition temperatures and behavior at an air-water interface for this series are similar to phosphatidylcholines with the same hydrocarbon chain length. The physical properties of the l derivatives were not significantly different from the dl derivatives. At 70 degrees C, the acyl chains were readily hydrolyzed at pH 7. The influence of the aliphatic chain length (n = 12-18) on transfection efficiency in vitro was determined using cationic liposomes prepared from these lipids or their mixtures with the helper lipids, dioleoylphosphatidylethanolamine (DOPE), dioleoylphosphatidylcholine, monooleoylglycerol, and cholesterol (Chol). The mixture of myristyl 3-myristoyloxy-4-trimethylammonium butyrate chloride (MMCE, 4d) with DOPE at a 1:1 molar ratio mediated the highest transfection efficiency in cell culture. The mixture of oleyl 3-oleoyloxy-4-trimethylammonium butyrate chloride (OOCE, 4f) with Chol at a 1:1 molar ratio gave the highest transfection efficiency after intravenous administration in mice. In vivo gene expression using 4f was comparable to values obtained with the best cationic lipids reported to date.

Animals↗

PubMed1998

Prostaglandin, tumor necrosis factor alpha and neutrophils: causative relationship in indomethacin-induced stomach injuries.

Tumor necrosis factor alpha (TNF-alpha) has been suggested to play a critical role in indomethacin-induced gastric mucosal damage, so we evaluated its mucosal level and its relationship with prostaglandin E2 and neutrophils in indomethacin-induced gastric mucosal injury in rats. Indomethacin caused a time- and dose-dependent increase in gastric mucosal erosion, which was accompanied by a reduction in prostaglandin E2 followed by an increase in TNF-alpha level and neutrophil infiltration in the gastric mucosa. Pretreatment with exogenous prostaglandin E2 totally abolished indomethacin-induced gastric mucosal injury and the TNF-alpha increase. Depletion of neutrophils by methotrexate or reduction of TNF-alpha concentration by pentoxifylline markedly reduced indomethacin-induced mucosal damage. Pentoxifylline but not methotrexate prevented the increase in mucosal TNF-alpha level induced by indomethacin. It is suggested that depletion of prostaglandin E2 followed by an increase of TNF-alpha production and neutrophil infiltration in the gastric mucosa are important sequential processes in indomethacin-induced ulceration. Prevention of one of these processes would inhibit ulcer formation.

Animals↗

PubMed1998

Telomerase from human leukemia cells: properties and its interaction with deoxynucleoside analogues.

Telomerase is a unique reverse transcriptase involved in the maintenance of genomic integrity. In an attempt to understand the properties of this enzyme and to study the effect of deoxynucleoside analogues, we have isolated and partially purified telomerase from the blast cells of a patient with acute myelogenous leukemia. During the course of purification of telomerase, three characteristic forms of this enzyme activity were separated. Two processive forms and one less processive form were noted. All forms of the enzyme activities could be abolished by RNase A and proteinase K treatments, implying that they are ribonucleoproteins. The major form of telomerase was characterized with respect to divalent ion requirements, effect of salt and nonionic detergents. The Km of deoxynucleoside triphosphates was determined with a modified telomerase repeat array protocol assay. Studies with deoxynucleoside analogues indicated that 3'-azido-3'deoxythymidine triphosphate is much more inhibitory than 2',3'-dideoxy 2',3'didehydrothymidine triphosphate, and the cytidine analogue ddCTP was not inhibitory. ddGTP was the most potent inhibitor among all dideoxynucleosides studied.

Chromatography, Ion Exchange↗

PubMed1998

Isolation of two functional retinoid X receptor subtypes from the Ixodid tick, Amblyomma americanum (L.).

Retinoid X receptors (RXR) play a central role in a variety of nuclear signaling pathways in both vertebrates and invertebrates. Vertebrate RXRs are encoded by a multigene family whereas the insect RXR homologue, ultraspiracle (USP), is encoded by a single gene. To determine if acarines possess an RXR homologue similar to insect USPs, we isolated cDNAs encoding two distinct RXR genes, AamRXR1 and AamRXR2, from the ixodid tick, Amblyomma americanum (L.). The DNA binding domains share 95 and 87% identity, respectively, with DNA binding domains from insect USP and vertebrate RXR proteins. However, the ligand binding domains of the AamRXRs are more similar to vertebrate RXRs than to insect USP ligand binding domains (approximately 71 vs approximately 52%). Northern blot and RT-PCR analysis reveal both unique and overlapping patterns of AamRXR1 and AamRXR2 expression. Transactivation analysis show that both AamRXRs encode proteins which can form functional ecdysteroid receptors but are unlikely to bind retinoic acids.

Alternative Splicing↗

PubMed1998

Histone H2A.F/Z subfamily: the smallest member and the signature sequence.

The nucleotide sequence of a 700 basepair cDNA obtained from rabbit bladder was determined. It encodes a 123 amino acid protein, which is the smallest member of histone H2A.F/Z subfamily. The known H2A.F/Z variants are highly conserved in their central core regions of about 100 amino acids but more divergent in their N- and C-terminal ends. In addition to the seven amino acid signature sequence previously known for the H2A proteins, all the cloned H2A.F/Z variants contain an identical peptide sequence, L-E-Y-L-T-A-E-V-L-E-L-A-G-N-A. This 15 amino acid motif is proposed here as the signature sequence to identify new members of the H2A.F/Z subfamily.

Amino Acid Sequence↗

PubMed1998

Osteogenic protein-1 and related bone morphogenetic proteins regulate dendritic growth and the expression of microtubule-associated protein-2 in rat sympathetic neurons.

Osteogenic protein-1 (OP-1) is expressed in the developing nervous system and it has been found to induce dendritic growth in sympathetic neurons. To further characterize this phenomenon, the effects of OP-1 were compared to those of other members of the bone morphogenetic protein (BMP) family of growth factors. Recombinant human OP-1, BMP-6, BMP-2 and the Drosophila 60A protein induced dendritic growth in rat sympathetic neurons in a concentration-dependent manner with EC50-values of 1.8, 1.0, 1.7 and 2.7 ng/ml, respectively. In contrast, BMP-3 and cartilage-derived morphogenetic protein-2 (CDMP-2) as well as other classes of growth factors were inactive at concentrations up to 50 ng/ml. The dendritic growth induced by OP-1, BMP-6, BMP-2 and 60A was accompanied by increased expression of microtubule-associated protein-2 (MAP2) without changes in the expression of the phosphorylated forms of the M and H neurofilament subunits. These results suggest that several members of the BMP family have the capacity to regulate the morphological development of sympathetic neurons and that they may act by induction of specific cytoskeletal proteins.

Animals↗

PubMed1998

Selective Pneumocystis carinii dihydrofolate reductase inhibitors: design, synthesis, and biological evaluation of new 2,4-diamino-5-substituted-furo[2,3-d]pyrimidines.

Nonclassical antifolates, 2,4-diamino-5-substituted-furo[2, 3-d]pyrimidines 3-12 with bridge region variations of C8-S9, C8-N9, and C8-O9 and 1-naphthyl, 2-naphthyl, 2-phenoxyphenyl, 4-phenoxyphenyl, and 2-biphenyl side chains were synthesized as phenyl ring appended analogues of previously reported 2, 4-diamino-5-(anilinomethyl)furo[2,3-d]pyrimidines. The phenyl ring appended analogues were designed to specifically interact with Phe69 of dihydrofolate reductase (DHFR) from Pneumocystis carinii (pc) to afford selective inhibitors of pcDHFR. Additional substituted phenyl side chains which include 2,5-dichloro, 3,4-dichloro, 3,4,5-trichloro, 3-methoxy, and 2,5-dimethoxy analogues 13-17 were also synthesized. The compounds were prepared by nucleophilic displacement of 2,4-diamino-5-(chloromethyl)furo[2,3-d]pyrimidine(2) with the appropriate thiol, amine, or naphthol. Compound 2 was obtained from 2,4-diamino-6-hydroxypyrimidine and 1, 3-dichloroacetone. The compounds were evaluated as inhibitors against DHFR from P. carinii, Toxoplasma gondii, and rat liver. Two analogues, 2,4-diamino-5-[(2'-naphthylthio)methyl]furo[2, 3-d]pyrimidine (5) and 2,4-diamino-5-[(2'-phenylanilino)methyl]furo[2,3-d]pyrimidine (11) showed significant selectivity and potency for pcDHFR compared to trimethoprim. The X-ray crystal structure of 5 with pcDHFR was also carried out, which corroborated the design rationale and indicated a hydrophobic interaction of the naphthalene ring of 5 and Phe69 of pcDHFR which is responsible, in part, for the more than 18-fold selectivity of 5 for pcDHFR as compared with rat liver DHFR.

Animals↗

PubMed1998

Agreement and reproducibility of automatic versus manual measurement of QT interval and QT dispersion.

To determine whether the automatic measurement of the QT interval is consistent with the manual measurement, this study evaluated the reproducibility and agreement of both methods in 70 normal subjects and 54 patients with hypertrophic cardiomyopathy. The mean, minimum, and maximum QT interval and QT dispersion were computed in a set of 6 consecutive electrocardiograms (3 in the supine and 3 in the standing position) obtained from each subject. The automatic method determined the T-wave end as the intersect of the least-squares-fit line around the tangent to the T-wave downslope with the isoelectric baseline. Manual measurements were obtained using a high-resolution digitizing board. QT dispersion was defined as the difference between the maximum and minimum QT interval and as standard deviations of the QT interval duration in all and precordial leads. In patients with hypertrophic cardiomyopathy, the absolute values of the QT interval and QT dispersion were significantly higher than those in normal subjects (p < 0.0001). In both groups, the intrasubject variability of the QT interval was significantly lower with automatic than with manual measurement (p < 0.05). The agreement between automatic and manual QT interval measurements was surprisingly poor, but it was better in patients with hypertrophic cardiomyopathy (r2 = 0.46 to 0.67) than in normal subjects (r2 = 0.10 to 0.25). In both groups, the reproducibility and agreement of both methods for QT dispersion were significantly poorer than for QT interval. Hence, the automatic QT interval measurements are more stable and reproducible than manual measurement, but the lack of agreement between manual and automatic measurement suggests that clinical experience gained with manual assessment cannot be applied blindly to data obtained from the automatic systems.

Adolescent↗

PubMed1998

Posterior tibial nerve somatosensory cortical evoked potentials in adolescent idiopathic scoliosis.

STUDY DESIGN: Somatosensory-evoked potentials were used to evaluate neurologic function in patients with adolescent idiopathic scoliosis. OBJECTIVES: To compare the somatosensory-evoked potentials between patients with adolescent idiopathic scoliosis and healthy control individuals, and to determine the incidence of abnormal somatosensory function in patients with adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Somatosensory-evoked potentials are sensitive in detecting structural lesions in the somatosensory pathway. Previous studies on somatosensory function in patients with idiopathic scoliosis have demonstrated statistical differences in somatosensory-evoked potential latency between scoliotic and normal groups. However, no documentation of the actual incidence of abnormal somatosensory-evoked potentials is available. SUBJECTS AND METHODS: Posterior tibial nerve somatosensory cortical evoked potentials were evaluated on 147 young patients with adolescent idiopathic scoliosis and 31 healthy control individuals. RESULTS: Seventeen patients with idiopathic scoliosis showed pathologic evoked potentials. Among them were seven with absent somatosensory-evoked potential waveform and 10 with delayed latency. The results were reproducible on repeated measurement. CONCLUSIONS: Adolescent idiopathic scoliosis could be subdivided according to the somatosensory-evoked potential findings into two subgroups, those with and those without a somatosensory pathologic process. Potential clinical significance in predicting curve progression in idiopathic scoliosis could be pursued further.

Adolescent↗

PubMed1998

Metabolism of all-trans-retinol in normal human cell strains and squamous cell carcinoma (SCC) lines from the oral cavity and skin: reduced esterification of retinol in SCC lines.

Retinoids, metabolites and synthetic derivatives of vitamin A (retinol), have been shown to inhibit carcinogenesis in various epithelial tissues in animal model systems and to have clinical efficacy as chemotherapeutic agents against certain types of cancer, including squamous cell carcinomas (SCCs). We examined the metabolism of [3H]retinol in normal human cell strains and SCC lines from the oral cavity and skin, and we report here that the cultured normal human epithelial cell strains esterified [3H]retinol to a much greater extent than the SCC lines. Furthermore, microsomal extracts of normal cell strains (e.g., OKF4) exhibited about 7-fold more palmityl-CoA-dependent, phenylmethylsulfonyl fluoride-resistant retinol esterification activity than extracts from SCC lines (e.g., SCC25). The fact that the esteriflcation of retinol was phenylmethylsulfonyl fluoride resistant suggests that the enzyme acyl-CoA:retinol acyltransferase is involved. Culture of both the normal and SCC lines in the presence of 1 microM all-trans-retinoic acid (RA) for 48 h enhanced the formation of [3H]retinyl esters from [3H]retinol. All of the cell lines examined can also metabolize [3H]retinol to [3H]RA, [3H]14-hydroxy-4,14-retroretinol, [3H]retinaldehyde, and [3H]3,4-didehydroretinol, but this metabolism occurs to varying extents in different cell lines. Culture of the cells in the presence of RA for 48 h did not affect the subsequent metabolism of [3H]retinol to [3H]RA and [3H]14-hydroxy-4,14-retroretinol, but it did reduce the metabolism of [3H]retinol to [3H]3,4-didehydroretinol. When cultured for 6-10 h in the presence of nanomolar concentrations of exogenous [3H]retinol, both the normal and SCC lines had much higher intracellular [3H]retinol concentrations, in the micromolar range. No correlation was seen between CRABP II or CRBP I mRNA levels and the levels of either intracellular [3H]retinol or [3H]retinol metabolism in these lines. The reduced ability to esterify retinol in these tumor cells may result in inappropriate cell growth and the loss of normal differentiation responses because of the lack of a sufficient amount of internal retinol stored as retinyl esters.

Carcinoma, Squamous Cell↗

PubMed1998

Distribution of free seleno-amino acids in plant tissue of Melilotus indica L. grown in selenium-laden soils.

Accumulation of specific groups of seleno-amino acids in plant tissue reflects not only the Se tolerance of a plant species, but also Se toxicity to animals. The distribution of seleno-amino acids in a Se-tolerant grassland legume species (Melilotus indica L.) grown in Se-laden soils was studied using high-resolution gas chromatography- and gas chromatography-mass spectrometry. Five seleno-amino acids including selenocystine, selenomethionine, selenocysteine, Se-methylselenocysteine, and gamma-glutamyl-Se-methylselenocysteine were identified and measured for their plant tissue concentrations. Se-methylselenocysteine, a nonprotein seleno-amino acid, was found in the plant tissue. Its concentration ranged from 15.3 mumol kg-1 for the plants growing in soil of low Se concentration to 109.8 mumol kg-1 for the plants grown in soil of high Se concentration. Accumulation of the nonprotein seleno-amino acid in this species resembles that in Se accumulator plants. gamma-Glutamyl-Se-methylselenocysteine was detected in the plant. However, its concentration was very low. It might not become a toxic element in the food chain. Results of plant tissue Se accumulation analysis indicated that there was a five-fold increase in tissue selenocysteine concentration when the total tissue Se increased from 5.07 to 22.02 mg kg-1, but there was no further increase in tissue selenocysteine concentration when the tissue total Se concentration increased from 22.0 to 117.4 mg kg-1. Selenomethinone constituted more than 50% of the total seleno-amino acid in the plant. More research is needed to reveal whether the mechanisms limiting the accumulation of selenocysteine and preferential accumulation of selenomethionine found in this study play any role in Se tolerance in this species.

Amino Acids↗

PubMed1998

Quantitative 1H MRI and MRS microscopy of individual V79 lung tumor spheroids.

In this Communication 1H MRI and MRS microscopy experiments of individual V79 lung tumor spheroids with diameters between 550 and 650 micrometer are reported. The results have been used to determine the T1, T2, and D values as well as the concentrations of water, total choline, creatine/phosphocreatine, and mobile lipids in the viable rims and in the necrotic centers.

Animals↗

PubMed1998

The relationship between constitutive nitric oxide synthase (cNOS) and pregnancy induced hypertension.

To study the relationship between constitutive nitric oxide synthase (cNOS) and pregnancy induced hypertension (PIH), cNOS expression and localization in placental villi of PIH patients (n = 15) and normal pregnancy patients (n = 15) were immunohistochemically studied. The positive immunostaining of cNOS was located in trophocytes and cytoplasm of vascular endothelial cells. The positive rate in PIH patients was much higher than that in cases of normal pregnancy. The positive rates were 34.40% in mild, 44.74% in middle and 50.14% in severe PIH patients respectively. There was a significant difference in positive rate among the mild, middle and severe PIH patients (P < 0.01). It is concluded that the increase of cNOS activity probably was the results of protective or compensatory mechanism of PIH course.

Adult↗

PubMed1998

Formation of plasmid DNA strand breaks induced by low-energy ion beam: indication of nuclear stopping effects.

Plasmid pGEM 3zf(+) was irradiated by nitrogen ion beam with energies between 20 and 100 keV and the fluence kept as 1x10(12)ions/cm2. The irradiated plasmid was assayed by neutral electrophoresis and quantified by densitometry. The yields of DNA with single-strand and double-strand breaks first increased then decreased with increasing ion energy. There was a maximal yield value in the range of 20-100 keV. The relationship between DNA double-strand breaks (DSB) cross-section and linear energy transfer (LET) also showed a peak-shaped distribution. To understand the physical process during DNA strand breaks, a Monte Carlo calculation code known as TRIM (Transport of Ions in Matter) was used to simulate energy losses due to nuclear stopping and to electronic stopping. It can be assumed that nuclear stopping plays a more important role in DNA strand breaks than electronic stopping in this energy range. The physical mechanisms of DNA strand breaks induced by a low-energy ion beam are also discussed.

DNA Damage↗

PubMed1998

Analysis of the cardiac rhythm preceding episodes of paroxysmal atrial fibrillation.

AIMS: This study seeks to elucidate whether there was a common mode of initiation of paroxysmal atrial fibrillation (PAF) episodes that might suggest new therapies. METHODS: A library of 177 digitized and analyzed 24-hour Holter recordings from PAF pharmacotherapy trials was studied. All noise-free PAF episodes > or =0.5 minutes were identified. PAF episodes and the preceding 2 minutes of sinus rhythm were printed as tachograms and visually inspected. Heart rate and ectopic beat behavior were used to characterize modes of PAF onset by comparing half-minute segments of the final 2 minutes of sinus rhythm. RESULTS: Thirty-four recordings (from 19 patients, aged 61.7 +/- 11.5 years) provided 231 PAF episodes suitable for analysis. No patients had a consistent mode of PAF onset. This was confirmed by systematic analysis of the five patients with the most episodes. Overall, a highly significant increase in ectopic beats, from 1.34 to 6.52 min(-1) (p < 0.001) was found, but heart rate did not significantly change (mean heart rate at onset = 64 beats/min). PAF was initiated by a solitary ectopic beat in more than half of the cases. No consistent evidence for short-long-short sequences, seen in ventricular arrhythmias, was found. CONCLUSION: The mode of onset of atrial fibrillation is inconsistent, both across a population with PAF and within individuals. This has implications for understanding the mechanisms of atrial fibrillation onset in human beings and for the treatment of the disorder.

Atrial Fibrillation↗

PubMed1998

Evidence supporting a role for ATP as non-adrenergic non-cholinergic inhibitory transmitter in the porcine ileum.

The aim of this study was to investigate the nature of the non-adrenergic non-cholinergic (NANC) inhibitory transmitter of the circular muscle of the porcine ileum. For this purpose, the effects of putative NANC mediators i.e. NO, vasoactive intestinal polypeptide (VIP) and ATP were measured in isolated organ bath experiments (in basal conditions and after incubation with neostigmine 3 x 10[-5] M) and using the microelectrode technique. The NO donor sodium nitroprusside (NaNP) up to 10(-4) M, VIP up to 10(-7) M and ATP up to 10(-4) M failed to cause significant relaxation in the basal state. However, all of them induced marked relaxations when the tissue had been preincubated with neostigmine (3 x 10[-5] M) which was added to increase basal mechanical activity. The resting membrane potential (RMP) was unaffected by NaNP(up to 10(-4) M and VIP up to 10(-7) M whereas ATP (up to 10[-4] M) induced a transient hyperpolarization. The inhibitory junction potentials (IJPs) induced by electrical field stimulation (EFS) were not affected by N omega-nitro-L-arginine (L-NNA) (10[-4] M) whereas suramin, a purinoceptor antagonist, decreased (10[-4] M) or abolished (10[-3] M) the IJPs. Relaxations induced by ATP in neostigmine preincubated tissue were resistant to 10(-6) M tetrodotoxin, an axonal blocker, and inhibited by suramin. Apamin (10[-6] M, a small conductance calcium activated potassium channel blocker, completely abolished the IJP (n=5) and significantly decreased the relaxation induced by ATP (n=5). The present data provide support to the hypothesis that ATP is the NANC inhibitory transmitter in the porcine ileum acting on P2 muscular receptors. Nevertheless, VIP and NaNP do also cause relaxation of preparations preincubated with neostigmine.

Adenosine Triphosphate↗

PubMed1998

Involvement of dopamine D1 and D2 receptors in Fos immunoreactivity induced by stepholidine in both intact and denervated striatum of lesioned rats.

Stepholidine (SPD), a natural product, has been demonstrated in previous studies as a D1 agonist and D2 antagonist. In this work SPD-induced Fos immunoreactivity was examined. In the normal rats, Fos was induced in the striatum by SPD (1-20 mg/kg, i.p.) dose-dependently. The distribution of Fos-positive cells induced by SPD showed a rostral-caudal decline, matching the distribution of D2 dopamine receptors. The Fos-positive cells were mainly found in striatal neurons retrogradely labeled with horseradish peroxidase (HRP) from GP but not from SN, and could be abolished by the pretreatment of a D2 agonist LY171555 (2 mg/kg, i.p.), suggesting that the Fos expression in normal rats was due to the D2 antagonistic action of SPD. In the unilateral 6-hydroxydopamine-lesioned rats, SPD (4 mg/kg, i.p.) induced Fos expression in intact and denervated side of the striatum with different characteristics. Similar to that of normal rats, the Fos expression in intact side possessed the rostral-caudal gradient and could be abolished by the pretreatment of LY171555. However, in the denervated side, the Fos positive cells were widely distributed, and mainly found in striatal neurons retrogradely labeled from SN but not from GP. Furthermore, this expression was prevented by the pretreatment of SCH23390 (0.2 mg/kg, i.p.) but not LY171555, suggesting that the Fos expression in denervated side was due to the D1 agonistic action of SPD. Therefore, we concluded that the Fos expression induced by SPD in intact and denervated striatum was mediated via D2 and D1 receptor respectively, supporting the previous standpoint that SPD possesses the dual action, i.e antagonist to D2 and agonist to D1 receptors. Furthermore, it is suggested that the contralateral turning behavior induced by SPD may result from the D1-mediated excitation of striatonigral neurons of the denervated side of the lesioned rats.

Animals↗