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Biomedical subjects

Q Zhong

Publications and source records attributed to Q Zhong.

At least 37 records · Page 2Linked to original sources

CD4+ T cell-independent vaccination against Pneumocystis carinii in mice.

Host defenses are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4+ T lymphocytes. Moreover, deficient CD4+ T lymphocytes impair vaccination approaches to prevent opportunistic infection. Therefore, we investigated a CD4+ T cell-independent vaccine approach to a prototypic AIDS-defining infection, Pneumocystis carinii (PC) pneumonia. Here, we demonstrate that bone marrow-derived dendritic cells (DCs) expressing the murine CD40 ligand, when pulsed ex vivo by PC antigen, elicited significant titers of anti-PC IgG in CD4-deficient mice. Vaccinated animals demonstrated significant protection from PC infection, and this protection was the result of an effective humoral response, since adoptive transfer of CD4-depleted splenocytes or serum conferred this protection to CD4-deficient mice. Western blot analysis of PC antigen revealed that DC-vaccinated, CD4-deficient mice predominantly reacted to a 55-kDa PC antigen. These studies show promise for advances in CD4-independent vaccination against HIV-related pathogens.

Adoptive Transfer↗

[Retention of selenium volatility using lime in coal combustion].

For understanding the volatility of selenium, the effect of the contents of exchangeable cations of coal on it, and the retention of selenium using CaO in coal combustion, the sequential chemistry extraction, the fixed bed and circulating fluidized bed (CFB) combustion, X-ray diffraction (XRD) and atomic fluorescence spectrometry (AFS) were undertaken. The results showed that the volatility of selenium was more than 97% in coal combustion at 815 degrees C, and the volatility of selenium was affected by the content of exchangeable cations of coal in low-middle temperature. It was identified that lime can restrain the volatility of selenium. In fixed bed combustion of coal, the retention rates of selenium volatility were between 11.6% and 50.7% using lime. In circulating fluidized bed combustion of coal, partitioning of selenium changed very much in ash of different size fraction between without lime and with lime. Comparing with combustion without lime, the content of selenium in ash from chimney was less than fourth times and that in leaching water from chimney decreased by two orders of magnitude using lime. Retention of selenium volatility using lime is so effective in coal combustion, especially in CFB combustion of coal.

Calcium Compounds↗

[The effect analysis of tuberculosis control project loaned by World Bank in Guangdong province].

OBJECTIVE: To evaluate the effect of tuberculosis control project loaned by World Bank in Guangdong province. METHODS: The registration and the treatment effect of pulmonary tuberculosis patients according to Guangdong tuberculosis report were analyzed. RESULTS: The above program had been conducted widespread since 1995. Over the past five years, 601,913 cases of suspicious tuberculosis patients have been received and diagnosed, in which 111,164 infectious patients (containing 91,612 newly-attacked infectious cases) were found. Just in 1999, the number of newly-attacked infectious patients was 1.2 times to that(19,858 newly-attacked infectious cases) of 1981-1990 prior to this program. And the average cure rate of infectious patients reached to 95.2%. The cure rate showed an uptrend amounting to 97.2% from 87.6%. CONCLUSION: Satisfactory effect have been achieved by the World-Bank loaned TB control project in Guangdong province.

China↗

Transforming growth factor beta inhibits the phosphorylation of pRB at multiple serine/threonine sites and differentially regulates the formation of pRB family-E2F complexes in human myeloid leukemia cells.

Transforming growth factor beta (TGFbeta)1 induced dephosphorylation of pRb at multiple serine and threonine residues including Ser249/Thr252, Thr373, Ser780, and Ser807/811 in MV4-11 cells. Likewise, TGFbeta1 caused the dephosphorylation of p130, while inhibiting accumulation of p107 protein. Phosphorylated pRb was detected to bind E2F-1 and E2F-3, which appears to be a major form of pRb complexes in actively cycling cells. TGFbeta1 significantly downregulated pRb-E2F-1 and pRb-E2F-3 complexes as a result of inhibition of E2F-1 and E2F-3. In contrast, complexes of E2F-4 with pRb and with p130 were increased markedly upon TGFbeta1 treatment, whereas p107 associated E2F-4 was dramatically decreased. In agreement with these results, p130-E2F-4 DNA binding activity was dominant in TGFbeta1 treated cells, whereas p107-E2F-4 DNA binding activity was only found in proliferating cells. Our data strongly suggest that inhibition of E2Fs and differential regulation of pRb family-E2F-4 complexes are linked to TGFbeta1-induced growth inhibition. E2F-4 is switched from p107 to p130 and pRb when cells are arrested in G1 phase by TGFbeta1.

Blotting, Western↗

Molecular dynamics simulation of four-alpha-helix bundles that bind the anesthetic halothane.

The mutation of a single leucine residue (L38) to methionine (M) is known experimentally to significantly increase the affinity of the synthetic four-alpha-helix bundle (Aalpha(2))(2) for the anesthetic halothane. We present a molecular dynamics study of the mutant (Aalpha(2)-L38M)(2) peptide, which consists of a dimer of 62-residue U-shaped di-alpha-helical monomers assembled in an anti topology. A comparison between the simulation results and those obtained for the native (Aalpha(2))(2) peptide indicates that the overall secondary structure of the bundle is not affected by the mutation, but that the side chains within the monomers are better packed in the mutant structure. Unlike the native peptide, binding of a single halothane molecule to the hydrophobic core of (Aalpha(2)-L38M)(2) deforms the helical nature of one monomer in a region close to the mutation site. Increased exposure of the cysteine side chain to the hydrophobic core in the mutant structure leads to the enhancement of the attractive interaction between halothane and this specific residue. Since the mutated residues are located outside the hydrophobic core the observed increased affinity for halothane appears to be an indirect effect of the mutation.

Amino Acid Sequence↗

The major transition state in folding need not involve the immobilization of side chains.

During protein folding in which few, if any, definable kinetic intermediates are observable, the nature of the transition state is central to understanding the course of the reaction. Current experimental data does not distinguish the relative contributions of side chain immobilization and dehydration phenomena to the major rate-limiting transition state whereas this distinction is central to theoretical models that attempt to simulate the behavior of proteins during folding. Renaturation of the small proteinase inhibitor cystatin under oxidizing versus reducing conditions is the first experimental case in which these processes can be studied independently. Using this example, we show that sidechain immobilization occurs downstream of the major folding transition state. A consequence of this is the existence of states with disordered side chains, which are distinct from kinetic protein folding intermediates and which lie within the folded state free energy well.

Animals↗

Two possible conducting states of the influenza A virus M2 ion channel.

Molecular dynamics simulations have been performed on protonated four-helix bundles based on the 25-residue Duff-Ashley transmembrane sequence of the M2 channel of the influenza A virus. Well-equilibrated tetrameric channels, with one, two and four of the H37 residues protonated, were investigated. The protonated peptide bundles were immersed in the octane portion of a phase-separated water/octane system, which provided a membrane-mimetic environment. The simulations suggest that there could be two conducting states of the M2 channel corresponding to tetramers containing one or two protonated histidines. The more open structure of the doubly protonated state suggests it would have the higher conductance.

Amino Acid Sequence↗

Glucose-dependent insulinotropic peptide signaling pathways in endothelial cells.

Glucose-dependent insulinotropic peptide (GIP) potentiates glucose-induced insulin secretion. In addition, GIP has vasoconstrictive or vasodilatory properties depending on the vascular bed affected. In order to assess whether this effect could be related to differences in GIP receptor expression, several different endothelial cell types were examined for GIP receptor expression. GIP receptor splice variants were detected and varied depending on the endothelial cell type. Furthermore, stimulation of these cells with GIP led to cell type dependent differences in activation of the calcium and cAMP signaling pathways. To our knowledge this is the first physiological characterization of receptors for GIP in endothelial cells.

Alternative Splicing↗

Structure and dynamics of excited electronic states at the adsorbate/metal interface: C6F6/Cu(111).

Excited state electron transfer at the adsorbate/metal interface represents a key step in molecular electronic devices. The dynamics of such processes are governed by ultrafast energy relaxation which can be probed directly by time-resolved two-photon photoemission (2PPE). Using 2PPE spectroscopy we investigate the energetics and lifetimes of the unoccupied electronic states of C6F6 adsorbed on Cu(111) as a model system for electron transfer at organic/metal interfaces. With increasing C6F6 layer thickness we find a pronounced decrease in the energetic position of the lowest unoccupied state, which is accompanied by a strong increase in its lifetime as well as a decrease in the effective electron mass. The frequently employed dielectric continuum model which describes delocalized (quantum well) states within adsorbate layers does not give a consistent explanation of these findings. By adsorption of Xe overlayers onto C6F6/Cu(111) we can show that, even for one monolayer of C6F6, the excited state must be localized predominantly inside the C6F6 layer and thus originates from a molecular state (presumably an antibonding sigma* orbital). With increasing coverage this state becomes more delocalized within the adsorbate layer, which reduces the coupling to the metal substrate and thus enhances the excited state lifetime.

Journal Article↗

Molecular ratio between borna disease viral-p40 and -p24 proteins in infected cells determined by quantitative antigen capture ELISA.

We developed the antigen capture enzyme-linked immunosorbent assay (ELISA) systems for quantification of Borna disease virus (BDV) major antigens, p40 and p24. Using these ELISAs, we quantified the two proteins in various BDV-infected materials, including the cell lysates and culture supernatants as well as the homogenates of experimental animal brains. The ELISAs were also applied to measure the infectious titer of BDV in persistently infected cell lines. Quantitative analysis with these ELISAs allowed us to measure the molecular ratio between the p40 and p24 in infected samples. Interestingly, the ratio of p24 to p40 in persistently infected cells was much higher than that observed in acutely infected cells although the ratios in the supernatants from both cell lines were quite similar. BDV-inoculated gerbil brain cells showed a relatively high ratio of p24 to p40 as compared with acutely infected cells. These observations suggested that the molecular ratio between the proteins strongly depended on the infectious status of BDV in the host cells. The ELISA system developed here could be a convenient method for the quantification of BDV infection and may also be beneficial for understanding viral replication and infectious status in the host cells.

Animals↗

Functional parathyroid hormone receptors are present in an umbilical vein endothelial cell line.

Acute parathyroid hormone exposure induces vascular smooth muscle relaxation. In contrast, continuous infusion of parathyroid hormone leads to vasoconstriction and an elevation of blood pressure. Despite the known effects of parathyroid hormone on vascular smooth muscle, possible direct effects on the vascular endothelium have not previously been investigated. Using a human umbilical vein endothelial cell line, we found that parathyroid hormone increased both intracellular calcium and cellular cAMP content in these endothelial cells. Furthermore, exposure of these cells to increasing concentrations of parathyroid hormone stimulated both [(3)H]thymidine incorporation and endothelin-1 secretion. Parathyroid hormone/parathyroid hormone-related peptide receptor mRNA could be detected at low levels in these cells. In summary, these data demonstrate that endothelium-derived cells contain functional parathyroid hormone receptors. The potential physiological role of these receptors remains to be determined.

Calcium↗

Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors.

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid peptide synthesized and secreted from endocrine cells in the small intestine. The role of GIP in coupling nutrient intake and insulin secretion, the incretin effect, is well known. We report that GIP receptor messenger RNA and protein are present in normal bone and osteoblast-like cell lines, and that high affinity receptors for GIP can be demonstrated by [125I]GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated increases in cellular cAMP content and intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I messenger RNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblast-like cells and that GIP modulates the function of these cells.

Alkaline Phosphatase↗

Fifty-six cases of protrusion of lumbar intervertebral disc treated by penetration and oral administration of Chinese decoction plus traction.

Fifty-six cases of the protrusion of the lumbar intervertebral disc in the treatment group were treated by drug-penetration and oral administration of traditional Chinese decoction plus traction, and the other 35 cases in the control group by oral administration of Chinese decoction and traction. The results showed that the cure rate in the treatment group was 83.9%, and that in the control group was 57.1%, with a statistically significant difference between the two groups (P < 0.01), indicating that the former is a more effective therapy for protrusion of the lumbar intervertebral disc.

Adult↗

Expression of BRC repeats in breast cancer cells disrupts the BRCA2-Rad51 complex and leads to radiation hypersensitivity and loss of G(2)/M checkpoint control.

BRCA2 is a breast tumor suppressor with a potential function in the cellular response to DNA damage. BRCA2 binds to Rad51 through its BRC repeats. In support of the biological significance of this interaction, we found that the complex of BRCA2 and Rad51 in breast cancer MCF-7 cells was diminished upon conditional expression of a wild-type, but not a mutated, BRC4 repeat using the tetracycline-inducible system. Cells expressing a wild-type BRC4 repeat showed hypersensitivity to gamma-irradiation, an inability to form Rad51 radiation-induced foci, and a failure of radiation-induced G(2)/M, but not G(1)/S, checkpoint control. These results strongly suggest that the interaction between BRCA2 and Rad51 mediated by BRC repeats is critical for the cellular response to DNA damage.

Amino Acid Sequence↗

Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response.

BRCA1 encodes a tumor suppressor that is mutated in familial breast and ovarian cancers. Here, it is shown that BRCA1 interacts in vitro and in vivo with hRad50, which forms a complex with hMre11 and p95/nibrin. Upon irradiation, BRCA1 was detected in discrete foci in the nucleus, which colocalize with hRad50. Formation of irradiation-induced foci positive for BRCA1, hRad50, hMre11, or p95 was dramatically reduced in HCC/1937 breast cancer cells carrying a homozygous mutation in BRCA1 but was restored by transfection of wild-type BRCA1. Ectopic expression of wild-type, but not mutated, BRCA1 in these cells rendered them less sensitive to the DNA damage agent, methyl methanesulfonate. These data suggest that BRCA1 is important for the cellular responses to DNA damage that are mediated by the hRad50-hMre11-p95 complex.

Acid Anhydride Hydrolases↗

The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage.

The Nijmegen breakage syndrome (NBS), a chromosomal instability disorder, is characterized in part by cellular hypersensitivity to ionizing radiation. Repair of DNA double-strand breaks by radiation is dependent on a multifunctional complex containing Rad50, Mre11, and the NBS1 gene product, p95 (NBS protein, nibrin). The role of p95 in these repair processes is unknown. Here it is demonstrated that Mre11 is hyperphosphorylated in a cell cycle-independent manner in response to treatment of cells with genotoxic agents including gamma irradiation. This response is abrogated in two independently established NBS cell lines that have undetectable levels of the p95 protein. NBS cells are also deficient for radiation-induced nuclear foci containing Mre11, while those with Rad51 are unaffected. An analysis of the kinetic relationship between Mre11 phosphorylation and the appearance of its radiation-induced foci indicates that the former precedes the latter. Together, these data suggest that specific phosphorylation of Mre11 is induced by DNA damage, and p95 is essential in this process, perhaps by recruiting specific kinases.

Cell Cycle↗