Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing evidence points at an important function of Vitamin D metabolites for growth regulation in various tissues, including MM. Using array CGH, amplification of 24-OHase was recently detected as a likely target oncogene of the amplification unit 20q13.2 in breast cancer cell lines and tumors. Additionally, amplification of 1alpha-OHase has been reported in human malignant glioma. Using immunohistochemistry, we have now detected nuclear Vitamin D receptor (VDR) immunoreactivity in primary cutaneous malignant melanoma (MM), indicating that Vitamin D metabolites may be of importance for the growth regulation in these tumors. Using Southern analysis, we have analyzed MM and metastases for evidence of amplification of 1alpha-OHase or 24-OHase genes. Our results do not support the hypothesis that amplification of 1alpha-OHase or 24-OHase genes may be of importance for pathogenesis or progression of MM.
J Steroid Biochem Mol Biol 2004 May
PMID:No evidence for amplification of 25-hydroxyvitamin D-1alpha-OHase (1alpha-OHase) or 1,25-dihydroxyvitamin D-24-OHase (24-OHase) genes in malignant melanoma (MM). 1522 66

Fertilization at increased times after ovulation is associated with poor reproductive outcomes. This study examines the effects of post-ovulatory ageing on egg membrane function through analyses of mouse eggs collected at 13 and 22 h post-HCG ('young' and 'aged' eggs, respectively). Experiments in which fertilized zona pellucida-free young and aged eggs are challenged with additional sperm reveal that aged eggs are less able to establish a membrane block to prevent polyspermy, since sperm penetrate 24% of fertilized aged eggs but are unable to penetrate fertilized young eggs. This is not due to a failure of aged eggs to respond to fertilization, as the extent of sperm-induced cortical granule exocytosis is similar in aged and young eggs. Post-ovulatory ageing also affects egg membrane receptivity to sperm as a subset of zona pellucida-free aged eggs are slow to fertilize or resistant to fertilization. Sperm binding to young and aged eggs is similar, but aged eggs develop cytoskeletal abnormalities that may affect membrane/cortical function, such as the ability of the egg membrane to support sperm-egg fusion. These data demonstrate that the poor reproductive outcomes associated with post-ovulatory ageing could be a result of reduced fertilization, due to reduced egg membrane receptivity to sperm, or a result of increased incidence of polyspermy, due to the reduced ability to establish a membrane block to polyspermy. This analysis of egg membrane function deficiencies provides insights into post-ovulatory ageing and has implications for assisted reproductive technologies.
Mol Hum Reprod 2005 Jan
PMID:Membrane and cortical abnormalities in post-ovulatory aged eggs: analysis of fertilizability and establishment of the membrane block to polyspermy. 1551 58

The apoptosis of granulosa cells is involved in follicular atresia and degeneration of the corpus luteum. The mechanisms that regulate follicular atresia and luteal degeneration remain obscure. Survivin is a member of the family of inhibitors of apoptosis protein that is expressed during fetal development and in cancer tissues. The present study investigates the expression of survivin, as well as its regulation and function in granulosa cells. We identified survivin at the protein level in granulosa cells and detected not only survivin but also splice-variant transcripts in human and mouse granulosa-luteal cells. One-step real-time PCR analysis revealed that HCG increases the amount of survivin mRNA expressed in cultured human granulosa cells. These results suggest that survivin is involved in supporting luteal function, and that HCG contributes to this role.
Mol Hum Reprod 2005 Mar
PMID:HCG up-regulates survivin mRNA in human granulosa cells. 1570 57

We have previously shown that both HCG and insulin-like growth factor-II (IGF-II) stimulate trophoblastic invasion. Furthermore, the invasion-promoting function of IGF-II resulted from IGF-II mannose 6-phosphate receptor (IGF-II/M6PR) activation. Since HCG and IGF-II did not have an additive effect on cell migration of extravillous trophoblast (EVT) cell line, HTR-8 SVneo, we hypothesized that HCG actions are mediated via alterations in the expression and/or function of IGF-II axis. HCG treatment (50-50,000 mU/ml) of the HTR-8/SVneo cells did not alter the expression of either insulin-like growth factor-I or IGF-II mRNA or peptide synthesis, but caused (i) an increase in the (125)I-IGF-II binding to EVT cells, and (ii) an increase in the externalization rate of the IGF-II binding sites without affecting their internalization. This effect was due to the increase in the number of IGF-II binding sites in the plasma membrane without any change in the IGF-II binding affinity. Although HCG did not influence the abundance of IGF-II/M6PR mRNA or protein, anti-IGF-II/M6PR antibody decreased HCG-induced migration of EVT, supporting the hypothesis that HCG might stimulate EVT migration by increasing IGF-II binding to the plasma membrane and subsequently by increasing the IGF-II effect probably mediated via the IGF-II/M6PR.
Mol Hum Reprod 2005 Apr
PMID:HCG increases trophoblast migration in vitro via the insulin-like growth factor-II/mannose-6 phosphate receptor. 1574 84

X-linked ichthyosis (XLI) is often associated with a recurrent microdeletion at Xp22.31 due to non-allelic homologous recombination between the CRI-S232 low-copy repeat regions flanking the STS gene. The clinical features of these patients may include mental retardation (MR) and the VCX-A gene has been proposed as the candidate MR gene. Analysis of DNA from four XLI patients with MR by array-comparative genomic hybridization (array-CGH) on a 150 kb resolution X chromosome-specific array revealed a 1.5 Mb interstitial microdeletion with breakpoints in the CRI-S232 repeat sequences, each of which harbors a VCX gene. We demonstrate that the recombination sites in all four cases are situated in the 1 kb repeat unit 2 region present at the 3' ends of the VCX-A and VCX-B genes thereby deleting VCX-A and VCX-B1 but not VCX-B and VCX-C. Array-CGH with DNA of an XLI patient with MR and an inherited t(X;Y)(p22.31;q11.2) showed an Xpter deletion of 8.0 Mb resulting in the deletion of all four VCX genes and duplication of both VCY homologs. These data confirm the role of VCX-A in the occurrence of MR in XLI patients. Moreover, we propose a VCX/Y teamwork-dependent mechanism for the incidence of mental impairment in XLI patients.
Hum Mol Genet 2005 Jul 01
PMID:Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis. 1588 81

Von Hippel-Lindau (VHL) disease is an autosomal dominant tumor syndrome, in which hemangioblastomas (HBs), clear cell renal cell carcinomas (RCCs), and pheochromocytomas are the most frequently encountered tumors. The differential diagnosis of dedifferentiated tumors in general can be difficult, as standard histologic and immunohistochemical investigations do not always allow a definitive diagnosis. We used molecular genetic analysis to resolve the differential diagnosis of sarcomatoid RCC versus pheochromocytoma of a (peri)renal tumor in a VHL patient. Germline mutation analysis identified the C407T mutation, which has been related to a VHL phenotype in which pheochromocytomas are rare. Chromosomal imbalances detected in the tumor by CGH showed a pattern typical for RCCs and not for pheochromocytomas. CGH analysis of the multiple tumors of this VHL patient revealed a comparable karyotype in the metastatic tumors and the (peri)renal tumor. Concordantly, although the germline mutation was detected in all analyzed tumors, LOH 3p was only detected in the (peri)renal mass and most metastases. Overall, based on all genetic data, this tumor corroborated a diagnosis of metastatic sarcomatoid RCC. In line with these observations is the immunopositivity for the RCC-specific RC38 detected in the (peri)renal mass and the metastases that was not detected in pheochromocytomas. The RCC specific marker G250 was uninformative as it stains positive in all types of VHL tumors. This case report illustrates the promising role of genetic analysis in the differential diagnosis of histologically dedifferentiated tumors.
Diagn Mol Pathol 2005 Jun
PMID:Molecular analysis as a tool in the differential diagnosis of VHL disease-related tumors. 1590 96

The sequencing of the human genome and development of high-throughput microarray technologies have enhanced the detection of copy number alterations in cancer research and the study of constitutional chromosomal abnormalities. Microarray-based comparative genomic hybridization (array CGH) has integrated molecular and traditional cytogenetics and has begun to impact the clinician's approach to medical genetics. Clinical applications of array CGH may define new genetic syndromes, expand the phenotype of existing syndromes and characterize a genomic signature of some cancers. As array CGH becomes the initial diagnostic approach for the investigation of constitutional and acquired chromosomal abnormalities, the combination of bioinformatics, robotics and microarray technology will set the stage for a new generation of high-resolution and high-throughput tools for genetic analysis, diagnosis and gene discovery.
Expert Rev Mol Diagn 2005 May
PMID:Array-based comparative genomic hybridization in clinical diagnosis. 1593 18

The aim of our study was to determine whether conventional staging in patients with testicular germ-cell-tumors (GCT) could be supplemented by quantification of beta-human choriogonadotropin mRNA levels in peripheral blood using kinetic fluorescence RT-PCR. Blood samples from 41 patients with GCT of different clinical stages (CS) were pre-therapeutically examined by kinetic fluorescence RT-PCR with the LightCycler for beta-human chorionic gonadotropin (beta-HCG) mRNA expression levels. The controls comprised of samples taken from patients 3 months after treatment, from patients with inflammatory testicular diseases or non-germ-cell-tumors and from healthy males (n=66). Six positive results [cut-off level: normalized beta-HCG mRNA (Nbeta-HCG) >400 relative gene expression (RGE)] were found in controls (specificity 90.9%, 95% CI: 76.9-97.3%). The overall ratio of positive PCR results in the group of GCT patients was 82.92% (34/41) (CS I 18/23, CS IIa-b 6/7, CS >IIb 10/11) (sensitivity 82.9%, 95% CI: 65.1-91.2%). The average Nbeta-HCG level in patients with clinical stage I tumors was 63772.0+/-125720.5 (mean +/- standard deviation) relative gene expression (RGE), 35076.0+/-52253.5 RGE in those with CS IIa-b tumors and 87298.3+/-120895.3 RGE in those with CS >IIb tumors. Kinetic fluorescence RT-PCR for tumor-specific gene products is, in contrast to qualitative RT-PCR, a promising approach to improve conventional staging in clinical low-stage testicular germ-cell-tumors. With high specificity, its sensitivity is higher than that of the corresponding serum tumor marker (82.92% vs 48.72%).
Int J Mol Med 2005 Jul
PMID:Kinetic fluorescence RT-PCR is highly sensitive for detection of germ-cell-tumor-specific transcripts in peripheral blood. 1594 91

Numerous cytological and biochemical alterations occur as mammalian oocytes age post-ovulation. Some of these changes can predispose cells to aneuploidy. The objective of this study was to test the hypothesis that the level of MAD2 spindle assembly checkpoint (SAC) transcripts decrease as mouse oocytes age post-ovulation and that this decrease was associated with chromosome missegregation. Female Institute of Cancer Research (ICR) mice were superovulated and oocytes collected at 14 h, 19 h and 24 h post-HCG for cytogenetic and quantitative real-time rapid cycle fluorescent RT-PCR analyses. Premature centromere separation (PCS) is now generally recognized as a predisposition to aneuploidy. The data showed that the frequencies of PCS-incomplete (PCS-I) did not significantly (P > 0.05) increase with time post-ovulation; whereas the proportions of oocytes displaying PCS-complete (PCS-C) and premature anaphase (PA) were significantly (P < 0.01) greater at 19 h and 24 h post-HCG, respectively. The higher frequencies of PCS-C and PA found at 19 h and 24 h coincided with decreased levels of MAD2 transcripts at these same times. Although the decline in MAD 2 transcripts with oocyte aging represents only one of many potential mechanisms responsible for aneuploidy, a compromised SAC appears to have a role in the unfavourable reproductive outcome associated with post-ovulatory aged oocytes.
Mol Hum Reprod 2005 Sep
PMID:Post-ovulatory aging of mouse oocytes leads to decreased MAD2 transcripts and increased frequencies of premature centromere separation and anaphase. 1620 98

Small, submicroscopic, genomic deletions and duplications (1 kb to 10 Mb) constitute up to 15% of all mutations underlying human monogenic diseases. Novel genomic technologies such as microarray-based comparative genomic hybridization (array CGH) allow the mapping of genomic copy number alterations at this submicroscopic level, thereby directly linking disease phenotypes to gene dosage alterations. At present, the entire human genome can be scanned for deletions and duplications at over 30,000 loci simultaneously by array CGH ( approximately 100 kb resolution), thus entailing an attractive gene discovery approach for monogenic conditions, in particular those that are associated with reproductive lethality. Here, we review the present and future potential of microarray-based mapping of genes underlying monogenic diseases and discuss our own experience with the identification of the gene for CHARGE syndrome. We expect that, ultimately, genomic copy number scanning of all 250,000 exons in the human genome will enable immediate disease gene discovery in cases exhibiting single exon duplications and/or deletions.
Hum Mol Genet 2005 Oct 15
PMID:Identification of disease genes by whole genome CGH arrays. 1624 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>