AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed wit...AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed with breast cancer and 26 patients with benign pathology of the breast. Molecular subtype classification was performed based on the immunohistochemical reports of the tumor piece. HPV genome detection and genotyping from fresh breast biopsies was performed using the INNO-LIPA HPV Genotyping Extra test(Innogenetics, Ghent, Belgium). CD3+, CD4+, CD8+ and natural killer(NK)+ cells levels from peripheral blood samples from patients with breast cancer and benign pathology were measured by flow cytometry. RESULTS Luminal A was the most frequent breast cancer molecular subtype(33.33%). HPV was detected in 25% of the breast cancer patients, and genotype 18 was the most frequent in the studied population. The mean of CD3+, CD4+ and CD8+ subpopulations were decreased in patients with breast cancer, in relation to those with benign pathology, with a statistically significant difference in CD8+ values(P = 0.048). The mean of NK+ cells was increased in the benign pathology group. The average level of CD3+, CD4+, CD8+ and NK+ cells decreased as the disease progressed. HER2+ and Luminal B HER2+ tumors had the lowest counts of cell subsets. HPV breast cancer patients had elevated counts of cellular subsets. CONCLUSION Determining level changes in cellular subsets in breast cancer patients is a useful tool to evaluate treatment response.展开更多
AIM: To determine if efforts to improve antiretroviral therapy(ART) adherence minimizes the negative impact of depression on human immunodeficiency virus(HIV) outcomes. METHODS: A cross-sectional study of a clinic-bas...AIM: To determine if efforts to improve antiretroviral therapy(ART) adherence minimizes the negative impact of depression on human immunodeficiency virus(HIV) outcomes. METHODS: A cross-sectional study of a clinic-based cohort of 158 HIV seropositive(HIV+) African Americans screened for major depressive disorder(MDD) in 2012. CD4 T lymphocyte(CD4+) counts were obtained from these individuals. Self-report on adherence to ART was determined from questionnaire administered during clinic visits. The primary outcome measure was conditional odds of having a poorer CD4+ count(< 350 cells/mm3). Association between CD4+ count and antidepressant-treated or untreated MDD subjects was examined controlling for self-reported adherence and other potential confounders. RESULTS: Out of 147 individuals with available CD4+ T lymphocyte data, 31% had CD4+ count < 350 cells/mm^3 and 28% reported poor ART adherence. As expected the group with > 350 cells/mm^3 CD4+ T lymphocyte endorsed significantly greater ART adherence compared to the group with < 350 cells/mm3 CD4+ T lymphocyte count(P < 0.004). Prevalence of MDD was 39.5% and 66% of individuals with MDD took antidepressants. Poor CD4+ T lymphocyte count was associated with poor ART adherence and MDD. Adjusting for ART adherence, age, sex and education, which were potential confounders, the association between MDD and poor CD4+ T lymphocyte remained significant only in the untreated MDD group.CONCLUSION: Therefore, CD4+ count could be a clinical marker of untreated depression in HIV+. Also, mental health care may be relevant to primary care of HIV+ patients.展开更多
Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus ha...Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.展开更多
Objective To characterize the human immunodeficiency virus （HIV） -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome...Objective To characterize the human immunodeficiency virus （HIV） -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level. Methods Twenty-five HIV-I B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef〉Vpr〉Gag〉Pol〉Vpu〉Env〉Rev〉Vif〉Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-γ production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-1-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.展开更多
AIM: To construct the plasmid pcHEV23 containing fragments of HEV ORF2 and ORF3 chimeric gene and to assess its ability to elicit specific immunologic response in mice.METHODS: The gene encoding the structural protein...AIM: To construct the plasmid pcHEV23 containing fragments of HEV ORF2 and ORF3 chimeric gene and to assess its ability to elicit specific immunologic response in mice.METHODS: The gene encoding the structural protein of HEV ORF2 fragment and full-length ORF3 was amplified by PCR. The PCR products were cloned into an eucaryotic expression plasmid pcDNA3. The resulting plasmid pcHEV23 was used as a DNA vaccine to inoculate BALB/c mice intramuscularly thrice at a dose of 100 or 200 μg.Mice injected with empty pcDNA3 DNA or saline served as control and then specific immune responses in the mice were detected.RESULTS: After 2-3 times of inoculation, all mice injected with pcHEV23 had anti-HEV IgG seroconversion and specific T lymphocyte proliferation. The lymphocyte stimulation index in the group immunized with pcHEV23(3.1±0.49) was higher than that in the control group (0.787±0.12, P＜0.01). None in the control group had a detectable level of anti-HEV IgG.CONCLUSION: DNA vaccine containing HEV ORF2 and ORF3 chimeric gene can successfully induce specific humoral and cellular immune response in mice.展开更多
Human T-cell leukemia virus type 1(HTLV-1),the first human retrovirus discovered,is the etiological agent of adult-T-cell leukemia/lymphoma.The HTLV-1 encoded Tax protein is a potent oncoprotein that deregulates gene ...Human T-cell leukemia virus type 1(HTLV-1),the first human retrovirus discovered,is the etiological agent of adult-T-cell leukemia/lymphoma.The HTLV-1 encoded Tax protein is a potent oncoprotein that deregulates gene expression by constitutively activating nuclear factor-κB(NF-κB).Tax activation of NF-κB is critical for the immortalization and survival of HTLV-1-infected T cells.In this review,we summarize the present knowledge on mechanisms underlying Tax-mediated NF-κB activation,with an emphasis on post-translational modifications of Tax.展开更多
基金Supported by FONACIT Project,No.G2005000408PEII Project,No.2012001201
文摘AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed with breast cancer and 26 patients with benign pathology of the breast. Molecular subtype classification was performed based on the immunohistochemical reports of the tumor piece. HPV genome detection and genotyping from fresh breast biopsies was performed using the INNO-LIPA HPV Genotyping Extra test(Innogenetics, Ghent, Belgium). CD3+, CD4+, CD8+ and natural killer(NK)+ cells levels from peripheral blood samples from patients with breast cancer and benign pathology were measured by flow cytometry. RESULTS Luminal A was the most frequent breast cancer molecular subtype(33.33%). HPV was detected in 25% of the breast cancer patients, and genotype 18 was the most frequent in the studied population. The mean of CD3+, CD4+ and CD8+ subpopulations were decreased in patients with breast cancer, in relation to those with benign pathology, with a statistically significant difference in CD8+ values(P = 0.048). The mean of NK+ cells was increased in the benign pathology group. The average level of CD3+, CD4+, CD8+ and NK+ cells decreased as the disease progressed. HER2+ and Luminal B HER2+ tumors had the lowest counts of cell subsets. HPV breast cancer patients had elevated counts of cellular subsets. CONCLUSION Determining level changes in cellular subsets in breast cancer patients is a useful tool to evaluate treatment response.
基金Supported by In whole with Federal funds from the National Cancer Institute,National Institutes of Health,under Contract,No.HHSN261200800001E
文摘AIM: To determine if efforts to improve antiretroviral therapy(ART) adherence minimizes the negative impact of depression on human immunodeficiency virus(HIV) outcomes. METHODS: A cross-sectional study of a clinic-based cohort of 158 HIV seropositive(HIV+) African Americans screened for major depressive disorder(MDD) in 2012. CD4 T lymphocyte(CD4+) counts were obtained from these individuals. Self-report on adherence to ART was determined from questionnaire administered during clinic visits. The primary outcome measure was conditional odds of having a poorer CD4+ count(< 350 cells/mm3). Association between CD4+ count and antidepressant-treated or untreated MDD subjects was examined controlling for self-reported adherence and other potential confounders. RESULTS: Out of 147 individuals with available CD4+ T lymphocyte data, 31% had CD4+ count < 350 cells/mm^3 and 28% reported poor ART adherence. As expected the group with > 350 cells/mm^3 CD4+ T lymphocyte endorsed significantly greater ART adherence compared to the group with < 350 cells/mm3 CD4+ T lymphocyte count(P < 0.004). Prevalence of MDD was 39.5% and 66% of individuals with MDD took antidepressants. Poor CD4+ T lymphocyte count was associated with poor ART adherence and MDD. Adjusting for ART adherence, age, sex and education, which were potential confounders, the association between MDD and poor CD4+ T lymphocyte remained significant only in the untreated MDD group.CONCLUSION: Therefore, CD4+ count could be a clinical marker of untreated depression in HIV+. Also, mental health care may be relevant to primary care of HIV+ patients.
文摘Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.
文摘Objective To characterize the human immunodeficiency virus （HIV） -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level. Methods Twenty-five HIV-I B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef〉Vpr〉Gag〉Pol〉Vpu〉Env〉Rev〉Vif〉Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-γ production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-1-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.
基金Supported by the Grants from the Natural Science Foundation of Zhejiang Province, No. RC01054, Science Technology Department of Zhejiang Province, No. F11023 and Key Project of Health Bureau of Zhejiang Province
文摘AIM: To construct the plasmid pcHEV23 containing fragments of HEV ORF2 and ORF3 chimeric gene and to assess its ability to elicit specific immunologic response in mice.METHODS: The gene encoding the structural protein of HEV ORF2 fragment and full-length ORF3 was amplified by PCR. The PCR products were cloned into an eucaryotic expression plasmid pcDNA3. The resulting plasmid pcHEV23 was used as a DNA vaccine to inoculate BALB/c mice intramuscularly thrice at a dose of 100 or 200 μg.Mice injected with empty pcDNA3 DNA or saline served as control and then specific immune responses in the mice were detected.RESULTS: After 2-3 times of inoculation, all mice injected with pcHEV23 had anti-HEV IgG seroconversion and specific T lymphocyte proliferation. The lymphocyte stimulation index in the group immunized with pcHEV23(3.1±0.49) was higher than that in the control group (0.787±0.12, P＜0.01). None in the control group had a detectable level of anti-HEV IgG.CONCLUSION: DNA vaccine containing HEV ORF2 and ORF3 chimeric gene can successfully induce specific humoral and cellular immune response in mice.
基金Supported by Grants from the United States Public Health Service/National Institutes of Health,No.RO1CA135362,RO1GM083143 and PO1CA128115
文摘Human T-cell leukemia virus type 1(HTLV-1),the first human retrovirus discovered,is the etiological agent of adult-T-cell leukemia/lymphoma.The HTLV-1 encoded Tax protein is a potent oncoprotein that deregulates gene expression by constitutively activating nuclear factor-κB(NF-κB).Tax activation of NF-κB is critical for the immortalization and survival of HTLV-1-infected T cells.In this review,we summarize the present knowledge on mechanisms underlying Tax-mediated NF-κB activation,with an emphasis on post-translational modifications of Tax.
