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)

A newly established human leukemia cell line, OM9;22, is reported, with B-precursor immunophenotype (CD10+ CD19+ CD22+ HLA- DR+ C mu-) and CD13 antigen, originated from a 19-year-old female patient with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL). The OM9;22 cells carry a Philadelphia (Ph) translocation and hybrid message detected by a minor-breakpoint cluster region (BCR) exon 1/ABL exon 2 junctional probe using reverse transcriptase polymerase chain reaction. The genetic alterations are consistent with those observed in the donor's leukemia cells, allowing us to conclude that this cell line is a minor-BCR rearranged Ph-positive ALL (Ph+ ALL). Colony formation of the OM9;22 cells in methylcellulose culture is enhanced by the addition of human interleukin 7 (IL-7). In liquid culture, more than 80% of IL-7-treated OM9;22 cells express CD20 antigen but fail to express surface immunoglobulins or cytoplasmic mu-chain, indicating that the cells have a potential of limited maturation by IL-7. By contrast, IL-4 suppresses the colony formation of the OM9;22 cells. These findings suggest that this cell line might be a model of B-precursor human leukemia with proliferative capability by IL-7.
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PMID:Interleukin-7 enhances colony growth and induces CD20 antigen of a Ph+ acute lymphoblastic leukemia cell line, OM9;22. 768 4

Nucleotide sequences of the heavy and light chain variable (VH and VL) regions of a human monoclonal antibody (4-35-7), which recognized HLA-A1, A23 and A24, were determined by means of the reverse transcriptase-polymerase chain reaction. This antibody was generated by Epstein-Barr virus transformation of lymphocytes obtained from a multiparous donor, followed by fusion with mouse myeloma cells. The VH gene segment belonged to the VHIII gene family, and used the DXP4 and JH4 gene segments. This VH gene segment had 92.9% homology to the germline gene VH26, and contained 21 nucleotide substitutions. Fourteen of them generated the replacements of amino acids, while 7 failed to generate the replacement. The ratio of replacement to silent mutations in complementarity determining regions (CDRs) was 7.0. The VL gene segment belonged to the VkI gene family, and used Jk4. This VL gene segment showed 96.1% homology to the germline gene HK102, and contained 11 nucleotide substitutions. Seven of them generated the replacement of amino acids, while 4 failed to generate the replacement. The high ratio of replacement to silent mutations in CDRs of the VH gene segment suggested that the multiparity caused the processes of antigenic selection and somatic mutation, and generated this anti-HLA antibody.
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PMID:Nucleotide sequences of the variable regions of a human monoclonal antibody against HLA-A1, A23, and A24. 769 91

When administered as single agents, both interferon gamma (IFN-gamma) and interleukin 6 (IL-6) significantly increase carcinoembryonic antigen (CEA) and HLA class I antigen expression on the surface of human colorectal tumour cells. Studies were carried out to determine whether by combining those cytokines a synergistic enhancement of CEA and HLA expression could result. The findings revealed that the administration of 20 units IFN-gamma along with 1.7 ng IL-6, concentrations of each cytokine that individually induced minimal antigenic changes, together synergistically increased CEA and HLA class I as well as induced qualitative changes in HLA expression on WiDr human colon carcinoma cells. The magnitude of the synergistic increases in CEA and HLA class I expression were reminiscent of the level of antigen augmentation observed when administering 20- to 100-fold higher amounts of each cytokine as a single agent. Also, the addition of IL-6 potentiated the IFN-gamma induction of HLA class II expression. The combined administration of IL-6 potentiated the IFN-gamma did not have any additive or synergistic effects on the growth suppression of those tumour cells. Interestingly, utilization of specific neutralizing antibodies for type I interferons abrogated the increases of CEA and HLA expression seen with IL-6 treatment alone or in combination with IFN-gamma. Moreover, reverse transcriptase/polymerase chain reaction analyses revealed a constitutive expression as well as a temporal increase of IFN-beta mRNA transcripts in colon tumour cells treated with IL-6. Therefore, the findings provide indirect evidence that IFN-beta production seems to play a critical role in the ability of IL-6 to upregulate antigen expression alone or in combination with IFN-gamma. These findings provide insight into cytokine combinations that synergistically upregulate tumour-associated and normal HLA antigen expression on the surface of human tumour cells. Those results provide the rationale for the combined use of such cytokines to heighten tumour cell recognition in monoclonal antibody- or cell-mediated-based immunotherapeutic approaches.
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PMID:Synergistic effects of IL-6 and IFN-gamma on carcinoembryonic antigen (CEA) and HLA expression by human colorectal carcinoma cells: role for endogenous IFN-beta. 778 31

MLL (also known as ALL-I, HTRX, or HRX) gene translocations are among the most common chromosomal abnormalities recognized in both B-lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, MLL gene rearrangements are uncommon in T-cell ALL. We recently detected an MLL gene rearrangement in a patient with typical T-cell ALL. We recently detected an MLL gene rearrangement in a patient with typical T-cell ALL (CD2+, CD4+, CD5+, CD7+, CD8+, HLA DR-) and an apparently normal karyotype (46,XX). The rearrangement was cloned and characterized; a DNA fragment distal to the breakpoint was mapped by fluorescence in situ hybridization (FISH) to 19p13, indicating that the leukemic blasts had undergone a cytogenetically undetected rearrangement involving chromosomes 11 and 19. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated an in-frame fusion mRNA between the amino terminus of MLL and the carboxy terminus of ENL (also known as MLLT1 or LTG19), a gene that has been mapped to 19p13. In addition, MLL sequences distal (telomeric) to the breakpoint were deleted from the genome, which precludes the formation of a reciprocal ENL/MLL fusion protein. These findings suggest that an MLL/ENL fusion protein (and not a reciprocal ENL/MLL fusion) was likely to be pathogenic in this patient, and they reinforce previous studies showing that leukemic blasts with apparently normal karyotype may harbor MLL rearrangements. Additionally, this report provides the first conclusive evidence of an MLL/ENL gene fusion characterized at a molecular level in a patient with T-cell ALL.
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PMID:Complex MLL rearrangement in a patient with T-cell acute lymphoblastic leukemia. 852 89

A healthy adult having no serologically detectable HLA class I A locus antigens was identified. The parents of the individual are consanguineous. Results of a family study indicated that the individual is homozygous for the B46-Cw1-DR8.1 haplotype, which was shown to be positively associated with A*0207 in our previous study. The HLA-A null individual is healthy and exhibits no apparent immunological abnormality. Total RNAs extracted from peripheral blood were converted to cDNAs. The reverse transcriptase-polymerase chain reaction (PCR) product, which is of the same size as the normally expressed gene, was easily obtained from the cDNAs with HLA-A locus-specific primers. The nucleotide sequence of this null allele (A*0215N) was the same as that of A*0207 except for a single nucleotide substitution which resulted in a stop codon in exon 4. From its nucleotide sequence, a truncated molecule was expected to be produced; however, the immunoprecipitation study failed to detect the predicted product. Genomic DNAs from 29 unrelated individuals who expressed only one HLA-A antigen with HLA-B46, were analyzed by a PCR-sequence-specific oligonucleotide method. None of the samples possessed this stop codon. Therefore, A*0215N is likely to be a rare allele generated by a single point mutation from A*0207.
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PMID:HLA-A null allele with a stop codon, HLA-A*0215N, identified in a homozygous state in a healthy adult. 853 10

In utero transplantation of preimmune fetal sheep with human hematopoietic stem cells results in stable long-term hematopoietic chimerism. To clarify the mechanisms of support of human stem cells in chimeric sheep, we established stromas from bone marrow of 30 sheep transplanted in utero with human hematopoietic stem cells from adult bone marrow adult peripheral blood, or fetal liver. We examined the stromas for the presence or absence of human stromal elements in vitro. Human stromal elements were detected in 12 sheep as assessed by polymerase chain reaction (PCR) using human HLA-DQalpha-specific primers. The human origin of the PCR product was confirmed by Southern blotting using an HLA-DQalpha-specific probe. However, none of these stromal cells were positive for CD45 or CD14 as determined by fluorescence-activated cell sorting (FACS) analysis or by message expression using reverse transcriptase (RT)-PCR. In an attempt to further characterize these cells fibroblasts were isolated by panning, and DNA analysis confirmed the human origin of these cells in the same lambs. Of the fetuses injected with the highly enriched cells from adult human bone marrow 36% were found to harbor cells capable of forming human stromal elements in vitro in their marrow. Of those injected with human fetal liver and peripheral blood stem cells, 42 and 40%, respectively, exhibited in vitro human stromal cell-forming ability. These results indicate the long-term persistence of cells capable of giving rise to components of human marrow stroma in vitro in the human/sheep xenograft model.
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PMID:Detection of human cells in human/sheep chimeric lambs with in vitro human stroma-forming potential. 859 79

In situ hybridization studies have shown that at early but not late stages of gestation, human placental stromal cells, many of which are macrophages (Hofbauer cells), contain HLA-G message. In this study, the HLA-G protein was identified in the macrophage-like stromal cells by immunohistochemistry using the anti-HLA-G mAb, 87G. Expression of the HLA-G gene was then analyzed in macrophage cell lines (U937, HL-60, THP-1) and blood monocytes. HLA-G mRNA identified by using reverse transcriptase PCR was consistent with production of a transcript containing intron 4, which codes for a soluble form of HLA-G. Low levels of HLA-G mRNA were identified in mononuclear phagocytes by Northern blot hybridization, and little if any HLA-G Ag was detectable. By contrast, essentially all of the cells displayed high levels of HLA-B/C H chains detected by the mAb, 4E, and B2m. Treatment of macrophage cell lines and monocytes with IFN-gamma increased steady-state levels of HLA-G mRNA, stimulated higher levels of cell surface and intracellular HLA-G Ag in a dose-dependent manner, and increased the proportions of HLA-G relative to HLA-B/C. INF-alpha and IFN-beta enhanced steady-state levels of HLA-G mRNA and in some lines modestly increased the numbers of weakly positive cells but were poor inducers of cell-surface and intracellular HLA-G and did not increase HLA-G relative to HLA-B/C. Thus, mononuclear phagocytes express low levels of HLA-G mRNA and protein, and IFN-gamma selectively enhances expression of this HLA class Ib gene relative to HLA class Ia, which could influence the repertoire of peptides presented during embryogenesis as well as during inflammatory situations in adults. Soluble HLA-G might influence both fetal and maternal immune responses.
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PMID:Expression of HLA-G in human mononuclear phagocytes and selective induction by IFN-gamma. 866 91

Chronic myelogenous leukemia is a clonal proliferative disorder of pluripotent hematopoietic stem cells. Cure may be achieved by myeloablative conditioning treatment and marrow transplantation. In addition, allogeneic marrow can exert a graft-versus-leukemia effect. The graft-versus-leukemia effect may be directed against leukemia-specific antigens or against antigens on all hematopoietic cells, or it can be part of a graft-versus-host reaction. We report an informative post-transplant course of a patient with yet another leukemia-specific effect. This patient was transplanted with marrow from his HLA-identical sister in an advanced phase of CML and developed acute and chronic GVHD. After a severe pneumonia a high proportion of his metaphases in the bone marrow were male and Philadelphia chromosome negative. Later all metaphases were again female and leukemic cells could not be detected by reverse transcriptase polymerase chain reaction analysis (RT-PCR) for BCR/ABL. This course indicates that normal hematopoietic stem cells may survive intensive chemotherapy, bone marrow transplantation and GVHD. They may be recruited from a dormant state into proliferation during severe infections. In contrast, CML may be eliminated by the graft-versus-host reaction that recognizes recruited cells and spares dormant cells.
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PMID:Graft-versus-host reaction spares normal stem cells in chronic myelogenous leukemia. 870 5

Numerous studies of human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) have examined their ability to recognize B-cell lines expressing recombinant HIV-1 proteins, but relatively few data regarding the lysis of HIV-1-infected cells by CTL are available. We studied the ability of HIV-1-specific CTL clones of defined epitope specificity and HLA restriction to lyse infected CD4+ cells at serial time points following infection. CD4+ cell lines were acutely infected with HIV-1 IIIB at a high multiplicity of infection, and the kinetics of cell lysis were examined and compared with the kinetics of viral replication. Intracellular HIV-1 p24 expression was detected by 1 to 2 days after infection, reaching over 98% positive cells by day 4. Recognition of the infected cells by HLA A2- and B14-restricted CTL clones closely paralleled intracellular p24 expression and preceded peak virion production. The maximal levels of lysis with Gag-, reverse transcriptase-, and envelope-specific clones were different, however. The Gag- and envelope-specific clones lysed infected cells at levels equivalent to peptide-sensitized controls, whereas lysis by the reverse transcriptase-specific clones plateaued at a lower level. Peptide titration curves indicated that this effect was not due to differences in sensitivity to the cognate epitopes for the different clones. Although HIV-1 infection induced an approximately 50% decrease in class I HLA expression on the surface of infected cells, lysis by CTL clones was unaffected. These studies indicate that HIV-1-specific CTL can efficiently lyse HIV-1-infected CD4+ cells and suggest that the partial downregulation of class I molecules in infected cells does not significantly affect recognition by CTL.
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PMID:Efficient lysis of human immunodeficiency virus type 1-infected cells by cytotoxic T lymphocytes. 870 96

Increased stimulation of Th2 cytokines may contribute to the development of persistent ocular chlamydial infection, resulting in the blinding pathological changes of trachoma. Proliferation and cytokine production profiles of PBMC in response to stimulation with antigens of Chlamydia trachomatis were compared in 30 patients with severe conjunctival scarring due to trachoma and in 30 age-, sex- and location-matched controls. Interferon-gamma (IFN-gamma) and IL-4 were detected at the single-cell level by ELISPOT assay. Transcription of the genes encoding IFN-gamma, IL-4 and IL-10 was detected in mRNA isolated from parallel cultures of PBMC using reverse transcriptase-polymerase chain reaction (RT-PCR). Incubation with the chlamydial heat shock protein (hsp)60 resulted in increased numbers of IL-4-producing cells in PBMC isolated from patients with scarring disease and increased secretion of IFN-gamma from PBMC of control subjects. Incubation with the chlamydial major outer membrane protein (MOMP) increased the number of IFN-gamma-producing cells in the control group only. Messenger RNA encoding IL-4 was only detected in PBMC of patients with scarring disease after in vitro stimulation with chlamydial antigens, but IFN-gamma mRNA and IL-10 mRNA were also more frequently detected in this group. Thirty-eight subjects were HLA-DRB1 and -DQB1 typed. Associations were observed between certain HLA class II alleles and cellular immune responses to chlamydial antigens. No HLA associations were found with clinical status, and overall we found no evidence of strong associations and the type of immune response. These data are consistent with a role for Th2 cells and cytokines in the pathogenesis of trachomatous scarring.
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PMID:T helper type-1 (Th1)/Th2 profiles of peripheral blood mononuclear cells (PBMC); responses to antigens of Chlamydia trachomatis in subjects with severe trachomatous scarring. 880 30


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