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Biomedical subjects

D Qin

Publications and source records attributed to D Qin.

At least 19 recordsLinked to original sources
PubMed2002

Screening of upper digestive tract cancer with dilute hydrochloric acid and alcohol in a Chinese high-risk population--a follow-up study of 12 years.

This is a 12-year follow-up study on screening with a mixture of 2% hydrochloric acid and 18% alcohol for upper digestive tract cancer in a Chinese high-risk population. A public screening for upper digestive tract cancer was conducted from November 1979 to May 1984 by giving a mixture of 2% hydrochloric acid and 18% alcohol to 7280 subjects in high-risk population in Yaocun village, Linxian County, Henan province. The subjects were given 15 ml of this mixture in the morning or at noon before lunch when fasting. Five minutes later, irritative reactions (retrosternal discomfort, warmth, pain or pyrosis) was felt in subjects suffering from oesophageal cancer, oesophagitis, gastritis, mucosal dysplasia or ulcer (positive group). Those with normal oesophageal or gastric mucosa felt nothing (negative group). The overall positive rate was 23.2% (1689/7280). In oesophageal or gastric cancer subjects, the positive rate of these symptoms was 88.7%. In subjects with mucosal dysplasia, it was 71.2%. A total of 26 upper digestive tract cancer patients were found. As a result of 12 years' follow-up, 271 persons with upper digestive tract cancer among the 1689 positive group subjects have been discovered, giving an annual morbidity rate of 1.34%. Among the 5591 negative group subjects, 136 persons have been found to suffer from this cancer, giving an annual morbidity rate of 0.2%. This illustrated that the annual morbidity rate of upper digestive tract cancer in the positive group was 6.65 times of that of the negative group ( <0.0001). In conclusion, screening of upper digestive tract cancer with dilute hydrochloric acid in alcohol is simple, safe, non-traumatic, effective and readily acceptable in a high-risk area in China. It may be feasible in other parts of the world, especially the developing countries.

Central Nervous System Depressants↗
PubMed2001

Improved efficacy of chemotherapy for glioblastoma by radiation-induced opening of blood-brain barrier: clinical results.

PURPOSE: To improve the efficacy of chemotherapy for glioblastoma through the radiation-induced opening of the blood-brain barrier (BBB). METHODS AND MATERIALS: In two previous articles, we have described the results of brain scanning using technetium 99m-labeled somatostatin and the measurement of methotrexate (MTX) concentrations in blood and cerebrospinal fluid (CSF) after i.v. injection. We discovered that the BBB and blood-cerebrospinal fluid barrier opened to a certain extent after 20- to 40-Gy irradiation, thus increasing the degree to which MTX permeated the brain tissue. On the basis of these findings, we retrospectively analyzed the outcome in 56 patients with glioblastoma given either chemotherapy (CCNU) after 20- to 40-Gy irradiation (28 patients) or radiation therapy alone (28 patients). RESULTS: The 1-, 3-, and 5-year survival rates were 57.14%, 22.50%, and 15.00% in the combined-therapy group and 17.86%, 7.14%, and 3.57% in the radiotherapy alone group, respectively. The respective median survival times were 29.11 +/- 6.99 and 9.86 +/- 3.45 months (p < 0.001), which represented a statistically significant difference. CONCLUSION: Our study further confirms that opening of the BBB induced by irradiation with 20-40 Gy may optimize the effects of intracranial chemotherapy.

Adolescent↗
PubMed2001

Downregulation of K(+) channel genes expression in type I diabetic cardiomyopathy.

Type I diabetic cardiomyopathy has consistently been shown to be associated with decrease of repolarising K(+) currents, but the mechanisms responsible for the decrease are not well defined. We investigated the streptozotocin (STZ) rat model of type I diabetes. We utilized RNase protection assay and Western blot analysis to investigate the message expression and protein density of key cardiac K(+) channel genes in the diabetic rat left ventricular (LV) myocytes. Our results show that message and protein density of Kv2.1, Kv4.2, and Kv4.3 are significantly decreased as early as 14 days following induction of type I diabetes in the rat. The results demonstrate, for the first time, that insulin-deficient type I diabetes is associated with early downregulation of the expression of key cardiac K(+) channel genes that could account for the depression of cardiac K(+) currents, I(to-f) and I(to-s). These represent the main electrophysiological abnormality in diabetic cardiomyopathy and is known to enhance the arrhythmogenecity of the diabetic heart. The findings also extend the extensive list of gene expression regulation by insulin.

Animals↗
PubMed2001

Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2.

Mutations in the cyclic nucleotide binding domain (CNBD) of the human ether-a-go-go-related gene (HERG) K+ channel are associated with LQT2, a form of hereditary Long QT syndrome (LQTS). Elevation of cAMP can modulate HERG K+ channels both by direct binding and indirect regulation through protein kinase A. To assess the physiological significance of cAMP binding to HERG, we introduced mutations to disrupt the cyclic nucleotide binding domain. Eight mutants including two naturally occurring LQT2 mutants V822M and R823W were constructed. Relative cAMP binding capacity was reduced or absent in CNBD mutants. Mutant homotetramers carry little or no K+ current despite normal protein abundance and surface expression. Co-expression of mutant and wild-type HERG resulted in currents with altered voltage dependence but without dominant current suppression. The data from co-expression of V822M and wild-type HERG best fit a model where one normal subunit within a tetramer allows nearly normal current expression. The presence of KCNE2, an accessory protein that associates with HERG, however, conferred a partially dominant current suppression by CNBD mutants. Thus KCNE2 plays a pivotal role in determining the phenotypic severity of some forms of LQT2, which suggests that the CNBD of HERG may be involved in its interaction with KCNE2.

Amino Acid Sequence↗
PubMed2001

Follicular dendritic cell accessory activity crosses MHC and species barriers.

Productive follicular dendritic cell (FDC)-B cell interactions appear to involve critical ligand-receptor interactions. Immune complexes (IC) on FDC activate complement and provide FDC with a complement-derived CD21 ligand (CD21L), which bind CD21, while antigen in the IC binds on the B cell-BCR. Further, FDC-FcgammaRIIB binds Fc regions of antibodies in IC and reduces coligation of BCR and FcgammaRIIB minimizing an inhibitor of B cell activation. Given that Fc receptors and complement receptors bind immunoglobulins and complement fragments of other species, we reasoned that FDC accessory activity should cross MHC and species barriers. This prediction was tested using memory lymphocytes from OVA-immune mice and TT-immune humans in combination with FDC from murine lymph nodes and human tonsils. Human and murine FDC converted IC into potent immunogens (specific antibody increased from background to thousands of ng / ml). MHC barriers did not restrict this activity and human FDC worked with murine lymphocytes and murine FDC worked with human lymphocytes. Furthermore, stimulation via MHC-dependent allogeneic or zenogeneic mechanisms did not promote antibody production by FDC. Polyclonal responses stimulated by lipopolysaccharide and pokeweed mitogen were also promoted (10 - 100-fold) and anti-CD21 blocked FDC activity. These results substantiate the hypothesis that FDC are necessary for strong recall responses and that FDC-CD21L is critical.

Animals↗
PubMed2001

Spatial alterations of Kv channels expression and K(+) currents in post-MI remodeled rat heart.

OBJECTIVE: The hypothesis being tested in the present study is that increased anisotropic properties occurs in the remodeled post-infarction heart due to spatial alterations in Kv channels expression and K(+) currents of the remodeled myocardium. METHODS: Three to 4 weeks post myocardial infarction (MI) in the rat, we measured the two components of the outward K(+) current, I(to-fast (f)) and I(to-slow(s)) in the epicardium (epi) and endocardium (endo) of noninfarcted remodeled left ventricle (LV) using patch clamp techniques. Alterations in mRNA and/or protein levels of potassium channel genes Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 were measured in epi, midmyocardium (mid), and endo regions of LV and in the right ventricle (RV). RESULTS: In sham operated rat heart, the density of I(to-f) was 2.3 times greater in epi compared to endo myocytes. In post-MI heart, the density of I(to-f) and I(to-s) decreased to a similar degree in LV epi and endo but the difference in I(to-f) density between epi and endo persisted. The mRNA and/or protein levels of Kv1.4, Kv2.1, Kv4.2 and Kv4.3 but not Kv1.5 decreased to a varying extent in different regions of LV but not in RV of post-MI heart. CONCLUSIONS: Our results suggest that regional downregulation of Kv channels expression and density of K(+) currents can be a significant determinant of increased spatial electrophysiological heterogeneity and contribute to increased electrical instability of the post-MI heart.

Analysis of Variance↗
PubMed2001

Follicular dendritic cells: beyond the necessity of T-cell help.

Follicular dendritic cells (FDCs) are potent accessory cells for B cells, but the molecular basis of their activity is not understood. Several important molecules involved in FDC-B-cell interactions are indicated by blocking the ligands and receptors on FDCs and/or B cells. The engagement of CD21 in the B-cell coreceptor complex by complement-derived CD21 ligand on FDCs delivers a crucial signal that dramatically augments the stimulation delivered by the binding of antigen to the B-cell receptor (BCR). The engagement of Fc gamma receptor IIB (FcgammaRIIB) by the Ig crystallizable fragment (Fc) in antigen-antibody complexes held on FDCs decreases the activation of immunoreceptor tyrosine-based inhibition motifs (ITIMs), mediated by the crosslinking of BCR and FcgammaRIIB. Thus, FDCs minimize a negative B-cell signal. In short, these ligand-receptor interactions help to signal to B cells and meet a requirement for B-cell stimulation that goes beyond the necessity of T-cell help.

Animals↗
PubMed2001

Synchronization of separation and determination based on multichannel mode-filtered light detection with capillary electrophoresis.

A novel method for the synchronization of separation and determination is described, in which a mode-filtered light detector is used as an online detector in capillary electrophoresis. An instrument is described which has been developed for this purpose. The round capillary used in conventional capillary electrophoresis is replaced by an annular column, which is constructed from a naked optical fibre inserted into a fused-silica capillary. In fact, the annular electrophoresis column itself forms part of the mode-filtered light sensor. Along the side of the annular column are several detection channels for gathering and transmitting the mode-filtered light to a charge-coupled device (CCD). Every channel provides information on the sample from the point at which it is located. Using capillary isotachophoresis incorporating the annular column, the analytes in a sample containing alanine (10.0 mM) and glycine (9.7 mM) were simultaneously separated and determined using multichannel mode-filtered light detection with a detection limit of 1.5 mM.

Journal Article↗
PubMed2001

Alterations of sodium channel kinetics and gene expression in the postinfarction remodeled myocardium.

INTRODUCTION: After a myocardial infarction (MI), the heart undergoes a remodeling process that includes hypertrophy of noninfarcted left ventricular myocytes. Alterations in the genetic expression, including reexpression of fetal isogene patterns, can result in electrophysiologic changes that contribute to the arrhythmogenicity of post-MI heart. The present study investigated possible alterations in gene expression of Na+ channel subtypes, as well as the kinetics of the Na+ current (I(Na)), in 3- to 4-week-old post-MI rat remodeled left ventricular myocardium. METHODS AND RESULTS: Using a macropatch technique, we showed increased Na+ channel bursting activity during sustained depolarization in post-MI remodeled myocytes resulting in a large slow component of the I(Na) decay. A tetrodotoxin-sensitive current contributed 18% to the prolonged APD90 of isolated post-MI myocytes compared with 6% in control myocytes. Our molecular studies revealed that, in addition to the rat heart I (rH I) subtype, thought to be the predominant subtype that encodes a tetrodotoxin-resistant isoform, the brain subtypes NaCh I and NaCh Ia also are expressed in the rat myocytes. Post-MI remodeled myocardium showed increased expression of NaCh I protein with reversion of the NaCh Ia/NaCh I isoform ratio toward the fetal phenotype. CONCLUSION: Our findings raise the possibility that the increase in the slow component of I(Na) in post-MI remodeled myocytes is secondary to the increased expression of NaCh I. Additional studies are required to address these questions and to characterize the functional role of the NaCh I subtypes in cardiac myocytes.

Animals↗
PubMed2001

Calcineurin inhibition ameliorates structural, contractile, and electrophysiologic consequences of postinfarction remodeling.

INTRODUCTION: After myocardial infarction (MI), the heart undergoes an adaptive remodeling process characterized by hypertrophy of the noninfarcted myocardium. Calcineurin, a Ca2+-calmodulin-regulated phosphatase, has been shown to participate in hypertrophic signal transduction. METHODS AND RESULTS: We investigated the effects of calcineurin inhibition by cyclosporin A on key structural, contractile, and electrophysiologic alterations of post-MI remodeling. Male Sprague-Dawley rats were divided into four groups: (1) sham-operated; (2) sham + cyclosporin A; (3) post-MI (left anterior descending coronary artery ligation); and (4) MI + cyclosporin A. Cyclosporin A (25 mg/kg/day) was initiated 2 days before surgery and continued for 30 days. Hypertrophy was evaluated by echocardiography and by changes in membrane capacitance of isolated myocytes from noninfarcted left ventricle (LV). The effects of cyclosporin A on hemodynamics and cardiac dimensions were investigated, and changes in diastolic function were correlated with changes in protein phosphatase 1 activity and the basal level of phosphorylated phospholamban. The effects of cyclosporin A on Kv4.2/Kv4.3 genes expression and transient outward K+ current (I(to)) density also were evaluated. One of 12 rats in the post-MI group and 2 of 12 rats in the post-MI + cyclosporin A group died within 48 hours after MI. There were no late deaths in either MI group. There was no evidence of heart failure (lung congestion and/or pleural effusion) in the two groups 4 weeks post-MI. Calcineurin phosphatase activity increased 1.9-fold in post-MI remodeled LV myocardium, and cyclosporin A administration resulted in an 86% decrease in activity. There were statistically significant decreases of LV end-diastolic pressure, LV end-diastolic diameter, and LV relative wall thickness in the post-MI + cyclosporin A group compared with the post-MI group. On the other hand, there was no significant difference in LV end-systolic diameter or peak rate of LV pressure increase between the two post-MI groups. Protein phosphatase 1 activity was elevated by 36% in the post-MI group compared with sham, and this correlated with a 79% decrease in basal level of p16-phospholamban. In the post-MI + cyclosporin A group, the increase in protein phosphatase 1 activity was much less (18% vs 36%; P < 0.05), and the decrease in basal level of p16-phospholamban was markedly ameliorated (20% vs 79%; P < 0.01). The decreases in mRNA levels of Kv4.2 and Kv4.3 and I(to) density in the LV of the post-MI + cyclosporin A group were significantly less compared with the post-MI group. CONCLUSION: Our results show that calcineurin inhibition by cyclosporin A partially ameliorated post-MI remodeled hypertrophy, diastolic dysfunction, decrease in basal level of phosphorylated phospholamban, down-regulation of key K+ genes expression, and decrease of K+ current, with no adverse effects on systolic function or mortality in the first 4 weeks after MI.

Animals↗
PubMed2001

[Elevation distribution of precipitation chemistry in middle/upper troposphere in summer, the northern slope of central Himalayas].

During 1997 summer, fresh snow samples were collected from four snowfall events from the elevation of 5800 to 7000 m in the Dasuopu Glacier region on the northern slope of Mt. Xixabangma (28 degrees 33'N, 85 degrees 44'E), in order to understand the elevation distribution of the middle/upper tropospheric components in the remote region. The correlation between SO4(2-), NO3-, Ca2+ and Mg2+ in precipitation differs with type of air mass, indicating the dominant sources of ions vary in short-term (e.g. several days) during summer low dust period. In general, with elevation increases, the concentrations of NO3-, Ca2+ and Mg2+ decreases, while SO4(2-) increases, which are influenced by the variation of dominant sources of ions.

Air Pollutants↗
PubMed2001

[Chemical characteristics of fresh snow in Mount Everest Region].

The chemistry of fresh snow samples collected in August and September, 1998 from Mount Everest was studied and compared with other fresh snow samples collected in different seasons in this region. The results indicated that major species in precipitation were very low in late summer in Mount Everest region and may be representative of the background of precipitation chemistry of remote regions in the wold. Chemical Characteristics of fresh snow in different seasons had distinct differences and they may reflect different moist source and climatic status. The precipitation in August and September was mainly come from Indian summer monsoon and in April and May it was influenced deeply by the dust of semi-arid and arid regions in central Asia. This indicates the precipitation in this region is climatic sensitively.

Calcium↗
PubMed2001

Capsaicin inhibits Jurkat T-cell activation by blocking calcium entry current I(CRAC).

Capacitative calcium entry (CCE) through stores-operated Ca2+ channels is an absolute requirement for normal activation of T lymphocytes. Organic blockers/inhibitors of the channel(s) that carry the inward Ca2+ current (I(CRAC)) responsible for CCE are few. Here we show that capsaicin, the pungent ingredient of hot chili pepper, blocks receptor-stimulated Ca2+ entry in Jurkat T cells. Indo-1 measurements of intracellular calcium show that capsaicin blocks CCE without affecting release of inositol-1,4,5-trisphosphate-sensitive internal Ca2+ stores with an IC50 of 32 microM. Block of Ca2+ entry by capsaicin is identical whether CCE is evoked by T-cell receptor (TCR) stimulation, heterologous muscarinic M1 receptor stimulation, or via thapsigargin depletion of internal Ca2+ stores. Patch-clamp experiments show that capsaicin rapidly and reversibly blocks I(CRAC) with an identical dose response as seen with indo-1 measurements. The major voltage-gated K+ channel in Jurkat cells, Kv1.3, is also blocked by capsaicin. Although Kv1.3 block may contribute to reducing CCE by changes in membrane potential, block of I(CRAC) is the primary mechanism by which capsaicin reduces CCE. Capsaicin analogs capsazepine and resiniferatoxin also produce inhibition of CCE via block of I(CRAC). Upon application of capsaicin to Jurkat cells in culture we observed an inhibition of interleukin-2 (IL-2) production in response to TCR stimulation. The dose dependence of capsaicin's reduction of IL-2 was comparable with its block of I(CRAC), thereby illustrating the functional relevance of capsaicin's block of lymphocyte CCE. Thus, capsaicin and its numerous analogs may have potential use as immunomodulatory drugs and should be further investigated in models of inflammation and T-cell activation.

Calcium Channel Blockers↗
PubMed2001

[Therapeutic effect on glioblastoma of chemotherapy on the basis of brain irradiation].

OBJECTIVE: To study the efficacy of chemotherapy for glioblastoma on the basis of brain irradiation. METHODS: It was previously reported that the permeability of the blood brain barrier (BBB) to methotrexate could be increased by brain irradiation. In this study, glioblastoma patients were divided into 2 groups, 28 patients in each group. On group of patients was treated with CCNU or BCNU after having given 20-40 Gy irradiation to the brain. The other group of patients received radiation treatment alone. RESULTS: The 1-, 3-, and 5-year survival rate of the two groups of patients was 57.1%, 22.5%, 15.0% and 17.9%, 7.1%, 3.6%, respectively. The median survival time was 29.7 +/- 7.0 and 9.7 +/- 3.5 months, respectively (P < 0.001). CONCLUSION: Increase in permeability of the BBB after 20-40 Gy brain irradiation may provide an optimal chance for intracranial chemotherapy of glioblastoma.

Adolescent↗
PubMed2000

Structure of the FHA1 domain of yeast Rad53 and identification of binding sites for both FHA1 and its target protein Rad9.

Forkhead-associated (FHA) domains have been shown to recognize both pThr and pTyr-peptides. The solution structures of the FHA2 domain of Rad53 from Saccharomyces cerevisiae, and its complex with a pTyr peptide, have been reported recently. We now report the solution structure of the other FHA domain of Rad53, FHA1 (residues 14-164), and identification of binding sites of FHA1 and its target protein Rad9. The FHA1 structure consists of 11 beta-strands, which form two large twisted anti-parallel beta-sheets folding into a beta-sandwich. Three short alpha-helices were also identified. The beta-strands are linked by several loops and turns. These structural features of free FHA1 are similar to those of free FHA2, but there are significant differences in the loops. Screening of a peptide library [XXX(pT)XXX] against FHA1 revealed an absolute requirement for Asp at the +3 position and a preference for Ala at the +2 position. These two criteria are met by a pThr motif (192)TEAD(195) in Rad9. Surface plasmon resonance analysis showed that a pThr peptide containing this motif, (188)SLEV(pT)EADATFVQ(200) from Rad9, binds to FHA1 with a K(d) value of 0.36 microM. Other peptides containing pTXXD sequences also bound to FHA1, but less tightly (K(d)=4-70 microM). These results suggest that Thr192 of Rad9 is the likely phosphorylation site recognized by the FHA1 domain of Rad53. The tight-binding peptide was then used to identify residues of FHA1 involved in the interaction with the pThr peptide. The results are compared with the interactions between the FHA2 domain and a pTyr peptide derived from Rad9 reported previously.

Amino Acid Motifs↗
PubMed2000

Fc gamma receptor IIB on follicular dendritic cells regulates the B cell recall response.

Generation of the B cell recall response appears to involve interaction of Ag, in the form of an immune complex (IC) trapped on follicular dendritic cells (FDCs), with germinal center (GC) B cells. Thus, the expression of receptors on FDC and B cells that interact with ICs could be critical to the induction of an optimal recall response. FDCs in GCs, but not in primary follicles, express high levels of the IgG Fc receptor Fc gamma RIIB. This regulated expression of Fc gamma RIIB on FDC and its relation to recall Ab responses were examined both in vitro and in vivo. Trapping of IC in spleen and lymph nodes of Fc gamma RII-/- mice was significantly reduced compared with that in wild-type controls. Addition of ICs to cultures of Ag-specific T and B cells elicited pronounced Ab responses only in the presence of FDCs. However, FDCs derived from Fc gamma RIIB-/- mice supported only low level Ab production in this situation. Similarly, when Fc gamma RIIB-/- mice were transplanted with wild-type Ag-specific T and B cells and challenged with specific Ag, the recall responses were significantly depressed compared with those of controls with wild-type FDC. These results substantiate the hypothesis that FcgammaRIIB expression on FDCs in GCs is important for FDCs to retain ICs and to mediate the conversion of ICs to a highly immunogenic form and for the generation of strong recall responses.

Animals↗
PubMed2000

Inhibition of protein kinase C(alpha) by dequalinium analogues: dependence on linker length and geometry.

Analogues of a bipartite compound, dequalinium (DECA) (quinolinium, 1,1'-(1,10-decanediyl)bis(4-amino-2-methyl diiodide)), were tested for inhibition of protein kinase C(alpha) (PKC(alpha)). In vitro assays of monomeric and dimeric analogues support a model in which DECA inhibits PKC(alpha) by an obligatory two-point contact, a unique mechanism among PKC inhibitors. The presence of unsaturation in the center of the C(10)-alkyl linker produced geometric isomers with different inhibitory potencies: cis IC(50) = 52 +/- 12 microM and trans IC(50) = 12 +/- 3 microM, where the trans isomer was equipotent to that of the saturated C(10)-DECA. DECA analogues with longer, saturated linkers (C(12), C(14), or C(16)) exhibited enhanced inhibitory potencies which reached a plateau with the C(14)-linker (IC(50) = 2.6 +/- 0.2 microM). Metastatic melanoma cells treated with 250 nM C(12)-, C(14)-, or C(16)-DECA and irradiated with long-wave UV light (which causes irreversible inhibition of PKC(alpha) by DECA) confirmed the linker-dependent inhibition of intracellular PKC(alpha) activity.

Animals↗