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

Current approaches to the analysis of antigens involved in the cellular immune response to mycobacterial infection rely on the initial identification and isolation of molecular components using monoclonal antibodies. In order to overcome the constraints of this approach, we have utilized a procedure involving T-cell recognition of antigens fractionated by polyacrylamide gel electrophoresis (SDS-PAGE) and added to proliferation assays after blotting onto nitrocellulose membranes. Analysis of human T-cell responses to Mycobacterium tuberculosis and Mycobacterium bovis BCG by this procedure revealed distinctive patterns of reactivity to different molecular weight components indicative of the selective recognition of immunodominant and species-specific determinants. Human T-cell clones were subsequently derived, and SDS-PAGE immunoblotting was used to identify the antigen recognized by each clone. Three epitopes defined by individual T-cell clones were identified on separate polypeptides with molecular weights 16,000-18,000 (clone P53), 18,000-20,000 (clone P57) and 52,000-55,000 (clone P35). This study demonstrates the potential application of T-cell cloning in conjunction with SDS-PAGE immunoblotting for the dissection and analysis of the cellular immune response to pathogenic agents during human infection.
 ...
PMID:A novel approach to the identification of T-cell epitopes in Mycobacterium tuberculosis using human T-lymphocyte clones. 243 13

PCR has been used successfully for the direct detection of Mycobacterium tuberculosis in uncultured patient samples. Its potential is hindered by the risk of false-positive results as a result of either amplicon carryover of cross-contamination between patient samples. In the present study, we investigated whether residual amplifiable human or M. tuberculosis DNA could remain in sterile bronchoscopes and potentially be a cause of false-positive PCR results in subsequent patient samples. Sterilized bronchoscopes were flushed with sterile saline, and the collected eluate was submitted for PCR amplification of IS6110 sequences and exon 8 of the human p53 gene. Of a total of 55 washes of sterile bronchoscopes from two institutions, 2 (3.6%) contained amplifiable M. tuberculosis DNA and 11 (20%) contained residual human DNA. These findings indicate that residual DNA can remain in sterilized bronchoscopes and can be a source of false-positive PCR results.
 ...
PMID:Amplification of residual DNA sequences in sterile bronchoscopes leading to false-positive PCR results. 881 88

A high incidence of non-Hodgkin's lymphoma of the pleural cavity has developed in Japanese patients with long-standing pyothorax (38 years on average) resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Patients with pyothorax-associated lymphoma (PAL) have long been exposed to antituberculous drugs, antibiotics, bacterial or viral products, and frequent diagnostic radiation for the confirmation of pneumothorax and pyothorax. We analyzed p53 mutations on paraffin-embedded specimens from 21 patients with PAL by PCR-single-strand conformational polymorphism followed by direct sequencing. An unusually high frequency of p53 mutations (14 of 21 cases, 67%) was detected in the PAL specimens, and mutations consisted of 13 nucleotide substitutions and 1 deletion. Furthermore, 10 of 13 substitutions (77%) occurred at dipyrimidine sites (CC:GG to CT:GA substitution). Such specificity has not been reported, except for solar light-related skin cancer and AIDS-related lymphoma in some parts. An UV light mimetic agent may be produced in the long history of chronic inflammation in tuberculosis or immunodeficient patients.
 ...
PMID:Frequent p53 mutations at dipyrimidine sites in patients with pyothorax-associated lymphoma. 951 88

The Bcg/Nramp1 gene controls early resistance and susceptibility of macrophages to mycobacterial infections. We previously reported that Mycobacterium tuberculosis-infected (Mtb) B10R (Bcgr) and B10S (Bcgs) macrophages differentially produce nitric oxide (NO-), leading to macrophage apoptosis. Since TNF-alpha and IL-10 have opposite effects on many macrophage functions, we determined the number of cells producing TNF-alpha and IL-10 in Mtb-infected or purified protein derivative-stimulated B10R and B10S macrophages lines, and Nramp1+/+ and Nramp1-/- peritoneal macrophages and correlated them with Mtb-mediated apoptosis. Mtb infection and purified protein derivative treatment induced more TNF-alpha+Nramp1+/+ and B10R, and more IL-10+Nramp1-/- and B10S cells. Treatment with mannosylated lipoarabinomannan, which rescues macrophages from Mtb-induced apoptosis, augmented the number of IL-10 B10R+ cells. Anti-TNF-alpha inhibited apoptosis, diminished NO- production, p53, and caspase 1 activation and increased Bcl-2 expression. In contrast, anti-IL-10 increased caspase 1 activation, p53 expression, and apoptosis, although there was no increment in NO- production. Murine rTNF-alpha induced apoptosis in noninfected B10R and B10S macrophages that was reversed by murine rIL-10 in a dose-dependent manner with concomitant inhibition of NO- production and caspase 1 activation. NO- and caspase 1 seem to be independently activated in that aminoguanidine did not affect caspase 1 activation and the inhibitor of caspase 1, Tyr-Val-Ala-Asp-acylooxymethylketone, did not block NO- production; however, both treatments inhibited apoptosis. These results show that Mtb activates TNF-alpha- and IL-10-dependent opposite signals in the induction of macrophage apoptosis and suggest that the TNF-alpha-IL-10 ratio is controlled by the Nramp1 background of resistance/susceptibility and may account for the balance between apoptosis and macrophage survival.
 ...
PMID:TNF-alpha and IL-10 modulate the induction of apoptosis by virulent Mycobacterium tuberculosis in murine macrophages. 1022 55

Mycobacterium tuberculosis-induced macrophage apoptosis can be inhibited by mannosylated lipoarabinomannan (ManLAM), although it induces tumor necrosis factor (TNF)-alpha and NO production, which participate in apoptosis induction. ManLAM also modulates Ca(+2)-dependent intracellular events, and Ca(+2) participates in apoptosis in different systems. Ca(+2) was assessed for involvement in M. tuberculosis-induced macrophage apoptosis and for modulation by ManLAM. The role of Ca(+2) was supported by the blockade of apoptosis by cAMP inhibitors and the Ca(+2) chelator, BAPTA/AM. These agents also inhibited caspase-1 activation and cAMP-responsive element-binding protein translocation without affecting TNF-alpha production. Infection of macrophages with M. tuberculosis induced an influx of Ca(+2) that was prevented by ManLAM. Similarly, M. tuberculosis infection-altered mitochondrial permeability transition was prevented by ManLAM and BAPTA/AM. Finally, ManLAM and BAPTA/AM reversed the effects of M. tuberculosis on p53 and Bcl-2 expression. ManLAM counteracts the alterations of calcium-dependent intracellular events that occur during M. tuberculosis-induced macrophage apoptosis.
 ...
PMID:Mannosylated lipoarabinomannan antagonizes Mycobacterium tuberculosis-induced macrophage apoptosis by altering Ca+2-dependent cell signaling. 1088 3

Infection with the human immunodeficiency virus (HIV) invariably leads to the development of acquired immunodeficiency syndrome (AIDS) in most infected humans, yet does so rarely, if at all, in HIV-infected chimpanzees. The differences between the two species are not due to differences in cellular receptors or an inability of the chimpanzee to be infected, but rather to the lack of pan-immune activation in the infected primate. This results in reduced apoptotic death in CD4+ T-helper lymphocytes and a lower viral load. In humans the degree of chronic immune activation correlates with virus load and clinical outcome with high immune activation leading to high viral loads and the more rapid progression to AIDS and death. The type of immune perturbation seen in HIV-associated AIDS is similar to that of chronic graft-versus-host disease (GVHD) where reduced cell-mediated immune (CMI) responses occur early in the course of the disease and where humoral responses (HI) predominate. A reduced CMI response occurs in a number of chronic infectious diseases, including tuberculosis and leishmaniasis. More recently, it has become increasingly apparent that the CMI response is suppressed in virtually all malignant diseases, including melanoma and colorectal and prostate cancer. This raises the possibility that, as the malignant process develops, the cancer cells evolve to subvert the CMI response. Moreover, the reduced CMI response seen in colorectal cancer (CRC) patients is completely reversed following curative surgery strongly supporting the hypothesis that CRC can suppress the systemic immune response. Wound healing, ovulation, embryo implantation, and fetal growth are all associated with suppressed CMI and neovascularization (the formation of new blood vessels) or angiogenesis (the formation of new blood vessels from an existing vasculature). If unresolved, wound healing results in chronic inflammation, which can give rise to the phenomenon of "scar cancers." Indeed all the chronic inflammatory conditions known to be associated with the subsequent development of malignant disease, including chronic obstructive airway disease (COPD), ulcerative colitis (UC), and asbestosis, give rise to similar proangiogenic, suppressed CMI, and HI-predominant environments. In keeping with this CMI-associated cytokines such as interleukin (IL)-2 and interferon (IFN)-gamma tend to be antiangiogenic, whereas HI cytokines such as IL-6 tend to be proangiogenic. Furthermore, chronic immune activation leads to the synthesis and release of factors such as macrophage inflammatory protein (MIP)-1 that inhibit apoptosis through suppression of p53 activity. The "Golden Triangle" of suppressed CMI, angiogenesis, and reduced apoptosis would provide the ideal environment for the serial mutations to occur that are required for the development of malignant disease. If the observed association is relevant to carcinogenesis, then treatments aimed at reducing the components of these inflammatory conditions may be useful both in the setting of chemoprevention and the therapeutic management of established disease.
 ...
PMID:Chronic immune activation and inflammation in the pathogenesis of AIDS and cancer. 1188 29

The mortality rate of lung cancer in Asian women has increased significantly in the past few decades. Environmental factors include tobacco smoke (active and environmental), other indoor pollutions (cooking oil vapours, coal burning, fungus spores), diet, and infections. Active tobacco smoking is not the major factor. The relative risk of lung cancer among non-smoking women ever exposed to environmental smoke from their husbands was 1.20 from a meta-analysis. Cooking oil vapours associated with high temperature wok cooking and indoor coal burning for heating and cooking in unvented homes, particularly in rural areas, are risk factors for Chinese women. Chronic benign respiratory diseases due to the fungus Microsporum canis probably accounts for the high incidence of lung cancer in northern Thai women at Sarapee. Diets rich in fruits, leafy green vegetables, and vitamin A are protective, while cured meat (Chinese sausage, pressed duck and cured pork), deep-fried cooking, and chili increased the risk. Tuberculosis is associated with lung cancer. Also, a Taiwanese study showed that the odds ratio of papillomavirus (HPV) 16/18 infection in non-smoking female lung cancer patients was 10.1, strongly suggesting a causative role. Genetic factors have also been studied in Chinese women, including human leucocyte antigens, K-ras oncogene activation, p53 mutation, polymorphisms of phase I activating enzymes (cytochrome P450, N-acetyltransferase slow acetylator status), and phase II detoxifying enzymes (glutathione-S-transferases, N-acetyltransferase rapid acetylator status). New molecular screening technology would facilitate identification of molecular targets for future studies. The interaction between environmental and genetic factors should also be further elucidated.
 ...
PMID:Lung cancer in Asian women-the environment and genes. 1613 62

The aim of the study was to investigate a relation between p53 and HER2/neu expression in resected lung tumors and the response of those tumors to neoadjuvant chemotherapy. The study population included 67 consecutive patients with non-small cell lung cancer (NSCLC) in stage II or III who were operated on at the Institute of Tuberculosis, Warsaw, Poland, between 20 April 2001 and 10 March 2003. All patients received two cycles of chemotherapy consisting of cisplatin and vinorelbine prior to the operation. The response to therapy was assessed as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), on the basis of CT scans performed before and after neoadjuvant chemotherapy. p53 and HER2/neu protein expression were evaluated by immunohistochemistry (IHC) using antibodies against p53 (clone PAb 1801, Novocastra) and against HER2/neu (Dako) in paraffin-embedded specimens of tumors. A response to therapy (CR+PR) was observed in 27 patients, while 40 patients (SD+PD) were regarded as resistant to therapy. Resistance was observed significantly more often in tumors above 3 cm in diameter. p53 expression was found in 16 tumors (23.9%) and HER2/neu in 26 tumors (38.8%). We observed a nonsignificant tendency to chemoresistance in tumors with HER-2/neu overexpression and also in tumors with p53 overexpression. If we consider HER-2/neu and p53 together, chemoresistance was observed statistically significantly more often when one or both markers were positive (p<0.05). This significance was independent of tumor size.
 ...
PMID:p53 and HER2/neu expression in relation to chemotherapy response in patients with non-small cell lung cancer. 1684 10

CD8+ T cells play a pivotal role in protection against Mycobacterium tuberculosis infection. We identified a novel HLA-A*0201-restricted CD8+ T-cell epitope on a dominant secreted antigen of M. tuberculosis, MPT51, in HLA-A*0201 transgenic HHD mice. HHD mice were immunized with plasmid DNA encoding MPT51 with gene gun bombardment, and gamma interferon (IFN-gamma) production by the immune splenocytes was analyzed. In response to overlapping synthetic peptides covering the mature MPT51 sequence, the splenocytes were stimulated to produce IFN-gamma by only one peptide, p51-70. Three-color flow cytometric analysis of intracellular IFN-gamma and cell surface CD4 and CD8 staining revealed that the MPT51 p51-70 peptide contains an immunodominant CD8+ T-cell epitope. Further analysis using computer algorithms permitted identification of a bona fide T-cell epitope, p53-62. A major histocompatibility complex class I stabilization assay using T2 cells confirmed that this epitope binds to HLA-A*0201. The T cells were capable of lysing MPT51 p53-62 peptide-pulsed T2 cells. In addition, MPT51 p53-62-specific memory CD8+ T cells were found in tuberculin skin test-positive HLA-A*0201+ healthy individuals. Use of this HLA-A*0201-restricted CD8+ T-cell epitope for analysis of the role of MPT51-specific T cells in M. tuberculosis infection and for design of vaccines against tuberculosis is feasible.
 ...
PMID:Identification of an HLA-A*0201-restricted T-cell epitope on the MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis, by MPT51 overlapping peptide screening. 1821 86

Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). The recognition of typical morphological features usually allows to distinguish CD from UC. Several infectious diseases like tuberculosis as well as other disorders can mimic IBD and need to be excluded before immunosuppressive treatment is started or surgical intervention planned. IBD is associated with an increased risk for the development of colorectal adenocarcinoma. There is a strong relationship between the presence of intraepithelial neoplasia (IEN) in patients with CD or UC and colon cancer. Thus, the differentiation between biopsies with reactive atypia, low-grade IEN and high-grade IEN is of great importance. Furthermore, distinction between dysplasia-associated lesions or masses (DALM) and sporadic adenoma-like masses (ALM) is crucial as prophylactic colectomy is usually recommended for DALM and polypectomy may be sufficient for ALM. Various features like localization of the lesion, architecture, inflammation and immunohistochemical evaluation of additional markers, e.g. p53 and beta-catenin, may be helpful in the distinction of DALM versus ALM. Finally, the use of modern immunosuppressive therapies may go along with an increased susceptibility towards infections, e.g. cytomegalovirus colitis or Epstein-Barr virus-induced lymphoproliferative disorders, and a high degree of awareness by clinicians and pathologists is required in order not to miss these life-threatening complications of IBD.
 ...
PMID:Diagnostic standards in the pathology of inflammatory bowel disease. 1989 78


1 2 3 4 Next >>