Biomedical subjects

P Lu

Publications and source records attributed to P Lu.

At least 55 records · Page 3Linked to original sources

PubMed2001

Concentrations and flux of rare earth elements in a semifield plot as influenced by their agricultural application.

The concentrations of rare earth elements (REs) in atmospheric particles, soil, soil water, surface runoff, and different parts of corn in an experimental plot in the suburb of Beijing, China were measured and the flux of REs was estimated. The concentration of REs in air particles with diameter less than 10 microm is 36 ng/m3 and, by ratio analysis, the origin of REs in the atmosphere was likely local soil. The concentration of soluble REs is 0.69 microg/L in rainwater, 5-7 microg/L in surface runoff, as well as 1-4 microg/L in soil water and the application of RE mixture has no observed influences on their concentrations. The concentration of soluble REs in surface runoff and soil water was dominated by aqueous-solid-phase partitioning. By estimation of the flux, most of the REs applied will remain in the soil phase and continued application of REs will cause an accumulation of REs in agricultural soil.

China↗

PubMed2001

Enzyme kinetics of cytochrome P450-mediated reactions.

The most common drug-drug interactions may be understood in terms of alterations of metabolism, associated primarily with changes in the activity of cytochrome P450 (CYP) enzymes. Kinetic parameters such as Km, Vmax, Ki and Ka, which describe metabolism-based drug interactions, are usually determined by appropriate kinetic models and may be used to predict the pharmacokinetic consequences of exposure to one or multiple drugs. According to classic Michaelis-Menten (M-M) kinetics, one binding site models can be employed to simply interpret inhibition (pure competitive, non-competitive and uncompetitive) or activation of the enzyme. However, some cytochromes P450, in particular CYP3A4, exhibit unusual kinetic characteristics. In this instance, the changes in apparent kinetic constants in the presence of inhibitor or activator or second substrate do not obey the rules of M-M kinetics, and the resulting kinetics are not straightforward and hamper mechanistic interpretation of the interaction in question. These unusual kinetics include substrate activation (autoactivation), substrate inhibition, partial inhibition, activation, differential kinetics and others. To address this problem, several kinetic models can be proposed, based upon the assumption that multiple substrate binding sites exist at the active site of a particular P450, and the resulting kinetic constants are, therefore, solved to adequately describe the observed interaction between multiple drugs. The following is an overview of some cytochrome P450-mediated classic and atypical enzyme kinetics, and the associated kinetic models. Applications of these kinetic models can provide some new insights into the mechanism of P450-mediated drug-drug interactions.

Algorithms↗

PubMed2001

Drug transport by reconstituted P-glycoprotein in proteoliposomes. Effect of substrates and modulators, and dependence on bilayer phase state.

The P-glycoprotein multidrug transporter (Pgp) is an active efflux pump for chemotherapeutic drugs, natural products and hydrophobic peptides. Pgp is envisaged as a 'hydrophobic vacuum cleaner', and drugs are believed to gain access to the substrate binding sites from within the membrane, rather than from the aqueous phase. The intimate association of both Pgp and its substrates with the membrane suggests that its function may be regulated by the biophysical properties of the lipid bilayer. Using the high affinity fluorescent substrate tetramethylrosamine (TMR), we have monitored, in real time, transport in proteoliposomes containing reconstituted Pgp. The TMR concentration gradient generated by Pgp was collapsed by the addition of either the ATPase inhibitor, vanadate, or Pgp modulators. TMR transport by Pgp obeyed Michaelis--Menten kinetics with respect to both of its substrates. The Km for ATP was 0.48 mM, close to the K(m) for ATP hydrolysis, and the K(m) for TMR was 0.3 microM. TMR transport was inhibited in a concentration-dependent fashion by verapamil and cyclosporin A, and activated (probably by a positive allosteric effect) by the transport substrate colchicine. TMR transport by Pgp reconstituted into proteoliposomes composed of two synthetic phosphatidylcholines showed a highly unusual biphasic temperature dependence. The rate of TMR transport was relatively high in the rigid gel phase, reached a maximum at the melting temperature of the bilayer, and then decreased in the fluid liquid crystalline phase. This pattern of temperature dependence suggests that the rate of drug transport by Pgp may be dominated by partitioning of drug into the bilayer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Substrate inhibition kinetics for cytochrome P450-catalyzed reactions.

Most cytochrome P450 (P450 or CYP)-catalyzed reactions are adequately described by classical Michaelis-Menten kinetic parameters (e.g., Km and Vmax), which are usually determined by a saturation profile of velocity of product formation versus substrate concentration. In turn, these parameters may be used to predict pharmacokinetics. However, some P450 enzymes exhibit atypical or non-Michaelis-Menten kinetics, due largely to substrate inhibition at higher concentrations of substrate. Although the mechanism of substrate inhibition is unknown, ignoring it and truncating the data can lead to erroneous estimates of kinetic parameters. In the present study, 13 P450 marker substrates were examined with 10 recombinant P450 proteins, and 6 were found, to varying degrees, to exhibit substrate inhibition. To understand the nature of the inhibition, a kinetic model was proposed (assuming that two binding sites exist on the enzyme) and used to fit the experimental data. The derived data indicated that 1) the K(I) values (substrate inhibition) were approximately 1.2- to 10-fold greater than the respective K(S) values; 2) both K(S) and K(I) values may be affected by the interaction of the two bound substrates within the enzyme, exhibited by a factor alpha (alpha = 5.1-23.3); and 3) enzyme activity was inhibited markedly (39-97%) at excess concentrations of the substrates (beta = 0.03-0.61). These findings suggest that substrates have access to both the inhibitory site and catalytic site simultaneously (K(I) > K(S)). Furthermore, the two sites, in the presence of substrate, can interact with each other. Therefore, the degree of inhibition of the enzyme is dependent on the concentration of the substrate (usually >K(I)) that sufficiently occupies the inhibitory site.

Antineoplastic Agents↗

PubMed2001

Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin bind to different domains within the active site of cytochrome P450 3A4.

Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin, marker substrates for cytochrome P450 3A4 are commonly used within the pharmaceutical industry to screen new chemical entities as inhibitors of CYP3A4 in a high-throughput manner to predict the potential for drug-drug interactions. However, it has been observed that inhibition data obtained with a given CYP3A4 probe substrate may not correlate well with results from a different probe. As a consequence, the choice of the probe compound becomes an important consideration in such screens. In the present study, kinetic interactions between either two of the above three substrates were evaluated, and three-dimensional nonlinear regression analysis was performed to understand the kinetic mechanisms of drug interaction. Our results demonstrate that the kinetic interaction between each pair of substrates does not appear to be competitive and that the interactions are characterized by an unchanged or a decrease in both apparent K(m) (a = 0.21-0.72, a change of K(m) in the absence of the effector) and V(max) (alpha and beta = 0.09-0.75, changes of V(max) in the absence of the effector). These data suggest that 1) the three substrates bind to different domains; 2) at least two substrates can coexist in the active site of CYP3A4; and 3) the two bound substrates interact kinetically with each other (e.g., through steric hindrance), thereby leading to a change in both apparent kinetic parameters and partial inhibition. Selection of multiple substrates, which are shown not to be competitive, is necessary to accurately predict CYP3A4 inhibition and the potential for drug-drug interaction.

Baculoviridae↗

PubMed2001

Isolation and specific detection of two major schistosoma gut-associated circulating antigens.

OBJECTIVES: To investigate the nature of the common epitopes of Schistosoma japonicum (S. japonicum) circulating anodic (CAA) and circulating cathodic antigen (CCA) and to try to obtain sufficient purified material to set up a standard series for quantitative determinations. METHODS: Isolation of the two worm fractions from a trichloroacetic acid (TCA) soluble preparation of S. japonicum adult worm antigen (AWAj-TCA) via Mono-Q anion exchange chromatography was performed and analysis of specific reactivity of the eluted fractions was done by antigen-capture Enzyme Linked Immuno Sorbent Assay (ELISA) specific for CAA or CCA with reference to affinity purified preparations of S. mansoni CAA and CCA. RESULTS: When an ionic strength gradient was used, CCA was eluted in two major peaks, an unbound fraction CCA-1, and a major bound fraction, CCA-2. Two additional minor peaks, CCA-3 and CCA-4, were eluted at higher ionic strengths. CAA was only detected in the bound fraction, partly overlapping with CCA-3. In the CCA-1 and CCA-2 fractions, reactivity was only found in the antigen-capture ELISA using anti-CCA McAbs both for capture and detection. The CAA fraction was predominantly found to be positive in the antigen-capture ELISA using anti-CAA McAbs both for capture and detection. However, in ELISA using combined anti-CAA and anti-CAA McAbs for capture and detection, this fraction showed some reactivity. CONCLUSION: The two CCA fractions contain molecules which bear at least two CCA-epitopes; the CAA fraction contains molecules which contain at least two CAA-epitopes, and one CCA-epitope.

Animals↗

PubMed2001

[The study on human leucocyte antigen DQ region genes polymorphism in unexplained habitual abortion patients].

OBJECTIVE: To investigate whether human leucocyte antigen DQ (HLA-DQ) genes polymorphism are related to the susceptibility to unexplained habitual abortion. METHODS: HLA-DQA1 and HLA-DQB1 gene typings are performed by polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP) technique in 32 cases of unexplained habitual abortion and 54 women with normal pregnancy history. RESULTS: In unexplained habitual abortion group, the frequency of DQB1 * 0604, 0605 allele is increased significantly compared with that of controls(12.5% and 2.8%, P < 0.05) and the frequency of DQB1 * 0501, 0502 allele is decreased significantly (3.1% and 11.1%, P < 0.05). The frequency of DQA1 alleles do not differ significantly between two groups. Furthermore, the frequency of DQA1 * 01/DQB1 * 0604,0605 haplotype in patients is significantly increased than that of controls (12.5% and 2.8%, P < 0.05). CONCLUSION: The results suggest that DQB1 * 0604,0605 allele and DQA1 * 01/DQB1 * 0604,0605 haplotype may be a susceptible gene and haplotype of unexplained habitual abortion, while DQB1 * 0501,0502 allele may be a protective factor for habitual abortion.

Abortion, Habitual↗

PubMed2001

Genotype and allele frequency of the 27-bp tandem repeat polymorphism in the endothelial nitric oxide synthase gene in Chinese population.

Genotype and allele frequency of the polymorphic 27-bp repeat, a variable number of tandem repeats (VNTR) located in intron 4 of the endothelial nitric oxide synthase gene, were analyzed in 316 healthy Chinese individuals. Four genotypes, namely 6/5-repeats heterozygous, 5/5-repeats homozygous, 5/4-repeats heterozygous and 4/4-repeats homozygous, were identified. Both observed genotype and allele frequencies of this VNTR in Chinese were similar to those of Japanese, while the 4/4-repeats genotype differed significantly from that of Caucasians in Spain, and all ones did from those of African-American in United States.

Alleles↗

PubMed2001

[Significance of the CT scan in renal tuberculosis].

OBJECTIVE: To elucidate the features and clinical significance of CT scan in the diagnosis of renal tuberculosis. METHODS: The CT findings and the clinical characteristics of 42 cases with renal TB were retrospectively analyzed. RESULTS: Unilateral renal TB was found in 34 cases, bilateral in 8 cases. The typical CT features were characterized by one or more cysts surrounding the calyx with thin adjacent cortex (34/50), thickened wall of ureters and calyx, hydronephrosis (22/50) and kidney calcification (8/50). Atypical features presented with single or multiple low density nodes in the renal parenchyma (6/50). 30 patients receiving contrast enhanced CT scan showed that intensified Hu (by 20 approximately 120 HU) in the affected kidney. Multiple lymph nodes calcification in abdomen was found in 2 patients, calcification and low density nodes in spleen and liver in 4 patients, vertebral damage and paravertebral abscess in 6 patients and post-abdominal abscess in 1 patient. CONCLUSION: CT scan examination is not only useful in the diagnosis of renal tuberculosis, but also of significance in assessing the severity of the disease, renal function and the involvement of other organs in the abdomen.

Adolescent↗

PubMed2001

[A century of developmental history of laparoscopic surgery].

Till the year 2001, the development of laparoscopic surgery will have gone through a total of one hundred years. Laparoscopic surgery has made a great progress during the last more than a decade. In retrospect its history, the development of laparoscopic surgery underwent three main eras, viz. diagnostic laparoscopy, operative laparoscopy and the modern laparoscopy era. Although the laparoscopic technology started rather late in China, it develops very quickly. Along with the development of high -- tech, laparoscopic surgery will have a promising future.

History, 20th Century↗

PubMed2000

Multiple types of calcium signals are associated with cell division in zebrafish embryo.

Recent studies suggested that a Ca(2+) signal is involved in the regulation of cell division. For example, using a confocal imaging technique, we have shown that a localized Ca(2+) elevation was clearly associated with the onset of cytokinesis in zebrafish embryo [Chang and Meng (1995) J. Cell Biol. 131:1539-1545]. This finding was later confirmed in studies using aequorin as a Ca(2+) probe. Here, we used a 4-D confocal measurement technique to further characterize the properties of the Ca(2+) signal associated with cell division. We found evidence that there were three types of Ca(2+) signals associated with different stages of cell cleavage in embryonic cell. The first type was repetitive Ca(2+) spikes that emerged several minutes before the first cell cleavage began. These Ca(2+) spikes were first distributed broadly over the central region of the blastodisc and then gradually localized in the equatorial region; they appeared to play the role of determining the position of the first cleavage plane. The second type was a calcium wave that propagated along the cleavage furrow and appeared to guide the furrow extension during the progression of cytokinesis. The third type was a group of post-cleavage calcium spikes that appeared to be responsible for furrow deepening and maintenance of the contractile band. When this type of Ca(2+) transient was blocked by injecting BAPTA or heparin, cell cleavage regressed and the structure of the contractile band could no longer be maintained.

Animals↗

PubMed2000

Excretion pattern investigation of urinary normal and modified nucleosides of breast cancer patients by RP-HPLC and factor analysis method.

Modified nucleosides, formed post-transcriptionally in RNA by a number of modification enzymes, are excreted in abnormal levels in the urine of patients with malignant tumors. To test their usefulness as tumor markers, and to compare them with the conventional tumor markers, a reversed-phase high-performance liquid chromatographic (RP-HPLC) method and a factor analysis method have been used to study the excretion pattern of nucleosides of breast cancer patients. A clear cut differentiation of the breast cancer group and the healthy individuals in two clusters without overlapping was obtained.

Adult↗

PubMed2000

Interspecies comparison and role of human cytochrome P450 and flavin-containing monooxygenase in hepatic metabolism of L-775,606, a potent 5-HT(1D) receptor agonist.

1. Quantitative species differences and human liver enzymes involved in the metabolism of L-775,606, a potent and selective 5-HT1D receptor agonist developed for the acute treatment of migraine headache, have been investigated in vitro. 2. In human, monkey, dog and rat liver microsomes, formation of the hydroxylated M1 and the N-dealkylated M2 was mediated by enzyme(s) of high-affinity (apparent Km approximately 1-6 microM), and that of the two N-oxide isomers (M3) was catalysed by those of low affinity (apparent Km approximately 50-110 microM). In dog, M3 constituted a major pathway (approximately 40%), whereas in all other species it was a minor metabolite (< 5%). 3. In human liver microsomes, a marked inhibition (> or =80%) of M1 and M2 formation was observed by SKF525-A, troleandomycin, ketoconazole and anti-CYP3A antibodies, whereas the inhibition was modest (approximately 20-40%) with quercetin. Of seven cDNA-expressed human P450 tested, only CYP3A4 and CYP2C8 were capable of oxidizing L-775,606, resulting primarily in M1 and M2. However, CYP3A4 possessed much higher affinity (> or = 20-fold) and much higher intrinsic activity (> 100-fold) than CYP2C8. 4. In contrast, N-oxidation was not inhibited by any inhibitors of P450 tested, but rather was reduced significantly by heat treatment and methimazole, and was increased substantially with an incubation pH>7.4. Human flavin-containing monooxygenase form 3 (FMO3) catalysed exclusively the N-oxidation to M3, with apparent Km and optimum pH comparable with those observed in human liver microsomes. 5. These results demonstrated quantitative interspecies differences in the metabolism of L-775,606. In human, metabolism of L-775,606 to the principal metabolites, M1 and M2, was mediated primarily by CYP3A4 with minimal contribution from CYP2C8, whereas the minor N-oxidative pathway was catalysed mainly by FMO3.

Animals↗

PubMed2000

Effects of delaying puberty on bone mineralization in female rats.

The effect of delaying puberty on bone mineralization was studied using female rats as a model. Repeated injections of gonadotrophin-releasing hormone antagonist (GnRHa) were used to suppress the onset of puberty from the age of 6-10 weeks. A group of control female rats was given aqueous solution injections at the same age and for the same duration. The effect of delaying puberty on bone mineralization was examined using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (QCT), both methods being adapted for small animals. Bone mineral parameters were measured at baseline and at the ages of 10, 17 and 24 weeks in total body, femur and spine. Compared to controls, bone mineral content (BMC) and bone mineral density (BMD), as measured by DXA, were significantly decreased in GnRHa-treated rats in total body and femur at 10 and 24 weeks of age (P < 0.05). The results were even more significant after adjusting for weight. After this adjustment, spine BMC and BMD at 10, 17 and 24 weeks were significantly lower in the treatment group (P < 0.05). Trabecular BMD at the distal femur in the GnRHa treated group as measured by peripheral QCT was significantly lower (P < 0.05). However, cortical bone in the mid-femur had higher BMD, concurrent with lower cortical thickness in the treatment group. In conclusion, a delay in the onset of sexual maturation may cause prolonged, possibly irreversible defect in bone mineralization.

Absorptiometry, Photon↗

PubMed2000

Characterization and complementation of a Pichia stipitis mutant unable to grow on D-xylose or L-arabinose.

Pichia stipitis CBS 6054 will grow on D-xylose, D-arabinose, and L-arabinose. D-Xylose and L-arabinose are abundant in seed hulls of maize, and their utilization is important in processing grain residues. To elucidate the degradation pathway for L-arabinose, we obtained a mutant, FPL-MY30, that was unable to grow on D-xylose and L-arabinose but that could grow on D-arabinitol. Activity assays of oxidoreductase and pentulokinase enzymes involved in D-xylose, D-arabinose, and L-arabinose pathways indicated that FPL-MY30 is deficient in D-xylitol dehydrogenase (D-XDH), D- and L-arabinitol dehydrogenases, and D-ribitol dehydrogenase. Transforming FPL-MY30 with a gene for xylitol dehydrogenase (PsXYL2), which was cloned from CBS 6054 (GenBank AF127801), restored the D-XDH activity and the capacity for FPL-MY30 to grow on L-arabinose. This suggested that FPL-MY30 is critically deficient in XYL2 and that the D-xylose and L-arabinose metabolic pathways have xylitol as a common intermediate. The capacity for FPL-MY30 to grow on D-arabinitol could proceed through D-ribulose.

Arabinose↗

PubMed2000

[Computerized surgical simulation with 3D reconstruction of upper limbs].

This paper reports our study on how to realize computerized surgical simulation through reconstructing 3D anatomy of upper limbs. CT images and serial sections of upper limbs were matched to reconstruct 3D images. We compiled the computer programs of 3D reconstruction and surgical simulation with borland C++ computer language, and built 3D digital model of anatomic structure of upper limbs. The results showed that all structures reconstructed could be displayed alone, in any group or totally. While operating, we could choose one of three segments of the upper limbs model and operate on any parts and in any direction. The surgical simulation system could be used to design operative schemes, choose the best operative paths, and teach the processes of operations and anatomy. It could run in 586-personal computers.

Arm↗

PubMed2000

Immunolocalization of heat shock protein 70 during reparative dentinogenesis.

OBJECTIVE: To investigate the immunolocalization of heat shock protein 70 (hsp 70) during reparative formation and to discuss the role of heat shock response in dental pulp injury and repair. METHODS: A single cavity was prepared in the mesial surface of the first molars of both maxilla and mandible in Wistar rat. The animals were sacrificed at 3, 15, and 30 days post-operation. After the histological process, the paraffin sections were reacted with monoclonal antibodies against rat hsp 70 using the strept-avidin-biotin-peroxidase complex method. RESULTS: Immunolocalization demonstrated heavy staining for hsp 70 in normal pulp and at different stages of dental pulp repair. In normal pulp, immunoreactivity was visualized in the odontoblasts and the pulp fibroblast. In the group sacrificed at 3 days, heavy staining was located in the odontoblast process and cytoplasm. After 15 days, the newly formed odontoblast-like cells were strongly stained. At 30 days, the same staining intensity was observed in odontoblast-like cells and in pulp cells. No staining was seen in reparative dentin. CONCLUSION: These results demonstrated that heat shock protein 70 might play an important role as a molecular chaperone during reparative dentin formation.

Animals↗

PubMed2000

The research and development of noncontact 3-D laser dental model measuring and analyzing system.

OBJECTIVE: To research and develop a new laser scanning 3-dimensional digitization system for collecting, showing, and measuring the data of dental casts. MATERIAL AND METHODS: According to the 3-dimensional measuring method, by using 2 pulsate motors to make the synthetic movement of the dental cast, a special semiconductor laser, and 2 special line array CCD, the 3-D data could be found anywhere on the surface of the dental cast. The program, developed with Visual C++ language under the Windows (Windows tm) system, can control the scanner, rebuild the 3-D graphics and measure the data of the dental cast. RESULTS: The system offers 70 x 70 x 70 mm measurement scope, 0.01 mm resoling power, < 0.1 mm mean deviation, and 25 mins for single cast scanning. CONCLUSION: The advantages of this system are its precision, simplicity, high efficiency, and wide range of measurements with complete direct view. This system also supplied new information that cannot be found with traditional measurement methods.

Computer Graphics↗