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)

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)
 ...
PMID:[An autopsy case of HTLV-I associated myelopathy (HAM)]. 275 64

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.
 ...
PMID:Acute myelopathy and cerebellar signs associated with uveitis with positive serum and cerebrospinal fluid antibodies to HTLV-I. 770 52

Malignant meningiomas are rarely encountered neoplasms. Few studies have examined MIB1 (marker of cell proliferation) or p53 (tumor suppressor gene) immunoreactivity in these tumors. This study retrospectively examines 23 malignant meningiomas (defined by the presence of either unequivocal brain invasion or metastasis) including MIB1 and p53 immunohistochemistry. The patients included 13 women and 10 men who ranged in age from 22 to 82 years (mean 63 years). Initial clinical presentation included weakness or numbness in 10 patients, visual signs or symptoms in 7 patients, and headaches in 6 patients. Histologically, nuclear pleomorphism was present in 23 of 23 tumors, disorganized architecture in 22 of 22, necrosis in 20 of 23, prominent nucleoli in 17 of 23, and hypervascularity in 4 of 23. One to 18 mitotic figures per 10 high power fields (HPF) (mean 6.1) were observed. Metastases were present in six patients (bone: 3 patients; lung: 2 patients; skin: 2 patients; kidney: 1 patient; and liver: 1 patient). MIB1 indices (positive tumor cells per 1,000 tumor cells evaluated x 100) in 20 tumors ranged from 1.3 to 24.2 (mean 11.7). p53 nuclear staining was observed in only 2 of 20 tumors. Follow-up information was available in 21 patients: 6 died of tumor (mean 27 months); 9 are alive with residual tumor (mean 35 months); 5 are alive with no evidence of tumor (mean 12 months); and 1 died 13 days postoperatively. There was no obvious correlation of the MIB1 index and tumor behavior. The majority of malignant meningiomas are characterized by nuclear pleomorphism, architectural disorganization, necrosis, prominent nucleoli, and increased mitoses. MIB1 labeling in most malignant meningiomas was high, consistent with the generally rapid growth of these tumors. Only a rare malignant meningioma demonstrated p53 alteration by immunostaining.
 ...
PMID:Malignant meningioma: a clinicopathologic study of 23 patients including MIB1 and p53 immunohistochemistry. 865 46

A 71-yr-old woman presented with progressive weakness, bone pain, polydipsia, and epigastric pain. Laboratory studies established the diagnosis of primary hyperparathy roidism with excessively elevated levels of parathyrod hormone (PTH) complicated by renal failure and anemia. Preoperative imaging using (99m)technetium hexakis 2-methoxy-isobutylisonitrile (MIBI) demonstrated an area of intense uptake in the mediastinum, which on T(2) -weighted magnetic resonance imaging revealed the presence of a hyperintense mediastinal mass of 25 mm in diameter adjacent to the ascending aorta Surgical exploration and resection of the mass were performed, and histological examination of the tumor revealed solid masses of epithelial cells growing in a trabecular pattern, hyaline bands, and low mitotic activity. Immunohistochemical staining of the tumor specimens using monoclonal mouse antihuman antibodies revealed markedly positive immunoreactivity of tumor cells for p53 protein and absence of nuclear immunoreactivity for the retinoblastoma tumor-suppressor protein, findings consistent with parathyroid carcinoma. Improved imaging techniques and advances in molecular pathology of parathyroid disorders may help to improve clinical management of patients with parathyroid neoplasia.
 ...
PMID:Mediastinal Parathyroid Tumor: Giant Adenoma or Carcinoma? 1211 37

Autosomal recessive proximal spinal muscular atrophy (SMA) is a severe neurodegenerative disease of childhood causing weakness and wasting secondary to motor neuron dysfunction. Over 97% of cases are caused by deletions or mutations within the survival motor neuron (SMN) gene. The SMN protein is highly expressed within brain, spinal cord and muscle, and is decreased in SMA patients. It has been shown to have an important role in RNA metabolism, but the reason for the specific motor neuron loss is still unclear. We have used a novel antibody array technology to look for differences in the expression patterns of primary muscle cultures from a type II SMA patient and a normal control. A relatively small number of differences were found within a group of proteins that function as both RNA binding proteins and transcription factors. Interactions between a number of these proteins are well established, and three of them bind in turn to p53 which interacts with SMN. A number of the changes were confirmed with western blot analysis both in the primary muscle cultures and in skeletal muscle samples from SMA patients and controls. Changes at the mRNA level were also confirmed with oligonucleotide arrays. These results suggest that a common transcription pathway may be altered in the disease state, and suggests that down-regulation of transcription factors contributes to SMA pathogenesis.
 ...
PMID:Protein expression changes in spinal muscular atrophy revealed with a novel antibody array technology. 1284 76

This study demonstrated, for the first time, the following events related to p19(ARF) involvement in mammary gland development: 1) Progesterone appears to regulate p19(ARF) in normal mammary gland during pregnancy. 2) p19(ARF) expression levels increased sixfold during pregnancy, and the protein level plateaus during lactation. 3) During involution, p19(ARF) protein level remained at high levels at 2 and 8 days of involution and then, declined sharply at day 15. Absence of p19(ARF) in mammary epithelial cells leads to two major changes, 1) a delay in the early phase of involution concomitant with downregulation of p21(Cip1) and decrease in apoptosis, and 2) p19(ARF) null cells are immortal in vivo measured by serial transplantion, which is partly attributed to complete absence of p21(Cip1) compared with WT cells. Although, p19(ARF) is dispensable in mammary alveologenesis, as evidenced by normal differentiation in the mammary gland of pregnant p19(ARF) null mice, the upregulation of p19(ARF) by progesterone in the WT cells and the weakness of p21(Cip1) in mammary epithelial cells lacking p19(ARF) strongly suggest that the functional role(s) of p19(ARF) in mammary gland development is critical to sustain normal cell proliferation rate during pregnancy and normal apoptosis in involution possibly through the p53-dependent pathway.
 ...
PMID:p19ARF determines the balance between normal cell proliferation rate and apoptosis during mammary gland development. 1510 43

Recent studies have been reported the roles of the estrogen receptor (ER), progesterone receptor (PR) and p53 in the development of a pelvic organ prolapse (POP). The pathogenesis of stress urinary incontinence (SUI) is related to that of POP in the weakness of pelvic support. Therefore, this study was carried out to assess the relationship between ER, PR, p53 and the development of SUI, and to elucidate the biomolecular pathophysiology of SUI. The periurethral fascia was obtained from 6 menopausal patients diagnosed with SUI and 10 menopausal patients without SUI who visited the Department of Obstetrics and Gynecology, Severance Hospital, Seoul, Korea. The relative ER, PR and p53 protein levels in the periurethral fascia were obtained by western blot analysis and densitometry. A Mann-Whitney U test was used for statistical analysis (p < 0.05). The mean age (+/- SD) of the 16 patients was 59.0 +/- 5.5 years (range, 50-74 years). The mean body mass index was 25.2 +/- 2.7 kg/m2 (21.8 - 30.8) and the average number of vaginal deliveries was 2.8 +/- 1.9 (1.0 - 9.0). The ER level (0.33 +/- 0.17 vs. 1.86 +/- 0.83, p= 0.02) and the p53 level (1.25 +/- 0.67 vs. 4.71 +/- 2.40, p= 0.01) were lower in the experimental group. However, the PR level of the two groups were similar (0.64 +/- 0.13 vs. 0.48 +/- 0.33, p=0.56). The p53 and ER levels were significant lower in the study group. This suggests that p53 and ER might be important factors in the development of SUI. Further prospective studies about the association of ER, p53 and SUI will be needed to elucidate the molecular pathogenesis of SUI.
 ...
PMID:The role of estrogen receptor, progesterone receptor and p53 in development of stress urinary incontinence. 1551

The identification of the cellular targets of small molecules with anticancer activity is crucial to their further development as drug candidates. Here, we present the application of a large-scale RNA interference-based short hairpin RNA (shRNA) barcode screen to gain insight in the mechanism of action of nutlin-3 (1). Nutlin-3 is a small-molecule inhibitor of MDM2, which can activate the p53 pathway. Nutlin-3 shows strong antitumor effects in mice, with surprisingly few side effects on normal tissues. Aside from p53, we here identify 53BP1 as a critical mediator of nutlin-3-induced cytotoxicity. 53BP1 is part of a signaling network induced by DNA damage that is frequently activated in cancer but not in healthy tissues. Our results suggest that nutlin-3's tumor specificity may result from its ability to turn a cancer cell-specific property (activated DNA damage signaling) into a weakness that can be exploited therapeutically.
 ...
PMID:An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors. 1647 81

Search for cancer-predisposing single-nucleotide gene polymorphisms is complicated due to weakness of expected associations. We introduced a novel design for molecular epidemiological study, which relies on selection of highly demonstrative cases and controls. It is assumed that patients with clinical features of hereditary predisposition (e.g., cancer bilaterality, or young onset, or presence of family history, etc.) are more likely to accumulate at-risk alleles than randomly recruited cases. Furthermore, subjects with characteristics of cancer tolerance, e.g., elderly tumor-free smokers, may serve as a "supercontrol" for the rapid assessment of polymorphic candidates. The utility of the "comparison of extremes" design has already been exemplified in a series of reports. However, the use of elderly subjects for cancer case-control studies may possess a bias; for example, factors contributing to cancer predisposition may nevertheless be advantageous for the overall longevity, as they could compensate age-related decline of tissue maintenance and renewal. For example, there is some evidence for a dual role of the apoptosis-deficient Pro/Pro genotype of p53 gene, which may simultaneously increase both cancer risk and survival. Comprehensive studies on distribution of cancer-related gene polymorphisms in elderly population remain to be done.
 ...
PMID:Use of elderly tumor-free subjects as a "supercontrol" for cancer epidemiological studies: pros and cons. 1845 7

Mitochondrial DNA depletion syndrome (MDS) is characterized by a reduction in mtDNA copy number and has been associated with mutations in eight nuclear genes, including enzymes involved in mitochondrial nucleotide metabolism (POLG, TK2, DGUOK, SUCLA2, SUCLG1, PEO1) and MPV17. Recently, mutations in the RRM2B gene, encoding the p53-controlled ribonucleotide reductase subunit, have been described in seven infants from four families, who presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis. All children died before 4 months of age. We sequenced the RRM2B gene in three unrelated cases with unexplained severe mtDNA depletion. The first patient developed intractable diarrhea, profound weakness, respiratory distress, and died at 3 months. The other two unrelated patients had a much milder phenotype and are still alive at ages 27 and 36 months. All three patients had lactic acidosis and severe depletion of mtDNA in muscle. Muscle histochemistry showed RRF and COX deficiency. Sequencing the RRM2B gene revealed three missense mutations and two single nucleotide deletions in exons 6, 8, and 9, confirming that RRM2B mutations are important causes of MDS and that the clinical phenotype is heterogeneous and not invariably fatal in infancy.
 ...
PMID:Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene. 1850 29


1 2 3 Next >>