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)

About half of human conceptions are estimated not to be implanted in the uterus, resulting in unrecognizable spontaneous abortions, and about 5% of human births have a recognizable malformation. In order to find clues to the mechanisms of malformation and abortion, we compared the incidences of radiation-induced malformations and abortions in p53 null (p53-/-) and wild-type (p53+/+) mice. After X-irradiation with 2 Gy on day 9.5 of gestation, p53-/- mice showed a 70% incidence of anomalies and a 7% incidence of deaths, whereas p53+/+ mice had a 20% incidence of anomalies and a 60% incidence of deaths. Similar results were obtained after irradiation on day 3.5 of gestation. This reciprocal relationship of radiosensitivity to anomalies and to embryonic or fetal lethality supports the notion that embryonic or fetal tissues have a p53-dependent "guardian" of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of cells with apoptotic DNA fragments was greatly increased in tissues of the p53+/+ fetuses but not in those of the p53-/- fetuses.
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PMID:p53-dependent apoptosis suppresses radiation-induced teratogenesis. 861 8

Sixty molar and nonmolar placentas with hydropic features [23 complete moles, 14 partial moles, 8 moles-not further classified, and 15 hydropic, nonmolar placentas] were evaluated immunohistochemically for expression of Ki-67, proliferating cell nuclear antigen (PCNA), and p53, and the results were compared with DNA ploidy and S-phase fractions derived from flow cytometric analysis. The data were evaluated to determine if proliferation marker staining could aid in distinguishing mole from non-mole and partial from complete mole. PCNA and p53 expression did not discriminate between moles and non-moles. However, the percentage of rimming villous cytotrophoblast nuclei reactive for Ki-67 differed significantly between moles and non-moles (p < 0.001). All molar specimens contained at least one medium-sized villus with > 70% Ki-67-positive cells, whereas the maximum percentage of reactive cells in hydropic abortuses was 22%. These results suggest that percentage Ki-67 positivity in rimming cytotrophoblast nuclei may aid in distinguishing a mole from a nonmolar, hydropic abortion.
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PMID:p53 PCNA, and Ki-67 in hydropic molar and nonmolar placentas: an immunohistochemical study. 878 6

Ninety-four cases of early abortion have been studied. Five histological groups of lesion have been identified by routine histological techniques on abortion materials, group I corresponding to partial hydatidiform mole. Cytogenetic analyses have revealed chromosome anomalies in near 50% of cases with a prevalence of triploidies followed by trisomies and monosomies. Normal histological findings are more often associated with normal karyotypes and group I with abnormal karyotypes but a specific correlation between histological pattern and cytogenetic anomalies is lacking. Neither some histochemical reactions nor the well preserved immunohistochemical reactivities of beta-hCG, hPL, PLAP, AFP, cytokeratin, vimentin, desmin, factor VIII, CD 68, MIB1 (growth fraction), EGF-R, p53 and c-erbB-2 oncoproteins have disclosed specific chromosome anomalies. They have only allowed a better definition of histological groups. A simple histological evaluation, although extended to immunohistochemical reaction may not substitute the cytogenetic analyses, not even for purposes of preselection.
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PMID:[Correlation of the histological and cytogenetic pictures in placental tissue from early abortion. Does immunohistochemistry have a role?]. 900 96

Studies in normal, gene-deleted, transgenic and mutant mice have examined apoptotic cell death and its role in B lymphopoiesis in bone marrow. Apoptotic activity has been quantitated among phenotypically defined populations of precursor B cells using flow cytometry of apoptotic cells and an established model of B-cell development. In normal mice, the frequencies of apoptotic cells (apoptotic index) and accumulation of apoptotic cells during short-term culture (apoptotic rate) are maximal at around the pro/pre-B-cell transition and among immature B lymphocytes. The brief period between onset of apoptosis and clearance by macrophages (apoptotic transit time) is similar for most precursor B-cells. Apoptosis-modulating factors produce substantial changes in apoptotic activity among pro-B and pre-B cells, associated with altered expression of bcl-2 family proteins. Pro-B-cell apoptosis, normally extensive, is markedly suppressed in the absence of p53. Complete pro-B-cell abortion in RAG-2 deletion provides an assay for apoptotic fractions in other experimental systems. Pre-B-cell apoptosis is enhanced by deficiencies of interleukin (IL)-7, Abl protooncogene or colony-stimulating factor (CSF)-1 and overexpression of heat-stable antigen, and is inhibited by IL-7 and p190bcr/abl transgenes. CSF-1 and melatonin administration inhibit pre-B-cell apoptosis, probably via stromal cell stimulation. Such apoptotic modulation has implications for B-cell homeostasis, quality control, immunodeficiency and neoplasia.
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PMID:Apoptosis and its modulation during B lymphopoiesis in mouse bone marrow. 1093 1

It is not clear what type of cells will inhibit vasculogenesis and under what circumstances. Here we examined the human spontaneous abortion villi and discovered that cells in the vasculogenesis-inhibited environment appear to be pro-apoptotic as indicated by strong staining of bak. In particular, an increasing laminin receptor (LNR) expression in cytoplasm and on apical membrane, being most likely mediated by p53 because of coexpression, was observed in the pro-apoptotic syncytiotrophoblasts. The transcriptional increase and translocation of the receptors to the cytoplasm and apical membrane may be used as a pathological marker, indicating a change of the structure and function of integrins in the non-vasculogenesis micro-environment.
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PMID:Translocation of P53-regulated laminin receptors in pro-apoptotic microcircumstance of human vasculogenesis inhibition. 1102 53

Gestational trophoblastic diseases are a group of interrelated diseases of trophoblastic tissue that include partial hydatidiform mole, complete hydatidiform mole, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. P63 is a p53 homologue that, in normal placentas, is expressed in the cytotrophoblast cells. The role of p63 in gestational trophoblastic diseases, however, merits further investigation. Immunohistochemistry with the p63 antibody (clone 4A4) was performed in formalin-fixed paraffin-embedded samples of hydropic abortion (n=10), partial hydatidiform mole (n=12), complete hydatidiform mole (n=12) and choriocarcinoma (n=5). P63 expression was quantitatively assessed as 0 (no stained cells), + (less than 10% positive cells), ++ (10-50% positive cells), and +++ (more than 50% positive cells). The intensity was scored as 0 (absence), + (weak), ++ (moderate), or +++ (strong). Statistical analysis was carried out by the Fisher test. In contrast to the other diagnoses, none of the choriocarcinomas analyzed exhibited p63-positive cells. There was no difference in distribution of p63 positive cells between hydropic abortion, partial hydatidiform mole, and complete hydatidiform mole. Concerning the intensity of immunostaining, there was difference only between partial hydatidiform mole and complete hydatidiform mole. According to our results, p63 might be useful to differentiate a choriocarcinoma from other gestational trophoblastic diseases. Besides, since the intensity of p63 expression was much stronger in partial hydatidiform mole and complete hydatidiform mole than in hydropic abortion, this feature may be helpful in distinguishing these two diagnoses in challenging cases.
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PMID:P63 expression in hydropic abortion and gestational trophoblastic diseases. 1602 31

Recurrent pregnancy loss (RPL) has been associated with low expression of apoptosis-and angiogenesis-related genes. The p53 tumour suppressor gene has been shown to induce apoptosis and angiogenesis. Recently, a low increased frequency of a p53 codon 72 polymorphism has been reported among women experiencing RPL. This study investigated the prevalence of p53 codon 72 polymorphism among women with a history of RPL, to determine whether this polymorphism may serve as a risk factor for miscarriage. Buccal swabs were obtained from 205 women with a history of two or more consecutive spontaneous abortions and 25 women with at least two live births and not more than one elective abortion. DNA was extracted from the buccal swabs and PCR amplification of p53 arginine(Arg)72 and proline(Pro)72 variants was performed. The frequency of homozygous Arg and Pro or heterozygous Arg/Pro genotypes among RPL patients and controls were not significantly different. No significant differences in allelic frequencies of p53 were observed. In addition, the allelic frequencies between controls and those previously reported were the same. It is concluded that p53 codon 72 polymorphisms do not serve as a susceptibility factor affecting the chances of miscarriage in an unselected population.
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PMID:Role of p53 codon 72 polymorphism in recurrent pregnancy loss. 1656 30

Implantation failure is the most frequent cause of lack of pregnancy after IVF and embryo transfer. Successful implantation requires trophoblastic growth into the endometrium to stimulate its own blood supply. The p53 tumour suppressor gene has been shown to regulate cell growth and induce angiogenesis. Therefore, the prevalence of p53 codon 72 polymorphism was investigated among women with a history of recurrent implantation failure to determine whether this polymorphism may serve as a risk factor for implantation failure. DNA was extracted from the buccal swabs obtained from 70 women experiencing implantation failure and polymerase chain reaction amplification of p53 arginine (Arg) 72 and proline (Pro) 72 variants were performed. The frequency of homozygous Arg and Pro or heterozygous Arg/Pro genotypes was compared with frequencies among 205 women experiencing recurrent pregnancy loss and 20 control women. The frequency of Pro72 was significantly higher (P=0.003) among women experiencing recurrent implantation failure compared with women experiencing recurrent miscarriage and with control women. It is concluded that p53 codon 72 polymorphisms may serve as a susceptibility factor affecting the chances of recurrent implantation after IVF or embryo transfer.
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PMID:p53 tumour suppressor gene polymorphism is associated with recurrent implantation failure. 1700 66

The endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to disrupt hormone signalling, reduce fertility, interfere with embryo development and cause spontaneous miscarriage in humans. The precise mechanisms of its effects on early implantation in humans are still unclear. In this study, we examined the relationship between mitochondrial function and dioxin-induced toxicity in JAR cells, a human trophoblast-like cell line. Several experiments were performed to address the effects of TCDD on cell viability, reactive oxygen species (ROS) generation, oxidative damage (indicated by the presence of lipoperoxides and oxidized DNA bases), mitochondrial DNA (mtDNA) copy number, ATP content, mtDNA mutations and the protein levels of p53, Bax, Bcl2, cytochrome c and caspase 3. Increased oxidative damage and mitochondrial dysfunction in TCDD-treated trophoblast-like cells was demonstrated. A 2.58-fold increase in lipid peroxides was detected in cells treated with 2 nM TCDD for 4 h. The oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine was significantly increased by TCDD treatment in a time-dependent manner. Meanwhile, reductions in mtDNA copy number and ATP content and an increase in mtDNA deletions were found. Furthermore, we observed increased apoptosis, p53 accumulation, Bax overexpression, cytochrome c release and sequential caspase 3 activation after TCDD exposure. These results indicate that oxidative damage and mitochondrial dysfunction may be responsible for the apoptotic effects of TCDD.
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PMID:Endocrine disruptor, dioxin (TCDD)-induced mitochondrial dysfunction and apoptosis in human trophoblast-like JAR cells. 2008 59

Single nucleotide polymorphisms (SNPs) in the p53 gene have been studied extensively in humans. The aims of this study were to determine the frequency of the Arg/Pro SNP in p53 in Thoroughbred mares on one stud in Brazil and to correlate p53 genotypes with reproductive performance. SNPs were detected by PCR-restriction fragment length polymorphism in blood samples from 105 horses and confirmed by sequencing. The allele frequency in Thoroughbred mares at codon 72 in exon 4 was 73.3% Arg/Pro, 17.1% Arg/Arg and 9.6% Pro/Pro. The presence of Arg/Pro was significantly associated with abortion (P=0.02), while Pro/Pro mares had a lower probability of abortion (P<0.05). Using a logistic regression model, the dominance effect was significant (P=0.044; odds ratio 7.94) for abortion and additive effects were not significant (P=0.26). p53 may play a role in equine reproduction.
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PMID:Association between single nucleotide polymorphisms in p53 and abortion in Thoroughbred mares. 2241 90


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