Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-seven patients with AML and MLL gene rearrangement were analyzed by a reverse transcriptase polymerase chain reaction (RT-PCR) for the MLL-AF9 translocation. The MLL-AF9 fusion transcript was detected in six patients. In five patients, the breakpoint of the AF9 gene was located within the recently described site A; in one patient, a novel breakpoint (AF9 site D) mapped to a position 377 bp 3' of site A. Five patients could be serially monitored for a period of 4-23 months. Two patients became two-step PCR negative in bone marrow and peripheral blood. Molecular remission was achieved rapidly after one cycle of induction chemotherapy. Both patients are in continuous complete remission (CR) at 22 and 15 months, respectively. Two patients who had achieved hematological CR did not become PCR negative and MLL-AF9 fusion transcripts were detectable in all samples after induction and consolidation chemotherapy. One patient relapsed 5 months after achieving CR. The other patient received allogeneic bone marrow transplantation from an HLA-identical sibling 2 months after achieving hematological CR and became PCR negative 4 weeks after transplantation. In the fifth patient, hematological CR could not be achieved with two cycles of intensive induction chemotherapy, and MLL-AF9 transcripts were present in all samples tested. Our data indicate that MLL-AF9 RT-PCR is specific for the t(9;11) translocation. PCR negativity can be achieved in responding patients already 1 month after induction chemotherapy. The fast reduction of MLL-AF9 positive blast cells below the detection limit of RT-PCR seems to be a prerequisite for long-term CR. The results of RT-PCR may be useful for treatment decisions (eg BMT).
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PMID:Monitoring of minimal residual leukemia in patients with MLL-AF9 positive acute myeloid leukemia by RT-PCR. 1051 52

The RelB gene product is a member of the nuclear factor (NF)-kappaB family of transcription factors. It has been identified recently within mouse antigen-presenting cells and human monocyte-derived dendritic cells (DC). Disruption of the mouse RelB gene is accompanied, amongst other phenotypes, by abnormalities in the antigen-presenting cell lineages. In order to define RelB expression during human DC differentiation, we have analysed RelB mRNA by reverse transcriptase-polymerase chain reaction and RelB protein by intracellular staining in CD34+ precursors and different types of DC preparations. RelB mRNA was not detected in CD34+ precursor populations. Fresh blood DC (lineage-human leucocyte antigen-DR+ (lin-HLA-DR+)) lacked RelB mRNA and cytoplasmic RelB protein but a period of in vitro culture induced RelB expression in blood DC. Purified Langerhans' cells (LC) (CD1a+ HLA-DR+) failed to express RelB mRNA. Immunocytochemical staining identified RelB protein in human skin epithelium. RelB protein was expressed in a very few CD1a+, CD83+ or CMRF-44+ dermal DC but was not present in CD1a+ LC. Tonsil DC (lin-HLA-DR+ CMRF-44+) were positive for RelB mRNA and RelB protein. Intestinal DC (HLA-DR+) also lacked immunoreactive RelB protein. The majority of interdigitating CD83+, CMRF-44+, CMRF-56+ or p55+ DC located in paracortical T-lymphocyte areas of lymph node and tonsil contained RelB protein. The expression of RelB mRNA and RelB protein correlates with the activated phase of blood DC and the postmigration cell (activated) stage of tissue DC development.
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PMID:Expression of the RelB transcription factor correlates with the activation of human dendritic cells. 1054 Feb 17

Two novel B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) cell lines, designated NALM-33 and NALM-34, were established from a 72 year-old male patient with ALL at relapse. Subcultures of each initial flask were first made after eight weeks of continuous incubation; thus, the two cell lines are simultaneous sister cell lines. The cells proliferate consistently singly and free-floating in suspension. They are negative for Epstein-Barr virus (EBV) infection by polymerase chain reaction (PCR) and are negative for mycoplasma infection. They have the morphological appearance of lymphoblasts with a scanty rim of cytoplasm, fine nuclear chromatin and distinct nucleoli. The primary leukemic blasts showed a common ALL phenotype with CD19+, CD10+, CD13-, HLA-DR+ and Igs-; the cell lines NALM-33/-34 display an identical immunophenotype. They fulfill "European Group for the Immunological Characterization of Leukemias (EGIL)" criteria as BCP leukemia B-II type. While the immunoglobulin heavy chain genes were found uniquely to be in their germline configuration, rearrangement of both kappa and lambda light chain genes was noted by Southern blot analysis. CDR-II detection by reverse transcriptase-PCR was also not detected. NALM-33/-34 did not respond significantly to the proliferative stimuli of various hematopoietic cytokines. In the cytogenetic analysis, they revealed the t(8;14)(q24.1;q32) with additional numerical and structural chromosomal abnormalities. The extensive immunological, cytogenetic and functional characterization of NALM-33/-34 suggests that these two novel cell lines may represent unique and relevant in vitro model systems for BCP-type leukemia cells.
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PMID:Novel B-cell precursor leukemia sister cell lines, NALM-33 and NALM-34, established from a patient with acute lymphoblastic leukemia. 1060 89

Regulation of HLA-DQ gene transcription is a complex phenomenon because the allelic polymorphism associated with these genes and their promoters is a putative source of differential allele expression. Both transcriptional and post-transcriptional regulation could account for the density of the molecules expressed at the cell surface and then for the specificity of the immune response. Different methods have been developed to evaluate the functional consequences of this polymorphism, but at present no universal method allows measurement of either the steady-state level or the half-life time of mRNA species of both DQA1 and DQB1 polymorphic genes in heterozygous cell lines. Here, we propose a potent method, based on relative quantification of reverse transcriptase-polymerase chain reaction products, which analyzes the differential expression of all DQA1 or DQB1 allele combinations. This method is used to analyze the differential expression of HLA-DQB1*020110402 alleles in the human heterozygous lymphoblastoid B-cell line. Nucleotidic sequences of the proximal upstream regulatory region of these alleles exhibit significant differences. We show that the DQB1*0402 promoter is able to mediate a transcription strength twice as efficiently as *0201. In addition, the *0402 mRNA steady-state level is also governed by a remarkable post-transcriptional regulation. Indeed, an important part (20%) of the *0402 primary transcript is derived by alternative splicing in a short mRNA translated into a nonfunctional protein. Despite their variable sequence and length, no difference in the half-life of DQB1*0201 and both DQB*0402 mRNAs was observed in B-lymphoblastoid cells. The implications of these findings are discussed.
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PMID:In vivo analysis of HLA-DQ gene expression in heterozygous cell lines. 1063 Feb 95

We investigated the cytotoxicity mechanisms of alloantigen-specific human CD4(+) and CD8(+) cytotoxic T lymphocytes (CTLs) using cells from family members with the Fas gene mutation. Alloantigen-specific CD4(+) and CD8(+) CTL bulk lines and clones were generated from 2 individuals by stimulation of their peripheral blood lymphocytes with allogeneic Fas(-/-) or Fas(+/-) cell lines that were established from B-lymphocytes of a patient with Fas deficiency and her mother, respectively. Both CD4(+) and CD8(+) CTL bulk lines and clones directed against allogeneic HLA antigens exerted cytotoxicity against Fas(-/-) and Fas(+/-) cells to almost the same degree. The cytotoxicity of CD4(+) and CD8(+) CTLs appeared to be Ca(2+)-dependent and was completely inhibited by concanamycin A, an inhibitor of perforin-mediated cytotoxicity. Messenger RNAs for the major mediators of CTL cytotoxicity, Fas ligand, perforin, and granzyme B were all detected in these CD4(+) CTLs with the use of the reverse transcriptase polymerase chain reaction. The majority of CD4(+) CTL clones that showed Fas-independent cytotoxicity were T(H)0, as determined by their cytokine production profile. These data, obtained with the use of a novel experimental system, clearly show that the main pathway of cytotoxicity mediated by alloantigen-specific human CD4(+) as well as by CD8(+) CTLs is granule exocytosis, and not the Fas/Fas ligand system.
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PMID:Granule exocytosis, and not the fas/fas ligand system, is the main pathway of cytotoxicity mediated by alloantigen-specific CD4(+) as well as CD8(+) cytotoxic T lymphocytes in humans. 1073 6

The long-term efficacy of combination antiretroviral therapy may relate to augmentation of anti-human immunodeficiency virus type 1 (HIV-1) CD8(+) T-cell responses. We found that prolonged treatment of late-stage HIV-1-infected patients with a protease inhibitor and two nucleoside reverse transcriptase inhibitors failed to restore sustained, high levels of HIV-1-specific, HLA class I-restricted, cytotoxic-T-lymphocyte precursors and gamma interferon (IFN-gamma) production by CD8(+) T cells. In some patients, particularly those initiating three-drug combination therapy simultaneously rather than sequentially, there were early, transient increases in the frequency of anti-HIV-1 CD8(+) T cells that correlated with decreases in HIV-1 RNA and increases in T-cell counts. In the other patients, HIV-1-specific T-cell functions either failed to increase or declined from baseline during triple-drug therapy, even though some of these patients showed suppression of plasma HIV-1 RNA. These effects of combination therapy were not unique to HIV-1 specific T-cell responses, since similar effects were noted for CD8(+) T cells specific for the cytomegalovirus pp65 matrix protein. The level and breadth of CD8(+) cell reactivity to HLA A*02 HIV-1 epitopes, as determined by IFN-gamma production and HLA tetramer staining after combination therapy, were related to the corresponding responses prior to treatment. There was, however, a stable, residual population of potentially immunocompetent HIV-1-specific T cells remaining after therapy, as shown by tetramer staining of CD8(+) CD45RO(+) cells. These results indicate that new strategies will be needed to target residual, immunocompetent HIV-1-specific CD8(+) T cells to enhance the effectiveness of antiretroviral therapy in patients with advanced immunodeficiency.
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PMID:Anti-human immunodeficiency virus type 1 (HIV-1) CD8(+) T-lymphocyte reactivity during combination antiretroviral therapy in HIV-1-infected patients with advanced immunodeficiency. 1075 25

Human ejaculate spermatozoa contain multiple mRNA species carried over from earlier stages in spermatogenesis. To date, gene-specific RT-PCR or in situ hybridization has detected transcripts for beta-actin, heat shock proteins (HSP) 70 and 90, protamines (PRM) 1 and 2, transition protein (TNp) 2, HLA II, beta-integrins, and, most recently, phosphodiesterase subtypes. We have further evidence for a complex population of transcripts based on screening a human testis cDNA library with a heterologous spermatozoal probe. High levels of transcribed repetitive sequences are present in human spermatozoa, including medium reiteration repeats (MERs) and short and long nuclear interspersed repeats (SINES and LINES). Both SINES and LINES belong to the retroposon class of repeat elements, which are thought to proliferate via an intermediate RNA that is converted to DNA by an RNA-dependent DNA polymerase (reverse transcriptase). We have circumstantial evidence for the presence of an RT in ejaculate sperm based on the detection of transcripts for ORF2 of LINE 1 encoding such an enzyme. Our data suggests the following: 1. Ejaculate spermatozoa may be a very useful tool in the identification of genes linked to an infertile phenotype. 2. Spermatozoa (or spermatids) may express a reverse transcriptase, the role of which is unknown. 3. RNA isolated from spermatozoa or washed semen samples may facilitate the detection of mutations and deletions in testis-expressed AZF-linked genes.
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PMID:Analysis and significance of messenger RNA in human ejaculated spermatozoa. 1082 80

Genes of the MAGE-A family are expressed in several types of solid tumors but are silent in normal tissues with the exception of male germline cells, which do not carry HLA molecules.Therefore, peptides encoded by MAGE-A genes are strictly tumor-specific antigens that can be recognized by CTL and constitute promising targets for immunotherapy. The expression of 6 genes of the MAGE-A family was tested with reverse transcriptase-polymerase chain reaction in lymphoma samples. Among 38 samples of non-Hodgkin lymphoma, 1 anaplastic large cell lymphoma expressed genes MAGE-A1, -A2, -A3, -A4, and -A12, and 1 lymphoepithelioid T-cell lymphoma expressed gene MAGE-A4. Five of 18 samples (28%) from patients with Hodgkin disease expressed gene MAGE-A4. In tissue sections, staining by a monoclonal antibody that recognizes the MAGE-A4 protein was observed in 11 of 53 samples (21%) from patients with Hodgkin disease. In the positive samples, the Reed-Sternberg cells were strongly stained whereas the surrounding cells were not. These results indicate that Hodgkin disease may be a target for specific immunotherapy involving MAGE-A4 antigens.
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PMID:Expression of gene MAGE-A4 in Reed-Sternberg cells. 1082 39

Chimeric papillomavirus (PV) virus-like particles (VLPs) based on the bovine papillomavirus type 1 (BPV-1) L1 protein were constructed by replacing the 23-carboxyl-terminal amino acids of the BPV1 major protein L1 with an artificial "polytope" minigene, containing known CTL epitopes of human PV16 E7 protein, HIV IIIB gp120 P18, Nef, and reverse transcriptase (RT) proteins, and an HPV16 E7 linear B epitope. The CTL epitopes were restricted by three different MHC class I alleles (H-2(b), H-2(d), HLA-A*0201). The chimeric L1 protein assembled into VLPs when expressed in SF-9 cells by recombinant baculovirus. After immunization of mice with polytope VLPs in the absence of adjuvant, serum antibodies were detected which reacted with both polytope VLPs and wild-type BPV1L1 VLPs, in addition to the HPV16E7 linear B cell epitope. CTL precursors specific for the HPV16 E7, HIV P18, and RT CTL epitopes were also detected in the spleen of immunized mice. Polytope VLPs can thus deliver multiple B and T epitopes as immunogens to the MHC class I and class II pathways, extending the utility of VLPs as self-adjuvanting immunogen delivery systems.
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PMID:Papillomavirus virus-like particles for the delivery of multiple cytotoxic T cell epitopes. 1091 8

High numbers of inflammatory cells are found in a subgroup of patients with idiopathic dilated cardiomyopathy (IDCM). We hypothesized that the extent of inflammation is linked to myocardial TNF-alpha expression in human IDCM. Fourteen patients who consecutively underwent endomyocardial biopsy (EMB) were stratified into two groups-a group with low and a group with high myocardial inflammatory index (MII)-based on immunohistochemical analysis of cellular infiltration and HLA I and II expression. Myocardial TNF-alpha messenger RNA (mRNA) expression was determined by reverse transcriptase polymerase chain reaction, TNF-alpha protein was localized by immunohistochemistry and TNF-alpha serum levels were measured by EIA. IDCM patients with a high MII (n=6) showed a 1. 9-fold higher TNF-alpha mRNA expression when compared to IDCM patients with low MII (n=8, P=0.020). TNF-alpha protein was detected at perinuclear regions of cardiac myocytes and the endothelium. TNF-alpha serum levels were 3.0 (0.55) pg/ml in patients with high MII compared to 1.35 (0.20) pg/ml in patients with low MII (P=0.017). According to immunolocalization cardiac myocytes and the endothelium seem to be the major source of TNF-alpha production. Whether the elevated systemic level of TNF-alpha found in patients with high MII are elaborated by the myocardium or are produced by other tissues representing a general immune activation is not clear.
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PMID:Tumour necrosis factor-alpha expression in idiopathic dilated cardiomyopathy: correlation to myocardial inflammatory activity. 1093 Mar 9


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