Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy (HAART). Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients we...Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy (HAART). Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4+ T cell counts 〈 100/mm^3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4+ (naive CD4+ T cell defined by CD45RA+ and CD62L+, memory CD4+ T cell defined by CD45RA-), CD8+ T cell, plasma HIV viral load, and clinical manifestations on before, during, and after HAART (5 different regimes) on 1, 3, 6, 9, and 12 months. Before HAART mean CD4+ T cell counts were 32 ± 31 (range 2-91)/mm^3, and plasma HIV viral load were 5.07 ± 0.85(range 2.04-5.70) log copies/mL. In 1 month's time patients treated with HAAT had mean CD4+ and CD8+ T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4+ T cells were memory CD4+ T cells, as for naive CD4+ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months' HAAT. Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAAT.展开更多
The growth factor midkine (MK) is a cytokine that inhibits HIV infection in cell cultures in an autocrine and paracrine manner by blocking the attachment of HIV particles to permissive cells. MK mRNA is systematical...The growth factor midkine (MK) is a cytokine that inhibits HIV infection in cell cultures in an autocrine and paracrine manner by blocking the attachment of HIV particles to permissive cells. MK mRNA is systematically expressed in adult peripheral blood lymphocytes from healthy donors, while its expression becomes markedly but transiently increased upon in vitro treatment of lymphocytes with IL-2 or IFN-7 and activation of T lymphocytes by PHA or through the engagement of the CD28 antigen. The binding of MK to cells occurs specifically at a high and a low affinity binding site. This low affinity-binding site is the cell-surface expressed nucleolin, which is implicated in the mechanism of the initial attachment of HIV particles to cells. Accordingly, the nucleolin-binding HB-19 pseudopeptide has no effect on the MK binding to the high affinity binding site, whereas it prevents the binding of MK to the low affinity binding site, thus suggesting the low affinity receptor of MK is the cell-surface-expressed nucleolin. Confocal immunofluorescence laser microscopy revealed the colocalization of MK and the cell-surface-expressed nucleolin at distinct spots. The use of various deletion constructs of nucleolin then indicates that the extreme C-terminal end of nucleolin, containing repeats of the amino acid motif RGG, as the domain that binds MK. The specific binding of MK to the surface nucleolin is independent of heparan sulfate and chondroitin sulfate proteoglycans. After binding to cells, MK enters cells by an active process in which nucleolin and lipid rafts appear to be implicated. The potent and the distinct anti-HIV action of MK along with its enhanced expression in lymphocytes by various physiological stimuli, point out that MK is a cytokine that could be involved in HIV pathogenesis.展开更多
Natural killer T (NKT) cells are a unique T cell population that have important immunoregulatory functions and have been shown to be involved in host immunity against a range of microorganisms. It also emerges that ...Natural killer T (NKT) cells are a unique T cell population that have important immunoregulatory functions and have been shown to be involved in host immunity against a range of microorganisms. It also emerges that they might play a role in HIV-1 infection, and therefore be selectively depleted during the early stages of infection. Recent studies are reviewed regarding the dynamics of NKT depletion during HIV-1 infection and their recovery under highly active antiretroviral treatment (HAART). Possible mechanisms for these changes are proposed based on the recent developments in HIV pathogenesis. Further discussions are focused on HIV's disruption of NKT activation by downregulating CDld expression on antigen presentation cells (APC). HIV-1 protein Nefis found to play the major role by interrupting the intracellular trafficking of nascent and recycling CDld molecules.展开更多
In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed t...In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat cysteine rich peptide increase CCR5 expression in human monocytes, and this activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5 expression in monocytes. These results provide insight into a new mechanism by which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.展开更多
Objective: To analyze HIV replication and immune functionchanges among Chinese patients with HIV/ARC/AIDS andtheir association with disease progression. Methods: T cell subsets, plasma cytokine concentrations andviral...Objective: To analyze HIV replication and immune functionchanges among Chinese patients with HIV/ARC/AIDS andtheir association with disease progression. Methods: T cell subsets, plasma cytokine concentrations andviral loads from 42 HIV+ individuals, and 13 ARC/AIDSpatients, and 10 controls were analyzed by flow cytometry(FCM), quantitative ELISA and reversetranscription-polymerase chain reaction (RT-PCR),respectively. Results: CD4 cell counts and plasma IL-2 in HIV/AIDSpatients were significantly less than in normal control subjects(P<0.001). The plasma concentrations sIL-2R, TNF-α, andNeopterin increased significantly with decreasing CD4 cellcounts. Plasma IL-2 among AIDS/ARC patients was also lessthan in HIV+ patients (P<0.01). CD4 cell counts, the ratio ofCD4 to CD8 and plasma IL-2 levels decreased significantlywith infection duration. CD4 cell counts declined an averageof 43/ml per year. In contrast, the concentration of plasmasIL-2R, sTNFR-I, and Neopterin increased an average of9.03pg/ml, 8.69pg/ml, 2.11ng/ml per yean respectively.Furthermore, a significant reverse linear correlation wasobserved between CD4 cell count, CD4/CD8 ratio, and CD3,CD4 and CD8 counts with plasma levels of sTNFR-I,Neopterin, and HIV RNA load. A positive linear correlationwas noted between plasma sIL-2R levels and changes ofplasma IL-6 level (P<0.001), IL-10(P<0.001), TNF-α(P<0.001),sTNFR-I (P<0.005), and Neopterin (P<0.002) and betweenIL-6 and TNF-α(P<0.001), Neopterin and IL-10 (P<0.05),sTNFR-I (P<0.001), plasma viral load and sTNFR-I (P<0.001),and Neopterin (P<0.002). Conclusion: These findingr suggest a close relationshipbetween IL-6 and TNF-aimmune activation, HIV replicationand disease progression in primary HIV infections and AIDSpatients. Declining CD4 cells and plasma IL-2, and increasingviral load, sIL-2R, TNF-α, sTNFR-I, and Neopterin might beconsidered as important predictors of the progression of HIVinfection to AIDS.展开更多
The relation between microtubules architecture in the cytoskeletal structure inside the dendrites and soma and the emergence of neuron function and firing action potential crosses the tiny line between physics and bio...The relation between microtubules architecture in the cytoskeletal structure inside the dendrites and soma and the emergence of neuron function and firing action potential crosses the tiny line between physics and biology. As decoherence is a fundamental mechanism in some biological process such as photosynthesis and others examples, the gravitational quantum approach may contribute to elucidate if neuron function really emerges from quantum coherence in neuronal microtubules. The Einstein equation correlates the stress-energy tensor Tμv to a specific divergence-free combination Ricci tensor Rμv and the metric. In the semiclassical formulation, we have Gμv = Rμv -1/2gμvR=8πG/C^4〈ψ|μvψ〉 which describes the quantum field in curved space-time geometry. But for a more precise equation in relation to the stress-energy tensor, we know that in a non-zero temperature, the wave-function is not enough to describe the physical reality. A more precise equation demands a formulation in the density-matrix form but for now there is no Diosi-Penrose model with density-matrix formulation. Such a density-matrix description can be viewed as a probability mixture of different wave-functions. Using some algebra and rules related to the mathematical manipulation of the density-matrix applied to operators, such the stress energy tensor, we found the von Neumann-Einstein equation for the general relativity equation in the density matrix operator form, Gμv = 8πG/C^4Tr[pTμv]. Thus density-matrix operator--instead of just a wave function of pure states--applied to the stress-energy tensor gives the curvature of space time, given by Einstein tensor, Gμv. The quantum fluctuation in the gravitational space-time field might feed back to decohere the quantum density-matrix. As long as decoherence can be viewed as the loss of information from a system to the environment, the density-matrix p is also related to that process and considering the measurement problem, density-matrix /garter is a more complete description of the possible outcome of the measurement. It is possible that some characteristics of the special microtubulin-associated proteins (MAP) that capes the dendritic-somatic microtubulins which could induces longer-lived nuclear spin states prevented from de-polymerization and suitable for long term information encode and memory. Understand the mechanism by which the hyper-phosphorylation in type tau-MAP displacements from microtubulins results in neurofibrillary tangles and cognitive dysfunctions in Alzheimer's disease.展开更多
文摘Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy (HAART). Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4+ T cell counts 〈 100/mm^3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4+ (naive CD4+ T cell defined by CD45RA+ and CD62L+, memory CD4+ T cell defined by CD45RA-), CD8+ T cell, plasma HIV viral load, and clinical manifestations on before, during, and after HAART (5 different regimes) on 1, 3, 6, 9, and 12 months. Before HAART mean CD4+ T cell counts were 32 ± 31 (range 2-91)/mm^3, and plasma HIV viral load were 5.07 ± 0.85(range 2.04-5.70) log copies/mL. In 1 month's time patients treated with HAAT had mean CD4+ and CD8+ T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4+ T cells were memory CD4+ T cells, as for naive CD4+ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months' HAAT. Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAAT.
文摘The growth factor midkine (MK) is a cytokine that inhibits HIV infection in cell cultures in an autocrine and paracrine manner by blocking the attachment of HIV particles to permissive cells. MK mRNA is systematically expressed in adult peripheral blood lymphocytes from healthy donors, while its expression becomes markedly but transiently increased upon in vitro treatment of lymphocytes with IL-2 or IFN-7 and activation of T lymphocytes by PHA or through the engagement of the CD28 antigen. The binding of MK to cells occurs specifically at a high and a low affinity binding site. This low affinity-binding site is the cell-surface expressed nucleolin, which is implicated in the mechanism of the initial attachment of HIV particles to cells. Accordingly, the nucleolin-binding HB-19 pseudopeptide has no effect on the MK binding to the high affinity binding site, whereas it prevents the binding of MK to the low affinity binding site, thus suggesting the low affinity receptor of MK is the cell-surface-expressed nucleolin. Confocal immunofluorescence laser microscopy revealed the colocalization of MK and the cell-surface-expressed nucleolin at distinct spots. The use of various deletion constructs of nucleolin then indicates that the extreme C-terminal end of nucleolin, containing repeats of the amino acid motif RGG, as the domain that binds MK. The specific binding of MK to the surface nucleolin is independent of heparan sulfate and chondroitin sulfate proteoglycans. After binding to cells, MK enters cells by an active process in which nucleolin and lipid rafts appear to be implicated. The potent and the distinct anti-HIV action of MK along with its enhanced expression in lymphocytes by various physiological stimuli, point out that MK is a cytokine that could be involved in HIV pathogenesis.
文摘Natural killer T (NKT) cells are a unique T cell population that have important immunoregulatory functions and have been shown to be involved in host immunity against a range of microorganisms. It also emerges that they might play a role in HIV-1 infection, and therefore be selectively depleted during the early stages of infection. Recent studies are reviewed regarding the dynamics of NKT depletion during HIV-1 infection and their recovery under highly active antiretroviral treatment (HAART). Possible mechanisms for these changes are proposed based on the recent developments in HIV pathogenesis. Further discussions are focused on HIV's disruption of NKT activation by downregulating CDld expression on antigen presentation cells (APC). HIV-1 protein Nefis found to play the major role by interrupting the intracellular trafficking of nascent and recycling CDld molecules.
文摘In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat cysteine rich peptide increase CCR5 expression in human monocytes, and this activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5 expression in monocytes. These results provide insight into a new mechanism by which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.
文摘Objective: To analyze HIV replication and immune functionchanges among Chinese patients with HIV/ARC/AIDS andtheir association with disease progression. Methods: T cell subsets, plasma cytokine concentrations andviral loads from 42 HIV+ individuals, and 13 ARC/AIDSpatients, and 10 controls were analyzed by flow cytometry(FCM), quantitative ELISA and reversetranscription-polymerase chain reaction (RT-PCR),respectively. Results: CD4 cell counts and plasma IL-2 in HIV/AIDSpatients were significantly less than in normal control subjects(P<0.001). The plasma concentrations sIL-2R, TNF-α, andNeopterin increased significantly with decreasing CD4 cellcounts. Plasma IL-2 among AIDS/ARC patients was also lessthan in HIV+ patients (P<0.01). CD4 cell counts, the ratio ofCD4 to CD8 and plasma IL-2 levels decreased significantlywith infection duration. CD4 cell counts declined an averageof 43/ml per year. In contrast, the concentration of plasmasIL-2R, sTNFR-I, and Neopterin increased an average of9.03pg/ml, 8.69pg/ml, 2.11ng/ml per yean respectively.Furthermore, a significant reverse linear correlation wasobserved between CD4 cell count, CD4/CD8 ratio, and CD3,CD4 and CD8 counts with plasma levels of sTNFR-I,Neopterin, and HIV RNA load. A positive linear correlationwas noted between plasma sIL-2R levels and changes ofplasma IL-6 level (P<0.001), IL-10(P<0.001), TNF-α(P<0.001),sTNFR-I (P<0.005), and Neopterin (P<0.002) and betweenIL-6 and TNF-α(P<0.001), Neopterin and IL-10 (P<0.05),sTNFR-I (P<0.001), plasma viral load and sTNFR-I (P<0.001),and Neopterin (P<0.002). Conclusion: These findingr suggest a close relationshipbetween IL-6 and TNF-aimmune activation, HIV replicationand disease progression in primary HIV infections and AIDSpatients. Declining CD4 cells and plasma IL-2, and increasingviral load, sIL-2R, TNF-α, sTNFR-I, and Neopterin might beconsidered as important predictors of the progression of HIVinfection to AIDS.
文摘The relation between microtubules architecture in the cytoskeletal structure inside the dendrites and soma and the emergence of neuron function and firing action potential crosses the tiny line between physics and biology. As decoherence is a fundamental mechanism in some biological process such as photosynthesis and others examples, the gravitational quantum approach may contribute to elucidate if neuron function really emerges from quantum coherence in neuronal microtubules. The Einstein equation correlates the stress-energy tensor Tμv to a specific divergence-free combination Ricci tensor Rμv and the metric. In the semiclassical formulation, we have Gμv = Rμv -1/2gμvR=8πG/C^4〈ψ|μvψ〉 which describes the quantum field in curved space-time geometry. But for a more precise equation in relation to the stress-energy tensor, we know that in a non-zero temperature, the wave-function is not enough to describe the physical reality. A more precise equation demands a formulation in the density-matrix form but for now there is no Diosi-Penrose model with density-matrix formulation. Such a density-matrix description can be viewed as a probability mixture of different wave-functions. Using some algebra and rules related to the mathematical manipulation of the density-matrix applied to operators, such the stress energy tensor, we found the von Neumann-Einstein equation for the general relativity equation in the density matrix operator form, Gμv = 8πG/C^4Tr[pTμv]. Thus density-matrix operator--instead of just a wave function of pure states--applied to the stress-energy tensor gives the curvature of space time, given by Einstein tensor, Gμv. The quantum fluctuation in the gravitational space-time field might feed back to decohere the quantum density-matrix. As long as decoherence can be viewed as the loss of information from a system to the environment, the density-matrix p is also related to that process and considering the measurement problem, density-matrix /garter is a more complete description of the possible outcome of the measurement. It is possible that some characteristics of the special microtubulin-associated proteins (MAP) that capes the dendritic-somatic microtubulins which could induces longer-lived nuclear spin states prevented from de-polymerization and suitable for long term information encode and memory. Understand the mechanism by which the hyper-phosphorylation in type tau-MAP displacements from microtubulins results in neurofibrillary tangles and cognitive dysfunctions in Alzheimer's disease.