In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
AIM: To study the prevalence and risk factors associated with triple infection with human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) in an urban clinic population. METHODS: Re...AIM: To study the prevalence and risk factors associated with triple infection with human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) in an urban clinic population. METHODS: Retrospective chart review of 5639 patients followed at St. Luke's-Roosevelt Hospital HIV Clinic (Center for Comprehensive Care) in New York City, USA from January 1999 to May 2007. The following demographic characteristics were analyzed: age, sex, race and HIV risk factors. A multiple logistic regression analysis was performed to evaluate the influence of demographic factors on acquisition of these viruses. RESULTS: HIV/HBV, HIV/HCV and HIV/HBV/HCV infections were detected in 252/5639 (4.47%), 1411/5639 (25.02%) and 89/5639 (1.58%) patients, respectively. HIV/HBV co-infections were associated with male gender (OR 1.711; P = 0.005), black race (OR 2.091, P 〈 0.001), men having sex with men (MSM) (OR 1.747, P = 0.001), intravenous drug use (IDU) (OR 0.114, P 〈 0.001), IDU and heterosexual activity (OR 0.247; P = 0.018), or unknown (OR 1.984, P = 0.004).HIV/HCV co-infections were associated with male gender (OR 1.241; P = 0.011), black race (OR 0.788; P = 0.036), MSM (OR 0.565; P 〈 0.001), IDU (OR 8.956; P 〈 0.001), IDU and heterosexual activity (OR 9.106; P 〈 0.001), IDU and MSM (OR 9.179; P 〈 0.001), or transfusion (OR 3.224; P 〈 0.001). HIV/HBV/HCV coinfections were associated with male gender (OR 2.156; P = 0.015), IDU (OR 6.345; P 〈 0.001), IDU and heterosexual activity (OR 9.731; P 〈 0.001), IDU and MSM (OR 9.228; P 〈 0.001), or unknown (OR 4.219; P = 0.007). CONCLUSION: Our study demonstrates that coinfection with HBV/HCV/HIV is significantly associated with IDU. These results highlight the need to intensify education and optimal models of integrated care, particularly for populations with IDU, to reduce the risk of viral transmission.展开更多
ST elevation on ECG in the setting of mesenteric ischemia has been reported.[1] From three prior reports, only one had a true ST elevation myocardial infarction (STEMI) coexisting with mesenteric ischemia. In patien...ST elevation on ECG in the setting of mesenteric ischemia has been reported.[1] From three prior reports, only one had a true ST elevation myocardial infarction (STEMI) coexisting with mesenteric ischemia. In patients with a strong cardiac history, distinguishing between these two conditions can be challenging. We present the case of a 79-year-old Caucasian female presented with 3-h history acute-onset epigastric pain. Medical history was significant for ischemic heart disease with prior coronary artery bypass grafts.展开更多
The incidence of hepatocellular carcinoma(HCC)in patients with human immunodeficiency virus(HIV) is rising.HCC in HIV almost invariably occurs in the context of hepatitis C virus(HCV)or hepatitis B virus (HBV)co-infec...The incidence of hepatocellular carcinoma(HCC)in patients with human immunodeficiency virus(HIV) is rising.HCC in HIV almost invariably occurs in the context of hepatitis C virus(HCV)or hepatitis B virus (HBV)co-infection and,on account of shared modes of transmission,this occurs in more than 33% and 10% of patients with HIV worldwide respectively.It has yet to be clearly established whether HIV directly accelerates HCC pathogenesis or whether the rising incidence is an epiphenomenon of the highly active antiretroviral therapy(HAART)era,wherein the increased longevity of patients with HIV allows long-term complications of viral hepatitis and cirrhosis to develop.Answering this question will have implications for HCC surveillance and the timing of HCV/HBV therapy,which in HIV co-infection presents unique challenges.Once HCC develops,there is growing evidence that HIV co-infection should not preclude conventional therapeutic strategies,including liver transplantation.展开更多
Celiac disease(CD) is frequently associated with neurological disorders,but very few reports concern the association with ischemic stroke.A 26-year-old woman affected by CD with secondary amenorrhea,carrier of a homoz...Celiac disease(CD) is frequently associated with neurological disorders,but very few reports concern the association with ischemic stroke.A 26-year-old woman affected by CD with secondary amenorrhea,carrier of a homozygous 5,10-methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia,was affected by two occipital ischemic strokes within a period of 5 mo.At the time of the second stroke,while she was being treated with folic acid,acetylsalicylic acid and a gluten-free diet,she had left hemianopsia,left hemiparesthesias,and gait imbalance.Brain magnetic resonance imaging showed a subacute right occipital ischemic lesion,which was extended to the dorsal region of the right thalamus and the ipsilateral thalamocapsular junction.Antitransglutaminase and deamidated gliadin peptide antibodies were no longer present,while antinuclear antibodies,antineuronal antibodies and immune circulating complexes were only slightly elevated.Since the patient was taking folic acid,her homocysteine levels were almost normal and apparently not sufficient alone to explain the clinical event.A conventional cerebral angiography showed no signs of vasculitis.Finally,rare causes of occipital stroke in young patients,such as Fabry's disease and mitochondrial myopathy,encephalomyopathy,lactic acidosis and stroke-like symptoms,were also excluded by appropriate tests.Thus,the most probable cause for the recurrent strokes in this young woman remained CD,although the mechanisms involved are still unknown.The two main hypotheses concern malabsorption(with consequent deficiency of vitamins known to exert neurotrophic and neuroprotective effects) and immunemediated mechanisms.CD should be kept in mind in the differential diagnosis of ischemic stroke in young patients.展开更多
Antiretroviral therapy has achieved great success in suppressing human immunodeficiency virus(HIV)replication and transforming HIV infection from a fatal disease to a manageable chronic disease.However,the latent HIV ...Antiretroviral therapy has achieved great success in suppressing human immunodeficiency virus(HIV)replication and transforming HIV infection from a fatal disease to a manageable chronic disease.However,the latent HIV reservoir persists in the body of HIVinfected individuals and is prone to reactivation.Therefore,the development of new treatment methods aimed at a complete cure for HIV is needed.The leading strategy for HIV eradication is based on eliminating and preventing the reactivation of latent reservoirs through an approach known as“shock and kill.”This strategy involves the use of latency-reversing agents(LRAs)to activate the HIV provirus in latent viral reservoir cells.Many LRAs can be obtained from natural resources,including plants and marine organisms.In this review,we provide an overview of natural products used to eliminate HIV latency.展开更多
Interaction between the HIV-1 Vif protein and the cellular host APOBEC3G protein is a promising target for inhibition of HIV-1 replication. Considering that human cells are a very complicated environment for the study...Interaction between the HIV-1 Vif protein and the cellular host APOBEC3G protein is a promising target for inhibition of HIV-1 replication. Considering that human cells are a very complicated environment for the study of protein interactions, the goal of this study was to check whether fission yeast could be used as a model cell for studying the Vif-APOBEC3G interaction. Vif and APOBEC3G were expressed in fusion with GFP protein in the S. pombe SP223 strain. Subcellular localizations of Vif and APOBEC3G were observed with fluorescent microscopy. Codon optimization was used to over express the Vif protein in S. pombe cells. The degradation of APOBEC3G mediated by Vif was tested through expressing Vif and GFP-APOBEC3G proteins in the same cell. Western Blot analysis was used to measure the corresponding protein levels under different experimental conditions. The results showed that the Vif protein was predominantly localized in the nucleus of S. pombe cells, APOBEC3G was localized in the cytoplasm and concentrated at punctate bodies that were often in close proximity to the nucleus but were not necessarily restricted from other regions in the cytoplasm. Vif protein expression levels were increased significantly by using codon optimization and APOBEC3G was degraded when Vif was over-expressed in the same S. pombe cells. These results indicate that fission yeast is a good model for studying the interaction between the Vif and APOBEC3G proteins.展开更多
AIM: To evaluate the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among blood donors in Kolkata, Eastern India for two consecutive years and to co...AIM: To evaluate the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among blood donors in Kolkata, Eastern India for two consecutive years and to conduct a pilot study to explore the presence of HBV DNA among hepatitis B surface antigen (HBsAg) negative but anti-HBc positive blood donors. METHODS: Seroprevalence of HBsAg, anti-HCV and anti-HIV was studied among 113 051 and 106 695 voluntary blood donors screened in 2004 and 2005, respectively. Moreover, a pilot study on 1027 HBsAg negative donors was carried out for evaluating the presence of HBV DNA by PCR on HBsAg negative/anti- HBc positive donors. RESULTS: A statistically significant increase in the prevalence of HBV (1448 vs 1768, P < 0.001), HIV (262 vs 374, P < 0.001), HCV (314 vs 372, P = 0.003) and syphilis (772 vs 853, P = 0.001) infections was noted among blood donors of Kolkata West Bengal in 2005 as compared to 2004. Moreover, the exploratory study on 1027 HBsAg negative donors revealed that 188 (18.3%)of them were anti-HBc positive out of which 21% were positive for HBV DNA. CONCLUSION: The findings of this study underscore the significantly increasing endemicity of hepatitis viruses, syphilis and HIV among the voluntary blood donors of our community. The pilot study indicates a high rate of prevalence of HBV DNA among HBsAg negative/anti-HBc positive donors and thus emphasizes the need for a more sensitive and stringent screening algorithm for blood donations.展开更多
AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV...AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.展开更多
AIM:To determine whether SP-TAT-apoptin induces apoptosis and also maintains its tumor cell specificity. METHODS:In this study,we designed a secretory protein by adding a secretory signal peptide(SP) to the N terminus...AIM:To determine whether SP-TAT-apoptin induces apoptosis and also maintains its tumor cell specificity. METHODS:In this study,we designed a secretory protein by adding a secretory signal peptide(SP) to the N terminus of Transactivating Transcription(TAT)-apoptin(SP-TAT-apoptin),to test the hypothesis that it gains an additive bystander effect as an anti-cancer therapy. We used an artificial human secretory SP whose amino acid sequence and corresponding cDNA sequence were generated by the SP hidden Markov model. RESULTS:In human liver carcinoma HepG2 cells,SP-TAT-apoptin expression showed a diffuse pattern in the early phase after transfection. After 48 h,however,it translocated into the nuclear compartment and caused massive apoptotic cell death,as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay and annexin-V binding assay. SP-TAT-apoptin did not,however,cause any cell death in non-malignant human umbilical vein endothelial cells(HUVECs). Most importantly,the conditioned medium from Chinese hamster ovary(CHO) cells transfected with SP-TAT-apoptin also induced significant cell deathin HepG2 cells,but not in HUVECs. CONCLUSION:The data demonstrated that SP-TAT-apoptin induces apoptosis only in malignant cells,and its secretory property might greatly increase its potency once it is delivered in vivo for cancer therapy.展开更多
Eleven env mutants were designed and generated by site-directed mutagenesis of the regions around NAb epitopes and deletions of variable regions in env. The immunogenicities of the generated mutants were evaluated usi...Eleven env mutants were designed and generated by site-directed mutagenesis of the regions around NAb epitopes and deletions of variable regions in env. The immunogenicities of the generated mutants were evaluated using single-cycle infection neutralization assays with two pseudoviruses and IFN-γ ELISPOT. Overall, five mutants (dWt, M2, M5-2, M5-1 and dM7) induced higher neutralization activities for both pseudoviruses than plasmid Wt, while only two of the mutants (dWt and M5-2) showed significant differences (P<0.05). Two mutants (M2 and dM2) induced more Env-specific T cells than plasmid Wt. Statistically however, significance was only reached for mutant M2. Thus, properly modified HIV-1 Env may have the potential to induce potent cellular and humoral immune responses.展开更多
Penicillium marneffei (R marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involve- ment. However, no cases of P. mameffei infection with chylous ascites have been reported thus far. In thi...Penicillium marneffei (R marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involve- ment. However, no cases of P. mameffei infection with chylous ascites have been reported thus far. In this re- port, we describe the first case of acquired immune de- ficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with am- photericin B for 3 mo, while receiving concomitant ther- apy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 too. R marneffei should be considered in the differential di- agnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with R marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.展开更多
Combinations of DNA and recombinant-viral-vector based vaccines are promising AIDS vaccine methods because of their potential for inducing cellular immune responses. It was found that Gag-specific cytotoxic lymphocyte...Combinations of DNA and recombinant-viral-vector based vaccines are promising AIDS vaccine methods because of their potential for inducing cellular immune responses. It was found that Gag-specific cytotoxic lymphocyte (CTL) responses were associated with lowering viremia in an untreated HIV-1 infected cohort. The main objectives of our studies were the construction of DNA and recombinant Sendai virus vector (rSeV) vaccines containing a gag gene from the prevalent Thailand subtype B strain in China and trying to use these vaccines for therapeutic and prophylactic vaccines. The candidate plasmid DNA vaccine pcDNA3.1(+)-gag and recombinant Sendai virus vaccine (rSeV-gag) were constructed separately. It was verified by Western blotting analysis that both DNA and rSeV-gag vaccines expressed the HIV-1 Gag protein correctly and efficiently. Balb/c mice were immunized with these two vaccines in different administration schemes. HIV-1 Gag-specific CTL responses and antibody levels were detected by intracellular cytokine staining assay and enzyme-linked immunosorbant assay (ELISA) respectively. Combined vaccines in a DNA prime/rSeV-gag boost vaccination regimen induced the strongest and most long-lasting Gag-specific CTL and antibody responses. It maintained relatively high levels even 9 weeks post immunization. This data indicated that the prime-boost regimen with DNA and rSeV-gag vaccines may offer promising HIV vaccine regimens.展开更多
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
文摘AIM: To study the prevalence and risk factors associated with triple infection with human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) in an urban clinic population. METHODS: Retrospective chart review of 5639 patients followed at St. Luke's-Roosevelt Hospital HIV Clinic (Center for Comprehensive Care) in New York City, USA from January 1999 to May 2007. The following demographic characteristics were analyzed: age, sex, race and HIV risk factors. A multiple logistic regression analysis was performed to evaluate the influence of demographic factors on acquisition of these viruses. RESULTS: HIV/HBV, HIV/HCV and HIV/HBV/HCV infections were detected in 252/5639 (4.47%), 1411/5639 (25.02%) and 89/5639 (1.58%) patients, respectively. HIV/HBV co-infections were associated with male gender (OR 1.711; P = 0.005), black race (OR 2.091, P 〈 0.001), men having sex with men (MSM) (OR 1.747, P = 0.001), intravenous drug use (IDU) (OR 0.114, P 〈 0.001), IDU and heterosexual activity (OR 0.247; P = 0.018), or unknown (OR 1.984, P = 0.004).HIV/HCV co-infections were associated with male gender (OR 1.241; P = 0.011), black race (OR 0.788; P = 0.036), MSM (OR 0.565; P 〈 0.001), IDU (OR 8.956; P 〈 0.001), IDU and heterosexual activity (OR 9.106; P 〈 0.001), IDU and MSM (OR 9.179; P 〈 0.001), or transfusion (OR 3.224; P 〈 0.001). HIV/HBV/HCV coinfections were associated with male gender (OR 2.156; P = 0.015), IDU (OR 6.345; P 〈 0.001), IDU and heterosexual activity (OR 9.731; P 〈 0.001), IDU and MSM (OR 9.228; P 〈 0.001), or unknown (OR 4.219; P = 0.007). CONCLUSION: Our study demonstrates that coinfection with HBV/HCV/HIV is significantly associated with IDU. These results highlight the need to intensify education and optimal models of integrated care, particularly for populations with IDU, to reduce the risk of viral transmission.
文摘ST elevation on ECG in the setting of mesenteric ischemia has been reported.[1] From three prior reports, only one had a true ST elevation myocardial infarction (STEMI) coexisting with mesenteric ischemia. In patients with a strong cardiac history, distinguishing between these two conditions can be challenging. We present the case of a 79-year-old Caucasian female presented with 3-h history acute-onset epigastric pain. Medical history was significant for ischemic heart disease with prior coronary artery bypass grafts.
文摘The incidence of hepatocellular carcinoma(HCC)in patients with human immunodeficiency virus(HIV) is rising.HCC in HIV almost invariably occurs in the context of hepatitis C virus(HCV)or hepatitis B virus (HBV)co-infection and,on account of shared modes of transmission,this occurs in more than 33% and 10% of patients with HIV worldwide respectively.It has yet to be clearly established whether HIV directly accelerates HCC pathogenesis or whether the rising incidence is an epiphenomenon of the highly active antiretroviral therapy(HAART)era,wherein the increased longevity of patients with HIV allows long-term complications of viral hepatitis and cirrhosis to develop.Answering this question will have implications for HCC surveillance and the timing of HCV/HBV therapy,which in HIV co-infection presents unique challenges.Once HCC develops,there is growing evidence that HIV co-infection should not preclude conventional therapeutic strategies,including liver transplantation.
文摘Celiac disease(CD) is frequently associated with neurological disorders,but very few reports concern the association with ischemic stroke.A 26-year-old woman affected by CD with secondary amenorrhea,carrier of a homozygous 5,10-methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia,was affected by two occipital ischemic strokes within a period of 5 mo.At the time of the second stroke,while she was being treated with folic acid,acetylsalicylic acid and a gluten-free diet,she had left hemianopsia,left hemiparesthesias,and gait imbalance.Brain magnetic resonance imaging showed a subacute right occipital ischemic lesion,which was extended to the dorsal region of the right thalamus and the ipsilateral thalamocapsular junction.Antitransglutaminase and deamidated gliadin peptide antibodies were no longer present,while antinuclear antibodies,antineuronal antibodies and immune circulating complexes were only slightly elevated.Since the patient was taking folic acid,her homocysteine levels were almost normal and apparently not sufficient alone to explain the clinical event.A conventional cerebral angiography showed no signs of vasculitis.Finally,rare causes of occipital stroke in young patients,such as Fabry's disease and mitochondrial myopathy,encephalomyopathy,lactic acidosis and stroke-like symptoms,were also excluded by appropriate tests.Thus,the most probable cause for the recurrent strokes in this young woman remained CD,although the mechanisms involved are still unknown.The two main hypotheses concern malabsorption(with consequent deficiency of vitamins known to exert neurotrophic and neuroprotective effects) and immunemediated mechanisms.CD should be kept in mind in the differential diagnosis of ischemic stroke in young patients.
基金supported by the Japan Society for the Promotion of Science KAKENHI 17K08348 and 21K06619(Wei Li).
文摘Antiretroviral therapy has achieved great success in suppressing human immunodeficiency virus(HIV)replication and transforming HIV infection from a fatal disease to a manageable chronic disease.However,the latent HIV reservoir persists in the body of HIVinfected individuals and is prone to reactivation.Therefore,the development of new treatment methods aimed at a complete cure for HIV is needed.The leading strategy for HIV eradication is based on eliminating and preventing the reactivation of latent reservoirs through an approach known as“shock and kill.”This strategy involves the use of latency-reversing agents(LRAs)to activate the HIV provirus in latent viral reservoir cells.Many LRAs can be obtained from natural resources,including plants and marine organisms.In this review,we provide an overview of natural products used to eliminate HIV latency.
基金National Grand Fundamental Research 973 Program of China (2006CB504206).
文摘Interaction between the HIV-1 Vif protein and the cellular host APOBEC3G protein is a promising target for inhibition of HIV-1 replication. Considering that human cells are a very complicated environment for the study of protein interactions, the goal of this study was to check whether fission yeast could be used as a model cell for studying the Vif-APOBEC3G interaction. Vif and APOBEC3G were expressed in fusion with GFP protein in the S. pombe SP223 strain. Subcellular localizations of Vif and APOBEC3G were observed with fluorescent microscopy. Codon optimization was used to over express the Vif protein in S. pombe cells. The degradation of APOBEC3G mediated by Vif was tested through expressing Vif and GFP-APOBEC3G proteins in the same cell. Western Blot analysis was used to measure the corresponding protein levels under different experimental conditions. The results showed that the Vif protein was predominantly localized in the nucleus of S. pombe cells, APOBEC3G was localized in the cytoplasm and concentrated at punctate bodies that were often in close proximity to the nucleus but were not necessarily restricted from other regions in the cytoplasm. Vif protein expression levels were increased significantly by using codon optimization and APOBEC3G was degraded when Vif was over-expressed in the same S. pombe cells. These results indicate that fission yeast is a good model for studying the interaction between the Vif and APOBEC3G proteins.
基金grants partly from West Bengal State AIDS Prevention & Control Society, Kolkata and partly by Indian Council of Medical Research, New Delhi. Partha Kumar Chandra received a research associateship from West Bengal State AIDS Prevention & Control Society, Kolkata. Arup Banerjee received a senior research fellowship from Indian Council of Medical Research New Delhi Sibnarayan Datta received a senior research fellowship from University Grants Commission, New Delhi
文摘AIM: To evaluate the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among blood donors in Kolkata, Eastern India for two consecutive years and to conduct a pilot study to explore the presence of HBV DNA among hepatitis B surface antigen (HBsAg) negative but anti-HBc positive blood donors. METHODS: Seroprevalence of HBsAg, anti-HCV and anti-HIV was studied among 113 051 and 106 695 voluntary blood donors screened in 2004 and 2005, respectively. Moreover, a pilot study on 1027 HBsAg negative donors was carried out for evaluating the presence of HBV DNA by PCR on HBsAg negative/anti- HBc positive donors. RESULTS: A statistically significant increase in the prevalence of HBV (1448 vs 1768, P < 0.001), HIV (262 vs 374, P < 0.001), HCV (314 vs 372, P = 0.003) and syphilis (772 vs 853, P = 0.001) infections was noted among blood donors of Kolkata West Bengal in 2005 as compared to 2004. Moreover, the exploratory study on 1027 HBsAg negative donors revealed that 188 (18.3%)of them were anti-HBc positive out of which 21% were positive for HBV DNA. CONCLUSION: The findings of this study underscore the significantly increasing endemicity of hepatitis viruses, syphilis and HIV among the voluntary blood donors of our community. The pilot study indicates a high rate of prevalence of HBV DNA among HBsAg negative/anti-HBc positive donors and thus emphasizes the need for a more sensitive and stringent screening algorithm for blood donations.
基金the Universidad de Buenos Aires(SECyT-UBA,TB14)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET,PIP723)+1 种基金Agencia Nacional de Promoción Científica y Tecnológica(ANPCyT,PICT 01610)Ministerio de Salud Pǘblica de la Nación(Beca Carrillo-Oativia)
文摘AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.
基金the National Natural Science Foundation of China, No. 30672069 and No. 30470098
文摘AIM:To determine whether SP-TAT-apoptin induces apoptosis and also maintains its tumor cell specificity. METHODS:In this study,we designed a secretory protein by adding a secretory signal peptide(SP) to the N terminus of Transactivating Transcription(TAT)-apoptin(SP-TAT-apoptin),to test the hypothesis that it gains an additive bystander effect as an anti-cancer therapy. We used an artificial human secretory SP whose amino acid sequence and corresponding cDNA sequence were generated by the SP hidden Markov model. RESULTS:In human liver carcinoma HepG2 cells,SP-TAT-apoptin expression showed a diffuse pattern in the early phase after transfection. After 48 h,however,it translocated into the nuclear compartment and caused massive apoptotic cell death,as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay and annexin-V binding assay. SP-TAT-apoptin did not,however,cause any cell death in non-malignant human umbilical vein endothelial cells(HUVECs). Most importantly,the conditioned medium from Chinese hamster ovary(CHO) cells transfected with SP-TAT-apoptin also induced significant cell deathin HepG2 cells,but not in HUVECs. CONCLUSION:The data demonstrated that SP-TAT-apoptin induces apoptosis only in malignant cells,and its secretory property might greatly increase its potency once it is delivered in vivo for cancer therapy.
文摘Eleven env mutants were designed and generated by site-directed mutagenesis of the regions around NAb epitopes and deletions of variable regions in env. The immunogenicities of the generated mutants were evaluated using single-cycle infection neutralization assays with two pseudoviruses and IFN-γ ELISPOT. Overall, five mutants (dWt, M2, M5-2, M5-1 and dM7) induced higher neutralization activities for both pseudoviruses than plasmid Wt, while only two of the mutants (dWt and M5-2) showed significant differences (P<0.05). Two mutants (M2 and dM2) induced more Env-specific T cells than plasmid Wt. Statistically however, significance was only reached for mutant M2. Thus, properly modified HIV-1 Env may have the potential to induce potent cellular and humoral immune responses.
文摘Penicillium marneffei (R marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involve- ment. However, no cases of P. mameffei infection with chylous ascites have been reported thus far. In this re- port, we describe the first case of acquired immune de- ficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with am- photericin B for 3 mo, while receiving concomitant ther- apy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 too. R marneffei should be considered in the differential di- agnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with R marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.
文摘Combinations of DNA and recombinant-viral-vector based vaccines are promising AIDS vaccine methods because of their potential for inducing cellular immune responses. It was found that Gag-specific cytotoxic lymphocyte (CTL) responses were associated with lowering viremia in an untreated HIV-1 infected cohort. The main objectives of our studies were the construction of DNA and recombinant Sendai virus vector (rSeV) vaccines containing a gag gene from the prevalent Thailand subtype B strain in China and trying to use these vaccines for therapeutic and prophylactic vaccines. The candidate plasmid DNA vaccine pcDNA3.1(+)-gag and recombinant Sendai virus vaccine (rSeV-gag) were constructed separately. It was verified by Western blotting analysis that both DNA and rSeV-gag vaccines expressed the HIV-1 Gag protein correctly and efficiently. Balb/c mice were immunized with these two vaccines in different administration schemes. HIV-1 Gag-specific CTL responses and antibody levels were detected by intracellular cytokine staining assay and enzyme-linked immunosorbant assay (ELISA) respectively. Combined vaccines in a DNA prime/rSeV-gag boost vaccination regimen induced the strongest and most long-lasting Gag-specific CTL and antibody responses. It maintained relatively high levels even 9 weeks post immunization. This data indicated that the prime-boost regimen with DNA and rSeV-gag vaccines may offer promising HIV vaccine regimens.