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Z D Liu

Publications and source records attributed to Z D Liu.

36 records · Page 2Linked to original sources

Liquid extraction and ion-pair HPLC for determination of hydrophilic 3-hydroxypyridin-4-one iron chelators.

Hydrophilic 3-hydroxypyridin-4-ones (HPOs), such as 1-(2'-carboxyethyl)-2-methyl-3-hydroxypyridin-4-one (CP38), 1-(3'-hydroxypropyl)-2-methyl-3-hydroxypyridin-4-one (CP41) and 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP102), are orally active iron chelators and ester prodrugs of these molecules are currently under investigation. A liquid extraction method using acetonitrile and 2-propanol (80:20 v/v) under acidic and NaCl-saturated conditions has been developed in order to efficiently extract these HPOs from various matrices. The extracted HPOs were determined using a reversed phase polymer HPLC column (PLRP-S 100 A) and the gradient ion-pair mobile phase containing tetrabutylammonium chloride (5 mM) and EDTA (0.5 mM). The extraction recovery of these chelators in phosphate buffer, rat blood and liver homogenate varied from 85 to 94%. The coefficients of variation (C.V.) for within-day determination were in the range of 1.4-3.3% at 1 mM and 2.0-4.7% at 0.1 mM. High accuracy of determination was also achieved.

Chromatography, High Pressure Liquid↗

Synthesis, physicochemical properties and biological evaluation of aromatic ester prodrugs of 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP102): orally active iron chelators with clinical potential.

The synthesis of seven aromatic ester derivatives of 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridin-4-one is described. These ester prodrugs have been designed to target iron chelators to the liver, the major iron storage organ. In principle this should improve chelation efficacy and minimize toxicity. The distribution coefficients of these ester prodrugs between 1-octanol and MOPS buffer pH 7.4 were measured together with their rates of hydrolysis at pH 2 and pH 7.4, in rat blood and liver homogenate. Esters with heteroaromatic acid moieties were found to be less stable than benzoyl analogues. The in-vivo iron mobilisation efficacy of these ester prodrugs has been compared with that of the parent drug using a 59Fe-ferritin loaded rat model. Many prodrugs were found to enhance the ability of the parent hydroxypyridinone to facilitate 59Fe excretion. However, not all prodrugs provided increased efficacy, demonstrating that lipophilicity is not the only factor which influences drug efficacy. Furthermore, no clear correlation between efficacy and susceptibility to hydrolysis was detected. The picolinic and nicotinic ester derivatives appear to offer the best potential as prodrugs as they have a relatively low LogP value and yet lead to enhanced efficacy over the parent hydroxypyridinone.

Administration, Oral↗

[The influence of the 20 kDa protein from Bacillus thuringiensis subsp. israelensis on the cytolytic activity of CytA].

In order to understand the influence of the 20 kDa protein on the cytolytic activity of CytA protein, a set of PCR primers were designed to amplify 20 kDa protein and CytA protein genes. The genes were ligated to E. coli expression vector pUHE24 and transformed into E. coli XL1 and DH5 alpha. The clones, LZ20, LZcytA and LZ20A containing 20 kDa protein gene, cytA protein gene and 20 kDa-cytA genes were obtained respectively. The influence of the clones on the growth of E. coli cells was determined under induction of IPTG. The results showed that the growth of LZ20 cells were not affected, LZcytA cells were killed, and the growth of LZ20A cells were not affected. It was suggested that expression product of 20 kDa protein gene protected the host cells from the cytolytic effect of CytA protein. This was supported by using different host strains.

Bacillus thuringiensis↗

[Role of human and domestic animal reservoirs of schistosomiasis japonica in Dongting and Boyang Lake regions].

In Dongting and Boyang Lake regions, the main reservoirs of schistosomiasis were farm cattle (mostly buffaloes), pigs and mobile nonnatives. However, the role of these reservoirs in different types of endemic areas were not the same in the transmission of schistosomiasis. In islet-beach type area, the main infectious sources were pigs and local residents. The proportion of IRC (Index of Real Contamination) of local residents and pigs to the total IRC was 30.9% and 39.9% respectively. In fork-beach type area having luxuriant grass and abundant aquatic products, there were a number of buffaloes and people from other places. The proportion of IRC of the nonnative buffaloes and mobile nonnatives made up 51.9% and 21.8% of the total IRC respectively, the main reservoirs being from other places. The embankment-beach type area had a vast snail-infected area and a large number of buffaloes from both local and other places as well as mobile nonnatives. The proportion of IRC of buffaloes and nonnatives made up 69.8% and 21.4% of the total IRC respectively, serving as the main reservoirs. As regard to season differences, the infected buffaloes were the main reservoirs during dry seasons, especially from March to May, whereas the mobile nonnatives including fishermen and boatmen were the main infectious sources during flood seasons from June to October.

Animals↗

Surgical treatment of cervical spine tumors.

Of 40 patients with cervical spine tumor treated from 1980 to 1990, 24 had a primary tumor and 16 a metastatic tumor. Thirty-four patients were operated on through anterior and 5 through posterior approach. Preoperative neck pain was relieved and muscular strength of shoulder and arm increased after operation. Total excision methylmethacrylate or metal prosthesis replacement was used. Total excision of the lesion was emphasized for preventing the recurrence of the tumor. Indications and aims of the operation are discussed.

Adenoma↗

High efficient transfer and expression of human clotting factor IX cDNA in cultured human primary skin fibroblasts from hemophilia B patient by retroviral vectors.

To study the possibility of somatic gene therapy for hemophilia B via gene transfer to primary factor IX-deficient skin fibroblasts, we constructed four retroviral vectors containing factor IX cDNA driven by retroviral LTR promoter, SV40 early promoter and mouse MT-I promoter, respectively. These retroviral vectors were transfected into an amphotropic packaging cell line, PA317 cells, by electroporation, and a human fibrosarcoma cell line, HT1080 cells, was used to assay the factor IX-virus titers of these four virus-producing PA317 cells, which ranged from 2 x 10(4) to 5 x 10(5) cfu/ml. The factor IX proteins produced by bulk population of four virus-producing PA317 cells were determined by ELISA. Results showed that LTR promoter directed the highest production of factor IX at the rate of 584 ng/10(6) cells/24 h, while SV40 early promoter and MT promoter directed about 10 and 20 times less production of factor IX than LTR promoter. The highest expressed retroviral vector XL-IX was used to infect a line of factor IX-deficient human primary skin fibroblasts, FDIX cells. The factor IX secretion rate of the infected FDIX cells was about 549 ng/10(6) cells/24 h and over 75% of secreted factor IX was biologically active. We are convinced that this factor IX-deficient human primary skin fibroblast had been cured, or genetically corrected, by retroviral-mediated gene therapy in vitro.

Adult↗

[The RFLP of LDR152/PstI in the Chinese and its application to linkage analysis in a myotonic dystrophy family].

Myotonic dystrophy (DM) is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset. In the present paper, the DNA from 61 normal individuals and a DM family with 15 members of 4 generations were collected and digested with PstI, then hybridized with the LDR152 (D19S19). The results showed that the alleles for the PstI polymorphism were 19 and 11kb in size (gene frequencies were 0.4344 and 0.5656 respectively, which are obviously different from the previous data reported). In this DM family, the carriers who had lived most of their life without knowing that they had been infected with the disease were detected by the LDR152 and the estimation of DM risk on at-risk-individuals was also calculated.

Chromosomes, Human, Pair 19↗

Comparative efficacy of levo-praziquantel and praziquantel in treatment of schistosomiasis japonica at a single dose.

The result of a randomized double blind comparison of therapeutic efficacy of single doses of levo-praziquantel (L-PZQ) and praziquantel (PZQ) in the treatment of 139 matched pairs of proved cases of schistosomiasis japonica was reported, 268 were chronic early cases and 10 were late cases. The dosage of L-PQZ was 20 mg/kg, and that of PZQ was 40 mg/kg. Four and 6 months after treatment the stool-ova negative conversion rates were 94.8% and 96.3% for the L-PZQ group, and 97.1% and 94.0% for the PZQ group respectively (P greater than 0.05).

Adolescent↗

[Studies on the systematic status of a new species of Drosophila (sophophora)--from morphological to molecular level].

Bock and Wheeler (1972) reviewed the Drosophila melanogaster species group in which more than 70 species were classified into a number of subgroups. One of them is the takahashii species subgroup which is a large subgroup with 12 species. We collected many specimens of drosophilid fly in Mt. Huaping, Guangxi Province and Mt. Siming, Zhejiang Province in 1983, among which taxon A and taxon B were thought to be a new species, belonging to the takahashii subgroup and named as D. liui sp. n. However, after Prof. T. Okada examined this new species, he thought it is the same as the known species D. nepalensis Okada, 1955 from Nepal and later Dr. J. Toda examined the same species and thought it was the known species D. prostipennis Lin, in Bock and Wheeler 1972 from Taiwan and/or D. trilutea Bock and Wheeler 1972 from Borneo, so that D. liui sp. n. is considered as the species incertae sedis. In the present paper, we studied 6 species of this subgroup: D. takahashii, D. lutescens, D. liui sp. n., D. nepalensis, D. prostipennis and D. trilutea. Our studies from morphological to molecular level provided the evidences which can support the description of a new species, hence we draw the conclusion that D. liui sp. n. is a new member of the takahashii subgroup.

Animals↗

[The diagnosable rate of beta-thalassemia in Chinese population and the strategy for selecting genetic markers in prenatal diagnosis of the disease].

It is possible to use some beta-thalassemia gene linkage markers for prenatal diagnosis of the disease currently. But there are some limitations due to incomplete linkage between these genetic markers and beta-thalassemia gene in population. The diagnosable rate of the genetic markers and their combinations have been calculated according to the polymorphism distribution data of the seven genetic markers in Chinese population. Then according to the diagnosable rate of each genetic marker and their combinations, the following is deduced: (1) Precedent estimation to the diagnosable rate of prenatal diagnosis; (2) Select the optimum strategy for prenatal diagnosis of beta-thalassemia suitable for Chinese population. In this paper, an optimum line is presented, regarding to select genetic markers for prenatal diagnosis of beta-thalassemia in Chinese population. Meanwhile, the method of gene linkage analysis and that of using oligonucleotide probe are compared.

Asian People↗

Identification of partial mutational sites in human mitochondrial DNA in the Chinese and its significance.

A simple method for the identification of mutational sites in human mitochondrial DNA (mtDNA) was described. It was based on the human Cambridge sequence as a relative standard sequence and a single base pair substitution in mtDNA as a unique mutational form. The partial mutational sites can be determined using this method which was characterized by combining the restriction mapping with the analysis for the table of human mtDNA potential mutational sites with rapidity and simplicity. In the meanwhile, six mtDNA mutational sites found in Chinese population were identified by means of this method.

China↗

The distribution of P elements in D. melanogaster along the coast of China studied by DNA hybridization method.

The distribution of the P-M system in four local Drosophila melanogaster populations obtained in southern China has been examined by mating tests. There was no P strain. A HindIII fragment of the P element has been cloned, named as pPH 0.86, and used as probe in this study. The distribution of the P element itself in thirteen local D. melanogaster populations along the eastern coast of China has been studied by the method of DNA hybridization. It is found that all the populations obtained from the north of Shanghai carry P elements but few populations from the south of Shanghai carry P elements. In comparison with the mating test, the method of DNA hybridization is more direct and reliable. The origin and trends of distribution of P elements in China are discussed in this paper.

Animals↗

Mitochondrial DNA polymorphism in Chinese.

Human mitochondrial DNA (mtDNA) restriction endonuclease fragment patterns were analyzed using placenta DNA isolated from 273 individuals representing four different nationalities, the Han, the Uygur, the Kazakh and the Hui populations. Thirty-eight fragment patterns (morphs) were observed with the enzyme ApaI, BamHI, EcoRI, HindIII, HinfI, HhaI, HapII, KpnI, Mbol, PstI, PvuII, SacI, ScaL and XhoI. Fourteen new morphs, including some only existing in individual racial and national populations were observed, which indicates that there is a significant difference in the distribution of mtDNA morphs among various national and racial populations. By comparison with the mtDNA sequences in primate species, some mtDNA ancestral morphs were found to be retained in Oriental population today. This result provided indirect evidence that Asia may be one of the human original sources. Genetic distances among four national populations computed and employed in construction of an average linkage tree suggested that the Uygur and the Kazakh populations combined to form a branch at first, then the Han and the Hui came together to form another one, and at last, these two branches converged into a stem. Again, it was found that the internal variation within the Uygur and the Kazakh populations was greater than that within the Han and the Hui populations. These results showed a relationship among the four different national populations in China based on the molecular level.

China↗

Metabolism of 9-(2-chlorobenzyl)-, 9-(2-methylbenzyl)- and 9-(2-methoxybenzyl)-adenines by hamster hepatic microsomes.

It was previously found that 9-benzyladenine (BA) was extensively N1-oxidised by animal hepatic microsomes; further, mononitrosubstitution in the phenyl moiety of BA significantly modified the N1-oxidation rates of the corresponding substrates. In order to establish whether the electronic nature or a steric effect of the substituents in the phenyl moiety is the reason for the modification of N1-oxidation rate, the metabolism of some 2'-substituted 9-benzyladenines, i.e. 9-(2-chlorobenzyl)adenine (2CBA), 9-(2-methyl-benzyl)adenine (2MBA) and 9-(2-methoxybenzyl)adenine (2MOBA), by hamster hepatic microsomes was studied. It was found that the N1-oxide was still the major metabolite for 2CBA. However, only minor amounts of N1-oxides were formed during microsomal incubation with 2MBA and 2MOBA. On the other hand, in spite of the higher N1-oxidation rate of 2CBA, its total biotransformation rate was slightly lower than the other two substrates. Like other 9-aralkyladenines previously studied, dealkylation occurred for all three substrates. It was also found that another two metabolites formed in significant amounts in the incubates from both 2MBA and 2MOBA. These metabolites were not fully characterised and their structures unknown.

Adenine↗