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)

An autopsy case of HTLV-I associated myelopathy (HAM) was reported. The patient was a 55-year-old man from Kagoshima, who had no history of blood transfusion. He was admitted to our hospital because of muscle weakness of legs and dysuria, which having since one month ago. On admission, he was able to walk with assistance, but his legs were severely spastic, and Babinski's sign was positive bilaterally. Superficial sensation was normal, but vibration sense was mildly decreased in his legs. CSF showed mild mononuclear pleocytosis with elevated protein. Myelogram and CT were normal. Serum and CSF antibodies to HTLV-I were positive at titers of X4,096 and X128, respectively by immunofluorescent assay, and specific IgG bands (p19, p24, p28 and p53 in serum and p19, p24, p53 in CSF) were detected by western blot analysis. His paraparesis continued to worsen. He became bed-ridden within 2 months. He was received corticosteroid medication. He regained the ability to walk with assistance, and continued taking corticosteroid. In July 4, 1986, macrohematuria appeared and inoperable transitional cell carcinoma of rt. kidney was found by further examination. Chemotherapy were not effective against the carcinoma and he died on July 21, 1987. Neuropathological findings were summarized as follows: cerebral hemisphere was normal except for mild cellular infiltration in the leptomeninges; lesions consisted in unilateral pyramidal tract of pons & medulla and in partial anterior, posterior and lateral columns of the spinal cord; demyelination with axonal degeneration, marked gliosis, numerous lipid-laden macrophages and mild perivascular infiltration of mononuclear cells in these areas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsy case of HTLV-I associated myelopathy (HAM)]. 275 64

Sera from 39,898 blood donors were tested for HTLV-1 antibodies using two enzyme immunoassays (EIA). Sera testing initially reactive (IR) were retested in duplicate by both EIAs. Sera testing repeatedly reactive (RR) were further tested by two Western blots (WB) and by two radioimmunoprecipitation assays (RIPA). There were 176 (0.44%) EIA IR and 68 (0.17%) RR results. On WBs, 10 of the 68 EIA RR sera demonstrated reactivity to HTLV-1 gag gene-encoded core protein p24, with or without reactivity to other core proteins (p19, p28, p53/55). These ten sera were the only ones demonstrating reactivity on RIPAs to other HTLV-1 gene products - env gene-encoded glycoproteins gp46, gp61/68, or tat gene-encoded HTLV-1 transcriptional activator p40x. These ten sera were interpreted as positive for HTLV-1 antibodies. Of the remaining 58 EIA RR sera, 21 were negative by WBs and RIPAs, 37 sera demonstrated reactivity to various combinations of p19, p28, and p53/55, but not to p24 on WBs. These 37 sera were interpreted as "indeterminate", because they were negative by RIPAs. We conclude that: 1) EIA testing and WB/RIPA verification identified 10 (0.025%) HTLV-1 infected individuals among 39,898 low-risk blood donors; 2) anti-p24 may be a more sensitive and specific indicator of HTLV-1 infection than antibodies to p19, p28, or p53/55; and 3) presently, both WB and RIPA are needed to verify HTLV-1 EIA reactivity.
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PMID:Detection of antibodies to human T-lymphotropic virus type 1 (HTLV-1). 283 83

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

Three distinct monoclonal antibodies (MAbs) specific for human T-cell leukemia virus type-I (HTLV-I) core proteins with molecular weights of 24 kDa (p24), p19 or p15 were produced, characterized and compared. These antibodies were named NOR-1 (anti-p24, IgG2a), GIN-7 (anti-p19, IgG2b) and FR-45 (anti-p15, IgG2a). Immunofluorescence assay showed that they reacted specifically with methanol-fixed cells of virus-bearing cell lines, and that only GIN-7 bound, albeit weakly, to the surface of a small percentage of viable cells. Like natural antibodies to HTLV-I in human serum, GIN-7 stained the fixed cells brightly and diffusely, and gave more intense fluorescence than NOR-1 and FR-45, which stained restricted areas of the cells. NOR-1, GIN-7 and FR-45 specifically precipitated core proteins p24, p19 and p15, respectively, from a lysate of HTLV-IMT-2 labelled with 35S-cysteine. NOR-1 precipitated p53, p36, and p24, GIN-7 precipitated p53, p32, p28 and p19, and FR-45 precipitated p53, p36, and p15 from a lysate of 35S-cysteine-labelled MT-2 cells. GIN-7 also precipitated p32, p28 and p19 from a lysate of MT-2 cells, labelled by surface iodination, but NOR-1 and FR-45 did not detect any proteins in this lysate. GIN-7 also detected p28 in 3H-glucosamine-labelled MT-2 cells. Antibody binding competition assay showed that the sera of ATL patients significantly interfered with the binding of NOR-1 and GIN-7 but not with that of FR-45, to antigens of disrupted virus of MT-2 cells. This complete set of MAbs against the HTLV-I gag gene products is useful for biological and functional studies of the HTLV-I core proteins.
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PMID:Antigens related to three core proteins of HTLV-I (p24, p19 and p15) and their intracellular localizations, as defined by monoclonal antibodies. 300 Sep 53

Human T-cell leukemia virus producer cell line MT-2 was labeled with [32P]phosphoric acid, and its cell extracts were immunoprecipitated with mouse monoclonal antibodies (GIN-7, and KK-1) and rabbit sera (anti-p24, and anti-gp68). Analysis of the immunocomplexes on sodium dodecyl sulfate-polyacrylamide gell electrophoresis revealed that p53, p28, and p19 of adult T-cell leukemia-associated antigens were phosphorylated in vivo. Immunocomplexes of MT-2 cell extract with monoclonal antibody KK-1 were incubated with [gamma-32P]ATP in vitro and it was revealed that the phosphokinase activity was associated with p28. The phosphokinase activity of p28 was specific to the serine residue but was not to the tyrosine residue.
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PMID:28,000-dalton polypeptide (p28) of adult T-cell leukemia-associated antigen encoded by 24 S mRNA of human T-cell leukemia virus has an associated protein kinase activity. 608 30

The adult T-cell leukemia (ATL)-associated antigen complex (ATLA) was first discovered with indirect immunofluorescence by Hinuma et al. (1981). Biochemical analysis with MT-2 cells revealed that ATLA consisted mainly of human T-cell leukemia virus (HTLV) structural polypeptides and their precursors (Yamamoto and Hinuma 1982a; Schneider et al. 1984). In this study, we have investigated the molecular nature of the ATLA antigen complex in various HTLV-positive human cell lines established by different methods including independently established HTLV-infected HUT 102 cells. We found that HTLVs infecting these cell lines have similar core polypeptides, p24 and p19, as well as an envelope glycopolypeptide, gp46, in all these cells. The intracellular gp61 and p53 appear to be precursors of the viral envelope and core polypeptides, respectively. Interestingly, MT-2 and MT-2 related T-cell lines contain two different species of envelope proteins, gp68 and gp61, whereas cell lines not related to MT-2 express only gp61.
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PMID:Expression of HTLV-specific polypeptides in various human T-cell lines. 609 98

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

A 55-year-old man was admitted because of weakness in the legs of a few days duration. Neurological examination revealed paraparesis, ataxia of the left limbs, superficial hypoesthesia below the T-10 dermatome level and urinary retention. The antibody titers to human T-lymphotropic virus type I (HTLV-I) were x640 in the serum and x16 in the cerebrospinal fluid (CSF). The HTLV-I gag proteins, p19, p24, p46 and p53 were identified by Western blotting analysis of the serum and CSF. The CSF contained 691 white cells/c.mm; protein, 260 mg/dl; IgG, 84 mg/dl; and IgG index, 2.49. Although the paraparesis and urinary retention disappeared within 10 days, he developed right uveitis which responded well to corticosteroid treatment. With improvement of the sensory impairment, cerebellar signs and CSF pleocytosis as well as uveitis, he was discharged eight weeks after admission. HTLV-I uveitis is a recently established disease entity. The case emphasizes the need to test blood and CSF for HTLV-I antibodies if patients developed myelopathy and cerebellar signs of acute onset, especially when associated with uveitis.
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PMID:Acute myelopathy and cerebellar signs associated with uveitis with positive serum and cerebrospinal fluid antibodies to HTLV-I. 770 52

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

The cyclin-dependent kinase inhibitors known as p15, p16, p18 and p19 have been suggested as candidates for tumor suppressor genes. The main genetic alterations are deletions (bi- or monoallelic) or 5' CpG island methylation of p15 and p16; very few cases or cell lines had p18 or p19 deletions or hypermethylation. Hypermethylation and homozygous deletions of tumor suppressor genes establish a new paradigm of inactivation by lack of expression, in contrast to the previously identified tumor suppressors which are predominantly inactivated by point mutations followed by loss of the wild-type allele. Here, the literature data on alterations of this gene family in more than 4700 primary cases of leukemia or lymphoma and some 320 continuous leukemia-lymphoma cell lines are summarized. Among hematopoietic malignancies, the highest frequencies of p15del and p16del were seen in acute lymphoblastic leukemia (ALL) (>30%) with striking rates in T-ALL (>50%), but also high rates in B cell precursor (BCP)-ALL (>20%); the rates of deletions in chronic lymphoid leukemia (CLL), multiple myeloma, acute and chronic myeloid leukemia (AML and CML), and myelodysplastic syndromes (MDS) were rather low, only some B cell and T cell lymphomas showed increased frequencies. Results are quite different with regard to the second mode of inactivation, hypermethylation of the promoter region. Here, p15 is most often inactivated, at particularly high frequencies in the disorders lacking any p15/p16 deletions: 40-80% p15met in AML, MDS and multiple myeloma. Also p15met rates in BCP- and T-ALL cases were high (c. 40%). There is controversy concerning the prognostic impact of p15 and p16 aberrations with some studies describing a significant correlation between inactivation of these genes and poor prognosis, while most others did not detect any prognostic relevance, at least in pediatric ALL; there may be a worse prognosis for adults with B or T cell lymphomas. Despite the small number of cases studied, paired sequential analyses suggested that disease progression is associated with loss of p15/p16 activity in a certain percentage of adult patients. p15del/p16del and p15met/p16met were also detected in the large panel of leukemia-lymphoma cell lines studied. In general, the results in cell lines reproduce the data seen in primary cells with the important difference that the rates of p15/p16 inactivation are clearly higher in the cultured cells compared with the freshly explanted cells. Retrovirus- or electroporation-mediated ectopic gene transfer of p16 wild-type into p16-deficient cell lines led to growth inhibition, arrest in G1 (without apoptosis) and occasionally to differentiation, suggesting that the malignant phenotype of p16-/- cell lines can, at least partially, be reversed by restoring p16 gene expression. A striking inverse correlation between the absence of p16 (due to deletion) and presence of wild-type retinoblastoma gene was observed in cell lines confirming a common growth suppressor pathway; no comparable relationship of p16 inactivation with p53 was detected. Paired analysis of cell lines and corresponding primary cell material showed that in all instances tested both populations carried the same gene configuration of p15 and p16. Thus, p15del or p16del did not occur during establishment of the cell lines or during prolonged culture. It is likely that p15 or p16 deletions already acquired in vivo provide a dramatic growth advantage for the immortalization process in vitro, thus increasing the success rate for cell line establishment which is commonly extremely difficult. In conclusion, the present review suggests an involvement of the p15 and p16 tumor suppressor genes in leukemo- and lymphomagenesis. Future studies will determine their exact role in the development and progression of hematopoietic neoplasms. These genes may represent interesting targets for new therapeutic strategies.
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PMID:Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells. 963 10


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