Search PubMed⌕ Search

Biomedical subjects

W Chen

Publications and source records attributed to W Chen.

At least 649 records · Page 36Linked to original sources

[Comparative molecular field analysis(CoMFA) of allylamine and benzylamine antimycotics].

"Active analog approach" has been employed to search the pharmacophoric conformation of the allylamine and benzylamine antimycotics. A local minimum energy conformation, which is very similar to the crystallographically determined coordinate of naftifine or terbinafine, has been applied to build all compounds. Comparative molecular field analysis (CoMFA) has been used to examine the correlations between the activities against 6 common human pathogenic fungi and the physicochemical properties of 62 allylamine and benzylamine compounds which had been aligned by rms fit rule. The predictive abilities of the resulting 3D-QSAR models have been tested by 8 new synthetic compounds and 5 reported compounds. Finally, we propose an interaction pattern between allylamine, benzylamine antimycotics and the active site of pseudoreceptor based on the results of 2D-QSAR and 3D-QSAR.

Allylamine↗

[Protective effects of Ginkgo biloba extract on focal cerebral ischemia and thrombogenesis of carotid artery in rats].

Rat focal cerebral ischemia induced by occlusion and thrombogenesis of middle cerebral artery(MCAO) was used as experimental model to study the effects of extract of Ginkgo biloba (EGb) and the positive control drugs were urokinase and nimodipine on cerebral infarct size and neurological deficits. The results showed that cerebral ischemia and neurological deficits appeared in rat focal cerebral ischemic models, and the degree was of cerebral ischemia larger in occlusion model than in thrombogenesis model. The cerebral infarct size was significantly smaller and neurological deficits greatly improved at large dose of EGb(200 mg.kg-1, i.v.), the preventive effect appeared to be better than the treatment effect. The positive control drugs urokinase and nimodipine were also shown to distinctly decrease the cerebral infarct size and improve the neurological deficits in the models. Small dose of EGb(100 mg.kg-1, i.v.) was found to decrease the cerebral infarct size of thrombogenesis model, and improve neurological deficits of both thrombogenesis and occlusion model. EGb was also shown to inhibit the thrombogensis of rat common carotid artery stimulated by electrical current in dose-dependent manner. This experiment indicates that EGb might have beneficial effects on prevention and treatment of ischemic stroke and thrombogenesis.

Animals↗

[Thrombolysis by staphylokinase in rabbits with experimental pulmonary embolus].

Thrombolysis effect of recombinant staphylokinase (rSaK) developed in China was evaluated in rabbits with experimental pulmonary embolus model. 125I-labeled human fibrin blood clot was prepared in vitro and was injected through jugular vein resulting in a pulmonary embolus. Twenty thousands AU.kg-1(rSaK-H) or 5000 AU.kg-1(rSaK-L) of rSaK was infused in 0.5 h at constant rate by a peristaltic 20,000 U.kg-1. Another 20,000 AU.kg-1 of rSaK was infused within 2.5 h(rSaK-2.5 h). The residual labeled blood clot in lungs were found to be 62% +/- 11% (rSaK-H), 78% +/- 7% (rSaK-L), 92% +/- 7% (NS), 60% +/- 13% (SK), and 64% +/- 16% (rSaK-2.5 h). 125I-labeled degradation products in blood and urine were also statistically higher in thrombolytic agents treated group than those in NS controls. The results suggest that the thrombolytic effect of rSaK was determined by total dose and not determined by infusion time. Two of seven rabbits in the rSaK 2.5 h infusion group, the bleeding time was prolonged to more than 10 minutes while no prolongation was seen in rSaK high dose group. The clot lysis curves were very similar in 0.5 h or 2.5 h treatment of rSAK in vitro. Michaelis-Menten kinetics studies in vitro revealed that the Kms of rSaK and SK were almost the same, while a higher maximal velocity(34 kBq.min-1) was observed in rSaK than that in SK (10 kBq.min-1).

Animals↗

[Study on the design and application of the contact Nd:YAG laser scalper].

A method of designing the contact laser scalper is presented. The calculations using this method is in good agreement with the measured results in laboratory. Some operations on rabbits using the newly developed contact Nd:YAG laser scalper are performed and shown that the contact Nd:YAG laser is a promising medical equipment.

Aluminum Oxide↗

[The effect of ribozyme RzDS on duck hepatitis B virus].

To study the effect of ribozyme in vivo, the hammerhead ribozyme RzDS was designed and synthesized, which aims at the pregenome RNA of DHBV(LJ-76) at the 736 site of the genome. The RzDS cleaved efficiently its substrate in vitro. We constructed pJ-RzDS, in which RzDS was inserted into pJ120 plasmid under the control of PII promoter. After homogenous recombination with the vaccinia virus, Tian Tan strain, we got the recombinant(V-RzDS) which carried RzDS. V-RzDS was injected into nestling Beijing ducks preinfected with DHBV. On the tenth day after intravenous injection, DHBV DNA and DHBsAg in serum were detected. The quantity of DHBV DNA and DHBsAg were evidently lower than that of the controls, when V-RzDS injection was simultaneously given with DHBV. It suggests that RzDS can block replication and expression of DHBV in vivo.

Animals↗

[Microbial succession on lignite along with weathering].

Six different weathered lignite samples were examined by scanning electron microscopy. Few microorganisms were observed on lignit just excavated and only spores and short hyphae were observed on lignite samples excavated 5 months, 1 year and 4 years before sampling. When lignite samples were moistened with distilled water and incubated for 10 days, actinomycetes proliferated significantly on lignite samples that were just excavated or excavated 5 months before sampling. The growth of bacteria was observed on lignite samples excavated 1 year before sampling. Fungi increased in length and in number on lignite samples excavated 4 years before sampling. These findings of microbial succession on lignite samples along with weathering were consistent with results of the plate count method; actinomycetes are the first colonizers, then bacteria and fungi are the last degrader. The dominant microorganisms were Actinosynnema sp., Streptomyces sp. and Nocardia sp. among actinomycetes, two Arthrobacter sp. among bacteria and two Aspergillus sp. among fungi.

Actinomycetales↗

[Sequencing of a beta-amylase gene from Bacillus firmus].

The gene encoding a beta-amylase from Bacillus firmus 725 was sequenced. The sequenced DNA of 2012 bp contains one open reading frame of 1406 nucleotides without a translation stop codon. The deduced amino acid sequence homology with those known bacterial and some plant beta-amylase was 98% for Bacillus polymyxa 72, 98% for Bacillus polymyxa ATCC8523, 82% for Bacillus circulans, 54% for Clostridium thermosulfurogenes, 49% for Bacillus cereus BQ10-S1, 50% for Bacillus cereus var. mycoides, 36% for barley, and 36% for soybean Eleven well-conserved regions were found among the amino acid sequences of the nine beta-amylases.

Amino Acid Sequence↗

[Measurements of Ar(I) excitation temperatures and electron number densities in an ICP with and without the presence of Freon 12--the development of ICP technology for hazardous waste management].

For the management of refractory hazardous wastes, an innovative technology emerging recently is the application of ultra high temperature plasma. The preliminary study on destruction of Freon 12 by ICP (1-2kW) under a joint program between Xiamen Univ. and Hong Kong Baptist Univ. showed that the ICP technology indeed holds a great potential for hazardous wastes management. The destruction efficiency is more than 99.9999%. With and without the presence of Freon 12, Ar(I) excitation temperatures were measured by Boltzmann plot method and electron number densities the by H (beta) line broadening method. It was found that above the load coil, the excitation temperatures and electron number densities decrease with increasing the amount of Freon 12 presented in the central channel of the ICP, but inside the load coil region, the excitation temperatures are affected little by Freon 12. The conclusion of thermal pinch could be expected from this phenomenon.

Argon↗

[Characteristics of the absorption spectra of the mixtures of C42(Al), C32 (Si) and so on].

The mixtures containing C42 (A1), C32 (Si), C30 (Ca) and C28 (Fe) are produced by means of arc discharge and He gas convection. The spectra are measured and compared with the absorption spectra of all carbon molecules. The result shows that after imbeded in all carbon molecules, the Al, Si, Ca and Fe atoms do not change the positions of the absorption peak of original molecules, but only change the probability of pi --> pi* transition and n --> pi* transition of these molecules.

English Abstract↗

Binding of [3H]-SK&F 107260 and [3H]-SB 214857 to purified integrin alphaIIbbeta3: evidence for a common binding site for cyclic arginyl-glycinyl-aspartic acid peptides and nonpeptides.

The aggregation of activated platelets is mediated by the binding of fibrinogen to its cell surface receptor, the integrin alphaIIbbeta3. The recognition of fibrinogen by alphaIIbbeta3 depends, in part, on the tripeptide sequence Arg-Gly-Asp (RGD) in the adhesive protein. The interactions of a cyclic RGD-containing pentapeptide, [3H]-SK&F-107260, and a 1,4-benzodiazepine-based nonpeptide [3H]-SB-214857, with purified alphaIIbbeta3 have been investigated. Both compounds potently inhibit platelet aggregation at submicromolar concentrations. Binding of both [3H]-SK&F-107260 (Kd = 1.19 nM) and [3H]-SB-214857 (Kd = 1.85 nM) to alphaIIbbeta3 is of high affinity and fully reversible. The binding is monophasic, indicating a single class of noncooperative binding sites. The two radioligands exhibited similar values in binding to alphaIIbbeta3 purified on an RGD-affinity column (Bmax = 0.2 mol/mol alphaIIbbeta3) or to alphaIIbbeta3 purified over a lentil lectin column (Bmax = 0.03 mol/mol alphaIIbbeta3), suggesting that SK&F-107260 and SB-214857 interact with the same population of receptors. Binding of [3H]-SK&F-107260 and [3H]-SB-214857 to alphaIIbbeta3 require divalent cations, Mg++, Ca++ and Mn++ are able to support binding, with Mn++ being the most effective. Thirteen alphaIIbbeta3 antagonists, including four linear and three cyclic RGD peptides, five peptidomimetics, the fibrinogen gamma-chain dodecapeptide (HHLGGAKQAGDV) and the snake venom protein, echistatin, complete for [3H]-SK&F-107260 or [3H]-SB-214857 binding to alphaIIbbeta3. The affinity constants (Ki) of these compounds, determined by the two radioligand binding assays, are similar. Furthermore, these compounds exhibit the same rank order of potency in inhibiting biotinylated-fibrinogen binding to alphaIIbbeta3. Scatchard plot analyses of the [3H]-SK&F-107260 binding isotherms in the presence of unlabeled SB-214857 and gamma-chain dodecapeptide reveal competitive-type antagonism, indicating that SB-214857, gamma-chain dodecapeptide and SK&F-107260 interact with mutually exclusive binding sites on alphaIIbbeta3.

Binding, Competitive↗

Alternative pre-mRNA splicing of the sterol 27-hydroxylase gene (CYP 27) caused by a G to A mutation at the last nucleotide of exon 6 in a patient with cerebrotendinous xanthomatosis (CTX).

A recently identified G to A mutation at the last nucleotide of exon 6 of the sterol 27-hydroxylase gene (CYP 27) in a patient with cerebrotendinous xanthomatosis (CTX) was shown here to cause alternative pre-mRNA splicing of the gene. Northern blot analysis of the patient's RNA revealed a broadened band in the human CYP 27 mRNA region compared to that of the normal sample, indicating that there may exist differently spliced mRNA species in the patient. RT-PCR produced three fragments in the patient, one was full-length size and the other two were of smaller sizes. Sequence analysis confirmed that the nucleotide of the full-length size was identical to that of the normal full-length cDNA, except for the G to A mutation at codon 362, which corresponds to the last nucleotide of exon 6. One of the smaller size species lacked exon 6 and the other was absent from the 3' terminal 88 bp of exon 6 due to the use of an activated cryptic 5' splice site in exon 6. The correctly spliced mRNA harbouring the G to A mutation was responsible for the deficiency of the sterol 27-hydroxylase activity, as confirmed by transfection experiment. Transfection of constructed minigenes, with or without the mutation, showed that correctly spliced mRNA was observed in the normal minigene while the mutant minigene was differently spliced. This is the first report of a G to A substitution at the last nucleotide of an exon resulting in both normal and abnormal pre-mRNA splicings, including exon skipping and activating of a coding region cryptic 5' splice site. The results reveal a new molecular basis for the CTX and provide information on aberrant splicing of pre-mRNA in multi-exon genes.

Adult↗

Involvement of BCL6 in chromosomal aberrations affecting band 3q27 in B-cell non-Hodgkin lymphoma.

Chromosomal band 3q27 exhibits recurring and nonrecurring translocations and other rearrangements in approximately 8% of B-cell non-Hodgkin lymphomas (NHL) belonging to low-grade as well as diffuse aggressive histologies. The BCL6 gene, which encodes a zinc-finger transcription repressor protein and which maps to chromosomal band 3q27, is deregulated in t(3;14)(q27;q32) and other translocations by substitution of its transcription regulatory sequences by those of genes on the partner chromosomes. To delineate the cytogenetics and investigate the nature and consequence of BCL6 involvement in the spectrum of 3q27 aberrations seen in NHL, we analyzed a panel of 53 NHL tumors with 3q27 aberrations for BCL6 gene rearrangements and a subset of 32 of these for mutations. We identified four new recurring translocations involving 3q27, in addition to the previously recognized t(3;14)(q27;q32) and its variant, t(3;22)(q27;q11). Histologically, the 3q27 breaks were represented by 4% mantle cell lymphomas, 38% follicular center cell lymphomas, and 58% diffuse large B-cell lymphomas. Approximately 50% of the tumors exhibited BCL6 rearrangements, whereas 87.5% showed mutations in the 5' noncoding region which contains the transcription regulatory sequences. These results demonstrate that a substantial proportion of cytogenetically detected 3q27 breaks in NHLs do not represent BCL6-associated translocations. They also suggest alternate breakpoints which may lead to BCL6 deregulation, or involvement of other genes in 3q27 translocations. The frequent BCL6 mutation in these tumors is consistent with our previous observation of hypermutation of the 5' noncoding region of the gene in lymphomas arising in the germinal-center B-cells.

Chromosome Aberrations↗

Efficacy of ribavirin plus interferon alpha on viraemia of GB virus-C/hepatitis G virus: comparison with interferon alpha alone.

We investigated the efficacy of ribavirin plus interferon (IFN) alpha on GB virus-C (GBV-C)/hepatitis G virus (HGV) viraemia and compared it with that of interferon alpha alone in patients coinfected with hepatitis C virus (HCV) and GBV-C/HGV. Serum HCV and GBV-C/HGV-RNA were studied in eight patients with HCV and GBV-C/HGV coinfection, five received IFN alpha and three received oral ribavirin plus IFN alpha. Mean serum GBV-C/HGV titre at the end of therapy was significantly lower than the titre just before therapy and patients with lower pretreatment titre had a better sustained response rate. Sustained virological response of GBV-C/HGV to IFN alpha alone and ribavirin plus IFN alpha at the end of follow up was observed in one each, respectively. Thus, GBV-C/HGV in patients with HCV and GBV-C/HGV coinfection does respond to IFN alpha and ribavirin plus IFN alpha may not induce a higher sustained response.

Adult↗

Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides.

The effects of pituitary-derived melanocortin peptides are primarily attributed to ACTH-mediated adrenocortical glucocorticoid production. Identification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediated systemic effects of these peptides. Targeted disruption of the MC5-R produced mice with a severe defect in water repulsion and thermoregulation due to decreased production of sebaceous lipids. High levels of MC5-R was found in multiple exocrine tissues, including Harderian, preputial, lacrimal, and sebaceous glands, and was also shown to be required for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacrimal gland. These data show a requirement for the MC5-R in multiple exocrine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melanocortin peptides.

Animals↗

Production and characterization of monoclonal antibodies against mink leukocytes.

Three monoclonal antibodies (mAbs) were generated against mink leukocytes. One antibody reacted with all T lymphocytes, one with all monocytes and one had platelet reactivity. Under reducing conditions, the T lymphocyte reactive antibody immunoprecipitated 18 kDa, 23 kDa, 25 kDa and 32-40 kDa polypeptides and the platelet reactive antibody 17 kDa, 22 kDa plus two high molecular weight (> 100 kDa) polypeptides. Immunohistological studies of the mAbs were performed in order to localize the cellular distribution of the detected antigens in various organs. The T lymphocyte reactive antibody detected an antigen, which was widely distributed in the T cell area of lymph nodes and spleen and in the thymic medulla. We conclude that this antibody is an anti-CD3 mAb and suggest that the platelet reactive antibody reacts to the CD41/CD61 integrin molecule. In addition to our own mAbs, more than 100 mAbs against leukocytes of human and various animal species have been analysed for cross-reactivity to mink leukocytes. We found eight to cross-react with mink. Of particular importance was an anticanine CD11a mAb, an antihuman CD79a mAb and an antihuman bcl-2 mAb.

Animals↗

The number and location of glycans on influenza hemagglutinin determine folding and association with calnexin and calreticulin.

Calnexin and calreticulin are homologous molecular chaperones that promote proper folding, oligomeric assembly, and quality control of newly synthesized glycoproteins in the endoplasmic reticulum (ER). Both are lectins that bind to substrate glycoproteins that have monoglucosylated N-linked oligosaccharides. Their binding to newly translated influenza virus hemagglutinin (HA), and various mutants thereof, was analyzed in microsomes after in vitro translation and expression in live CHO cells. A large fraction of the HA molecules was found to occur in ternary HA- calnexin-calreticulin complexes. In contrast to calnexin, calreticulin was found to bind primarily to early folding intermediates. Analysis of HA mutants with different numbers and locations of N-linked glycans showed that although the two chaperones share the same carbohydrate specificity, they display distinct binding properties; calreticulin binding depends on the oligosaccharides in the more rapidly folding top/hinge domain of HA whereas calnexin is less discriminating. Calnexin's binding was reduced if the HA was expressed as a soluble anchor-free protein rather than membrane bound. When the co- and posttranslational folding and trimerization of glycosylation mutants was analyzed, it was observed that removal of stem domain glycans caused accelerated folding whereas removal of the top domain glycans (especially the oligosaccharide attached to Asn81) inhibited folding. In summary, the data established that individual N-linked glycans in HA have distinct roles in calnexin/calreticulin binding and in co- and posttranslational folding.

Amino Acid Substitution↗

Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action.

Long term administration of leptin decreases caloric intake and fat mass and improves glucose tolerance. Here we examine whether leptin acutely regulates peripheral and hepatic insulin action. Recombinant mouse leptin (0.3 mg/kg.h, Leptin +) or vehicle (Leptin -) were administered for 6 h to 4-month-old rats (n = 20), and insulin (3 milliunits/kg.min) clamp studies were performed. During physiologic hyperinsulinemia (plasma insulin approximately 65 microunits/ml), the rates of whole body glucose uptake, glycolysis, and glycogen synthesis and the rates of 2-deoxyglucose uptake in individual tissues were similar in Leptin - and Leptin +. Post-absorptive hepatic glucose production (HGP) was similar in the two groups. However, leptin enhanced insulin's inhibition of HGP (4.1 +/- 0.7 and 6.2 +/- 0.7 mg/kg.min; p < 0.05). The decreased HGP in the Leptin + group was due to a marked suppression of hepatic glycogenolysis (0.7 +/- 0.1 versus 4.1 +/- 0.6 mg/kg.min, in Leptin + versus Leptin -, respectively; p < 0.001), whereas the % contribution of gluconeogenesis to HGP was markedly increased (82 +/- 3% versus 36 +/- 4% in Leptin + and Leptin -, respectively; p < 0.001). At the end of the 6-h leptin infusion, the hepatic abundance of glucokinase mRNA was decreased, whereas that of phosphoenolpyruvate carboxykinase mRNA was increased compared with Leptin -. We conclude that an acute increase in plasma leptin 1) enhances insulin's ability to inhibit HGP, 2) does not affect peripheral insulin action, and 3) induces a redistribution of intrahepatic glucose fluxes and changes in the gene expression of hepatic enzymes that closely resemble those of fasting.

Animals↗