Biomedical subjects

Y R Feng

Publications and source records attributed to Y R Feng.

7 recordsLinked to original sources

PubMed2000

Inefficient formation of a complex among CXCR4, CD4 and gp120 in U937 clones resistant to X4 gp120-gp41-mediated fusion.

Certain subclones (designated as minus clones) of the promonocytic U937 cell line do not support efficient infection and fusion mediated by T cell line adapted (TCLA) X4 HIV-1 gp120-gp41 (Env) although the CXCR4 and CD4 concentrations at their surfaces are similar to those at the surfaces of clones susceptible to HIV-1 entry (plus clones) (H. Moriuchi et al., J. Virol. 71, 9664-9671, 1997). To test the hypothesis that inefficient formation of gp120-CD4-CXCR4 complexes could contribute to the mechanism of resistance to Env-mediated fusion in the minus clones, we incubated plus and minus cells with HIV-1 LAI gp120 and coimmunoprecipitated CD4 by using anti-CXCR4 antibodies. The gp120 induced inefficient coimmunoprecipitation of CD4 in the minus clones but not in the plus ones. Overexpression of CD4 resulted in significant restoration of the minus clones' susceptibility to fusion in parallel with an increase in the amount of the gp120-CD4-CXCR4 complexes. These results not only suggest that the resistance to TCLA X4 HIV-1 entry in the U937 minus clones is due to the inability of these cells to efficiently form complexes among CD4, gp120, and CXCR4, but also provide a direct evidence for the correlation between fusion and the cell surface concentration of the complexes among CXCR4, CD4, and gp120. These data and similar recent observations in macrophages suggest that inefficient complex formation among CXCR4, CD4, and gp120 could be a general mechanism of cell resistance to gp120-gp41-mediated fusion and a major determinant of HIV-1 evolution in vivo.

CD4 Antigens↗

PubMed1999

Constitutive cell surface association between CD4 and CCR5.

HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor. For most strains of HIV, this coreceptor is CCR5. Here, we provide evidence that CD4 is specifically associated with CCR5 in the absence of gp120 or any other receptor-specific ligand. The amount of CD4 coimmunoprecipitated with CCR5 was significantly higher than that with the other major HIV coreceptor, CXCR4, and in contrast to CXCR4 the CD4-CCR5 coimmunoprecipitation was not significantly increased by gp120. The CD4-CCR5 interaction probably takes place via the second extracellular loop of CCR5 and the first two domains of CD4. It can be inhibited by CCR5- and CD4-specific antibodies that interfere with HIV-1 infection, indicating a possible role in virus entry. These findings suggest a possible pathway of HIV-1 evolution and development of immunopathogenicity, a potential new target for antiretroviral drugs and a tool for development of vaccines based on Env-CD4-CCR5 complexes. The constitutive association of a seven-transmembrane-domain G protein-coupled receptor with another receptor also indicates new possibilities for cross-talk between cell surface receptors.

3T3 Cells↗

PubMed1999

Telomere dynamics in monkeys: increased cell turnover in macaques infected with chimeric simian-human immunodeficiency viruses.

To address the question of how cell turnover is affected by retroviral infections, we used the telomeric terminal restriction fragments (TRFs) as markers of cell replicative history and measured their length in macaques infected with chimeric simian-human immunodeficiency viruses (SHIVs). The TRF lengths of mononuclear cells in 104 samples, including longitudinal samples from nine cynomolgus and ten pig-tailed macaques infected with SHIV, and in samples from 26 uninfected macaques, were quantitated by an improved method, based on two-dimensional calibration of DNA sizes, pulsed field electrophoresis, and high-resolution Southern blot images. The average TRF lengths of peripheral blood mononuclear cells (PBMCs) from uninfected pig-tailed (14.9+/-1.6 kbp) and cynomolgus (14.1+/-1.8 kbp) macaques were about 3 and 5 kbp longer than those of human infants and 30-year-old adults, respectively. The rate of TRF length shortening in infected pig-tailed macaques was significantly (P = 0.035) higher (2.2-fold) than in uninfected monkeys. The TRFs in SHIV-infected cynomolgus monkeys, which, in general, had lower viral loads than pig-tailed macaques, shortened on average more rapidly (1.6-fold) than in uninfected animals, but the difference was not statistically significant. The TRFs of mononuclear cells from the lymph nodes of two rapidly progressing SHIV-infected macaques that developed AIDS and died also shortened in parallel but somewhat more rapidly than in the PBMCs. These results suggest that the rate of PBMC turnover in macaques could be increased several-fold during infections by immunodeficiency viruses, likely due to immune activation by SHIV antigens.

Animals↗

PubMed1999

Long-term telomere dynamics: modest increase of cell turnover in HIV-infected individuals followed for up to 14 years.

To quantify the long-term dynamics of telomere lengths and the effect of HIV infection on lymphocyte turnover rates, we measured in a blinded study longitudinal samples from 6 individuals using a highly accurate method based on two-dimensional calibration of DNA sizes. For two uninfected controls followed 8 and 10 years the average telomeric terminal restriction fragment (TRF) shortening rate in peripheral blood mononuclear cells (PBMCs) was 50 and 60 bp/year, respectively, in agreement with previous measurements of cross-sectional samples. The TRF lengths of PBMCs from two slow progressors followed for 14 years declined by a rate of 120 +/-10 bp/year, i.e. 2-fold higher than the rate of TRF shortening for uninfected individuals. The rate of TRF shortening was higher in CD8 (140 +/-10 bp/year) than in CD4 (100 +/-10 bp/year) cells. The CD8 cell TRFs of the two fast progressors shortened faster (240 +/-10 bp/year) and the rate of CD4 cell TRF shortening in one of the fast progressors was 160 bp/year. These data suggest that HIV infection causes only a modest increase in the lymphocyte turnover which we speculate could be due to chronic activation of the immune system, and may not result in the exhaustion of its regenerative capacity and immunopathogenesis.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Telomere dynamics in HIV-1 infected and uninfected chimpanzees measured by an improved method based on high-resolution two-dimensional calibration of DNA sizes.

We developed an improved method for accurately measuring telomere lengths based on two-dimensional calibration of DNA sizes combined with pulsed field electrophoresis and quantitative analysis of high-resolution gel images. This method was used to quantify the length of telomeres in longitudinal samples of peripheral blood mononuclear cells (PBMCs) from five chimpanzees infected with human immunodeficiency virus type 1 (HIV-1) and three uninfected animals, 14 to 27 years of age. The average length of the telomere restriction fragments (TRF) of infected and uninfected chimpanzees were 11.7 +/- 0.25 kbp, and 11.6 +/- 0.61 kbp, respectively, and were about 1 kbp and 3 kbp longer than those of human infants and 30 year old adults, respectively. There was a trend of a slight decrease (30-60 bp per year) in the TRF of two HIV infected chimpanzees over 30-35 months, while the TRF of one naive chimpanzee slightly increased over 20 months. Although the number of chimpanzees in this study is small and no statistically significant linear dependencies on time were observed, it appears that in chimpanzees, rates of shortening of the TRF are comparable or smaller than in adult humans and are not significantly affected by HIV-1 infection, which may be related to the inability of HIV-1 to cause disease in these animals.

Age Factors↗

PubMed1997

Inhibitory effect of artemether on proteinase of Schistosoma japonicum.

AIM: To study the effect of artemether (Art) on the thio proteinase ("hemoglobinase", Hem) of Schistosoma japonicum. METHODS: Hem was extracted from S japonicum adults. The inhibitory effect of Art on the activity of Hem to degrade human hemoglobin (Hgb) was examined with UV-photometer at 280 nm, SDS-PAGE and scanning at 600 nm on a chromoscanner. RESULTS: Human Hgb was degraded at pH 4.0 by the Hem. The activities of Hem preincubated at 37 degrees C with Art 0.14, 1.4, and 14 mmol.L-1, were inhibited by 30.2%, 39.8%, and 45.0%, respectively. CONCLUSION: Art possesses an inhibitory effect to Hem of S japonicum.

Animals↗

PubMed1997

[The sterilization effect of formaldehyde fumigating on the catheter place vertically].

UNLABELLED: The aim of this paper is to investigate the effect of formaldehyde fumigating on the sterilization of catheters with different diameters and placed in different positions. The lumen of cleaned catheters with different diameters was filled with a solution of live bacilli coil. The catheters were then dried by a drier and divided into 3 groups for formaldehyde fumigating sterilization. A segment of 5 cm of the middle section of the sterilized catheters was cut and incubated at 36 degrees C for 48 h with bouillon medium. For those segments with positive culture, bacteriologic identification was done. RESULTS: Group A, U = 6.85 and P < 0.01; Group B, chi 2 = 8 and P < 0.01; Group C, chi 2 = 13, P < 0.01. CONCLUSIONS: in the same conditions, fumigating in vertical direction is better than fumigation in horizontal direction and save time; in the same conditions, the positive culture rate is inversely related to the diameter of the catheters; for catheter with a diameter greater than 0.75 cm, fumigating vertically for 2 h is enough to obtain satisfactory sterilization effects.

Catheters, Indwelling↗