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X Qu

Publications and source records attributed to X Qu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Inhibition of C-raf expression by antisense oligonucleotides extends heart allograft survival in rats.

BACKGROUND: C-raf is a well-characterized serine/ threonine (Ser/Thr) protein kinase that is involved in the transduction of multiple signals of T cells. We demonstrate that the inhibition of C-raf mRNA expression prolongs heart allograft survival. METHODS: Three 20-mer C-raf antisense oligonucleotides, each with identical sequences, were synthesized with different chemical modifications: one as a uniform phosphorothioate oligodeoxynucleotide (PS oligo), a second with a PS backbone and 2'-methoxyethyl (ME) substitutions at the 2'-sugar positions in the first and last five nucleotides, and a third with a mixed PS and phosphodiester (PD) backbone and ME modifications on the first and last five nucleotides. RESULTS: Both ME-modified C-raf antisense oligos were at least 5-fold more effective than the PS C-raf antisense oligo in blocking C-raf mRNA expression in two cell lines. Similarly, each of the ME C-raf antisense oligos produced better heart allograft survival rates than did PS C-raf oligo. Furthermore, although the combination of PS C-raf antisense oligo with sirolimus (SRL) acted synergistically to extend heart allograft survival, the effect was potentiated by either of the ME-modified oligos. CONCLUSIONS: C-raf inhibition extends heart allograft survival, and ME-modification potentiates antisense activity.

Animals↗
PubMed2000

Brownian Dynamics Simulation of Film Formation of Mixed Polymer Latex in the Water Evaporation Stage.

Brownian dynamics simulations of the filming process of a mixed polymer latex in the water evaporation stage were performed in order to explore the effect of surface potential on latex particle packing and distribution at a temperature far below the glass transitions of polymers in bulk. Polymer latex particles are modeled as spheres that interact via DLVO potential with various surface charge densities for emulsifier-free emulsion polymerized particles and dispersion polymerized particles. It is found that the distribution of modeled poly(methyl methacrylate) and polystyrene latex particles in the finally formed film exhibits a noticeable dependence of surface potentials of latex particles. When the difference of the surface potentials between binary mixed latex particles is small, the particles distribute randomly. In contrast, when the difference of the surface potentials between binary mixed latex particles is large, heterocoagulation occurs and the polymer latex in which the repulsive electrostatic potential is weak will form clusters in the film. The results are in agreement with laser confocal fluorescence microscopy observations of fluorescent dye labeled poly(methyl methacrylate) and polystyrene mixed latex films. The correlation between latex particles increases with increasing repulsive electrostatic potential, and the spatial order can be obtained at the end of the water evaporation stage. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Purification of the newly found selenium-containing proteins in the arterial wall and brain of the rat.

Previously several selenium-containing proteins with different subunit molecular masses (M(r)) were detected in the arterial wall and brain of rats. In continuation of this work, after labeling of rats in vivo with [(75)Se]selenite, the new selenium-containing proteins of interest were purified on a Sephadex G-200 column followed by preparative isoelectric focusing. Nuclear analytical methods (gamma-counter and gamma-detector) were applied in the detection and identification of the (75)Se-labeled proteins. The two (75)Se-containing proteins from the arterial wall migrated as 15.0- and 67.0-kDa species on SDS-PAGE gels with pI values of 4.5 and 5.1, respectively. The three (75)Se-containing proteins from brain purified to homogeneity had M(r) values of 18.0, 30.0, and 42.9 kDa and pI values of 6.3, 6.5, and 6.0, respectively. Of these proteins, the 67.0-, 42.9-, and 30.0-kDa species may be yet not characterized selenoproteins with important biological functions.

Animals↗
PubMed2000

Selenium deficiency-induced alterations in the vascular system of the rat.

To enunciate the mechanisms whereby Se protects against cardiovascular diseases, weanling male Wistar rats were fed deficient (0.022 mg/kg diet) and adequate (0.159 mg/kg diet) Se diets for 14 and/or 39 wk. As the Se content and glutathione peroxidase activity were decreased and the lipid peroxide level was increased, the plasma 6-keto-PGF1alpha concentration of the Se-deficient group was markedly decreased in blood and tissues of the Se-deficient rats, as compared with the Se-adequate animals. Furthermore, the Se-deficient group had significantly lower plasma nitric oxide content and vascular nitric oxide synthase activity, higher erythrocyte sedimentation equation K value and aggregation index, and lower erythrocyte deformability than the Se-adequate group. Experimental Se deficiency also resulted in significant increases in serum total cholesterol and low-density lipoprotein cholesterol levels and a significant decrease in serum high-density lipoprotein cholesterol level. These results give some experimental supports to the hypothesis that low Se status and lipid peroxidation are involved in the etiology of cardiovascular diseases.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Hydroxyterephthalate as a fluorescent probe for hydroxyl radicals: application to hair melanin.

The known photoreactions of melanin include production of melanin free radicals and oxygen consumption. While qualitative descriptions of the intermediates and products of these processes have been published, no quantitative procedures have been reported that allow the convenient measurement of the products of oxygen reduction. We have used complementary fluorescence and electron spin resonance techniques to study free radical production from extracted hair melanin irradiated at wavelengths above 320 nm. As a comparison, sepia was also studied. Irradiation of aerated suspensions of melanin in the presence of terephthalic acid dianion (TA)++ gives rise to the characteristic fluorescence spectrum of the 2-hydroxyterephthalate ion (HTA, lambda e lambda = 315 nm, lambda em = 425 nm). Production of HTA has been studied as a function of time (at constant light flux) and in the presence of other substrates including hydroxyl radical sources and scavengers. The use of TA as a fluorescent probe can be conveniently adapted to other systems.

Electron Spin Resonance Spectroscopy↗
PubMed2000

Possible interactions between angiotensin II and insulin: effects on glucose and lipid metabolism in vivo and in vitro.

Angiotensin II (ANGII) increases insulin sensitivity in diabetic and non-diabetic subjects, even at subpressor doses, and because there is 'crosstalk' between ANGII and insulin-signaling pathways the underlying mechanism may not be due solely to changes in regional blood flow. A series of experimental studies was undertaken to evaluate the effects of ANGII on glucose and lipid metabolism in vivo and in vitro. Groups of fructose-fed, insulin-resistant Sprague-Dawley (SD) rats were pre-treated with 0.3 mg/kg per day of the AT(1)-receptor antagonist L-158 809 (n=16), or vehicle (n=16), by oral gavage. This was prior to an oral glucose tolerance test (day 5) and measurement of the effects of ANGII infusion (20 ng/kg per min i.v. for 3 h) on whole-body insulin sensitivity using the insulin suppression test (day 7). The effect of ANGII infusion on total triglyceride secretion rate (TGSR) was evaluated in normal SD rats pretreated for 7 days with L-158 809 (n=12) or vehicle (n=12). AT(1)- and AT(2)- receptor mRNA expression and [(3)H]2-deoxyglucose uptake were assessed in cultured L6 myoblasts. Short-term treatment with L-158 809 had no effect on glucose tolerance or fasting triglyceride levels in fructose-fed rats. ANGII infusion had no effect on insulin sensitivity in fructose-fed rats pretreated with vehicle (steady-state plasma glucose (SSPG) values 8.1+/-1.6 vs 8. 4+/-0.4 mmol/l), but pretreatment with L-158 809 resulted in ANGII having a modest insulin antagonist effect in this insulin-resistant model (SSPG values 9.6+/-0.3 vs 7.1+/-0.6, P<0.03). ANGII infusion had no significant effect on TGSR (e.g. 24.6+/-1.4 vs 28.4+/-0.9 mg/100 g per h in vehicle-treated animals). RT-PCR analysis showed that L6 cells express both AT(1)- and AT(2)-receptor mRNA. Incubation with ANGII (10(-9) and 10(-8) M) had no significant effect on the dose-response curve for insulin-stimulated [(3)H]2-deoxyglucose uptake. For example, C(I200) values (dose of insulin required to increase glucose uptake by 200%) were 4.5 x 10(-9) M (control) vs 3.9 x 10(-9) M and 6.2 x 10(-9) M, whereas the positive control (glucagon-like peptide-1) increased insulin sensitivity. Thus, ANGII infusion may have a modest insulin antagonist effect on glucose disposal in insulin-resistant fructose-fed rats pretreated with an AT(1)-blocker, but ANGII has no effect on TGSR or in vitro glucose uptake in L6 myoblasts. These findings are relevant to recent clinical discussions about the metabolic effects of ANGII and renin-angiotensin system blockade.

Analysis of Variance↗
PubMed2000

[Preliminary study on purification function of reed wetland for nutrients from land sources].

The preliminary study on purification function of reed wetland for nutrients from land sources were conducted by irrigation channels and lysimeters. The results show that the purification rates for N, P and CODcr are from 41.7%-64.71% in the channels and 60.0%-75.92% in the lysimeters. The contents of N and P reached the national second level standards of sea water after filtration by lysimeters. By harvest, the good recycle between wetland and land is formed without accumulation.

Ecology↗
PubMed2000

[Exploration of weight-reducing effect of Kintop in obese rats and its mechanism].

OBJECTIVE: To investigate the weight-reducing effect of Kintop and its probable mechanism in obese rats. METHODS: Body weight, Lee's index, total weight of celiac fat tissue, adipocyte size, blood glucose, blood lipid, expression of leptin in adipocyte (by ABC method), level of serum leptin (by RIA) of obese rats were chosen as the indexes to compare the weight-reducing effect of different dosages of Kintop. The administration of Kintop lasted 1 month. RESULTS: Good effect could be obtained by administration of medium dose Kintop (40 mg/100 g body weight per day) in simple obese rats. At the same time of reducing body weight, blood cholesterol and sugar levels also decreased in a certain degree. The adipocyte leptin expression reduced and serum leptin elevated in those rats with body weight reduced effectively by Kintop. CONCLUSION: Medium dose of Kintop administration for 1 month shows evident weight-reducing effect in simple obese rats, the effect might be related to raising the serum leptin level. Kintop also has the effect in lowering blood cholesterol level, and it could lower the blood sugar in obesity complicated with hyperglycemia by increasing the dosage appropriately.

Animals↗
PubMed2000

[Treatment of ureteric lithioasis with ureteroscope: report of 234 patients].

SUBJECT: To sum up the experience in the treatment of ureteric lithioasis with ureteroscope. METHODS: From January. 1991 to November 1998 234 patients with ureteric lithiasis were treated with lithotripsy of ureteroscopy. RESULTS: 185 of 234 the patients (79%) were successfully treated with lithotripsy of ureteroscopy. Three of the patients (1.3%) had operative complications (ureterperforation 2 patients and ureteral mucosa avulsion in 1). CONCLUSIONS: Lithotripsy of ureteroscope is one of the effective methods in the treatment of ureteric lithiasis, especially in the lower part of ureters.

Adult↗
PubMed2000

[Microsurgical treatment of cranial base meningioma].

OBJECTIVE: To improve the total removal rate of cranial base meningiomas, and to reduce the mortality and morbidity. METHODS: 103 patients with cranial base meningiomas were treated by microsurgery. Tumors of different position were resected by variant transcranial base approaches and the operative methods. RESULTS: and complications were analyzed retrospectively. RESULTS: Total removal of Simpson's 1 to 2 grade was performed in 63 patients, subtotal removal in 31 and partial removal in 9. Good postoperative recovery was noted in 75 patients, skull nerve paralysis in 24 and death 4. CONCLUSION: Using skull base microsurgery to resect cranial base meningiomas could shorten the distance of surgical approach and lessen the damage to brain.

Adolescent↗
PubMed2000

[Middle-aged and elderly patients with hydronephrosis induced by ureteric obstruction: etiology and diagnosis].

OBJECTIVE: To improve the etiologic diagnosis of middle-aged and elderly patients with ureteric obstruction. METHODS: The etiology and diagnosis were retrospectively studied in 141 middle-aged and elderly patients with hydronephrosis in recent 10 years. RESULT: 59 patients had ureterolithiasis, 51 ureteric cancer, 11 ureteric tuberculosis, 9 UPJ stricture, 6 uretero-cyst and 5 ureteric polyp. CONCLUSIONS: Ureterolithiasis and ureteric cancer contribute greatly to ureteric obstruction in middle-aged and elderly patients. Etiologically, B ultrasonography is suggested to be used as the first choice in diagnosis and follow-up of the middle-aged and elderly patients with hydronephrosis, especially those accompanied with hematuria.

Aged↗
PubMed1999

Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene.

The recessive autosomal disorder known as ICF syndrome (for immunodeficiency, centromere instability and facial anomalies; Mendelian Inheritance in Man number 242860) is characterized by variable reductions in serum immunoglobulin levels which cause most ICF patients to succumb to infectious diseases before adulthood. Mild facial anomalies include hypertelorism, low-set ears, epicanthal folds and macroglossia. The cytogenetic abnormalities in lymphocytes are exuberant: juxtacentromeric heterochromatin is greatly elongated and thread-like in metaphase chromosomes, which is associated with the formation of complex multiradiate chromosomes. The same juxtacentromeric regions are subject to persistent interphase self-associations and are extruded into nuclear blebs or micronuclei. Abnormalities are largely confined to tracts of classical satellites 2 and 3 at juxtacentromeric regions of chromosomes 1, 9 and 16. Classical satellite DNA is normally heavily methylated at cytosine residues, but in ICF syndrome it is almost completely unmethylated in all tissues. ICF syndrome is the only genetic disorder known to involve constitutive abnormalities of genomic methylation patterns. Here we show that five unrelated ICF patients have mutations in both alleles of the gene that encodes DNA methyltransferase 3B (refs 5, 6). Cytosine methylation is essential for the organization and stabilization of a specific type of heterochromatin, and this methylation appears to be carried out by an enzyme specialized for the purpose.

Alleles↗
PubMed1999

Substitution at the F-ring N-imide of the indolocarbazole antitumor drug NB-506 increases the cytotoxicity, DNA binding, and topoisomerase I inhibition activities.

The antitumor drug NB-506, which is currently undergoing phase I/II clinical trials, contains a DNA-intercalating indolocarbazole chromophore substituted with a glucose residue. In addition to interacting with DNA, the drug stabilizes the topoisomerase I-DNA covalent complex. To reinforce the DNA binding and anti-topoisomerase I activities of NB-506, an analogue containing a new substituent on the naphthalimide ring F was synthesized. The N-formylamino group of NB-506 has been replaced with a more hydrophilic group, N-bis(hydroxymethyl)methylamino. In this study we show that the incorporation of a longer substituent on the N6 position effectively reinforces both the interaction with DNA and the capacity of the drug to maintain the integrity of the topoisomerase I-DNA covalent complexes. The strength and the mode of binding of the drugs to DNA were studied by complementary biophysical techniques including absorption, fluorescence, and circular and linear dichroism. Various biochemical procedures were applied to investigate the effects on human topoisomerase I using plasmid DNA as well as restriction fragments. The drug binding sites and the positions of the topoisomerase I-mediated cleavage sites were mapped with nucleotide resolution using footprinting and sequencing techniques. Cytotoxicity measurements performed with various human cancer cell lines (HCT-116, DLD-1, MKN-45) indicate that the newly designed drug is 3 to 4 times more toxic to colon and gastric cancer cells than NB-506. Therefore, the results suggest that the antitumor activity of indolocarbazole-based drugs can be enhanced by incorporating DNA and/or topoisomerase I reactive groups. They also support the hypothesis that the substituent on the imide nitrogen on the F ring of NB-506 has direct interaction with the molecular target. The study helps to define the structure-activity relationships in the indolocarbazole series of antitumor agents targeting topoisomerase I.

Animals↗
PubMed1999

Spectral and physical characterization of the inverted terminal repeat DNA structure from adenoassociated virus 2.

An oligodeoxynucleotide (ODN) that includes elements found in secondary structures at the 5'- and 3'- ends of adenoassociated virus 2 virion DNA was synthesized by ligation of three overlapping ODNs. The most stable secondary structure was calculated to be branched, with a 61 bp duplex stem, terminating in a three-way junction with 9 bp arms. The electrophoretic mobility of the ODN is slower than expected for normal duplex DNA of the same size, suggesting a bent or branched conformation. CD spectra indicate that the ITR structure is largely B form DNA, although there is a slight blue shift compared to the spectra of the isolated stem and loop elements. Thermal melting experiments indicate that the hairpin is significantly more stable than the isolated stem and loop elements. Singular value decomposition of UV spectra obtained as a function of temperature indicates that four species contribute to changes in the spectra upon denaturation, indicating that the melting is not a simple two-state process. Characterization of the branched ODN by differential scanning calorimetry permits estimation of the enthalpy of melting by a model-free analysis, yielding DeltaHcal= 614 kcal mol-1. This value agrees with the enthalpy computed for the most stable secondary structure.

Base Sequence↗
PubMed1999

Prophylaxis of acute renal allograft rejection using FTY720 in combination with subtherapeutic doses of cyclosporine.

BACKGROUND: In rodent transplant models, FTY720 exerts a synergistic affect with cyclosporine (CsA) to prolong allograft survival. The present experiments sought to test this combination in subhuman primates. METHODS: Cynomolgus monkeys were transplanted with kidney allografts that were incompatible in mixed lymphocyte culture reactions. The animals were treated with daily intramuscular injections of CsA using doses selected to maintain whole blood trough concentrations at therapeutic values between 40 and 200 ng/ml. The 4 experimental groups included CsA without or with 0.1, 0.3, or 1 mg/kg/day FTY720 delivered daily by intravenous bolus injection. Therapeutic effects were suggested both by the graft histology of biopsy within the first 10 posttransplant days and by the length of host survival. RESULTS: Whereas recipients treated with CsA alone rejected kidney allografts at a median survival time of 8.5 days (n=4), those treated with either 0.1 or 0.3 mg/kg/day FTY720 in addition to CsA showed significant prolongation of kidney allograft survival to 71 days (n=3; P<0.04) or 63 days (n=5; P<0.05), respectively. The hosts in the 1.0 mg/kg/day FTY720 group survived 48 days, with 2 of 5 recipients succumbing at 9 or 17 days postgraft, suggesting possible complications caused by overimmunosuppression. Biopsies of the 0.1 mg/kg/day FTY720 group on posttransplant day 7 documented mild to moderate rejection (grade I), indicated by multiple focal areas of tubular destruction. The histology results of transplants in the 0.3 or 1 mg/kg/day FTY720 group showed only minimal interstitial inflammatory infiltrates (borderline grade), with no evidence of tubular or arterial damage. Serum creatinine values among the animals in the 0.1 mg/kg/day FTY720 group showed increases in 2 of 3 recipients by day 20 and in the third by day 41 postgraft. Among the 0.3 mg/kg/day FTY720 group, 3 of 5 recipients maintained baseline creatinine values to 45 days postgraft; 1 recipient had stable kidney function for 120 days postgraft. CONCLUSIONS: Addition of FTY720 therapy to a subtherapeutic CsA immunosuppressive regimen delays the rejection of renal allografts in subhuman primates.

Acute Disease↗
PubMed1999

Calories from carbohydrates: energetic contribution of the carbohydrate moiety of rebeccamycin to DNA binding and the effect of its orientation on topoisomerase I inhibition.

BACKGROUND: Only a few antitumor drugs inhibit the DNA breakage-reunion reaction catalyzed by topoisomerase. One is the camptothecin derivative topotecan that has recently been used clinically. Others are the glycosylated antibiotic rebeccamycin and its synthetic analog NB-506, which is presently in phase I of clinical trials. Unlike the camptothecins, rebeccamycin-type compounds bind to DNA. We set out to elucidate the molecular basis of their interaction with duplex DNA, with particular emphasis on the role of the carbohydrate residue. RESULTS: We compared the DNA-binding and topoisomerase-I-inhibition activities of two isomers of rebeccamycin that contain a galactose residue attached to the indolocarbazole chromophore via an alpha (axial) or a beta (equatorial) glycosidic linkage. The modification of the stereochemistry of the chromophore-sugar linkage results in a marked change of the DNA-binding and topoisomerase-I- poisoning activities. The inverted configuration at the C-1' of the carbohydrate residue abolishes intercalative binding of the drug to DNA thereby drastically reducing the binding affinity. Consequently, the alpha isomer has lost the capacity to induce topoisomerase-I-mediated cleavage of DNA. Comparison with the aglycone allowed us to determine the energetic contribution of the sugar residue. CONCLUSIONS: The optimal interaction of rebeccamycin analogs with DNA is controlled to a large extent by the stereochemistry of the sugar residue. The results clarify the role of carbohydrates in stereospecific drug-DNA interactions and provide valuable information for the rational design of new rebeccamycin-type antitumor agents.

Aminoglycosides↗