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Biomedical subjects

X L Han

Publications and source records attributed to X L Han.

15 recordsLinked to original sources
PubMed2007

Pooling batches in drug stability study by using constant-width simultaneous confidence bands.

One important study objective in drug stability studies is to estimate the shelf-life of a drug. A key statistical problem involved in this is how to assess the practical equivalence of different batches of the same drug so that different batches can be subgrouped to produce a single shelf-life for the drug. In this paper constant-width simultaneous confidence bands are proposed to quantify the magnitude of difference between different batches, with a particular view to establish the practical equivalence of different batches. This approach is suitable for the situation that the intercepts and slopes of the regression lines for the batches cannot be assumed to be equal. It is shown how constant-width simultaneous confidence bands can be easily constructed for the multiple comparison of several general linear regression models. In particular, it is shown that constant-width simultaneous confidence bands have a better chance to establish the equivalence than, and so are preferable to, the hyperbola-shaped simultaneous confidence bands considered.

Drug Stability↗
PubMed2001

[Study on mechanical properties of titanius alloy samples fabricated with vacuum-sintered powder metallurgy].

OBJECTIVE: To investigate mechanical properties of titanium alloy samples with vacuum-sintered powder metallurgy. METHODS: Titanium based metal powder mixtures were compacted into green bodies in the double action press and sintered at 1000 degrees centigrade for 15 minutes in a vacuum furnace at 0.025Pa. Then the mechanical properities of the sintered compacts were evaluated. RESULTS: Compressive strength of sintered bodies were 111-921MPa when compacted pressure increased from 100MPa to 300MPa. Compressive strength of sintered bodies increased with compacted pressure. Three particle sizes of titanium powder, -160 mesh, -200/+300 mesh, -300 mesh, did not affect the mechanical properties of sintered bodies. The compressive strength of sintered bodies with the plating of copper and tin were higher than those without the plating. Three-point bending strength and elastic modulus of sintered bodies were respectively 102-182MPa and 12193-26630 when compacted pressure affect the mechanical properties pf sintered compacts. Titanium powder plated with copper and tin is compacted and sintered easily, the mechanical properties of sintered compacts are greatly improved.

English Abstract↗
PubMed2000

[Studies on the sensitivity of Plasmodium falciparum to pyronaridine/sulfadoxine/pyrimethamine in vitro].

OBJECTIVE: To develop an in vitro method for the assessment of drug response in P. falciparum to pyronaridine/sulfadoxine/pyrimethamine (PND/S/P). METHODS: The PND/S/P microtest plate was designed, Rieckmann in vitro microtest(WHO standard kit) was used to test the sensitivity of P falciparum in continuous culture (FCC1/HN strain), and the data obtained were analyzed using a computer programme. Fractional inhibitory concentration (FIC) was calculated to test the possible synergy between PND and S/P. RESULTS: The effect of the PND/S/P plates was fairly stable and the ED50 values of pyronaridine, sulfadoxine and pyrimethamine were 0.11, 215.12 and 2.9 pmol, respectively. The FIC obtained confirmed the synergism between PND and S/P. CONCLUSION: The in vitro method can be used to assess the sensitivity of P. falciparum to pyronaridine/sulfadoxine/pyrimethamine.

Animals↗
PubMed1993

Isolation of cDNA encoding the human NF-E2 protein.

The human homolog of mouse NF-E2 was isolated from the K562 cell line and found to encode a member of the basic leucine-zipper family of DNA-binding regulatory proteins. The deduced amino acid sequence of the mouse and human proteins exhibited near identity. Comparison to the related protein, Nrf1, revealed significant homologies at isolated regions, particularly within the basic domain, suggesting that NF-E2 and Nrf1 are members of a distinct subfamily of basic leucine-zipper proteins that share similar DNA-binding properties. High levels of human NF-E2 mRNA were observed in human erythroleukemic cell lines examined. Extensive survey of human tissue samples found NF-E2 expression not limited to erythropoeitic organs. Expression in the colon and testis suggests that NF-E2 may participate in the regulation of genes other than globin.

Amino Acid Sequence↗
PubMed1993

Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast.

We have devised a complementation assay in yeast to clone mammalian transcriptional activators and have used it to identify a human basic leucine-zipper transcription factor that we have designated Nrf1 for NF-E2-related factor 1. Nrf1 potentially encodes a 742-aa protein and displays marked homology to the mouse and human NF-E2 transcription factors. Nrf1 activates transcription via NF-E2 binding sites in yeast cells. The ubiquitous expression pattern of Nrf1 and the range of promoters containing the NF-E2 binding motif suggest that this gene may play a role in the regulation of heme synthesis and ferritin genes.

Amino Acid Sequence↗
PubMed1992

Induction of covalent DNA adducts in rodents by tamoxifen.

The antiestrogen tamoxifen, increasingly used as adjuvant treatment for breast cancer, has been found to covalently modify DNA of rodents. For instance, the liver DNA of female Sprague-Dawley rats treated with a single injection of tamoxifen contained two DNA adducts. Four additional DNA adducts were formed and adduct concentrations increased 5- 7- and 10-15-fold after three and six tamoxifen injections, respectively, from levels observed after a single dose. The accumulation of DNA adducts with repeated administrations of tamoxifen to rodents may make this drug a poor choice for the chronic preventative treatment of breast cancer.

Acetylcysteine↗
PubMed1992

Regulation of biological functions by an insulin receptor monoclonal antibody in insulin receptor beta-subunit mutants.

We investigated the effects of MA-5, a human-specific monoclonal antibody to the insulin receptor alpha-subunit, on transmembrane signaling in cell lines transfected with and expressing both normal human insulin receptors and receptors mutated in their beta-subunit tyrosine kinase domains. In cell lines expressing normal human insulin receptors, MA-5 stimulated three biological functions: aminoisobutyric acid (AIB) uptake, thymidine incorporation, and S6 kinase activation. Under conditions where these biological functions were stimulated, there was no detectable stimulation of receptor tyrosine kinase. We then combined the use of this monoclonal antibody with cells expressing insulin receptors with mutations in the beta-subunit tyrosine kinase domain; two of ATP binding site mutants V1008 (Gly----Val) and M1030 (Lys----Met) and one triple-tyrosine autophosphorylation site mutant F3 (Tyr----Phe at 1158, 1162, and 1163). In cells expressing V1008 receptors, none of the three biological functions of insulin was stimulated. In cells expressing M1030 receptors, AIB uptake was stimulated to a small, but significant, extent whereas the other two functions were not. In cells expressing F3 receptors, AIB uptake and S6 kinase activation, but not thymidine incorporation, were fully stimulated. The data suggest, therefore, that (1) activation of insulin receptor tyrosine kinase may not be a prerequisite for signaling of all the actions of insulin and (2) there may be multiple signal transduction pathways to account for the biological actions of insulin.

Aminoisobutyric Acids↗
PubMed1992

Semisynthesis and purification of homogeneous plasmenylcholine molecular species.

Methods for the efficient use of limiting amounts of fatty acid probes in the synthesis of individual molecular species of plasmenylcholine have been developed. Plasmenylcholine molecular species were synthesized through acylation of homogeneous 1-O-(Z)-hexadec-1'-enyl-sn-glycero-3-phosphocholine utilizing fatty acid anhydrides generated in situ from combined pools of reactant and recycled fatty acids by repeated addition of small amounts (10 mol%) of N,N'-dicyclohexylcarbodiimide. The efficient generation of reactive anhydrides was accomplished through minimizing irreversible formation of N-acyl urea adducts by maintaining a persistent molar excess of fatty acid (with respect to carbodiimide) during the entire reaction time course. The synthesis of multiple different sn-2 labeled plasmenylcholine probes for utilization in fluorescence, ESR, or 2H NMR spectroscopy as well as isotopically labeled plasmenylcholines for metabolic studies has been achieved in good yield (40-50% of theoretical yield based on fatty acid) by these methods. Rapid and effective purification methods utilizing high-performance liquid chromatography were developed for both large- and small-scale purifications of individual reaction mixtures which collectively resulted in the isolation of homogeneous plasmenylcholine molecular species in high yield from limiting amounts of fatty acid probes.

Acylation↗
PubMed1991

Alterations in membrane dynamics elicited by amphiphilic compounds are augmented in plasmenylcholine bilayers.

The dynamics of binary mixtures of choline glycerophospholipids and lysophospholipids were examined by fluorescence spectroscopy to compare and contrast the effects of each subclass of lysophospholipids on plasmenylcholine and phosphatidylcholine membrane motional characteristics. The decrease in steady-state anisotropy resulting from the introduction of lysoplasmenylcholine into plasmenylcholine bilayers was 4-6-fold greater than that manifest from the introduction of lysophosphatidylcholine into phosphatidylcholine bilayers (i.e., delta r = 0.017 vs. 0.004 or 0.011 vs. 0.002 at 5 C degrees and 10 C degrees above their phase transition temperatures, respectively). Lysoplasmenylcholine was also more potent than lysophosphatidylcholine in perturbing the dynamics of membrane bilayers comprised of phosphatidylcholine as measured by alterations in the steady-state anisotropy of the diphenylhexatriene probe. Finally, lipid matrices comprised of plasmenylcholine were uniformly more susceptible to amphiphilic perturbation (mediated by lysoplasmenylcholine, lysophosphatidylcholine or long chain acylcarnitine) than matrices comprised of phosphatidylcholine. Collectively, these results demonstrate that accumulation of plasmalogen catabolites resulting from activation of plasmalogen-selective phospholipases A2 can potentiate alterations in membrane dynamics during signal transduction in plasmalogen-enriched bilayers.

Animals↗
PubMed1991

Proton nuclear magnetic resonance studies on the molecular dynamics of plasmenylcholine/cholesterol and phosphatidylcholine/cholesterol bilayers.

Physiologically relevant molecular species of plasmenylcholine and phosphatidylcholine were synthesized and their molecular dynamics and interactions with cholesterol were compared by determination of salient proton spin-lattice relaxation times and apparent activation energies for 1H-NMR observable motion. The molecular dynamics of PA PhosCho (1-hexadecanoyl-2-eicosatetra-5',8',11',14'-enoyl-sn-glycero-3-pho sphocholine) in multiple regions of the bilayer. Furthermore, the fluidity gradient of PA PhosCho was larger than that of PA PlasCho as ascertained by 1H spin-lattice relaxation time measurements. Introduction of cholesterol into each bilayer resulted in disparate effects on the dynamics of each subclass including: (1) increased motional freedom in the polar head group of PA PlasCho without substantial alterations in the dynamics of the polar head group of PA PhosCho; and (2) increased immobilization of the membrane interior in PA PlasCho in comparison to PA PhosCho. Analysis of Arrhenius plots of T1 relaxation times demonstrated that the apparent activation energies for vinyl and bisallylic methylene proton NMR observable motion in PA PhosCho were greater than that in PA PlasCho. Thus, comparisons of spin-lattice relaxation times and apparent activation energies demonstrate that vesicles comprised of PA PlasCho and PA PhosCho possess differential molecular dynamics and distinct interactions with cholesterol. Collectively, these results underscore the significance of the conjoint presence of the vinyl ether linkage and arachidonic acid as an important determinant of membrane dynamics in specialized mammalian membranes.

Cholesterol↗
PubMed1990

Plasmenylcholine and phosphatidylcholine membrane bilayers possess distinct conformational motifs.

The conformation of plasmenylcholine near the hydrophobic-hydrophilic interface in membrane bilayers was deduced by determination of critical internuclear distances utilizing truncated driven nuclear Overhauser enhancement. These experiments demonstrated that the beta-vinyl ether proton in plasmenylcholine was in close spatial proximity and nearly equidistant (approximately 3 A) to both the alpha- and beta-methylene protons of the sn-2 aliphatic chain. In contrast, the distances between the alpha-vinyl ether proton and the alpha- and beta-methylene protons of the sn-2 aliphatic chain were greater than or equal to 5 A. Furthermore, the distance between the N-CH3 protons in the polar head group and the methylene protons of the glycerol backbone in plasmenylcholine vesicles is larger than that present in phosphatidylcholine vesicles. Although the proximal portion of the sn-2 acyl chain in phosphatidylcholine is bent, conformational analysis utilizing these distance constraints demonstrated that the carbon atoms which comprise the proximal portion of the sn-2 aliphatic chain in plasmenylcholine are nearly coplanar, in register, and parallel to the sn-1 aliphatic chain. Taken together, these observations indicate that modest covalent alterations in the proximal portion of the sn-1 aliphatic chain in choline glycerophospholipids result in substantial changes in the molecular conformation and packing of hydrated phospholipid bilayers.

Lipid Bilayers↗
PubMed1989

[Change of kidney volume in patients with non-insulin-dependent diabetes mellitus (NIDDM)].

Kidney volume in 87 patients with NIDDM was measured by ultrasound scanning. The poorly controlled diabetics with HbA1 greater than 9.8% showed increased kidney volume (169.5 +/- 24.8 ml/1.73 m2) being larger than normal controls (155.6 +/- 17.3 ml/1.73 m2). The kidney volume was within normal range in diabetics (152.2 +/- 19.3 ml/1.73 m2) with good metabolic control (HbA1 less than 9.8%). There exists a positive correlation between kidney volume and HbA1 level (r = 0.5460, n = 87, P less than 0.01). After effective metabolic control of over 3 months, the increased kidney volume showed significant decrease with reduction of HbA1 level.

Adult↗