• 제목/요약/키워드: HIV

검색결과 917건 처리시간 0.038초

The Interaction of HIV-1 Inhibitor 3,3',3",3‴-Ethylenetetrakis-4-Hydroxycoumarin with Bovine Serum Albumin at Different pH

  • Dong, Sheying;Yu, Zhuqing;Li, Zhiqin;Huang, Tinglin
    • Bulletin of the Korean Chemical Society
    • /
    • 제32권6호
    • /
    • pp.2063-2069
    • /
    • 2011
  • We studied the interaction of 3,3',3'',3'''-ethylenetetrakis-4-hydroxycoumarin (EHC) with bovine serum albumin (BSA) in acetate buffer and phosphate buffer with different pH values by UV-vis absorption spectrometry and fluorescence spectrometry respectively. It was found that the pH values of the buffer solutions had an effect on the interaction process. In acetate buffer of pH 4.70, the carbonyl groups in EHC bound to the amino groups in BSA by means of hydrogen bond and van der Waals force, which made the extent of peptide chain in BSA changed. By contrast, in phosphate buffer of pH 7.40, hydrophobic force played a major role in the interaction between EHC and BSA, while the hydrogen bond and van der Waals force were also involved in the interaction. The results of spectrometry indicated that BSA could enhance the fluorescence intensity of EHC by forming a 1:1 EHC-BSA fluorescent complex through static mechanism at pH 4.70 and 7.40 respectively. Furthermore, EHC bound on site 1 in BSA.

Biochemical Properties of Second Site Mutation of Human Immunodeficiency Virus Integrase

  • Kim, Do-Jin;Oh, You-Take;Lee, Sang-Kwang;Shin, Cha-Gyun
    • BMB Reports
    • /
    • 제32권6호
    • /
    • pp.599-604
    • /
    • 1999
  • A highly conserved amino acid, glutamic acid (Glu), present at position 152 in the catalytic domain of the human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein has been known to be critical for enzymatic function since substitution of Glu 152 with other residues results in a complete loss of enzymatic activities. In order to better understand the role of Glu 152 as a conserved residue in enzymatic action, intragenic second site mutations have been introduced around residue 152 of a mutant IN (E152A), and their biochemical properties were analyzed in terms of enzymatic activities. Disintegration activities were found to be significantly restored in several second site mutant INs, while integration activities were only recovered weakly. However, endonucleolytic activities were not discovered in all the mutant INs. These findings indicate that the second site mutations can partially restore that catalytic structure of the active site disturbed by the E152A mutation and lead to the regaining of integration and disintegration activities. In addition, it is also suggested that endonucleolytic activity requires a more accurate structure of the catalytic site than that for the integration and disintegration activities.

  • PDF

Mechanism of T cell exhaustion in a chronic environment

  • Jin, Hyun-Tak;Jeong, Yun-Hee;Park, Hyo-Jin;Ha, Sang-Jun
    • BMB Reports
    • /
    • 제44권4호
    • /
    • pp.217-231
    • /
    • 2011
  • T cell exhaustion develops under conditions of antigen-persistence caused by infection with various chronic pathogens, such as human immunodeficiency virus (HIV) and myco-bacterium tuberculosis (TB), or by the development of cancer. T cell exhaustion is characterized by stepwise and progressive loss of T cell function, which is probably the main reason for the failed immunological control of chronic pathogens and cancers. Recent observations have detailed some of the intrinsic and extrinsic factors that influence the severity of T cell exhaustion. Duration and magnitude of antigenic activation of T cells might be associated with up-regulation of inhibitory receptors, which is a major intrinsic factor of T cell exhaustion. Extrinsic factors might include the production of suppressive cytokines, T cell priming by either non-professional antigenpresenting cells (APCs) or tolerogenic dendritic cells (DCs), and alteration of regulatory T (Treg) cells. Further investigation of the cellular and molecular processes behind the development of T cell exhaustion can reveal therapeutic targets and strategies for the treatment of chronic infections and cancers. Here, we report the properties and the mechanisms of T cell exhaustion in a chronic environment.

An Antiproliferative Ribonuclease from Fruiting Bodies of the Wild Mushroom Russula delica

  • Zhao, Shuang;Zhao, Yong Chang;Li, Shu Hong;Zhang, Guo Qing;Wang, He Xiang;Ng, Tzi Bun
    • Journal of Microbiology and Biotechnology
    • /
    • 제20권4호
    • /
    • pp.693-699
    • /
    • 2010
  • An antiproliferative ribonuclease with a new N-terminal sequence was purified from fruiting bodies of the edible wild mushroom Russula delica in this study. This novel ribonuclease was unadsorbed on DEAE-cellulose, but absorbed on SP-Sepharose and Q-Sepharose. It had a molecular mass of 14 kDa, as judged by fast protein liquid chromatography on Superdex 75 and SDS-polyacrylamide gel electrophoresis. Its optimal pH and optimal temperature were pH 5 and $60^{\circ}C$, respectively. The ranking of its activity toward various polyhomoribonucleotides was poly C> poly G>poly A>poly U. It could inhibit proliferation of HepG2 and MCF-7 cancer cells with an $IC_50$ value of $8.6\;{\mu}M$ and $7.2\;{\mu}M$, respectively. It was devoid of antifungal and HIV-1 reverse transcriptase inhibitory activity.

전이성 폐암으로 추정된 폐효모균증 (Pulmonary Cryptococcosis That Was Suspected to be Metastatic Lung Cancer)

  • 김종인;조성래;계여곤
    • Journal of Chest Surgery
    • /
    • 제42권1호
    • /
    • pp.123-126
    • /
    • 2009
  • 효모균증은 비둘기의 배설물에 의해 오염된 먼지나 토양에 주로 존재하는 cryptococcus neoformans에 의한 아급성 또는 만성 감염이다. 폐의 효모균증은 건강한 사람에게는 잘 발생하지 않으며 면역이 저하된 환자 특히 후천성 면역결핍증 환자에게서 호발 한다. 일반적으로 증상이 없이 단순 흉부 X-선 검사에서 고립성 또는 다발성 폐 결절이 관찰되며, 이런 경우에는 대부분 절제된 조직의 병리학적 소견으로 진단된다. 본 증례는 갑상선 암으로 수술 받은 32세 여자환자에서 추적관찰 중에 발견된 좌하엽폐의 종괴가 전이성 폐암으로 추정되어 좌하엽폐 절제술을 시행한 후 폐 효모균증으로 확인되었다.

전립선암 선별을 위한 PSA 측정의 보험의학적 의미 (Review of measurement of prostate specific antigen: in the aspect of insurance medicine)

  • 박광일
    • 보험의학회지
    • /
    • 제29권1호
    • /
    • pp.16-21
    • /
    • 2010
  • The measurement of prostate specific antigen (PSA) in screening for prostate cancer is recently performed as a routine check-up in clinical medicine and insurance medicine. Several factors may affect serum PSA levels. As prostate size increases with increasing age, the PSA concentration also rises. Increasing body mass index (BMI) is associated with a lower mean PSA concentration. Inhibitors of 5-alpha-reductase such as finasteride and dutasteride produce a 50 percent or greater decrease in serum PSA during the first three months of therapy, which persists as long as the drug is continued. Men who are regularly taking non-steroidal antiinflammatory drugs (NSAIDs) or acetaminophen have lower PSA levels. Emerging concepts regarding PSA testing that may help refine the interpretation of an elevated concentration include: PSA density, PSA velocity, and Free versus complexed or bound PSA. With many insurance companies, PSA level has become part of a standard battery of blood tests, along with HIV, cholesterol, liver enzymes, and other predictors of premature death. But, there is no clear proof of benefit, so we have to monitor the value of PSA test as a prostate cancer screening test in insurance medicine.

  • PDF

Zidovudine의 In Vitro 세포내 대사물의 측정을 통한 약효 검색법 개발 (In Vitro Determination of Intracellular Phosphorylated Metabolites of Antiviral Pyrimidine Analogs)

  • 한규원;김길수
    • Journal of Pharmaceutical Investigation
    • /
    • 제32권4호
    • /
    • pp.285-290
    • /
    • 2002
  • In order to assay the efficacy of newly synthesized antiviral compounds, in vitro studies of their active intracellular phosphorylated metabolites were established as compared with Zidovudine (ZDV). Antiviral base analogs require intracellular phosphorylation prior to the inhibition of HIV replication. Therefore, antiviral drugs concentrations in plasma have not reflected any direct relationship with activity or toxicity. A method has been developed to measure the concentration of total phosphorylated metabolites inside peripheral blood mononuclear cells using modified commercial radioimmunoassay (RIA). ZDV 5'-monophosphate was synthesized and used as a procedural control for RIA modification. PBMCs were isolated from whole blood and incubated with ZDV for 20 h to allow metabolic phosphorylation. Viable cells were extracted overnight with 60% methanol. After evaporation, the extract was reconstituted in Tris buffer. Samples were split into two fractions, one of which was treated with alkaline phosphatase (AP) to liberate phosphate groups. Concentrations of phosphorylated metabolites were determined by subtracting thε concentration of non-AP-treated fraction from that of the treated fraction. Recovery of phosphorylated ZDV from cell extracts was approximately 90%, and reproducibility was acceptable (coefficients of variation <15% for concentrations${\geq}$0.25 ng/mL). Intracellular concentrations $(0.135{\sim}5.019\;nmole/10^6\;cells)$ followed a nonlinear dose-response relationship over the range $0.015{\sim}2.996mM$ extracellular ZDV, with concentration-dependant saturation.

L-1,3-Dioxolane 및 L-1,3-Oxathiolane 피리미딘 뉴크레오사이드의 합성 (Synthesis of L-1,3-Dioxolane and L-1,3-Oxathiolane Pyrimidine Nucleosides)

  • 홍준희;박정하;송지연;최보길;정병호;김중협;이종교;정원근;천문우
    • 약학회지
    • /
    • 제38권6호
    • /
    • pp.775-781
    • /
    • 1994
  • $({\pm})-Dioxolane-T$ and$({\pm})-BCH-189$ are know to possess anti-HIV activities, and less to xicities compared to other dideoxynucleoside AIDS drugs. We have synthesized 34 different enantiomerically pure nucleosides by glycosylation of L-1,3-dioxolanyl acetate and L-1,3-oxathiolanyl acetate sugar moieties with uracil or 6-azauracil with alkyl chains$(C_1-C_3)$ on 5 or 6 position.

  • PDF

역상컬럼 및 고체분산체를 이용한 무정형 아데포비어디피복실의 제조 (Preparation of Amorphous Adefovir dipivoxil using Reverse Phase Column Chromatography and Solid Dispersion Method)

  • 윤명식;오다원;맹효찬;홍혜숙;박미경;이용택;이시범;조일환;문병석
    • 약학회지
    • /
    • 제54권4호
    • /
    • pp.316-321
    • /
    • 2010
  • Adefovir dipivoxil which was originally developed by Gilead Sciences has been used as treatments of HIV and HBV, especially a therapeutics for HBeAg positive and negative chronic patients. We developed highly efficient purification method using reverse phase column chromatography for mass production and a stable amorphous Adefovir dipivoxil using solid dispersion method. Reverse phase column chromatography led to highly pure product, more than 99.7% by HPLC and can be used for mass production compared with normal column chromatography. Solid dispersion method containing watersoluble polymer and Isomalt showed improved stability of amorphous Adefovir dipivoxil against heat and moisture.