Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A family is described where the father has the many skeletal, but none of the cardiac abnormalities associated with the Holt-Oram syndrome. His two daughters have similar skeletal anomalies, but with identical cardiac lesions, as does another patient, raising the possibility of an associated genetic marker.
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PMID:Holt-Oram syndrome and multiple ventricular septal defects: an association suggesting a possible genetic marker? 968 Feb 86

Holt-Oram syndrome is a distinct autosomal dominant entity presenting with upper limb defects and cardiac abnormality. No correlation between the severity of the heart and the limb defects has been established. Here we report variable clinical expression of Holt-Oram syndrome in three generations. The grandfather presented with typical upper limb defects: phocomelia of arms with three digits on each hand, congenital heart defect and narrow shoulders. His son manifested cardiac conduction disturbance with no congenital heart or skeletal defect. The granddaughter showed ventricular septal defect and moderate radial deviations of both hands with no obvious hypoplasia of the extremities. Clinical data of the presented family suggests lack of penetrance with respect to skeletal and structural cardiac abnormalities in the Holt-Oram syndrome.
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PMID:Variable clinical expression of Holt-Oram syndrome in three generations. 1002 74

ROC1 is a common component of a large family of ubiquitin E3 ligases that regulate cell cycle progression and signal transduction pathways. Here we present evidence suggesting that a conserved RING-H2 structure within ROC1 is critical for its ubiquitin ligation function. Mercury-containing sulfhydryl modification agents (rho-hydroxymercuribenzoate and mercuric chloride) irreversibly inhibit the ROC1-CUL1 ubiquitin ligase activity without disrupting the complex. Consistent with this, these reagents also eliminate the ability of the Skp1-CUL1-HOS-ROC1 E3 ligase complex to support the ubiquitination of IkappaBalpha. Site-directed mutagenesis analysis identifies RING-H2 finger residues Cys(42), Cys(45), Cys(75), His(77), His(80), Cys(83), Cys(94), and Asp(97) as being essential for the ROC1-dependent ubiquitin ligase activity. Furthermore, C42S/C45S and H80A mutations reduce the ability of ROC1 to interact with CUL1 in transfected cells and diminish the capacity of ROC1-CUL1 to form a stable complex with Cdc34 in vitro. However, C75S, H77A, C94S, and D97A substitutions have no detectable effect on ROC1 binding activities. Thus, the ROC1 RING-H2 finger may possess multiple biochemical properties that include stabilizing an interaction with CUL1 and recruiting Cdc34. A possible role of the RING finger in facilitating the Ub transfer reaction is discussed.
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PMID:The conserved RING-H2 finger of ROC1 is required for ubiquitin ligation. 1074 83

Normal and malignant cells of various origin differ in their sensitivity to oxidative stress. Therefore, we used normal and malignant mesenchymal cells--human osteosarcoma cells (HOS and 143B), human fibroblasts (WI38) and two primary cultures of normal human osteoblasts to test sensitivity to reactive aldehyde 4-hydroxynonenal (HNE), known as a second messenger of free radicals and a signaling molecule. Upon HNE-treatment, decrease in cell viability (by Trypan-blue), apoptosis induction (by TiterTACS TUNEL assay), HNE-protein binding (by HNE-His ELISA) were higher in malignant than in normal cells, while glutathione content was higher in normal cells. These results indicate that HNE affects the growth of malignant mesenchymal cells more than normal and that this effect was mainly related to lower glutathione concentration and higher binding of HNE to the cellular proteins. We thus assume that HNE and GSH homeostasis play an important role in the growth regulation of normal and malignant mesenchymal cells.
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PMID:Differential sensitivity to 4-hydroxynonenal for normal and malignant mesenchymal cells. 1726 9

Human immunodeficiency virus (HIV) is the primary etiologic agent responsible for the AIDS pandemic. In this work, we used a chimeric recombinant protein strategy to test the possibility of irreversibly destroying the HIV-1 virion using an agent that simultaneously binds the Env protein and viral membrane. We constructed a fusion of the lectin cyanovirin-N (CVN) and the gp41 membrane-proximal external region (MPER) peptide with a variable-length (Gly4Ser)x linker (where x is 4 or 8) between the C terminus of the former and N terminus of the latter. The His-tagged recombinant proteins, expressed in BL21(DE3)pLysS cells and purified by immobilized metal affinity chromatography followed by gel filtration, were found to display a nanomolar efficacy in blocking BaL-pseudotyped HIV-1 infection of HOS.T4.R5 cells. This antiviral activity was HIV-1 specific, since it did not inhibit cell infection by vesicular stomatitis virus (VSV) or amphotropic-murine leukemia virus. Importantly, the chimeric proteins were found to release intraviral p24 protein from both BaL-pseudotyped HIV-1 and fully infectious BaL HIV-1 in a dose-dependent manner in the absence of host cells. The addition of either MPER or CVN was found to outcompete this virolytic effect, indicating that both components of the chimera are required for virolysis. The finding that engaging the Env protein spike and membrane using a chimeric ligand can destabilize the virus and lead to inactivation opens up a means to investigate virus particle metastability and to evaluate this approach for inactivation at the earliest stages of exposure to virus and before host cell encounter.
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PMID:Chimeric Cyanovirin-MPER recombinantly engineered proteins cause cell-free virolysis of HIV-1. 2385 80

Holt-Oram Syndrome (HOS) is a rare autosomal dominant condition characterized by anomalies of the upper extremity and cardiac malformations. Mutations in the TBX5 gene are what cause HOS. The proband is an 8-year-old male who presented with upper-extremity abnormalities and a chest deformity. He was born to a nonconsanguineous marriage at full term. He has a history of ventricular septal defect. His mother presented with deformation in both hands and forearms, and was 9 weeks' pregnant. Mutation analysis for TBX5 gene revealed heterozygous p.L65Qfs*10 in both the patient and his mother. Molecular analysis of the fetus was normal for TBX5 gene in the 13th week of pregnancy. In conclusion, our case supports the fact that the HOS presents differently, case by case, even within the same family. The novel mutation reported here and phenotypic findings in the affected members may contribute to the phenotype-genotype correlation.
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PMID:A new mutation in the TBX5 gene in Holt-Oram syndrome: two cases in the same family and prenatal diagnosis. 2440 48