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Biomedical subjects

Z Qi

Publications and source records attributed to Z Qi.

At least 19 recordsLinked to original sources
PubMed2006

Regulatory effect of sulphatides on BKCa channels.

BACKGROUND AND PURPOSE: Sulphatides are sulphated glycosphingolipids expressed on the surface of many cell types, particularly neurones. Changes in sulphatide species or content have been associated with epilepsy and Alzheimer's disease. As the large conductance, calcium sensitive K(+) channel (BK(Ca)) are modulated by membrane lipids, the aim of the study was to explore possible effects of sulphatides on BK(Ca) channels. EXPERIMENTAL APPROACH: Using patch-clamp techniques, we studied effects of exogenous sulphatides on BK(Ca) channels expressed in Chinese hamster ovary cells. KEY RESULTS: Sulphatides reversibly increased the whole-cell current and the single channel open probability of BK(Ca) channels dose-dependently. The EC(50) value on the channel at +10 mV was 1.6 microM and the Hill coefficient was 2.5. In inside-out patches, sulphatides increased the single channel open probability from both intra- and extra-cellular faces of the membrane, but more effectively with external application. Furthermore, activation of the channels by sulphatides was independent of intracellular Ca(2+) concentration. Sulphatides also shifted the activation curve of the channels to less positive membrane potentials. Mutant BK(Ca) channels lacking a 59 aminoacid region important for amphipath activation (STREX) were less activated by the sulphatides. CONCLUSIONS AND IMPLICATIONS: Sulphatides are novel activators of BK(Ca) channels, independent of intracellular Ca(2+) or other signalling molecules but partly dependent on the STREX sequence of the channel protein. As changes of sulphatide content are associated with neuronal dysfunction, as in epilepsy and Alzheimer's disease, our results imply that these effects of sulphatides may play important pathophysiological roles in regulation of BK(Ca) channels.

Algorithms↗
PubMed2006

Microdissection-based high-resolution genomic array analysis of two patients with cytogenetically identical interstitial deletions of chromosome 1q but distinct clinical phenotypes.

We describe two boys with cytogenetically identical interstitial deletions in the q42.11-q42.13 region of the long arm of chromosome 1 detected by high-resolution G-banding analysis. These children share some phenotypic features but also exhibit distinct morphologic differences. We further characterized the deletions using a new technical strategy--microdissection-based high-resolution genomic array (MHGA) analysis--to define the breakpoints, genomic sizes, and gene contents of the deletions. This showed that the patients had distinguishable deletions that were adjacent but did not overlap, thus explaining the observed phenotypic differences. These results were surprising because we expected at least some degree of overlap to explain the features that were shared. MHGA can quickly give precise and detailed information about any rearrangement in the genome using as little material as a single cell. This novel strategy provides unique advantages for both clinical diagnosis and genomic research.

Child, Preschool↗
PubMed2006

Glomerular injury is exacerbated in diabetic integrin alpha1-null mice.

Excessive glomerular collagen IV and reactive oxygen species (ROS) production are key factors in the development of diabetic nephropathy. Integrin alpha1beta1, the major collagen IV receptor, dowregulates collagen IV and ROS production, suggesting this integrin might determine the severity of diabetic nephropathy. To test this possibility, wild-type and integrin alpha1-null mice were rendered diabetic with streptozotocin (STZ) (100 mg/kg single intraperitoneal injection), after which glomerular filtration rate (GFR), glomerular collagen deposition, and glomerular basement membrane (GBM) thickening were evaluated. In addition, ROS and collagen IV production by mesangial cells as well as their proliferation was measured in vitro. Diabetic alpha1-null mice developed worse renal disease than diabetic wild-type mice. A significant increase in GFR was evident in the alpha1-null mice at 6 weeks after the STZ injection; it started to decrease by week 24 and reached levels of non-diabetic mice by week 36. In contrast, GFR only increased in wild-type mice at week 12 and its elevation persisted throughout the study. Diabetic mutant mice also showed increased glomerular deposition of collagen IV and GBM thickening compared to diabetic wild-type mice. Primary alpha1-null mesangial cells exposed to high glucose produced more ROS than wild-type cells, which led to decreased proliferation and increased collagen IV synthesis, thus mimicking the in vivo finding. In conclusion, this study suggests that lack of integrin alpha1beta1 exacerbates the glomerular injury in a mouse model of diabetes by modulating GFR, ROS production, cell proliferation, and collagen deposition.

Animals↗
PubMed2004

Potential effects of tetrodotoxin exposure to human glial cells postulated using microarray approach.

Sodium channels play an important role in many neurological disorders and also in prostate cancer. Tetrodotoxin (TTX), a blocker of voltage-gated sodium channels has been chiefly used as a molecular probe for the study and characterization of these channels. The regulation of gene expression in response for the exposure of TTX to glial cells which are reported to be involved in neurodegenerative process is poorly understood. Therefore, the present study aims to develop a repository of genes and map it on a few pivotal neurodegenerative pathways to speculate the effect of TTX. Using Affymetrix GeneChip (HG-U133A), we have selected a subset of 692 differentially expressed genes, several of which are-cullin 4A (CUL4A), ubiquitin carrier protein (E2-EPF), proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional protease 7) (PSMB8), protein tyrosine phosphatase type IVA (PTP4A1), intercellular adhesion molecule 1 (ICAM1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caspase 1 (CASP1). These genes, which facilitate some of the neurodegenerative pathways, such as ubiquitin, proteasome, inflammation and kinases, were identified to be up- or down-regulated for the TTX treatment. Thus, the selected genes were further examined on ubiquitin-proteasome mediated inflammatory responses pathway as ample evidence for the role of glial cell-mediated inflammation in the neurodegenerative process are available. In summary, our result provides a basic understanding of the differentially expressed genes along with one of the possible pathway which may have been modulated by the exposure of TTX.

Cell Survival↗
PubMed2004

Additive effects of leflunomide and tacrolimus in prevention of islet xenograft rejection.

Leflunomide is a low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. As the mechanisms of action of leflunomide and tacrolimus are different, we postulated an additive or synergistic effect of the two drugs and investigated the effects of leflunomide alone, or in combination with a suboptimal dose of tacrolimus, on xenogeneic islet transplantation in a rat-to-mouse model. A total of 1200-1500 rat islets were transplanted under the left kidney capsule of streptozotocin-induced diabetic BALB/c mice. The median survival time (MST) of the untreated group was 6 days. Leflunomide at 5, 10 and 20 mg/kg/d administrated for 10 days significantly prolonged MST to 10, 16 and 20 days. A dose of tacrolimus (2 mg/kg/d) was associated with a graft survival of 9 (range 6-12) days; most grafts rejected during ongoing therapy. When tacrolimus (2 mg/kg/d) was combined with leflunomide (10 mg/kg/d), the survival time of the islet xenografts was increased further to 22 days, significantly longer than with leflunomide or tacrolimus alone. In summary, our findings demonstrate that leflunomide prolonged xenogeneic islet graft survival, and that its immunosuppressive effect was improved when combined with tacrolimus.

Animals↗
PubMed2003

Characterization of a functionally expressed stretch-activated BKca channel cloned from chick ventricular myocytes.

We have characterized electrophysiological and pharmacological properties of a stretch-activated BKca channel (SAKcaC) that was cloned from cultured chick ventricular myocytes (CCVM) and expressed in chinese hamster ovary cells (CHO) using the patch-clamp technique. Our results indicate that the cloned SAKcaC keeps most of the key properties of the native SAKcaC in CCVM, such as conductance, ion selectivity, pressure-, voltage- and Ca(2+)-dependencies. However, there was a slight difference between these channels in the effects of channel blockers, charybdotoxin (CTX) and gadolinium (Gd(3+)). The native SAKcaC was blocked in an all-or-none fashion characterized as the slow blockade, whereas the conductance of the cloned SAKcaC was gradually decreased with the blockers' concentration, without noticeable blocking noise. As the involvement of some auxiliary components was suspected in this difference, we cloned a BK beta-subunit from CCVM and coexpressed it with the cloned SAKcaC in CHO cells to examine its effects on the SAKcaC. Although the pharmacological properties of the cloned SAKcaC turned out to be very similar to the native one by the coexpression, it also significantly altered the key characteristics of SAKcaC, such as voltage- and Ca(2+)-dependencies. Therefore we concluded that the native SAKca in CCVM does not interact with the corresponding endogenous beta-subunit. The difference in pharmacological properties between the expressed SAKcaC in CHO and the native one in CCVM suggests that the native SAKca in CCVM is modulated by unknown auxiliary components.

Animals↗
PubMed2001

Phosphorylation of human N-myristoyltransferase by N-myristoylated SRC family tyrosine kinase members.

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the cotranslational and/or posttranslational transfer of myristate to the amino terminal glycine residue of a number of important proteins especially the non-receptor tyrosine kinases whose activity is important for tumorigenesis. Human NMT was found to be phosphorylated by non-receptor tyrosine kinase family members of Lyn, Fyn and Lck and dephosphorylated by the Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin. Deletion of 149 amino acids from the N-terminal end resulted in the absence of phosphorylation suggesting that the phosphorylation sites are located in the N-terminal end of NMT. Furthermore, a site-directed mutagenesis study indicated that substitution of tyrosine 100 with phenylalanine served NMT as a poor substrate for the Lyn kinase. A synthetic peptide corresponding to the amino-terminal region encompassing tyrosine 100 of NMT served as a good substrate for the Lyn and Fyn kinases. Our studies also indicated that NMT was found to interact with Lyn through its N-terminal end in a phosphorylation-dependent manner. This is the first study demonstrating the cross-talk between NMT and their myristoylated protein substrates in signaling pathways.

Acyltransferases↗
PubMed2001

[Isolation and study of one novel full-length gene related to human glioma].

OBJECTIVES: To obtain differentially expressed genes related to human glioma using cDNA microarray and make a preliminary study of one novel full-length gene. METHODS: Total RNA was extracted from human glioma tissues and normal brain tissues, and mRNA was used to make probes. After hybridization and washing procedure, the results of hybridization were scanned using computer system. One gene named 507E08 clone was subsequently analyzed by northern blotting, in situ hybridization, bioinformatics and radiation hybridization. RESULTS: Fifteen differentially expressed novel genes related to human glioma were obtained through four times of hybridization and scanning. Northern blotting and in situ hybridization confirmed that 507E08 clone was lowly expressed in normal human brain tissue and over-expressed in human glioma tissue. BLASTn and BLASTx analysis showed that the clone 507E08 was a novel full-length gene with the length of 2002 bp. This gene, called human ribosomal protein 14.22 gene, codes 203 amino acids and is located on chromosome 14 between D14S1066 Marker and D14S265 Marker. CONCLUSION: cDNA microarray technology can be successfully applied to identify differentially expressed genes with small amount of specimen, high quality, high speed, and high sensitivity. The novel full-length human ribosomal protein 14.22 gene may correlate with formation of human glioma.

Adult↗
PubMed2001

Molecular design and synthesis of artificial ion channels based on cyclic peptides containing unnatural amino acids.

A series of novel cyclic peptides composed of 3 to 5 dipeptide units with alternating natural-unnatural amino acid units, have been designed and synthesized, employing 5-(N-alkanoylamino)-3-aminobenzoic acid with a long alkanoyl chain as the unnatural amino acid. All cyclic peptides with systematically varying pore size, shape, and lipophilicity are found to form ion channels with a conductance of ca. 9 pS in aqueous KCl (500 mM) upon examination by the voltage clamp method. These peptide channels are cation selective with the permeability ratio P(Cl(-))/P(K(+)) of around 0.17. The ion channels formed by the neutral, cationic, and anionic cyclic peptides containing L-alanine, L-lysine, and L-aspartate, respectively, show the monovalent cation selectivity with the permeability ratio P(Na(+))/P(K(+)) of ca. 0.39. On the basis of structural information provided by voltage-dependent blockade of the single channel current of all the tested peptides by Ca(2+), we inferred that each channel is formed from a dimer of the peptide with its peptide ring constructing the channel entrance and its alkanoyl chains lining across the membrane to build up the channel pore. The experimental results are consistent with an idea that the rate of ion conduction is determined by the nature of the hydrophobic alkanoyl chain region, which is common to all the channels.

Amino Acid Sequence↗
PubMed2001

Exchangeability of N termini in the ligand-gated porins of Escherichia coli.

The ferric siderophore transporters of the Gram-negative bacterial outer membrane manifest a unique architecture: Their N termini fold into a globular domain that lodges within, and physically obstructs, a transmembrane porin beta-barrel formed by their C termini. We exchanged and deleted the N termini of two such siderophore receptors, FepA and FhuA, which recognize and transport ferric enterobactin and ferrichrome, respectively. The resultant chimeric proteins and empty beta-barrels avidly bound appropriate ligands, including iron complexes, protein toxins, and viruses. Thus, the ability to recognize and discriminate these molecules fully originates in the transmembrane beta-barrel domain. Both the hybrid and the deletion proteins also transported the ferric siderophore that they bound. The FepA constructs showed less transport activity than wild type receptor protein, but the FhuA constructs functioned with turnover numbers that were equivalent to wild type. The mutant proteins displayed the full range of transport functionalities, despite their aberrant or missing N termini, confirming (Braun, M., Killmann, H., and Braun, V. (1999) Mol. Microbiol. 33, 1037-1049) that the globular domain within the pore is dispensable to the siderophore internalization reaction, and when present, acts without specificity during solute uptake. These and other data suggest a transport process in which siderophore receptors undergo multiple conformational states that ultimately expel the N terminus from the channel concomitant with solute internalization.

Bacterial Outer Membrane Proteins↗
PubMed2001

Dynamic changes in hepatitis C virus genotypes and sequence patterns in plasma donors exposed to reinfection.

Sequential serum samples from four plasma donors (designated A, B, C, and D) at a Chinese blood bank with hepatitis C transmission problems were studied from 1994 to 1997. The samples were examined for antibodies to HCV, for HCV viremia by PCR and HCV genotyping. Co- and superinfections were studied by direct sequencing of the 5'-NCR, core, and HVR-1 regions, using low and high genotype-specific primers targeting the HVR-1, and by cloning of selected samples. Genotype changes occurred in all four donors: A (1b-2a-1b), B (1b-2a-2a/1b-1b), C (1b-2a), and D (1b/2a-1b). Donor D was married to donor B. The 1b isolates of donor A could not be sequenced in the HVR-1 due to low-level viremia. Two early 1b isolates from donors B and C showed high HVR-1 similarity. The later 1b isolates from B had changed significantly but were identical to the isolate from donor D. Spouses B and D also shared genotype 2a strains. The 2a isolates from donors A, B/D, and C differed by 8-10 nucleotides in the HVR-1. The frequent changes in genotype and the appearance of homologous isolates from different subjects indicate transmission at the blood bank. These four donors, all identified shortly after infection, developed very few mutations in the HVR-1 and few quasispecies during a period of 6-18 months. Highly specific primers proved to be superior to cloning for identification of minor virus populations. The results indicate nosocomial transmission of more than one strain at the blood bank studied.

Blood Banks↗
PubMed2001

Initial inhibition of tissue factor signalling reduces chronic vascular changes in isogenic rat aortic transplants.

Vascular changes are considered the major histopathological indicator of chronic allograft dysfunction. These changes are characterized by intimal thickening caused by accumulation of primarily smooth muscle cells. Contributing factors may be of both immunological and nonimmunological origin. Cold ischemia has been shown to trigger intimal proliferation in the absence of alloantigen in an isogenic rat aortic transplant model. We have used this model to investigate the impact of inhibition of tissue factor (TF) signalling on the progression of intimal thickening. Group 1 was treated with recombinant FVIIa inhibited in its active site (rFVIIai), and group 2 served as untreated controls. At 8 weeks the intimal area was measured with image analysis. Medial areas and the proportion of medial necrosis were determined. Animals treated with rFVIIai showed significantly less intimal thickening compared with controls: median 0.147 vs. 0.256 mm2, respectively (p = 0.008). A positive correlation between intimal hyperplasia and medial necrosis (r(s) = 0.79, p = 0.01), as well as adventitial inflammation (r(s) = 0.83, p = 0.009), was found. TF mRNA was not detected in the neointima at 8 weeks, as determined by in situ hybridization. We conclude that active site inhibited FVIIa (rFVIIai) given prior to and directly after implantation of aortic transplants significantly reduces intimal hyperplasia caused by nonimmunological factors in this model.

Animals↗
PubMed2001

Cyclooxygenase-2 selective inhibitors and the kidney.

Cyclooxygenases (COX) are the target of non-steroidal anti-inflammatory drugs (NSAIDs) which exert their therapeutic effect by blocking COX's capacity to metabolize arachidonate to a series of biologically active fatty acids, designated prostaglandins. NSAID use is associated with two major tonicities: gastrointestinal bleeding and renal dysfunction. In the setting of significant physiologic stress, renal function becomes dependent upon prostaglandins and NSAID use may be associated with acute deterioration of renal function, including development of sodium retention, edema, hypertension, hyperkalemia, and or papillary necrosis. Two isoforms, COX1 and COX2, have been identified. They are products of distinct genes and their expression is under different regulatory control. Both COX1 and COX2 are highly expressed in the kidney and both are inhibited by conventional NSAIDs. Accumulating data using recently developed selective COX2 inhibitors suggest that while these agents spare the gastrointestinal tract they have similar renal effects as non-selective NSAIDs. Therefore, caution should be taken when prescribing selective COX2 inhibitor to patients, especially to patients with predisposed physiologic stress.

Animals↗
PubMed2001

[Comparison of specific immune responses to duck hepatitis B virus in infected, immune, and uninfected ducks].

OBJECTIVE: To explore the factor in determining whether hepadnavirus infection is cleared or becomes chronic. METHODS: Experimental groups were established by inoculation with duck hepatitis B virus (DHBV) at different age and schedule. The kinetics of virus replication and the humoral and cell mediated immune response (CMI) by ducks acutely and chronically infected with, or immune to DHBV infection was measured. RESULTS: Infection of the adolescent animals with DHBV led to a transient viremia. The levels of anti-DHBs and anti-DHBc were higher in acutely infected group than in chronically infected group (P<0.05), but lower than in immune group (P<0.01). CMI analysis showed the response to DHBsAg and DHBcAg by peripheral blood mononuclear cells from acutely infected ducks (10 day pi) was stronger than that from chronically infected ones (P<0.05); however, the level of the response reduced over a period of 5 weeks. There were no differences regarding CMI response in acutely infected or immune ducks. CONCLUSIONS: The immune response especially antigen -specific immune response is the key factor in determining the outcome of the infection.

Animals↗
PubMed2001

[Experimental study on the effect of combination therapy with lamivudine and famciclovir against duck hepatitis B virus in vivo].

OBJECTIVE: To study the antiviral effect of combination therapy with the nucleoside analog lamivudine and famciclovir on duck hepatitis virus (DHBV) in vivo. METHODS: The Chongqing duck hepatitis B model was treated with lamivudine and famciclovir by intragastric administration for 4 weeks. DHBV DNA and DHBsAg in serum were observed by serum dot-blot hybridization and ELISA. ALT and AST in serum were also detected. Histological observation on the duck liver was done simultaneously. The trial was contrasted with a single acyclovir (ACV), famciclovir (FCV), or Lamivudine (3TC). RESULTS: Combination therapy with Lamivudine and famciclovir could significantly reduce the serum DHBV DNA level. After stopping the treatment for 1 week, serum DHBV DNA level did not return significantly. The change of DHBsAg was similar to DHBV DNA. The level of ALT, AST, and the features of liver histopathology in combination-treated ducks were not different from those in control ducks. CONCLUSIONS: The study confirms that combination therapy is superior to single antiviral agent in vivo for ducks with chronic DHBV carrier.

2-Aminopurine↗
PubMed2001

[Further correction for the original plant of baiying and shuyangquan].

Textual researches show that Baiyang and Shuyangquan in Shen Nong's Herbal Classic are not the herb medicine Baimaoteng. However, Kuqie in the Grand Dictionary of Chinese Medicine and Baiying can be substitutes of Baimaoteng for medicine. Shuyangquan has not been used for many years. From Ming and Qing dynasties, Shuyangquan's original plant should be Solanum septemlobtum Bunge. In the period of Tang and Song dynasties, its original plant should be S. japonense Nakai. Shuyangquan in Shen Nong's Herbal Classic should be S. dulcamara L. In The Grand Dictionary of Chinese Medicine, Kuqie and Qiannianbulanxin renamed as S. dulcamara was really a mistake.

Plants, Medicinal↗