Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two T-cell lines were established from peripheral blood mononuclear cells of two Moroccan patients with tropical spastic paraparesis and then named PR52 and PR144. The two cell lines showed a T lineage of activated CD4+ with high density of Tac+ (IL2 receptor). No expression of CD8 was observed. The virus particles were detected by reverse transcriptase activity and the viral antigens were also detected by immunofluorescence (IF) and Western blot. After six months of culture greater than 90% of the cells exhibited HTLVI antigen by IF. Lysate virus particles on Western blot analysis revealed p19,p24, and p53 gag protein similar to those detected in C91/PL virus particles from an adult T-cell leukemia (ATL) patient. gp46 and gp61 were also weakly detected. These two T-cell lines established will serve as substrate for further comparative studies on TSP and ATL isolates.
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PMID:Establishment of T-lymphoid cell lines from Morroccan patients with tropical spastic paraparesis. 152 May 34

A human T-cell line producing human T-cell leukemia virus type I (HTLV-I), MT-2, was injected intravenously into female F344 rats aged 5 weeks to make HTLV-I carrier rats. Antibody against HTLV-I was detected at the 5th week after MT-2 injection, and its titer reached a high plateau which continued from the 15th to the 27th week. The antibodies were against p19, p24, p28 and p53 of HTLV-I antigens from MT-2 cells. The gag, pX and LTR nucleotide sequences of HTLV-I provirus were demonstrated by using polymerase chain reaction (PCR) in the peripheral-blood mononuclear cells of 3 rats at the 44th week and 2 at the 66th to 68th week out of 8 F344 rats injected with MT-2 cells. Quantification of the HTLV-I proviral sequence revealed that 30 to 60 molecules were present in 10(5) peripheral-blood mononuclear cells, indicating that the rats were chronically infected with HTLV-I. HTLV-I-infected rats could serve as a small-animal model for studying the pathophysiological state of HTLV-I carriers and also that of HTLV-I infection on various HTLV-I-related diseases, including adult T-cell leukemia and HTLV-I-associated myelopathy.
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PMID:Infection of rats with HTLV-1: a small-animal model for HTLV-1 carriers. 168 81

Twelve long-term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-1) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long-term interleukin-2-dependent cell lines exhibited a pattern characteristic of CD4(+)-activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were never detected in uncultured PBMC, but they were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50% of the cells exhibited HTLV-I antigens by IF. However, numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high Mr polypeptides were detected by Western blot in cell lysates when comparing TSP- or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46.
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PMID:Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis. 230 64

Sera and cerebrospinal fluid (CSF) from patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were analyzed by Western blotting, and normal human leukocytes were transformed by co-cultivation with HAM patients' leukocytes. The sera and CSF from all HAM patients formed specific bands with HTLV-1 viral proteins, including p19, p24, p28, p32, p40 and p53. After 2-3 weeks of co-cultivation, scattered foci of cell aggregates were noted on macrophage sheets. Surface markers of the transformed cells were OKT3(+), OKT4(+), OKT8(-), IL-2 receptor(+) and EBNA(-). Chromosome analysis showed a normal karyotype. HTLV-1 viral genome was integrated into DNA isolated from transformed cell lines. Electron microscopy revealed type C virus particles in transformed T-cell lines. These results indicate that peripheral leukocytes from HAM patients can transform HTLV-1-negative leukocytes and HAM patients have the potential to acquire adult T-cell leukemia in the future.
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PMID:Transformation of human leukocytes by co-cultivation with HTLV-1-associated myelopathy patients' leukocytes. 288 13

We have investigated the isotypic and IgG subclass profile of the antibody response to HTLV-I structural proteins (gag and env) in patients with HTLV-I-associated myelopathy (HAM; n = 20), adult T-cell leukemia (ATL; n = 15), and HTLV-I-positive asymptomatic carriers (ASY; n = 21). IgG, IgM, and IgA were the predominant antibody responses in all HTLV-I-infected individuals; minimal IgE response was detectable in the HAM and ATL groups. Among the IgG subclasses, IgG1 was the most predominant antibody detected in responses to HTLV-I antigens, followed by IgG3 and IgG2; IgG4 could not be detected in any patient group. Levels of both IgG1 and IgG3 were significantly higher in patients with HAM, when compared to ATL and ASY (P < 0.01 for both comparisons). In addition, Ig isotypes and IgG subclass antibody in patient sera reactive with purified viral proteins and several immunodominant epitopes, represented by synthetic peptides, Gag-1a102-117, Env-1(191-214), Env-5(242-257), and recombinant proteins, MTA-1(162-209) and r21e303-440, were examined to delineate specific epitopes responsible for inducing the host immune responses of each isotype and subclass to the structural proteins of HTLV-I. IgG, IgM, and IgA responses were directed against both the gag and env gene products. Among IgG subclasses, the IgG1 and IgG3 responses were directed against both the gag (p53, p24, p19, and Gag-1a) and env (recombinant MTA-1, r21e, and synthetic Env-1, Env-5) proteins; IgG2 responses were mainly restricted to gag proteins. The frequency profile of HTLV-I-specific antigen recognition in all four IgG subclasses were similar in all of the clinical groups. These results further define the fine specificity of anti-HTLV-I immune reaction for understanding the mechanism of pathogenesis in these individuals and suggest that factors other than the humoral immune responses may be associated with the clinical manifestation of the disease.
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PMID:Isotypic and IgG subclass restriction of the humoral immune responses to human T-lymphotropic virus type-I. 768 Mar

We describe a Taiwanese woman with chronic progressive myelopathy, in whom Western blot analysis of the serum and cerebrospinal fluid (CSF) displayed positive reactions to human T-lymphotropic virus type I (HTLV-I) proteins, p19, p24, p28, p36, gp46 and p53. HTLV-I proviral genomes were detected in the peripheral blood mononuclear cells (PBMC) and CSF cells by nested polymerase chain reaction and Southern blot hybridization. HTLV-I was successfully isolated from PBMC stimulated with interleukin-2 (IL-2). The established cell line, named THAM-1, was an IL-2-independent T-cell line with CD2+, CD3+, CD4+, CD25+ and HLA-DR+. Retrovirus particles with type C morphology were observed in the THAM-1 cells by electron microscopy, and HTLV-I-related antigens were also demonstrated by immunocytochemical staining and Western blot assay. Southern blot analysis revealed that HTLV-I proviral genomes were integrated into the THAM-1 cellular DNA. In Northern blot analysis, two extra-species of RNA were detected in addition to three typical viral transcripts. For the first time, an HTLV-I-producing T cell line was established from a patient with HTLV-I-associated myelopathy in Taiwan, an HTLV-I non-endemic area.
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PMID:Establishment and characterization of an HTLV-I cell line from a Taiwanese patient with HTLV-I-associated myelopathy. 790 19

Eleven primary spindle cell carcinomas (SpCCs) of the gallbladder are reported. They occurred in eight women and three men ranging in age from 59 to 80 years (mean age, 66.5 years). Histologically, the tumors showed interlacing bundles of atypical spindle cells with eosinophilic cytoplasm, oval to elongated nuclei, and conspicuous nucleoli. Eight SpCCs contained tiny foci of neoplastic glands similar to those seen in adenocarcinoma, and two of these cases also had small foci of neoplastic squamous epithelium. A gradual transition between the squamous cell carcinoma and the spindle cell component was observed in one tumor. Immunohistochemically, all SpCCs were positive for at least one of the epithelial markers (epithelial membrane antigen, nine cases; AE1/AE3, nine cases; carcinoembryonic antigen, three cases; and EAB 903, one case), and the tumor cells also were immunoreactive to mesenchymal marker (vimentin, eight cases), muscle markers (alpha-smooth muscle actin, one case; desmin, one case), and histiocytic marker (HAM 56, one case). Abnormalities in tumor suppressor gene p53 expression also were found in two of the 11 SpCC cases using monoclonal antibody PAb 1801. In six cases for which data were available flow cytometry revealed aneuploidy in three SpCCs (50%). The survival curve of the SpCC cases (mean survival, 9 months) was less favorable than that of 224 cases of adenocarcinoma of the gallbladder (mean survival, 81 months) (P = .0011). These results indicate that SpCC of the gallbladder is an epithelial tumor with sarcomatoid components and its prognosis is unfavorable.
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PMID:Undifferentiated spindle cell carcinoma of the gallbladder: a clinicopathologic, immunohistochemical, and flow cytometric study of 11 cases. 827 77

Since the presence of anti-p53 antibody has been correlated with the mutation and accumulation of p53, the aim of this study was to detect anti-p53 antibody and understand its correlations with anti-Tof, -Rex, or -Tax antibody reactivity in HTLV-I infected people differing in their clinical status. A plasmid (pGEX-Tof) was constructed to express Tof recombinant protein (RP) in Escherichia coli. Serum samples from 50 asymptomatic carriers (ACs), 50 adult T-cell leukemia (ATL) and 50 HTLV-I-associated myelopathyltropical spastic paraparesis (HAM/TSP) patients were assayed for reactivity with different RPs by Western immunoblotting. The results showed that 2% of ACs, 4% of ATL patients and 6% of HAM/TSP patients had anti-p53 antibody. Therefore, anti-p53 antibody is not a useful serological marker for clinical management of HTLV-I infected people. Only 1 HAM/TSP patient had anti-Tof antibody whose specificity was further confirmed by antibody competition enzyme immunoassay. This study demonstrates that Tof protein is immunogenic in vivo, suggesting that it plays a role in the life cycle and pathogenesis of HTLV-I. The rate of anti-Rex antibody among HAM/TSP patients was significantly higher than that of ACs or ATL patients. In addition, 50% of ACs, 42% of ATL and 98% of HAM/TSP patients had anti-Tax antibody. McNemar's test showed that the presence of anti-p53 antibody did not have any correlation with the anti-Tax antibody in HTLV-I-infected people, while the correlation between anti-p53 and anti-Rex antibodies or anti-p53 and anti-Tof antibodies cannot be ruled out in this study.
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PMID:Antibody reactivities to tumor-suppressor protein p53 and HTLV-I Tof, Rex and Tax in HTLV-I-infected people with differing clinical status. 913 42

Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). T-cell transformation is mainly due to the actions of the viral phosphoprotein Tax. Tax interacts with multiple transcriptional factors, aiding the transcription of many cellular genes. Here, we report that the cyclin-dependent kinase inhibitor p21/waf1 is overexpressed in all HTLV-1-infected cell lines tested as well as in ATL and HAM/TSP patient samples. Tax was found to be able to transactivate the endogenous p21/waf1 promoter, as detected by RNase protection, as well as activate a series of wild-type and 5'-deletion constructs linked to a luciferase reporter cassette. Wild-type but not a mutant form of Tax (M47) transactivated the p21/waf1 promoter in a p53-independent manner and utilized a minimal promoter that contained E2A and TATA box sequences. The p21/waf1 protein was reproducibly observed to be complexed with cyclin A/cdk2 and not with any other known G(1), S, or G(2)/M cyclins. Functionally, the association of p21/cyclin A/cdk2 decreased histone H1 phosphorylation in vitro, as observed in immunoprecipitations followed by kinase assays, and affected other substrates, such as the C terminus of Rb protein involved in c-Abl and histone deacetylase-1 (HDAC1) regulation. Interestingly, upon the use of a stress signal, such as gamma-irradiation, we found that the p21/cyclin A/cdk2 complex was able to block all known phosphorylation sites on the Rb molecule. Finally, using elutriated cell cycle fractions and a stress signal, we observed that the HTLV-1-infected T cells containing wild-type Tax, which had been in early or mid-G(1) phase prior to gamma-irradiation, arrested in G(1) and did not undergo apoptosis. This may be an important mechanism for an oncogenic virus such as HTLV-1 to stop the host at the G(1)/S boundary and to repair the damaged DNA upon injury, prior to S-phase entry.
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PMID:Overexpression of p21(waf1) in human T-cell lymphotropic virus type 1-infected cells and its association with cyclin A/cdk2. 1090 81

Human T-cell lymphotropic virus type-1 (HTLV-1) is aetiologically associated with adult T-cell leukaemia/lymphoma (ATL). HTLV-1 infection can also lead to various non-malignant diseases, for example, HTLV-1 associated myelopathy/tropical spastic paraparesis and HTLV-1 uveitis. HTLV-1 is endemic in southern Japan and the Caribbean. HTLV-1 infection is mainly transmitted by either breast-feeding, sexual intercourse or blood transfusions. Primary prevention of HTLV-1 in endemic areas by screening of blood and by refraining from breast-feeding have been successful. The incidence of ATL is rather low among HTLV-1 carriers (<5%). The precise mechanism of development of ATL remains unknown. It is a multiple-step process which does not require viral expression in the later stages of leukaemogenesis. Many samples have mutations of the tumour suppressor genes, p53 and/or p16(INK4A). Four subtypes of ATL have been identified, each having distinctive clinical features. Monoclonal integration of HTLV-1 proviral DNA into tumour cells is found in each of the subtypes. At present, no effective therapy for ATL exists.
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PMID:Human T-lymphotropic virus type 1 infection. 1094 23


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