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Biomedical subjects

K Li

Publications and source records attributed to K Li.

At least 433 records · Page 24Linked to original sources
PubMed1976

Steroid metabolism by human mammary carcinoma.

The ability of human mammary tumors to convert 7alpha 3H-testerone to estrogens was examined in order to determine whether this bore any relationship to estrogen receptor and steroid sulfurylation levels; such levels being indicative of hormone dependency. In 8 out of 9 tumors, formation of estradiol-17beta from testosterone was demonstrated. Those tumors showing the lowest conversion of testosterone to estradiol-17beta possessed the highest levels of dehydroepiandrosterone sulfotransferase which lends support to data implicating sulfurylation in the regulation of steroid metabolism in human tumors. All tumors activated sulfate to adenosine-3'-phospho-5'-phosphosulfate and the concentrations were significantly correlated withe the recorded levels of dehydroepiandrosterone sulfate. Estrogen receptor levels did not show any obvious relationship to the other parameters.

Breast Neoplasms↗
PubMedDate not supplied

HPLC determination of captopril in human plasma and its pharmacokinetic study.

A simple and sensitive reversed-phase liquid chromatographic method has been developed and validated for the analysis of captopril in human plasma and the study of the pharmacokinetics of the drug in human body. Captopril was stabilized by forming an adduct with p-bromophenacyl bromide. The adduct formed and 4-chloro-2-nitroaniline (internal standard) were extracted with ethyl acetate:benzene (1:1), and then measured by HPLC using a Spherisorb C18 column as stationary phase and a water:acetonitrile:acetic acid mixture (44:55:0.2, v/v/v) as mobile phase. Captopril was quantified by absorbance at 258 nm. The method proved to be linear in the clinical range of 5-500 ng/mL. The lower limit of detection of captopril in plasma was 2 ng/mL. Intra-day and inter-day coefficients of variation of assay for captopril in plasma were 5.8%-8.5% (n = 7) and 8.0%-9.5% (n = 5), respectively. The recoveries of captopril were 90%-98% for plasma. The data obtained was fitted with 3P87 program on computer to study the pharmacokinetics. The results showed that the disposition of captopril was conformed to a two-compartment open model with Tmax = 0.56 h, Cmax = 266.5 ng/mL and AUC(zero)-infinity = 380.3 ng.h/mL. The method has been used to determine captopril in plasma samples from ten volunteers and provided data on the pharmacokinetics of the drug. The results inferred that captopril is absorbed rapidly and had a relatively short half-life time in healthy individuals.

Administration, Oral↗
PubMedDate not supplied

A high-performance liquid chromatographic method for the determination of nicardipine in plasma and its application to pharmacokinetics in humans.

A simple and sensitive reversed-phase liquid chromatographic method has been developed and validated for the analysis of nicardipine in human plasma and the study of the pharmacokinetics of the drug in human body. Nicardipine and nimodipine (internal standard) in plasma were extracted with hexane-butanol (12:1, v/v) after addition of borate buffer (0.5 mol/mL, pH = 9.0), and then measured by HPLC using a Hypersil C18 column as stationary phase and acetonitrile--KH2PO4 buffer (0.015 M, pH = 5.5)--triethylamine as mobile phase. Nicardipine was quantified by ultraviolet absorbance at 236 nm. The method proved to be linear in the clinical range of 5-200 ng/mL with a regression coefficient of 0.9998. The lower limit of detection of nicardipine in plasma was 2.5 ng/mL. Intra- and inter-day coefficients of variation of assay for nicardipine in plasma were 3.5-5.4% (n = 7) and 5.2-6.4% (n = 5), respectively. The recovery of nicardipine was 92.8-100.8% for plasma. The method has been used to determine nicardipine in plasma samples from 10 volunteers and provided data on the pharmacokinetics of the drug. The results inferred that nicardipine is absorbed rapidly and has a relatively short half-life in healthy individuals. The data obtained was fitted with a 3P87 program to study the pharmacokinetics. The results showed that the disposition of nicardipine was conformed to a two-compartment open model with Tmax = 1.6 +/- 0.3 h, Cmax = 109.8 +/- 38.7 ng/mL, T1/2 = 5.35 +/- 2.28 h and AUC0-->infinity = 322.1 +/- 69.6 ng/h/mI.

Adult↗
PubMedDate not supplied

Thalassaemia trait, red blood cell age and oxidant stress: effects on Plasmodium falciparum growth and sensitivity to artemisinin.

Knowledge of innate mechanisms of protection against malaria could be used to bolster the existing limited treatments. Oxidant stress may play a role in the protective mechanism and the effect of red blood cell (RBC) age has recently been recognized. This study investigated the role of oxidant stress in the protection against malaria in thalassaemic trait RBC (alpha and beta) using an experimental approach which controlled for cell age. 'Young', 'intermediate' and 'old' RBC obtained by Percoll fractionation and whole blood were used to set up malaria cultures. Antioxidants (vitamin E and dithiothreitol) and pro-oxidants (riboflavin, menadione and artemisinin) were added to modulate oxidant stress effect. Antioxidants improved parasite growth. The degree of improvement was significantly greater with increasing RBC age (P < 0.0001), and relatively greater in thalassaemic RBC (P < 0.0001). Pro-oxidants had a parasiticidal effect. With the exception of the 'old' RBC fraction, the median inhibitory concentration (IC50) for riboflavin and menadione was significantly higher in normal RBC. In contrast, the IC50 for artemisinin was significantly higher in 'old' thalassaemic RBC but was similar in the 'young' and 'intermediate' fractions and whole blood. These findings suggest that oxidant stress plays a role in mediating the protection against malaria in thalassaemic RBC. Vitamin E and other antioxidant supplementation could feasibly exacerbate clinical malaria. Conversely, pro-oxidant agents could act as useful adjuvants to therapy. It is important to confirm the reduced sensitivity to artemisinin in 'old' thalassaemic trait RBC, as such an effect may promote selective pressure for the emergence of resistant parasite strains with widespread use of artemisinin.

Age Factors↗
PubMedDate not supplied

Invasion and growth of Plasmodium falciparum is inhibited in fractionated thalassaemic erythrocytes.

Epidemiological and clinical studies have indicated that the thalassaemias may confer protection against malaria. The study reported here investigated this protective effect in vitro, using a new approach which controls for the potential effect of red cell size and age on the virulence of the parasite. A Percoll density gradient method was used to separate alpha- and beta-thalassaemic trait, haemoglobin H and normal red blood cells (RBC) into fractions of different density. Correlations between RBC density, age and size in fractions of all genotypes were established using red cell creatine as an index of cell age. The development of Plasmodium falciparum over 3 erythrocytic cycles (144 h) in whole blood as well as fractionated samples was monitored by slide microscopy and flow cytometry. A significantly reduced rate of parasite invasion and growth was demonstrated in RBC from all thalassaemic genotypes tested. Poor reinvasion rates were noted in the second and third cycles. Increased duration of culture and red cell age also had a greater negative impact on parasite growth in thalassaemic RBC. This poor growth rate was also associated with the arrest of parasite growth at the schizont stage (schizont maturation arrest) and the accumulation of abnormal, trophozoite/schizont stage parasites in the older thalassaemic RBC fractions. These findings suggest a defect in the number and viability of merozoites generated by parasites growing in thalassaemic RBC. Age related factors such as oxidant stress may play a key role in mediating this kind of protective mechanism and deserve further investigation.

Animals↗
PubMedDate not supplied

Microbial synthesis of 3-dehydroshikimic acid: a comparative analysis of D-xylose, L-arabinose, and D-glucose carbon sources.

3-Dehydroshikimic acid is a hydroaromatic precursor to chemicals ranging from L-phenylalanine to adipic acid. The concentration and yield of 3-dehydroshikimic acid microbially synthesized from various carbon sources has been examined under fed-batch fermentor conditions. Examined carbon sources included D-xylose, L-arabinose, and D-glucose. A mixture consisting of a 3:3:2 molar ratio of glucose/xylose/arabinose was also evaluated as a carbon source to model the composition of pentose streams potentially resulting from the hydrolysis of corn fiber. Escherichia coli KL3/pKL4.79B, which overexpresses feedback-insensitive DAHP synthase, synthesizes higher concentrations and yields of 3-dehydroshikimic acid when either xylose, arabinose, or the glucose/xylose/arabinose mixture is used as a carbon source relative to when glucose alone is used as a carbon source. E. coli KL3/pKL4.124A, which overexpresses transketolase and feedback-insensitive DAHP synthase, synthesizes higher concentrations and yields of 3-dehydroshikimic acid when the glucose/xylose/arabinose mixture is used as the carbon source relative to when either xylose or glucose is used as a carbon source. Observed high-titer, high-yielding synthesis of 3-dehydroshikimic acid from the glucose/xylose/arabinose mixture carries significant ramifications relevant to the employment of corn fiber in the microbial synthesis of value-added chemicals.

Arabinose↗
PubMedDate not supplied

Processing of major ABO-incompatible bone marrow for transplantation by using dextran sedimentation.

BACKGROUND: Various open and semi-closed methods are used for red cell (RBC) depletion and hematopoietic progenitor cell (HPC) enrichment of bone marrow (BM) in vitro, but with variable efficacy. A simple, efficient, and safe method using dextran 110k was developed. STUDY DESIGN AND METHODS: An equal volume of 4.5-percent dextran was applied to major ABO-incompatible BM in transfer bags and sedimentation was allowed for 30 minutes. RBCs, nucleated cells (NCs), and mononuclear cells (MNCs) from BM allografts before and after dextran sedimentation (DS) were counted. Flow cytometry, short-term cultures, and long-term cultures were performed to assay the respective recovery of CD34+ cells, colony-forming units (CFUs), and long-term culture-initiating cells (LTC-ICs). RESULTS: Sixteen BM collections were processed. The mean volume was 666 mL (range, 189-1355 mL). The mean +/-1 SD post-DS NC, MNC, CD34+ cell, and CFU counts per kg of the recipient's body weight were 4.11 +/-1.74 x 10(8), 8.98 +/- 3.68 x 10(7), 2.90 +/- 1.95 x 10(6), and 2.03 +/- 2.01 x 10(5), respectively, with the corresponding post-DS recovery being 90.6 percent, 90 percent, 92.4 percent, and 100.8 percent. The numbers of LTC-ICs in cultures (up to 12 weeks) of pre-DS and post-DS samples of five BM allografts were comparable (p = 0.91). Residual RBCs were 5.1 +/- 4.6 (0.1-14) mL with depletion of 96.5 +/- 3.2 percent. There was no significant difference in the mean absolute RBC count in post-DS BM allografts and in four ficoll-treated BM allografts (8.09 x 10(10) vs. 4.9 x 10(9); p = 0.206) and in eight major ABO-incompatible peripheral blood HPC collections (8.09 x 10(10) vs. 9.81 x 10(10); p = 0.87). No posttransplant hemolysis was encountered. Engraftment occurred at 22 +/- 7 days, which is similar to that of four transplants with ficoll-treated BM allografts (22 +/- 9; p = 0.611) and 54 unprocessed BM allografts (19 +/- 6; p = 0.129). CONCLUSION: DS is an efficient method of depleting RBCs in major ABO-incompatible BM allografts without significant loss of HPCs.

ABO Blood-Group System↗
PubMedDate not supplied

Genetic diversity present within the near-complete mtDNA genome of 17 breeds of indigenous Chinese pigs.

The genetic diversity present within the near-complete mitochondrial genome (15,982 bp) was determined from 17 indigenous Chinese pig breeds and 3 European breeds. Animals were selected from 17 Chinese breeds that reflect the large phenotypic diversity of Chinese pigs and represent each of the six breed types, which are grouped based on morphological characteristics. Analysis of nucleotide diversity confirmed a high level of divergence between animals of European versus Asian origin; however, much more limited variation was observed between the 17 indigenous Chinese breeds. Each had a unique haplotype, but the lowest pairwise sequence divergence was only 0.01 +/- 0.01%, observed between the Tongcheng and Yushan Black. Comparison of control region sequence diversity revealed the 17 Chinese breeds contain a lower average pairwise distance (0.61 +/- 0.19%) than a group of European commercial breeds (0.91 +/- 0.21%). The dendrogram constructed from the near-complete mtDNA sequences showed the Chinese sequences loosely clustering into two groups. Although some correspondence with geographic origin was present, notable differences between the dendrogram and the traditional pig breed grouping system were observed.

Animals↗