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1.
ScientificWorldJournal ; 2013: 389780, 2013.
Article in English | MEDLINE | ID: mdl-23476130

ABSTRACT

With improved HCV therapy, challenges regarding HCV diagnosis, such as seronegative window period, false positive readings, and differentiation between recent, chronic, and resolved infections, are of increasing importance. To address these challenges an innovative device--SMARTube HIV & HCV--was used. Blood samples were tested for anti-HCV antibodies before and after incubation in the SMARTube, which promotes the in vitro stimulation of in vivo HCV primed lymphocytes, thus enhancing levels of anti-HCV antibodies. Comparing antibody levels, in concordant samples before and after SMARTube, yielded the Stimulation Index (SI). Among 5888 fresh blood samples, from various populations and regions worldwide, 641 were seropositive using plasma, while SMARTube processing (yielding enriched plasma, termed SMARTplasma) enabled diagnosis of 10 additional carriers in high-risk cohorts, that is, earlier detection. Using SMARTplasma eliminated all false positive results, using the current assays. In addition we show that SI calculation may serve as an important tool for differentiating between those who recently seroconverted, carriers of long-term infection, and those who have cleared the virus. SMARTube and the SI could lead to better, more informative diagnosis of HCV infections and play an important role in changing the way we treat both the infected individuals and the epidemic as a whole.


Subject(s)
Hepatitis C Antibodies/blood , Hepatitis C, Chronic/diagnosis , Immunologic Tests/methods , Antibody Formation , Antiviral Agents/therapeutic use , Carrier State/diagnosis , Carrier State/virology , Early Diagnosis , False Positive Reactions , Hepacivirus , Humans , Immunologic Tests/instrumentation , Lymphocytes/immunology , Lymphocytes/virology , Sensitivity and Specificity , Severity of Illness Index
2.
Oncogene ; 21(39): 6017-31, 2002 Sep 05.
Article in English | MEDLINE | ID: mdl-12203114

ABSTRACT

cDNA microarray hybridization was used in an attempt to identify novel genes participating in cellular responses to prolonged hypoxia. One of the identified novel genes, designated Hi95 shared significant homology to a p53-regulated GADD family member PA26. In addition to its induction in response to prolonged hypoxia, the increased Hi95 transcription was observed following DNA damage or oxidative stress, but not following hyperthermia or serum starvation. Whereas induction of Hi95 by prolonged hypoxia or by oxidative stress is most likely p53-independent, its induction in response to DNA damaging treatments (gamma- or UV-irradiation, or doxorubicin) occurs in a p53-dependent manner. Overexpression of Hi95 full-length cDNA was found toxic for many types of cultured cells directly leading either to their apoptotic death or to sensitization to serum starvation and DNA damaging treatments. Unexpectedly, conditional overexpression of the Hi95 cDNA in MCF7-tet-off cells resulted in their protection against cell death induced by hypoxia/glucose deprivation or H(2)O(2). Thus, Hi95 gene seems to be involved in complex regulation of cell viability in response to different stress conditions.


Subject(s)
Brain Neoplasms/genetics , Glioma/genetics , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Amino Acid Sequence , Animals , Antineoplastic Agents/pharmacology , Base Sequence , Blotting, Northern , Blotting, Western , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Division , Cell Survival , Cloning, Molecular , DNA Primers/chemistry , Doxorubicin/pharmacology , Glioma/metabolism , Glioma/pathology , Humans , Hydrogen Peroxide/pharmacology , Hypoxia/metabolism , In Situ Nick-End Labeling , Mice , Mice, Nude , Molecular Sequence Data , Oligonucleotide Array Sequence Analysis , RNA, Messenger/metabolism , Rats , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino Acid , Tumor Cells, Cultured , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
3.
Mol Cell Biol ; 22(7): 2283-93, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11884613

ABSTRACT

Hypoxia is an important factor that elicits numerous physiological and pathological responses. One of the major gene expression programs triggered by hypoxia is mediated through hypoxia-responsive transcription factor hypoxia-inducible factor 1 (HIF-1). Here, we report the identification and cloning of a novel HIF-1-responsive gene, designated RTP801. Its strong up-regulation by hypoxia was detected both in vitro and in vivo in an animal model of ischemic stroke. When induced from a tetracycline-repressible promoter, RTP801 protected MCF7 and PC12 cells from hypoxia in glucose-free medium and from H(2)O(2)-triggered apoptosis via a dramatic reduction in the generation of reactive oxygen species. However, expression of RTP801 appeared toxic for nondividing neuron-like PC12 cells and increased their sensitivity to ischemic injury and oxidative stress. Liposomal delivery of RTP801 cDNA to mouse lungs also resulted in massive cell death. Thus, the biological effect of RTP801 overexpression depends on the cell context and may be either protecting or detrimental for cells under conditions of oxidative or ischemic stresses. Altogether, the data suggest a complex type of involvement of RTP801 in the pathogenesis of ischemic diseases.


Subject(s)
Apoptosis/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Gene Expression Regulation , Nuclear Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Animals , Apoptosis/drug effects , Base Sequence , Cell Differentiation , Cloning, Molecular , DNA-Binding Proteins/chemistry , Humans , Hydrogen Peroxide/pharmacology , Hypoxia/genetics , Hypoxia-Inducible Factor 1 , Hypoxia-Inducible Factor 1, alpha Subunit , In Situ Hybridization , Liposomes/metabolism , Lung/cytology , Lung/drug effects , Lung/metabolism , Mice , Molecular Sequence Data , PC12 Cells , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Reactive Oxygen Species/metabolism , Repressor Proteins , Sequence Homology, Amino Acid , Stroke/genetics , Transcription Factors/chemistry , Tumor Cells, Cultured , Up-Regulation
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