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Biomedical subjects

W Lu

Publications and source records attributed to W Lu.

At least 235 records · Page 13Linked to original sources

[Clinical study of weishu capsule in treating precancerous lesions of chronic atrophic gastritis].

OBJECTIVE: To explore the therapeutic effect and mechanism of Weishu capsule (WSC) in treating precancerous lesions of chronic atrophic gastritis (CAG). METHODS: Seventy-five cases of precancerous lesions of CAG were distributed to two groups randomly, the treated group (45 patients) treated with WSC by taken orally and the control group (30 patients) treated with Weining granule (WNG) orally. The treatment course of both groups were 6 months. The clinical and pathological effects and the changes in scores of atrophy, intestinal metaplasia and its subgroups, dysplasia, carcinoembryonic antigen (CEA) and proliferating cell nuclear antigen (PCNA) expression were observed before and after treatment. RESULTS: The total effective rate was 91% and the effective rate of atrophy, intestinal metaplasia, dysplasia in the treated group were 64%, 67% and 65% respectively, and the respective scores were lowered significantly after treatment. Compared with the control group the difference between the two groups was statistically significant (P < 0.01, P < 0.05). Immunohistochemical test showed that WSC could inhibit the subgroups of intestinal metaplasia, CEA and PCNA expression significantly (P < 0.01). CONCLUSION: WSC could significantly improve the clinical and pathological changes in the precancerous lesions of CAG. The mechanism might be related to the inducing and promoting effect of WSC on the differentiation and maturity of intestinal metaplasia cells and dysplasia cells. WSC could also inhibit and correct the abnormal proliferation of cells.

Adult↗

[A research on clinical values of corneal topography and keratometer in measuring astigmatism].

OBJECTIVE: To compare the accuracy of corneal topography, keratometer and cycloplegic retinoscopy in measuring astigmatism for refractive surgery. METHODS: Three hundred and sixty eyes with ametropia were randomly selected. The results of corneal topography, that of keratometer and cycloplegic retinoscopy in measuring astigmatism before refractive surgery were compared, and the measuring results of corneal topography and that of keratometer for 72 eyes after photorefractive keratectomy (PRK) and 95 eyes after laser in situ keratomileusis (LASIK) were also compared. RESULTS: No significant difference was found in axes of astigmatism among the three groups. As for diopters of astigmatism, there was no significant difference between the group of corneal topography (DeltaSim K) and the group of keratometer (DeltaK), but we found significant difference between the group of cycloplegic retinoscopy and the other two groups before and after refractive surgery. Significant difference was also found between DeltaSimK and DeltaK after PRK and LASIK. CONCLUSIONS: Our investigation demonstrates that before refractive surgery the keratometer has a similar clinical value as that of corneal topography, and the DeltaSim K value is related to the graphic pattern of corneal topography. However, keratometer is limited in measuring mild changes in corneal curvature after refractive surgery, while the astigmatism expressed by DeltaSim K in corneal topography is more accurate.

Adolescent↗

[A 24-hour solid state Holter recording and analyzing system].

The design and functions of a new type of multi-channel solid-state Holter system were introduced in this paper. The flash memory card based recorder can record 24 hours or more of data from up to all 12 leads. The full function scanner software can analysis automatically and archive with complete editing capabilities.

Electrocardiography, Ambulatory↗

[Studies on the chemical constituents of chloroform extract of Dracaena cochinchinensis].

Six compounds were isolated from Dracaena cochinchinensis (Lour.) S.C. Chen. Their structures were identified as 2,3,5,6-tetracchloro-1,4-dimethoxybenzene (I), 7-hydroxy-4'-methoxyflavan (II), 4'-hydroxy-3,5-dimethoxystilbene (III), 4'-hydroxy-2,6-dimethoxydihydrochalcone (IV), 4'-hydroxy-2,4,6-trimethoxydihydrochalcone (V) and 6-hydroxy-7-methoxy-3-(4'-hydroxybenzyl) chromane (VI) by chemical method and spectral analysis. IV and VI are new compounds.

Chalcone↗

[Studies on the pharmacokinetic-pharmacodynamic model of ketoprofen beta-CD inclusion complex in rabbits].

A simple HPLC-UV method was established to determine concentrations of ketoprofen (KP) in rabbit plasma following oral administration. Twelve rabbits were selected and divided into three groups. KP beta-CD inclusion complex suspension, KP entity suspension (in 0.5% CMC-Na) and 0.5% CMC-Na suspension (as a placebo group) were administered orally to the three groups of rabbits, respectively. Differences in the pharmacokinetics-pharmacodynamics (PK-PD) parameters between KP beta-CD inclusion complex and KP entity were examined. The results indicate that the established HPLC-UV method could be used to assay the concentrations of KP in rabbit plasma with good precision. The distribution phase T1/2 alpha of the complexated KP was 0.4 h, while that of the KP entity was 0.56 h, KP in beta-CD inclusion complex could be absorbed more rapidly. The early effect values of the KP inclusion complex were higher than those of the KP entity. The maximal antipyretic effect occurred after the peak of plasma concentration. The phenomenon indicates that the effect compartment of ketoprofen is in the peripheral compartment.

Animals↗

[An epidemiological survey of schistosome cercarial dermatitis among the residents living along the banks of the Huaihe River system].

AIM: To make an epidemiological survey of schistosome cercarial dermatitis among the residents living along the banks of the Huaihe River. METHODS: Making inquiries about signs and symptoms of schistosome cercarial dermatitis, and physical examinations of manifestation in the residents (fishermen and peasants). Cercariae shed from the Radix auricularia collected in the field were used to infect ducklings. The eggs and miracidia separated from the feces of the full grown ducks bred by fishermen were used to infect Radix auricularia. RESULTS: Schistosome dermatitis locally known as "duck itch" (meaning duck-fecesdermatitis) was discovered among the residents living along the Huaihe River bank. The main signs and symptoms of the dermatitis included diffuse erythema or red papular eruption with areorae, urticae, urticant itch or titillation around the affected areas (including thoracic part, abdomen and lower limbs etc). The cercariae with eye spot were found from Radix auricularia collected from Huaihe riverside and were identified to be the species of Trichobilharzia can both hatch miracidium, which laboratory-reared Radix auricularia were infected with miracidia hatched from the two types of eggs, rhomboid eggs and crescent eggs, found in the feces of full grown ducks bred by fishermen and shed the same cereariae with eye spot. Besides, adult worms of Trichobiharzia were obtained by dissecting both experimentally infected ducklings bred in the laboratory and naturally infected ducks bred in the Huaihe river-side area. The above-mentioned eggs, miracidia, cercariae and adult worms were all identified to belong to the life-phase of Trichobilharzia. CONCLUSION: The epidemic disease known as schistosoma cercarial dermatitis harmful to the health of the residents living along the banks of Huaihe River is caused by the cercariae of Trichobilharzia.

Adult↗

[The study of multi-phrase multi-criterion steretactic radiotherapy treatment planning].

Steretactic radiotherapy treatment planning is an important part of X-knife radiosurgery. In this paper the theory of multi-phrase-multi-criterion steretactic radiotherapy treatment planning is proposed, which is composed of three phrases. In the first stage, linear programming is used to reduce the resolution space. A kind of quadriatic programming is used in the second phrase in order to get high and well-distributed dose distribution. In the third phrase, an improved method of constrained simulated annealing is used to get the effect of conforming with the clinical practice. In correspondence with three-phrases optimization, three criterions are used respectively. The experiment results show that the theory proposed is correct.

Humans↗

[Application of constrained simulated annealing to 3D stereotactic radiotherapy treatment planning].

In this paper, linear programming and constrained simulated annealing are combined to optimize X-knife stereotactic radiotherapy treatment planning. In the first phase, linear programming reduces the resolution space, which is favourable to the adoption of little granularity in the second phase. Our experiment demonstrates that after the two-phase optimization, we attain the expected result.

Algorithms↗

[Clustering analysis of phonocardiagrams].

Through the development of the ART-2 neural network, we had constructed the 2-dimensional ART neural network appropriate for clustering the time-varying spectrums. After that, according to the character of phonocardiagram(PCG), we chose the scalogram of PCG to be the input feature of the network. By adjusting parameters the network was enabled to cluster the input PCGs to two clusters. The result demonstrates that the system we designed can pick out, from among 32 continuous PCGs, two PCGs which have the tendency toward abnormality. This result may be applicable to basic physiological studies and clinical diagnosis.

Cluster Analysis↗

Expression of dopamine transporter and vesicular monoamine transporter 2 mRNAs in rat midbrain after repeated amphetamine administration.

The dopamine transporter (DAT) in pre-synaptic membranes and the vesicular monoamine transporter 2 (VMAT2) in membranes of synaptic vesicles are involved in mediating the acute effects of amphetamine on dopamine transmission. Therefore, using a quantitative method of in situ hybridization and computerized image analysis, the expression of DAT and VMAT2 mRNAs was examined in rats treated for 5 days with amphetamine and killed 3 or 14 days after the last injection. We examined ventral tegmental area (VTA), substantia nigra (SN) and the transitional zone between VTA and SN. Each of these regions was further subdivided into rostral, intermediate and caudal portions. In control rats, autoradiographs revealed a gradient of both DAT and VMAT2 mRNA levels, decreasing gradually from rostral to caudal rat midbrain. After 3 days of withdrawal, a significant increase in DAT mRNA levels was found in rostral portions of VTA (117.9 + 5.8% of control group), SN (116.5 + 4.5%) and the transitional zone (119.6 + 5.6%) and in the intermediate portion of SN (113.5 + 4.3%). VMAT2 mRNA was significantly increased only in rostral and intermediate portions of the transitional zone (120.9 + 4.8 and 113.6 + 4.1%). After 14 days of withdrawal, there was a trend towards increased DAT mRNA levels in intermediate-caudal portions of midbrain, but a statistically significant increase was observed only in the intermediate portion of VTA (120.2 + 7.9%). No changes in VMAT2 mRNA levels were found. Thus, repeated amphetamine administration exerts modest and regionally selective effects on DAT and VMAT2 mRNA expression in subpopulations of midbrain dopamine neurons.

Amphetamine↗

Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone.

Benzene is a ubiquitous occupational hematotoxin and leukemogen, but people vary in their response to this toxic agent. To evaluate the impact of interindividual variation in enzymes that activate (i.e., CYP2E1) and detoxify (i.e., NQO1) benzene and its metabolites, we carried out a case-control study in Shanghai, China, of occupational benzene poisoning (BP; i.e., hematotoxicity), which we show is itself strongly associated with subsequent development of acute nonlymphocytic leukemia and the related myelodysplastic syndromes (relative risk, 70.6; 95% confidence interval, 11.4-439.3). CYP2E1 and NQO1 genotypes were determined by PCR-RFLP, and CYP2E1 enzymatic activity was estimated by the fractional excretion of chlorzoxazone (fe(6-OH)) for 50 cases of BP and 50 controls. Subjects with both a rapid fe(6-OH). and two copies of the NQO1 609C-->T mutation had a 7.6-fold (95% confidence interval, 1.8-31.2) increased risk of BP compared to subjects with a slow fe(6-OH) who carried one or two wild-type NQO1 alleles. In contrast, the CYP2E1 PstI/RsaI polymorphism did not influence BP risk. This is the first report that provides evidence of human susceptibility to benzene-related disease. Further evaluation of susceptibility for hematotoxicity and hematological malignancy among workers with a history of occupational exposure to benzene is warranted.

Benzene↗

Extracellular calcium sensed by a novel cation channel in hippocampal neurons.

Extracellular concentrations of Ca2+ change rapidly and transiently in the brain during excitatory synaptic activity. To test whether such changes in Ca2+ can play a signaling role we examined the effects of rapidly lowering Ca2+ on the excitability of acutely isolated CA1 and cultured hippocampal neurons. Reducing Ca2+ excited and depolarized neurons by activating a previously undescribed nonselective cation channel. This channel had a single-channel conductance of 36 pS, and its frequency of opening was inversely proportional to the concentration of Ca2+. The inhibition of gating of this channel was sensitive to ionic strength but independent of membrane potential. The ability of this channel to sense Ca2+ provides a novel mechanism whereby neurons can respond to alterations in the extracellular concentration of this key signaling ion.

Animals↗

Expression of mutated Nck SH2/SH3 adaptor respecifies mesodermal cell fate in Xenopus laevis development.

Nck is a widely expressed SH2/SH3 adaptor protein containing one SH2 and three SH3 domains. Although Nck is assumed to mediate the formation of protein-protein complexes during signaling, little is currently known about its specific function. We have constructed a series of Nck SH3 and SH2 domain mutants, expressed them in Xenopus laevis embryos, and monitored injected embryos for developmental abnormalities. This approach allows correlation of developmental phenotypes with the presence or absence of specific Nck protein-binding domains. We show that microinjection of RNA-encoding Nck with an inactivating mutation in the third SH3 domain (NckK229) into dorsal blastomeres of early embryos caused anterior truncation with high frequency, and membrane localization of both the first and second SH3 domains together was sufficient to induce this anterior-truncation phenotype. Molecular marker analysis of explants revealed that the expression of NckK229 ventralized dorsal mesoderm. Lineage tracing experiments demonstrated that the expression of Nck K229 in dorsal blastomeres affected the migratory properties of mesoderm cells in gastrulation and led to the adoption of a more posterior fate. These data suggest that protein(s) that bind the first and second SH3 domains of Nck can affect the response to signals that establish dorso-ventral patterning, and that protein(s) that bind the third SH3 domain antagonize the ventralizing effect of the first two SH3 domains.

Adaptor Proteins, Signal Transducing↗

Binding of amino acid side-chains to S1 cavities of serine proteinases.

The P1 or primary specificity residue of standard mechanism canonical protein inhibitors of serine proteinases, inserts into the S1 primary specificity cavity of the cognate enzyme upon enzyme-inhibitor complex formation. Both natural evolution and protein engineering often change the P1 residue to greatly alter the specificity and the binding strength. To systematize such results we have obtained all 20 coded P1 variants of one such inhibitor, turkey ovomucoid third domain, by recombinant DNA technology. The variants were extensively characterized. The association equilibrium constants were measured at pH 8.30, 21 (+/-2) degrees C, for interaction of these variants with six well characterized serine proteinases with hydrophobic S1, cavities. The enzyme names are followed by the best, worst and most specific coded residue for each. Bovine chymotrypsin A alpha (Tyr, Pro, Trp), porcine pancreatic elastase (Leu/Ala, Arg, Ala), subtilisin Carlsberg (Cys, Pro, Glu), Streptomyces griseus proteinase A (Cys, Pro, Leu) and B (Cys, Pro, Lys) and human leukocyte elastase (Ile, Asp, Ile). The data set was merged with Ka values for five non-coded variants at P1 of turkey ovomucoid third domain obtained in our laboratory by enzymatic semisynthesis. The ratios of the highest to the lowest Ka for each of the six enzymes range from 10(6) to 10(8). The dominant force for binding to these pockets is the hydrophobic interaction. Excess steric bulk (too large for the pocket), awkward shape (Pro, Val and Ile), polarity (Ser) oppose interaction. Ionic charges, especially negative charges on Glu- and Asp- are strongly unfavorable. The Pearson pro duct moment correlations for all the 15 enzyme pairs were calculated. We suggest that these may serve as a quantitative description of the specificity of the enzymes at P1. The sets of Streptomyces griseus proteinases A and B and of the two elastases are strongly positively correlated. Strikingly, chymotrypsin and pancreatic elastase are negatively correlated (-0.10). Such correlations can be usefully extended to many other enzymes and to many other binding pockets to provide a general measure of pocket binding specificity.

Amino Acid Sequence↗

Activation of Pak by membrane localization mediated by an SH3 domain from the adaptor protein Nck.

BACKGROUND: The adaptor protein Nck consists of three Src homology 3 (SH3) domains followed by one SH2 domain. Like the Grb2 adaptor protein, which is known to couple receptor tyrosine kinases to the small GTPase Ras, Nck is presumed to bind to tyrosine-phosphorylated proteins using its SH2 domain and to downstream effector proteins using its SH3 domain. Little is known, however, about the specific biological function of Nck. The Pak family of serine/threonine kinases are known to be activated by binding to the GTP-bound form of Cdc42 or Rac1, which are small GTPases of the Rho family that are involved in regulating the organization of the actin cytoskeleton. RESULTS: We present evidence that Nck can mediate the relocalization and subsequent activation of the Pak1 kinases. We show that Nck associates in vivo with Pak using the second of its three SH3 domains, and that localization of this individual Nck SH3 domain, or of Pak kinase itself, to the membrane results in activation of Pak and stimulation of downstream mitogen activated protein kinase cascades. Activation of downstream signaling by the membrane-localized Nck SH3 domain is blocked by a kinase-inactive mutant form of Pak1. CONCLUSION: These results demonstrate that localization of Pak1 to the membrane in the absence of other signals is sufficient for its activation, and imply that the Nck adaptor protein could function to link changes in tyrosine phosphorylation of cellular proteins to the Cdc42/Pak signaling pathway.

Adaptor Proteins, Signal Transducing↗

Probing intermolecular main chain hydrogen bonding in serine proteinase-protein inhibitor complexes: chemical synthesis of backbone-engineered turkey ovomucoid third domain.

Intermolecular main chain H-bonding networks are frequently encountered at the interface of complexes of protein proteinase inhibitors and their cognate enzymes. Studies of X-ray crystal structures of many protein inhibitors complexed with serine proteinases have revealed that the amide NH group of the P1 residue in the inhibitor donates an H-bond to the carbonyl C = O group of Ser214 and Ser195 Oy in the enzyme (Ser125 and Ser221 in subtilisins, respectively). To probe the energetic contribution of this backbone H-bond in the complexes of OMTKY3 with several serine proteinases, native chemical ligation was used for the total synthesis of a backbone-engineered analog of OMTKY3, in which the amide peptide bond between Thr17 (P2) and Leu18 (P1) was replaced by an ester bond, i.e., -CONH-to-COO-. This chemical "mutation" effectively eliminated the backbone H-bond donated by the NH group of Leu18. By measuring association equilibrium constants for synthetic wild-type OMTKY3 and the backbone-engineered ester analog interacting with a panel of six serine proteinases, we have determined that the P1 NH-->O substitution weakens the binding of OMTKY3 to its cognate enzymes by an average of 15-fold, i.e., 1.5 +/- 0.3 kcal/mol. These results place a quantitative value on the contribution of the intermolecular backbone H-bond in enzyme-inhibitor recognition.

Amino Acid Sequence↗