Biomedical subjects

S Qin

Publications and source records attributed to S Qin.

At least 19 recordsLinked to original sources

PubMed2006

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations.

Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia. Intra-ethnic differences in the genetic variation and haplotypes of UGT1A1 gene have been analyzed in the present study. Relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were also evaluated. We genotyped five functional polymorphisms including -3279T>G and -3156G>A in the enhancer region, (TA)6>7 in the TATA box, and 211G>A (G71R), 686C>A (P229Q) in the exon1 region of UGT1A1 in three groups of healthy Chinese ethnic populations, consisting of 264 subjects of She origin, 539 of Han origin and 273 of Dong origin. The distribution of -3279T>G, (TA)6>7, 211G>A of UGT1A1 differed greatly as between the three ethnic groups. All of six haplotypes differed considerably between at least two of the three groups, which highlighted the need to analyze clinically irinotecan toxicity relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population. Total bilirubin concentration in homozygous carriers of the -3279G and (TA)7 allele were significantly higher than those in heterozygous carriers or homozygous carriers of wild-type alleles. Carriers of the variant haplotypes (-3279G; -3156A; (TA)7; 211G; 686C) had higher serum T-Bil concentrations compared with the other groups. Our results indicate that heterogeneity among different ethnic populations is possibly the result of microevolution and is relevant to studies into the effect of tailored drug treatment.

Adult↗

PubMed2006

Persistent superconductivity in ultrathin Pb films: a scanning tunneling spectroscopy study.

By using a low temperature scanning tunneling microscope we have probed the superconducting energy gap of epitaxially grown Pb films as a function of the layer thickness in an ultrathin regime (5-18 ML). The layer-dependent energy gap and transition temperature (Tc) show persistent quantum oscillations down to the lowest thickness without any sign of suppression. Moreover, by comparison with the quantum-well states measured above Tc and the theoretical calculations, we found that the Tc oscillation correlates directly with the density of states oscillation at E(F) . The oscillation is manifested by the phase matching of the Fermi wavelength and the layer thickness, resulting in a bilayer periodicity modulated by a longer wavelength quantum beat.

Journal Article↗

PubMed2006

Loss pathways of N-nitrosodimethylamine (NDMA) in turfgrass soils.

N-nitrosodimethylamine (NDMA) is a potent carcinogen that is often present in municipal wastewater effluents. In a previous field study, it was observed that NDMA did not leach through turfgrass soils following 4 mo of intensive irrigation with NDMA-containing wastewater effluent. To better understand the loss pathways for NDMA in landscape irrigation systems, a mass balance approach was employed using in situ lysimeters treated with 14C-NDMA. When the lysimeters were subjected to irrigation and field conditions after NDMA application, very rapid dissipation of NDMA was observed for both types of soil used in the field plots. After only 4 h, total 14C activity in the lysimeters decreased to 19.1 to 26.1% of the applied amount, and less than 1% of the activity was detected below the 20-cm depth. Analysis of plant materials showed that less than 3% of the applied 14C was incorporated into the plants, suggesting only a minor role for plant uptake in removing NDMA from the vegetated soils. The rapid dissipation and limited downward movement of NDMA in the in situ lysimeters was consistent with the negligible leaching observed in the field study, and suggests volatilization as the only significant loss pathway. This conclusion was further corroborated by rapid NDMA volatilization found from water or a thin layer of soil under laboratory conditions. In a laboratory incubation experiment, prolonged wastewater irrigation did not result in enhanced NDMA degradation in the soil. Therefore, although NDMA may be present at relatively high levels in treated wastewater, gaseous diffusion and volatilization in unsaturated soils may effectively impede significant leaching of NDMA, minimizing the potential for ground water contamination from irrigation with treated wastewater.

Carbon Isotopes↗

PubMed2006

Characterization of carotenoid hydroxylase gene promoter in Haematococcus pluvialis.

Astaxanthin, a high-value ketocarotenoid is mainly used in fish aquaculture. It also has potential in human health due to its higher antioxidant capacity than beta-carotene and vitamin E. The unicellular green alga Haematococcus pluvialis is known to accumulate astaxanthin in response to environmental stresses, such as high light intensity and salt stress. Carotenoid hydroxylase plays a key role in astaxanthin biosynthesis in H. pluvialis. In this paper, we report the characterization of a promoter-like region (-378 to -22 bp) of carotenoid hydroxylase gene by cloning, sequence analysis and functional verification of its 919 bp 5'-flanking region in H. pluvialis. The 5'-flanking region was characterized using micro-particle bombardment method and transient expression of LacZ reporter gene. Results of sequence analysis showed that the 5'-flanking region might have putative cis-acting elements, such as ABA (abscisic acid)-responsive element (ABRE), C-repeat/dehydration responsive element (C-repeat/DRE), ethylene-responsive element (ERE), heat-shock element (HSE), wound-responsive element (WUN-motif), gibberellin-responsive element (P-box), MYB-binding site (MBS) etc., except for typical TATA and CCAAT boxes. Results of 5' deletions construct and beta-galactosidase assays revealed that a highest promoter-like region might exist from -378 to -22 bp and some negative regulatory elements might lie in the region from -919 to -378 bp. Results of site-directed mutagenesis of a putative C-repeat/DRE and an ABRE-like motif in the promoter-like region (-378 to -22 bp) indicated that the putative C-repeat/DRE and ABRE-like motif might be important for expression of carotenoid hydroxylase gene.

Base Sequence↗

PubMed2005

Chemokine-receptor expression on T cells in lung compartments of challenged asthmatic patients.

BACKGROUND: The interaction of chemokines with their receptors strongly influences the migration of leucocytes. OBJECTIVE: In order to assess the contribution of these molecules to the local recruitment of T cells in bronchial asthma, we analysed the expression of 14 chemokine receptors on lung-derived T cells. METHODS: Chemokine-receptor expression by T cells derived from the peripheral blood, the bronchoalveolar lavage fluid and the bronchial mucosa was analysed by flow cytometry and immunohistochemistry. Expression profiles in healthy and mildly asthmatic individuals were compared, the latter prior and after segmental allergen provocation. RESULTS: Compared with peripheral blood, alveolar T cells expressed significantly more CCR2, CCR5, CCR6, CXCR3 and CCR4. However, no differences were observed between healthy controls and unchallenged asthmatics. In patients developing significant inflammatory responses following specific allergen challenge, a marked increase in the percentage of CCR4+ and CCR7+, and reduced numbers of CXCR3-bearing alveolar T cells were detected. Following specific allergen challenge, chemokine-receptor expression profiles of T cells from the alveolar space and the mucosa or the submucosa were similar, excluding a particular subcompartmentalization of the chemokine/chemokine-receptor system. CONCLUSION: The expression of certain chemokine receptors by lung T cells suggests a contribution to the physiological recruitment of T cells to the lungs, both in healthy controls and unchallenged mild asthmatics. However, strong allergen-induced airway responses were associated with a specific chemokine-receptor profile, suggesting the involvement of certain chemokine receptors in the pathogenesis of allergic bronchial inflammation.

Adult↗

PubMed2004

An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium.

Screening of synthetic retinoids for activity against prostate carcinoma cell lines has identified antagonists of retinoic acid receptors (RARs) as potent growth inhibitors (Hammond et al, 2001, Br J Cancer 85, 453-462). Here we report that 5 days of exposure to a high-affinity pan-RAR antagonist (AGN194310) abolished growth of prostate carcinoma cells from 14 out of 14 patients, with half-maximal inhibition between 200 and 800 nM. It had similar effects (at approximately 250 nM) on the prostate carcinoma lines LNCaP, DU-145 and PC-3. AGN194310 inhibited the growth of normal prostate epithelium cells less potently, by 50% at approximately 1 microM. The growth of tumour cells was also inhibited more than that of normal cells when RARbeta together with RARgamma, but not RARalpha alone, were antagonised. Treatment of LNCaP cells with AGN194310 arrested them in G1 of cell cycle within 12 h, with an accompanying rise in the level of p21(waf1). The cells underwent apoptosis within 3 days, as indicated by mitochondrial depolarisation, Annexin V binding and DNA fragmentation. Apoptosis was caspase-independent: caspases were neither cleaved nor activated, and DNA fragmentation was unaffected by the pan-caspase inhibitor Z-VAD-FMK. The ability of AGN 194310 to induce apoptosis of prostate cancer cells and its differential effect on malignant and normal prostate epithelial cells suggests that this compound may be useful in the treatment of prostate cancer.

Apoptosis↗

PubMed2003

Expression of the lacZ reporter gene in sporophytes of the seaweed Laminaria japonica (Phaeophyceae) by gametophyte-targeted transformation.

The seaweed Laminaria japonica (Phaeophyceae) has a two-generation life cycle consisting of haploid gametophytes and diploid sporophytes. Female and/or male gametophytes were transformed using particle bombardment and the histological LacZ assay was performed on sporophytes generated by either parthenogenesis or inbreeding. Female gametophyte-targeted transformation resulted in similar lower efficiencies in both parthenogenetic and zygotic sporophytes, and only a chimeric expression pattern was observed. Male gametophyte-targeted transformation led to a higher efficiency, with 3.5% of the zygotic sporophytes stained completely blue (all-blue), implying the integration of lacZ at the one-cell stage. Polymerase chain reaction analysis using primers specific for a lacZ-vector juncture fragment and subsequent blotting indicated the presence of the introduced gene in the sporophytes. The method reported here has a potential for seaweed transformation using spore-based bombardment followed by the developmental process.

Genes, Reporter↗

PubMed2003

Carbon monoxide concentrations in paediatric sepsis syndrome.

Plasma carbon monoxide (CO) concentrations were measured in 12 patients with sepsis syndrome. CO concentrations were found to be significantly increased in patients compared with those in 30 normal controls. Patients with septic shock had significantly higher plasma CO concentrations than those without shock. Results suggest that CO might play an important role in paediatric sepsis syndrome.

Carbon Monoxide↗

PubMed2001

Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants.

BACKGROUND: Graft rejection after liver transplantation is associated with a lymphocytic infiltrate, the nature of which will be determined by, among various factors, the local activity of chemokines that attract particular subsets of effector cells to the graft. METHODS: The expression of chemokines and receptors in human liver allografts was studied by immunohistochemistry of tissue and flow cytometry of blood and liver-derived lymphocytes. Receptor function was assessed with in vitro chemotaxis. RESULTS: We report increased expression of chemokine receptors CXCR3, CXCR4, and CCR5 on circulating and graft-infiltrating lymphocytes after liver transplantation. Liver-derived T cells responded to the ligands for these receptors in vitro, which suggests that the receptors are functionally active. The chemokine ligands for these receptors were detected in rejecting allografts. CXCR3 ligands interferon-inducible protein 10 and monokine-induced by gamma interferon were detected on sinusoidal endothelium and interferon-inducible T-cell alpha chemoattractant was detected on portal and hepatic vascular endothelium, whereas the CXCR4 ligand, stromal-derived factor (SDF), was restricted to biliary epithelium. CCR5 ligands have previously been shown on portal endothelium. An in vitro model of T-cell alloactivation demonstrated a similar pattern of expression of functional CXCR3, CXCR4, and CCR5 on T cells. Increased expression of chemokine receptors, especially CCR3 and CCR5, was associated with redistribution of activated Kupffer cells in rejecting grafts. CONCLUSIONS: The patterns of chemokine expression in liver allografts during rejection suggest that the recruitment and positioning of lymphocytes is mediated by specific chemokines. Although ligands for the receptors CXCR3 and CCR5 are important for recruitment, the restriction of SDF to bile ducts suggests that CXCR4 may be involved in the retention of alloactivated lymphocytes at sites of graft damage.

Chemokine CXCL10↗

PubMed2001

A new complex variant t(4;15;17) in acute promyelocytic leukemia: fluorescence in situ hybridization confirmation and literature review.

We report a 37-year-old male with acute promyelocytic leukemia (APL) harboring a complex translocation (4;15;17). Karyotypic analysis with R-banding of bone marrow cells revealed 46,XY,t(4;15;17)(q21;q22;q21). Fluorescence in situ hybridization analysis using painting probes for chromosomes 4, 15 and 17 and reverse transcriptase polymerase chain reaction analysis revealed three derivative chromosomes: der(4)t(4;15)(q21;q22), der(15)t(4;15;17)(q21;q22;q21), and del(17)(q21q22). This is the third report of such a translocation and the first confirmed by molecular methods. Considering reported similar cases, it is possible that 4q21 is a nonrandom breakpoint in APL with complex translocations and the gene involved in 4q21 should be investigated.

Chromosomes, Human, Pair 15↗

PubMed2001

Bruton's tyrosine kinase is essential for hydrogen peroxide-induced calcium signaling.

Using Btk-deficient DT40 cells and the transfectants expressing wild-type Btk or Btk mutants in either kinase (Arg(525) to Gln), Src homology 2 (SH2, Arg(307) to Ala), or pleckstrin homology (PH, Arg(28) to Cys) domains, we investigated the roles and structure-function relationships of Btk in hydrogen peroxide-induced calcium mobilization. Our genetic evidence showed that Btk deficiency resulted in a significant reduction in hydrogen peroxide-induced calcium response. This impaired calcium signaling is correlated with the complete elimination of IP3 production and the significantly reduced tyrosine phosphorylation of PLCgamma2 in Btk-deficient DT40 cells. All of these defects were fully restored by the expression of wild-type Btk in Btk-deficient DT40 cells. The data from the point mutation study revealed that a defect at any one of the three functional domains would prevent a full recovery of Btk-mediated hydrogen peroxide-induced intracellular calcium mobilization. However, mutation at either the SH2 or PH domain did not affect the hydrogen peroxide-induced activation of Btk. Mutation at the SH2 domain abrogates both IP3 generation and calcium release, while the mutant with the nonfunctional PH domain can partially activate PLCgamma2 and catalyze IP3 production but fails to produce significant calcium mobilization. Thus, these observations suggest that Btk-dependent tyrosine phosphorylation of PLCgamma2 is required but not sufficient for hydrogen peroxide-induced calcium mobilization. Furthermore, hydrogen peroxide stimulates a Syk-, but not Btk-, dependent tyrosine phosphorylation of B cell linker protein BLNK. The overall results, together with those reported earlier [Qin et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 7118], are consistent with the notion that functional SH2 and PH domains are required for Btk to form a complex with PLCgamma2 through BLNK in order to position the Btk, PLCgamma2, and phosphatidylinositol 4,5-bisphosphate in close proximity for efficient activation of PLCgamma2 and to maximize its catalytic efficiency for IP3 production.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire.

CD56, an adhesion molecule closely related to neural cell adhesion molecule, is an immunophenotypic marker for several unique populations of PBLS: Although CD56(+) cells derive from multiple lymphocyte lineages, they share a role in immunosurveillance and antitumor responses. We have studied the chemokine receptor expression patterns and functional migratory responses of three distinct CD56(+) populations from human peripheral blood. NK-T cells were found to differ greatly from NK cells, and CD16(+) NK cells from CD16(-) NK cells. CD16(+) NK cells were the predominant population responding to IL-8 and fractalkine, whereas NK-T cells were the predominant population responding to the CCR5 ligand macrophage-inflammatory protein-1beta. CD16(-) NK cells were the only CD56(+) population that uniformly expressed trafficking molecules necessary for homing into secondary lymphoid organs through high endothelial venule. These findings describe a diverse population of cells that may have trafficking patterns entirely different from each other, and from other lymphocyte types.

Adult↗

PubMed2001

[Antigen presentation of eosinophils in mice].

OBJECTIVE: To explore whether or not eosinophils can present antigen to T lymphocytes in vivo, and to further elucidate the process and characteristics of antigen-presentation by eosinophils in vivo. METHODS: BALB/c mice were sensitized and challenged by ovalbumin to recruit eosinophil infiltration into the airways. The airway eosinophils were purified and were labeled with a fluorescent dye. The labeled eosinophils were instilled into the mouse tracheas, fluorescent microscope was used to observe the migration of endobronchial eosinophils in vivo. Single cell suspension was prepared from paratracheal lymph nodes of mice receiving antigen-exposed eosinophil instillation, and flow cytometry was used to determine proliferation response of T cells and to identify the subset of responding T cells. RESULTS: By 8 h after tracheal instillation, labeled eosinophils were visible in the subcapsular region and streaming through the subcapsular sinus (19.0 +/- 1.8/mm(2)). With increasing time, the numbers of eosinophils entering the regional lymph nodes increased, peaking at 24 h (59.2 +/- 7.2/mm(2)) and persisting for at least 120 h (29.6 +/- 2.8/mm(2)). In sensitized mice that received 5 x 10(5) antigen-exposed eosinophils, in vivo percentage of proliferating T cell in the paratracheal lymph nodes 1 d after eosinophil instillation (6.9% +/- 0.5%) were much higher than basic control value (3.2% +/- 0.3%, P < 0.01), peaked at day 3 (10.8% +/- 0.8%, P < 0.01), and then declined over 7 d (6.1% +/- 0.6%, P < 0.05). Eosinophil-induced in vivo T cell proliferation was antigen-specific, and the responding T cells were limited to CD4(+) cells. CONCLUSIONS: Eosinophils within the lumina of airways can process inhaled antigens, traffick to regional lymph nodes and function in vivo as antigen-presenting cells to stimulate responses of CD4(+) T cells.

Animals↗

PubMed2001

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗

PubMed2001

A physical map of human chromosome 14.

We report the construction of a tiling path of around 650 clones covering more than 99% of human chromosome 14. Clone overlap information to assemble the map was derived by comparing fully sequenced clones with a database of clone end sequences (sequence tag connector strategy). We selected homogeneously distributed seed points using an auxiliary high-resolution radiation hybrid map comprising 1,895 distinct positions. The high long-range continuity and low redundancy of the tiling path indicates that the sequence tag connector approach compares favourably with alternative mapping strategies.

Chromosomes, Artificial, Bacterial↗

PubMed2001

T cell phenotypes of the normal nasal mucosa: induction of Th2 cytokines and CCR3 expression by IL-4.

Mucosal environments such as that of the nose are points of first contact between the human organism and its environment. At these sites the immune system must be regulated to differentiate between and respond appropriately to pathogens and harmless contaminants. T cell-driven immune responses broadly fall into Th1- or Th2-type phenotypes, with increasing evidence that the recruitment of these T lymphocyte subsets is mediated by selective expression of specific chemokine receptors. We have investigated the immunology of the normal nasal mucosa. We show that nasal T cell lines from normal individuals, expanded by culture in IL-2, show reduced expression of the Th2-type cytokines IL-4 and IL-5 compared with lines derived from the blood of the same subjects. These T cells also show reduced expression of the Th2-selective chemokine receptor, CCR3, but similar levels of CCR4 compared with the blood-derived lines. This apparent suppression of Th2 cytokine and CCR3 expression by nasal T cells was reversed by addition of IL-4 to the culture medium. These data are consistent with the presence of a nasal mucosal microenvironment that suppresses Th2 responses and may represent a protective measure against atopic allergic disease in humans and a favoring of Th1 responses to infectious agents. In contrast, T cell expression of CCR1 was higher in the nose than in the blood regardless of the culture medium cytokine environment in keeping with a role for this receptor in tissue homing or lymphocyte activation.

Adult↗

PubMed2001

Expression of chemokine receptors by lung T cells from normal and asthmatic subjects.

The lung is an important tertiary lymphoid organ with constant trafficking of T cells through the lung in both health and disease. T cell migration is controlled by a combination of adhesion receptors and chemokines expressed on vascular endothelium and in the tissue, often in an organ-specific manner. This leads to selective accumulation of different T cell subsets, a process called lymphocyte homing. There is evidence for a distinct lung-homing pathway, but no specific lung-homing receptors have been described. We analyzed the chemokine receptor profile of lung T cells to determine the extent to which lung T cells shared homing pathways with other organs such as the gut and skin. In addition, we compared expression of receptors in normal and asthmatic individuals to determine whether different pathways were used in health and disease. We observed that lung T cells expressed a profile of chemokine and adhesion receptors distinct from that of gut- and skin-homing T cells although no chemokine receptor specific for the lung was found. In particular, lung T cells expressed CCR5 and CXCR3, but not CCR9 or cutaneous lymphocyte Ag, and only low levels of CCR4 and alpha(4)beta(7). No differences were observed between lung T cells from normal vs asthmatic subjects. This study provides added support for the concept of a lung-homing pathway separate from other mucosal organs such as the gut and suggests that the chemokine pathways that control T cell migration in normal homeostasis and Th2-type inflammatory responses are similar.

Antigens, Differentiation, T-Lymphocyte↗

PubMed2001

Differential expression of chemokine receptors on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages in rheumatoid arthritis.

OBJECTIVE: Since it is likely that monocytes utilize chemokines to migrate to the rheumatoid arthritis (RA) joint, we investigated the expression of C-C chemokine receptors (CCR) 1-6 and C-X-C receptor 3 (CXCR3) in the peripheral blood (PB), synovial fluid (SF), and synovial tissue of patients with RA as well as in the PB of normal subjects. METHODS: We compared chemokine receptor expression on CD14+ monocytes from normal PB, RA PB, and RA SF using 2-color flow cytometry. Correlations with patient clinical data were determined. Chemokine and receptor expression were investigated in RA synovial tissue by immunohistochemistry and 2-color immunofluorescence to identify CD68+ macrophages. RESULTS: Most normal PB monocytes expressed CCR1 (87%) and CCR2 (84%), but not CCRs 3, 4, 5, or 6 or CXCR3. RA PB monocytes expressed CCR1 (56%) and CCR2 (76%), with significantly more expressing CCR3 (18%), CCR4 (38%), and CCR5 (17%) compared with normal PB monocytes. Significantly fewer SF monocytes from RA patients expressed CCR1 (17%), CCR2 (24%), and CCR4 (6%) while significantly more expressed CCR3 (35%) and CCR5 (47%) compared with RA and normal PB monocytes; CCR6 and CXCR3 were rarely detected. Clinically, the erythrocyte sedimentation rate was inversely correlated with the expression of CCR1 and CCR4 by RA PB, and CCR5 expression by RA SF was correlated with the SF white blood cell count. CCR1-, CCR2-, and CCR5-immunoreactive cells were found in RA synovial tissue and colocalized with CD68+ macrophages. RA synovial tissue RANTES (regulated upon activation, normally T cell expressed and secreted chemokine)- and monocyte chemoattractant protein 1-immunoreactive cells colocalized with CCR1 and CCR2, respectively, on serial sections. Macrophage inflammatory protein 1alpha (MIP-1alpha) was principally restricted to vascular endothelium, and MIP-1beta+ macrophages were found throughout the sections. CONCLUSION: Monocytes mainly express CCR1 and CCR2 in normal and RA PB, CCR3 and CCR5 in RA PB and RA SF, and CCR4 in RA PB. The differential expression of chemokine receptors suggests that certain receptors aid in monocyte recruitment from the circulation while others are important in monocyte retention in the joint.

Adult↗