Biomedical subjects

Ying Liu

Publications and source records attributed to Ying Liu.

At least 361 records · Page 20Linked to original sources

PubMed2003

A multi-mechanistic drug release approach in a bead dosage form and in vitro/in vivo correlations.

An in vitro/in vivo relationship of a combined multi-mechanistic dosage form has now been established in the literature. In our previous study, we successfully prepared a combination of immediate release, enteric coated, and controlled-release (CR) beads and mathematically modeled in vitro and in vivo drug release characteristics of the combination based on the release profiles of individual beads. The objective of the present study is to develop in vitro/in vivo correlations (IVIVC) for three individual beads and the combination using theophylline as a model drug and the beagle dog as an animal model. In the study, an IVIVC correlation is estimated by two-stage procedures: deconvolution followed by comparison of the fraction of drug absorbed to the fraction of drug dissolved. The Wagner-Nelson mass balance method was used to deconvolute plasma drug concentration-time curves. In vitro, a two-stage medium (0.1 N HCl and pH 6.5 phosphate buffer) was used for the dissolution test; a 2h first stage (acidic) was selected based on the average gastric emptying time in a fasted dog. In vivo, t(lag) was used for the gastric emptying process for enteric coated beads and the combination, which contains enteric coated beads. A time-scaling technique was used to consider the rate difference between in vitro dissolution and in vivo absorption in the process of IVIVC. As shown in the results, a point-to-point correlation was established for each formulation. The linear regression analysis of the correlation was r2>0.99 for all three individual beads and 0.97 for the combined bead dosage form. The results suggest level A IVIVCs indicating an appropriateness for the in vitro and in vivo models used in this study.

Administration, Oral↗

PubMed2003

A multi-mechanistic drug release approach in a bead dosage form and in vivo predictions.

Our previous study has successfully prepared a combination of immediate release, enteric coated, and controlled release (CR) beads and mathematically modeled in vitro drug release characteristics of the combination based on the release profiles of individual beads. The objectives of the present study are to evaluate the combination and individual beads in vivo and to mathematically model in vivo drug input characteristics of the combination based on the in vivo input of individual beads. Beagle dogs were used as an animal model, and theophylline as a model drug. In vivo percent drug absorbed at different times (input function) after administration of a capsule bead dosage form was calculated using the Wagner-Nelson deconvolution method using intravenous injection of theophylline in each dog as a reference. The in vivo input functions of individual beads were each fitted to appropriate mathematical equations. The in vivo input function of the bead combination dosage form was calculated based on the individual mathematical equations (expected), and verified experimentally in vivo (experimental). The results showed that all bead dosage forms behave in vivo as defined in vitro. Enteric coated beads significantly delay the time to reach the maximum concentration of drug (tmax=4.9 h) compared to uncoated immediate release beads (2 h). The lag time of enteric coated beads is 1.1 h. CR beads showed both longer tmax (6 h) and mean residence time (MRT=9.7 h) compared to the uncoated immediate release beads (tmax=2 h and MRT=7.1 h) as designed in vitro. The in vivo input functions for the three individual beads can be fitted to equations as a function of square root of time. The combined bead dosage form showed tmax of 2.4 h and MRT of 7.9 h. The experimental and expected in vivo input profiles agreed to within +/- 12% (residues at individual data points). Our results suggest that the drug input function of a combined multi-mechanism oral dosage form can be predicted from the in vivo performance of individual formulations using the dog as an in vivo model.

Administration, Oral↗

PubMed2003

Cost savings for a preferred provider organization population with multi-condition disease management: evaluating program impact using predictive modeling with a control group.

Disease management programs have historically had difficulty demonstrating the financial value of their programs using statistically rigorous methods. This preliminary study utilized a predictive model built from a control group that consisted of individual employer groups whose benefits managers did not purchase disease management. The purpose of this evaluation was to examine the cost savings associated with Health Management Corporation's disease management program for asthma, diabetes, and coronary artery disease. Study and control group members were identified with exactly the same selection criteria as self-insured employer groups (n = 76,194) with preferred provider organization health plans that offered the disease management program. The study group consisted of members (n = 1,009) who were identified as having any of the three conditions and were eligible for the disease management program, regardless of the extent of their participation. The control group included members (n = 2,491) who were identified as having any of the same three conditions. The control group data were used to develop a predictive model designed to calculate expected medical claims costs for the study group. The gross savings of the disease management program was measured by calculating the difference between the expected medical claims costs predicted by the model and the actual medical claims costs for the study group. Preliminary analyses indicate that Health Management Corporation's disease management program produced a return on investment of $2.84: $1.00 and $1.45 gross savings per member per month.

Adolescent↗

PubMed2003

A test of linkage for complex discrete and continuous traits in nuclear families.

This article presents a score test for genetic linkage in nuclear families which applies to any trait having a distribution belonging to the exponential family, which includes binary and normal distributions, and distributions which are skewed or have nonnormal kurtosis. The specific distribution need not be specified and the method applies to sibships of arbitrary size. Tests of complex genetic effects are given, including unspecified mode of inheritance or additive, dominant, overdominant, and recessive modes of inheritance, covariates, multiple-locus models, including gene-gene interactions, and gene-environment interactions. The relation of our method to the Haseman-Elston methods is studied theoretically and by simulation.

Computer Simulation↗

PubMed2003

The corneal stroma is endowed with a significant number of resident dendritic cells.

PURPOSE: Dendritic cells (DCs) comprise a system of highly efficient antigen-presenting cells (APCs) that initiate immune responses. The purpose of this study was to examine the normal stroma for the presence of DCs and other bone marrow (BM)-derived cells. METHODS: Normal uninflamed corneas of BALB/c and other murine strains were excised, and immunofluorescence single- and double-staining for multiple markers was performed for examination by confocal microscopy. Corneal buttons were placed in culture and immunocytochemistry and flow cytometry performed. RESULTS: MHC class II(+)CD80(+)CD86(+) cells were found in the periphery of the anterior normal stroma. These cells were CD45(+), CD11c(+)CD11b(+) suggesting a BM-derived and monocytic DC lineage. In a surprising finding, significant numbers of MHC class II(-)CD80(-)CD86(-) cells were found in the center of the anterior stroma. These cells were also CD45(+)CD11c(+)CD11b(+) but CD3(-), GR-1(-), keratan sulfate(-), and CD8alpha(-), reflecting an immature precursor phenotype of myeloid DC. In addition to DC subsets in the anterior stroma, a CD11c(-)CD11b(+) population of BM-derived cells was found primarily in the posterior stroma, representing monocytes/macrophages. These cells were rarely present in the anterior third of the normal stroma. Further, CD14(+) precursor-type DCs were found throughout the stroma. These in vivo findings were not strain specific and were confirmed by immunocytochemistry and flow cytometry analyses of cells derived from corneal explants and by transmission electron microscopy. CONCLUSIONS: This study demonstrates that, in addition to the known Langerhans cells in the corneal epithelium, at least three BM-derived cell subsets reside in the normal corneal stroma.

Animals↗

PubMed2003

Corneal immunity is mediated by heterogeneous population of antigen-presenting cells.

Corneal antigen-presenting cells (APC), including dendritic cells (DC), were thought to reside exclusively in the peripheral cornea. Here, we present recent data from our group demonstrating that the central cornea is indeed endowed with a heterogeneous population of epithelial and stromal DC, which function as APC. Although the corneal periphery contains mature and immature resident bone marrow-derived CD11c(+) DC, the central cornea is endowed exclusively with immature and precursor DC, both in the epithelium and the stroma, wherein Langerhans cells and monocytic DC reside, respectively. During inflammation, a majority of resident DC undergo maturation by overexpressing major histocompatibility complex class II and B7 (CD80/CD86) costimulatory molecules. In addition to the DC, macrophages are present in the posterior corneal stroma. In transplantation, donor-derived DC are able to migrate to host cervical lymph nodes and activate host T cells via the direct pathway when allografts are placed in inflamed host beds. These data revise the tenet that the cornea is immune-privileged as a result of lack of resident lymphoreticular cells and suggest that the cornea is capable of diverse cellular mechanisms for antigen presentation.

Animals↗

PubMed2003

Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation.

Math1 is a basic helix-loop-helix transcription factor expressed in progenitor cells that give rise to dorsal commissural interneurons in the spinal cord, granule cells of the cerebellum, and sensory cells in the inner ear and skin. Transcriptional regulation of this gene is tightly controlled both temporally and spatially during nervous system development. The signals that mediate this regulation are likely integrated at the Math1 enhancer, which is highly conserved among vertebrate species. We have identified the zinc-finger transcription factor Zic1 as a regulator of Math1 expression. Zic1 binds a novel conserved site within the Math1 enhancer, and represses both the expression of endogenous Cath1 (chicken homolog of Math1) and the activity of a Math1 enhancer driven lacZ reporter when expressed in chick neural tubes. Repression by Zic1 blocks the autoregulatory activity of Math1 itself. Although previous reports have shown that Zic1 and Math1 are both induced by BMP signaling, these genes appear to have opposing functions, as Math1 acts to promote neuronal differentiation in the chick neural tube and excess Zic1 appears to block differentiation. Zic1-mediated repression of Cath1 transcription may modulate the temporal switch between the progenitor state and differentiating dorsal cell types during neural tube development.

Animals↗

PubMed2003

Expression of recombinant XVAX2 peptide-104 of Xenopus laevis and preparation of the antibody.

An N-terminal polypeptide (XVAX2-P104) of the XVAX2 protein, which is involved in controlling the dorsoventral patterning of the retina in Xenopus laevis, was expressed and purified as a Histagged fusion protein (pHis-XVAX2-P104), and it was employed to generate an anti-XVAX2 antibody in New Zealand white rabbits. ELISA analysis shows that the titer of the antibody is as high as approximately 1:100,000. The antibody could specifically recognize the full-length XVAX2 protein in extracts of Xenopus embryos, as determined by Western Blotting.

Animals↗

PubMed2003

[Clinical investigation on characteristics of traditional Chinese medical syndrome of hepatocirrhosis].

OBJECTIVE: To explore the characteristics of traditional Chinese medical syndrome (TCM syndrome) of hepatocirrhosis. METHODS: Clinical information from the four diagnosis methods of traditional Chinese medicine (TCM) and related laboratorial indexes were systematically collected from 223 hepatocirrhosis cases, and the multi-statistical methods including systematic cluster analysis, principal component analysis, stepwise discrimination and variance analysis were made with the software SAS 6.11. RESULTS: Multi-analysis showed that there were 3 categories of syndrome characteristics. Type 1 (134 cases): damp heat, blood stasis, deficiency of liver and spleen Qi; Type 2 (62 cases): deficiency of both Qi and Yin with severe deficiency of Qi, heat with severe dampness, blood stasis; Type 3 (27 cases): deficiency of both Qi and Yin with severe deficiency of Yin, stasis and heat or dampness. Analysis of the changes of the related laboratorial indexes among the three types of syndrome showed that Type 1 mainly manifested asthenia syndrome with sthenia syndrome, and its indexes of AST, ALT, GGT levels were markedly higher than those of Type 2 and Type 3, both of which mainly showed sthenia syndrome with asthenia syndrome, and that Type 3 was in active inflammation, deficiency of both Qi and Yin (deficiency of Yin > deficiency of Qi), and its FN, Alb, FV, FVII, PLT, PCT levels were obviously reduced. CONCLUSION: The multi-statistical methods can reveal the characteristics and regularity of TCM syndrome of hepatocirrhosis, and the 3 categories of syndrome characteristics basically conform to clinical manifestations. The result of TCM syndrome distribution and laboratorial indexes infer that damp heat is the pathological basis of hepatocirrhosis, and the degree of liver function disorder and liver damage may be the pathological basis of deficiency of Yin of both liver and kidney.

Adult↗

PubMed2003

Influence of A7-B7 disulfide bond deletion on the refolding and structure of proinsulin.

To probe the role of [A7-B7] disulfide bond in the structure and folding of proinsulin, [A7, B7Ser]-proinsulin was prepared. The differences in in vitro refolding, oxidation of free thiol groups, circular dichroism (CD) spectra, antibody and receptor binding assays, and sensitivity to tryptic digestion between the mutant and the wild type proteins were studied. The deletion of [ A7-B7] disulfide bond in proinsulin resulted in a significant decrease of alpha- helix content of the molecule and a great increase in sensitivity to tryptic digestion. The [A7-B7] disulfide bond deleted proinsulin showed a great loss of its receptor binding activity. The in vitro refolding study indicated that the r ate of the oxidation of free thiol groups in the mutant was a little slower at t he later stage as compared to the native molecule, but the deletion of [A7-B7 ] disulfide bond had little effect on the refolding yield. A possible proinsulin folding pathway way was proposed. During the folding, the intra-A chain disulfide bond forms first and very fast. The formation of the [A20-B19] disulfide bond is more crucial than [A7-B7] disulfide bond and forms very likely earlier than the latter.

Amino Acid Substitution↗

PubMed2003

Enhancement of antitumor effect of cisplatin against human ovarian carcinoma cells by mifepristone in vivo.

OBJECTIVE: To investigate in vivo the enhancement by mifepristone (RU486) of the antitumor effect of cisplatin (DDP) on human ovarian carcinoma. METHODS: mouse models bearing xenografted cisplatin-resistant ovarian carcinoma were established, in which the changes in tumor volume and the morphology of the implanted tumors were compared before and after treatment with RU486 and DDP. The expression of glucosylceramide synthase (GcS) mRNA was detected by reverse transcriptase-PCR. RESULTS: The morphology of the tumors in RU486 plus DDP group was significantly different as compared with that of the control group. In comparison with exclusive DDP treatment, combined treatment with RU486 and DDP resulted in significantly greater inhibition rates of the tumors (70.48% vs 21.55%, P < 0.01). GcS mRNA expression was lowered in both RU486 plus DDP and RU486 groups, especially in the former group, as compared with that in control group. CONCLUSION: At a non-toxic dose, RU486 may enhance the sensitivity of tumor cells to cisplatin in vivo, possibly through the mechanism of inhibiting GcS expression at the mRNA level.

Abortifacient Agents, Steroidal↗

PubMed2003

[An experimental research on inhibitory action of skeletal muscle conditioned medium on metastases of lung carcinomas].

BACKGROUND & OBJECTIVE: Malignant tumors spread and metastasize in the majority of the organs, but are very rare in skeletal muscles. This study was conducted to explore the effect of organic microenvironment of skeletal muscles on the proliferation of pulmonary large cell carcinomas with different metastatic potential and to investigate the mechanism of the rarity of metastases in skeletal muscles. METHODS: Primary culture of newborn Wistar rat skeletal muscle cells was established, and the murine skeletal muscle conditioned medium(MMCM)was prepared to test its effect in vitro on pulmonary large cell carcinomas with different metastatic potential (PLA-801C with lower potential and PLA-801D with relatively higher potential) by MTT assay. Adriamycin was used as positive control for MMCM; murine benign renal cells BHK-21 were used as negative control for lung carcinoma cells. RESULTS: Proliferation of tumor cell lines of both PLA-801C and PLA-801D was significantly restrained when cultured with MMCM, while BHK-21 cells were not affected(P< 0.05). Compared with PLA-801C (significant only in primary MMCM), PLA-801D showed significantly decreased proliferation even when cultured in higher reciprocal of MMCM dilution(1/16 of primary MMCM). CONCLUSION: Skeletal muscle cells could selectively inhibit the proliferation of cancerous cells in vitro while benign cells are not affected. Tumor cells with higher metastatic potential are more sensitive to this effect.

Animals↗

PubMed2003

[A study on visual search and selection of pull-down menu].

OBJECTIVE: To explore the characteristics of user's visual search and selection through interaction with pull-down menus. METHOD: The visual search time and selection time of interaction were recorded by eye tracking system, when 14 participants were performing the task of pull-down menu selection, with different menu length, type of menu item and position of target item. RESULT: It was found that selection time was influenced jointly by menu length, type of menu item and target location, while visual search time was only influenced by target location. CONCLUSION: The results of this experiment support the hypothesis that the pull-down menu was characteristic of serial, self-terminated and top-down.

Adult↗

PubMed2003

[CT findings and risk factor analysis of hepatic injury induced by three-dimensional conformal radiation therapy].

OBJECTIVE: To investigate the CT findings and define the risk factors for early hepatic injury induced by three- dimensional conformal radiation therapy in patients with primary liver cancer. METHOD: This study recruited 52 patients with primary liver cancer undergoing photon beam radiation at a total dose of 35 to 65 Gy (49.88+/-7.23 Gy) completed within 18 to 31 d. CT examinations were performed within 1 to 3 months after the completion of the therapy, and logistic regression was used to analyze the CT features of early hepatic injury, in an attempt to define the correlation of the injury occurrence with such factors as the patients' age, gender, treatment portal numbers, liver cirrhosis, transcatheter arterial embolization (TACE), postoperative recurrence, total radiation dose, target volume and fractional dose. RESULTS: Thirty-one (59.6%) patients showed CT features of hepatic injury, displayed as the area with hypodensity in consistency with the radiation coverage. The risk factors correlated to the injury occurrence included the total dose, target volume and fractional dose, but not the patients'age, gender, treatment portal number, liver cirrhosis, TACE, postoperative recurrence differences and radiation-induced hepatic injury. CONCLUSION: Early radiation-induced hepatic injury is related to fractional dose, total dose and target volume adopted in radiation therapy. Higher fractional dose, total irradiated dose and larger target volume may result in increased risk of injury.

Adult↗

PubMed2003

[A1166C polymorphism of the angiotensin II type 1 receptor gene and essential hypertension in Han, Tibetan and Yi populations].

OBJECTIVE: To clarify whether A1166C polymorphism of the angiotensin II type 1 receptor (AT(1)R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China. METHODS: This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in genomic DNA. The data were analyzed by ANCOVA, chi-square test, and multiple logistic regression. RESULTS: In normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (chi-square=4.166, P=0.125). The frequency of the A1166 allele in Tibetan male hypertensives was significantly higher than that in normotensives (chi-square=11.46, P=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (P=0.465) or Yi (P=0.357) populations. Body mass index in the Han and Yi populations (P=0.0001), age in the Tibetan and Yi populations (P=0.0001), and AA genotype in the Tibetan male population (P=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (P=0.0040). CONCLUSION: The A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT(1)R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT(1)R gene is probably not involved in the pathogenesis of essential hypertension in Han and Yi populations.

Alleles↗

PubMed2003

[Study on mechanisms of human gastric carcinoma cells apoptosis induced by genistein].

In order to study the apoptosic effect of genistein on human gastric carcinoma SGC-7901 cells, DAPI dyeing and DNA electrophoresis were used. Western Blot was used to detect the changes of the expression of p53 protein, Caspase-3 after SGC-7901 cells were exposed to genistein. The results showed that genistein induced cell apoptosis. Genistein also decreased the expression of mutant p53, and increased the protein expression of Caspase-3. These indicated that genistein could induce the apoptosis of gastric carcinoma cells. The inhibition of the expression of mutant p53 and enhance of the protein expression of Caspase-3 would be possible mechanism.

Adenocarcinoma↗

PubMed2003

Association between HLA-DQA1, -DQB1 gene polymorphisms and susceptibility to asthma in northern Chinese subjects.

OBJECTIVE: Human leukocyte antigen (HLA) class II genes, especially HLA-DQ genes, which are highly polymorphic, have been thought to be candidate loci for the etiology of asthma, and shown to be involved in antigenic presentation. This study was conducted to investigate whether susceptibility or resistance to asthma is associated with HLA-DQA1 and DQB1 genes polymorphism. METHODS: Venous blood samples were collected from northern Chinese population with Han ethnic. (1) One hundred and twenty-five unrelated asthmatic individuals and 52 subjects from 12 asthmatic pedigrees. (2) Ninety-six healthy controls without asthma and atopy with the same ethnic. Genomic DNA was extracted using standard phenol-chloroform method. The second exon of HLA-DQA1 and DQB1 genes were amplified by sequence-specific primer-polymerase chain reaction (SSP-PCR) method. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial reversibility by beta(2)-agonist evaluated. RESULTS: HLA-DQA1 * 0104 allele and HLA-DQB1 * 0201 allele were significantly higher in asthmatics than those in healthy controls (0.408 vs 0.177, P < 0.01; 0.568 vs 0.198, P < 0.01). Odds ratios (ORs) were 3.203 (95% CI 1.699 - 6.037), 5.328 (95% CI 2.883 - 9.849) respectively. Conversely, HLA-DQA1 * 0301 allele and HLA-DQB1 * 0301 were significantly decreased in asthmatics compared to healthy controls (0.296 vs 0.50, P < 0.01; 0.4 vs 0.563, P < 0.05); Logistic regression analysis showed that HLA-DQA1 * 0104 allele was associated independently with asthma etiology, OR [represented by Exp(B)] was 5.0942 with 95% CI 2.2520 - 21.1813; Spearman's analysis showed that HLA-DQA1 * 0104 allele and HLA-DQB1 * 0201 allele were positively associated with atopy, the correlation coefficient were 0.183 and 0.289 respectively, P < 0.01. By contrast, HLA-DQA1 * 0301 allele was negatively related to atopy, the correlation coefficient was -0.168, P < 0.05; linkage analysis did not support the view that HLA-DQA1/DQB1 genes were linked to asthma with LOD value being 0.72. CONCLUSIONS: HLA-DQA1 * 0104 allele and HLA-DQB1 * 0201 allele were implicated in susceptibility to asthma and atopy, HLA-DQA1 * 0301 allele and HLA-DQB1 * 0301 might be protective factor against asthma. Asthma and atopy are multifactorial disorders, HLA-DQA1 and DQB1 genes are involved in the regulation of immune specific response to common allergen.

Adult↗

PubMed2003

[Optimizing cultural conditions of measles vaccine working seed lot with orthogonal experiments].

OBJECTIVE: To improve the quality of measles vaccine and find out good combination of cultural factors of measles vaccine virus seeds. METHODS: Orthogonal experiments were made to confirm optimized cultural factors. 5 lots of optimized measles vaccine working seed lot were prepared. RESULTS: The titers of the optimized vaccine seed improved significantly (> or = 0.69 +/- 0.35 LgCCID50/1.0 ml, P < 0.05), compared with 5 lots of traditional working seed lot. With these seeds we trial-prepared 5 lots of lyophilized vaccines respectively, the titer and stability met the Chinese Requirements of Biological Products. CONCLUSION: The orthogonal experiment is a kind of good method for optimizing cultural conditions of measles vaccine working seed lot. The yield and quality of measles vaccine can be improved in the optimized working seed lot with high titer and good stability.

Culture Media↗