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Biomedical subjects

Li Qin

Publications and source records attributed to Li Qin.

26 records · Page 2Linked to original sources

Spot detection and image segmentation in DNA microarray data.

Following the invention of microarrays in 1994, the development and applications of this technology have grown exponentially. The numerous applications of microarray technology include clinical diagnosis and treatment, drug design and discovery, tumour detection, and environmental health research. One of the key issues in the experimental approaches utilising microarrays is to extract quantitative information from the spots, which represent genes in a given experiment. For this process, the initial stages are important and they influence future steps in the analysis. Identifying the spots and separating the background from the foreground is a fundamental problem in DNA microarray data analysis. In this review, we present an overview of state-of-the-art methods for microarray image segmentation. We discuss the foundations of the circle-shaped approach, adaptive shape segmentation, histogram-based methods and the recently introduced clustering-based techniques. We analytically show that clustering-based techniques are equivalent to the one-dimensional, standard k-means clustering algorithm that utilises the Euclidean distance.

Algorithms↗

Behavioral treatment of obesity in patients taking antipsychotic medications.

OBJECTIVE: Antipsychotic medications are associated with weight gain and metabolic dysregulation, yet little is known about the management of obesity among individuals with severe and persistent mental illness. Thus we sought to evaluate the potential utility of a behavioral weight control program for this population. METHOD: Outpatients receiving psychiatric care at a university medical center who had a body mass index (BMI; weight in kg/[height in m](2)) >or= 30 and were currently taking antipsychotic medication participated in a 12-week group behavioral weight control program. A medical chart review was conducted for each participant's body weight over the 10 months prior to beginning the program. A multiple baseline design was used to determine the impact of the intervention on BMI through 12-month posttreatment follow-up. We also assessed self-reported eating behavior, physical activity, and health-related quality of life. Data were collected from October 2000 to July 2003. RESULTS: Among 35 patients who began the program, 29 (83%) completed treatment, with mean (+/- SD) weight loss of 5.04 (+/- 7.52) pounds (p = .001) and improvements in eating, activity, and quality of life. At 3-month posttreatment follow-up (N = 27; 77%), total mean weight loss was 7.14 (+/- 11.47) pounds (p = .003). Results of a longitudinal model based on general estimating equations indicated that, relative to the pretreatment period, BMI decreased significantly during treatment and remained stable through 12-month posttreatment follow-up. CONCLUSION: Behavioral weight control is a promising approach to the treatment of obesity among outpatients taking antipsychotic medications, but longer and more robust interventions are needed.

Adult↗

Inhibitory effect of melatonin on the growth of H22 hepatocarcinoma cells by inducing apoptosis.

Whether melatonin not only inhibits the growth of H22 hepatocarcinoma cells but also induces apoptosis in vitro was assessed. The anti-proliferative effects of melatonin on tumor cells was observed by MTT assay and tumor cells growth curve assay. And the apoptosis of the cells was studied by acridine orange fluorescence assay and flow cytometry. The cell cycle of the tumor cells was also observed by flow cytometry. It was found that melatonin could significantly inhibit the growth of H22 hepatocarcinoma cells. Incubated with melatonin, chromatin condensation of the tumor cells was observed by fluorescence microscopy. Compared with control, the percentage of apoptotic cells was increased, and the proportion of G0/S increased but that of G2/M decreased. It was suggested that melatonin could directly inhibit the growth of H22 hepatocarcinoma cells by inducing apoptosis and extending the length of cell cycle of the tumor cells.

Antineoplastic Agents↗

Expression and purification of SARS coronavirus membrane protein.

To construct a recombinant plasmid Pet23a-M, the gene encoding severe acute respiratory syndrome (SARS) coronavirus membrane protein was amplified by RT-PCR and cloned into the expression plasmid Pet23a. Results of restriction endonuclease analysis, PCR detection and DNA sequencing analysis revealed that the cloned DNA sequence was the same as that reported. The recombinants were transformed into Escherichia coli (E. Coli) BL21 (DE3) and induced by Isopropyl-beta-D-thiogalactopyranoside (IPTG). The expression of 27 kD (1 kD=0.992 1 ku) protein was detected by SDS-PAGE and pured by metal chelated chromatography. Results of Western-blot showed that this expressed protein could react with antibodies in sera of SARS patients during convalescence. This provided the basis for the further study on SARS virus vaccine and diagnostic agents.

Cloning, Molecular↗

Temporal and spatial expression of integrins and their extracellular matrix ligands at the maternal-fetal interface in the rhesus monkey during pregnancy.

The integrin and extracellular matrix protein (ECM)-mediated adhesion and invasion of the receptive maternal uterine endometrium by trophoblasts is a critical event in the complex physiological process of pregnancy. Although the process has been largely characterized in mice, the relevant mechanism in primates remains unclear. We investigated the expression patterns and dynamic alterations of integrin subunits (alpha1, alpha5, alpha6, beta1, and beta4) and their ECM ligands, such as laminin (LN), type IV collagen (Col IV), and fibronectin (FN), at the maternal-fetal interface during Gestational Days 15, 25, 50, and 100 and at full term in 20 pregnant rhesus monkeys. Immunohistochemistry and in situ hybridization revealed that a relatively high expression of integrins occurred in trophoblast cells at Gestational Day 15, with the peak level occurring at Day 25. The expression level decreased from Day 50 to term. Along the invasive pathway, expression levels of integrin alpha1, alpha5, and beta1 subunits were gradually elevated from the proximal to distal column, reaching peak level in the trophoblast shell, but were reduced in those invasive extravillous cytotrophoblast (EVCT) cells in contact with the decidua. Integrin alpha1, alpha5, beta1, and beta4 subunits were also highly expressed in decidual stromal cells and moderately expressed in the maternal epithelium and endothelium. Immunoreactive FN, LN, and Col IV were distributed in EVCT and decidual stromal cells and part of the uterine epithelial and endothelial cells. These data suggest that the correlated expression of integrins and their ECM ligands at the maternal-fetal interface might be involved in regulation of cell proliferation and differentiation and the counterbalanced invasion-accelerating and invasion-restraining processes in trophoblast cells during the early stage of pregnancy.

Animals↗

Expression of P450 aromatase and 17beta-hydroxysteroid dehydrogenase type 1 at fetal-maternal interface during tubal pregnancy.

Steroidogenesis in the placenta has been studied widely, but little is known about steroid metabolism in ectopic pregnancy. Previous studies have indicated that trophoblast invasion and placentation in the uterus and the fallopian tube may be controlled by similar mechanisms. As far as 17beta-estradiol (E(2)) production is concerned, it has been well demonstrated that its biosynthesis in the placenta involves the action of P450 aromatase (P450arom) and 17beta-hydroxysteroid dehydrogenase type 1 (17HSD1). The purpose of this study was to characterize the expression pattern of P450arom and 17HSD1 at the fetal-maternal interface, particularly in various trophoblast cells, in tubal pregnancy. Using in situ hybridization, P450arom mRNA was localized in syncytiotrophoblast (ST) cells, which are mainly responsible for hormone production during pregnancy, whereas no signal was detected in villous cytotrophoblast (VCT), column CT and extravillous CT (EVCT) cells. Immunohistochemical assays revealed that 17HSD1 is present in ST cells, a large portion of EVCT cells and 20% of column CT cells. On the other hand, no expression of 17HSD1 was detected in VCT cells. In addition, 17HSD1 was found in epithelial cells of the fallopian tube. Interestingly, the expression level of 17HSD1 in fallopian tube epithelium during tubal pregnancy was significantly higher than that during normal cycle. Our data provide the first evidence that normal and tubal pregnancies possess identical expression of P450arom and 17HSD1 in ST cells and therefore, similar E(2) production in the placenta. Further, the association of 17HSD1 with EVCT cells indicates that 17HSD1 perhaps play a role in trophoblast invasion. Finally, increased expression of 17HSD1 in epithelial cells of fallopian tube may lead to a local E(2) supply sufficient for the maintenance of tubal pregnancy.

17-Hydroxysteroid Dehydrogenases↗

A predefined epitope-specific monoclonal antibody recognizes ELDEWA-epitope just presenting on gp41 of HIV-1 O clade.

Diverse variation of HIV-1 is a grave challenge for prevention of viral infection and immunotherapy. Monoclonal antibody (mAb) 2F5 recognizing an epitope ELDKWA (aa669-674) on HIV-1 envelope protein gp41 showed broad neutralizing activity against a lot of HIV-1 strains including primary isolates. However, viral mutation from ELDKWA to ELDEWA resulted in viral evasion from neutralization by mAb 2F5. Using ELDEWA-epitope-peptide (C-GFLDEWAGELDEWA) conjugated with carrier protein keyhole limpet hemocyanin (KLH), a mAb 14D9 (IgGl) was prepared and identified as the mAb with predefined ELDEWA-epitope specificity. The mAb 14D9 recognized the ELDEWA epitope, but not other three epitopes (ELDKWA, ELNKWA and ELEKWA). In comparison, mAb 2F5 could recognize only ELDKWA, but not three neutralization-resistant epitopes (ELDEWA, ELNKWA and ELEKWA). Interestingly, we searched several authoritative HIV sequence databases (http://hiv-web.lanl.gov) and found out that nearly all the viral isolates bearing the ELDEWA epitope belong to the O clade, the only exceptional viral isolate bearing the epitope ELDEWA has been demonstrated to be an intergroup M/O recombinant, which suggests that the ELDEWA-epitope on gp41 represents a specific epitope-marker of HIV-1 O clade. To confirm whether the mAb 14D9 recognizes gp41 of HIV-1 O clade, the rsgp41(IIIB), bearing ELDKWA-epitope was site-directed-mutated to the rsgp41 bearing ELDEWA-epitope. The mAb 14D9 could bind to rsgp41 bearing ELDEWA-epitope in immunoblotting analysis, did not bind to rsgp41 bearing ELDKWA-epitope. These experimental results suggest that the mAb 14D9 with predefined ELDEWA-epitope specificity may be applied to HIV-1 O clade identification.

AIDS Vaccines↗

Comparison of Pgp- and MRP-mediated multidrug resistance in leukemia cell lines.

Drug resistance is a major cause of the failure of anticancer chemotherapy. Multidrug resistance is often caused by overexpression of the P-glycoprotein (Pgp) or the multidrug resistance-related protein (MRP). In the present study, we compared daunorubicin (DNR) accumulation, subcellular distribution, and the effect of modulators on drug accumulation and subcellular distribution in the Pgp-expressing K562 cell line and the MRP-expressing HL60 cell line using reverse-transcriptase polymerase chain reaction, MTT (3-[4, 5-dimethylthiazol-z-yl]-2,5-diphenyltetrazolium bromide) drug cytotoxicity assay, fluorocytometry, and confocal laser scanning microscopy. The 2 resistant cell lines exhibit similar levels of resistance to DNR and decreased drug accumulation. Altered drug subcellular distribution in the resistant cell lines compared to that in the sensitive cell lines was shown and, moreover, differences in drug distributions between the 2 resistant cell lines were found. DNR fluorescence in the resistant HL60 cell line was distributed into punctate regions in the cytoplasm; the nucleus and other cytoplasm were almost negative. In contrast, the resistant K562 cells showed a bright fluorescent signal located in the peripheral cytoplasm and perinuclear region; the nucleus and other cytoplasmic regions showed no signal. Use of the modulator verapamil increased drug accumulation and restored the altered subcellular distribution of the drug in the 2 resistant cell lines. The Golgi apparatus inhibitor brefeldin A had similar action in the resistant HL60 line but had little effect in the resistant K562 line. Therefore, our study suggested that there were differences between the 2 resistant cell lines in the compartments sequestering DNR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗