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

Primary vesicoureteric reflux (VUR) is one of the more common genetic disorders. Little is yet known about the genetics of this potentially manageable childhood condition, which is characterised by regurgitation of urine from the bladder to the kidney. The VUR phenotype is associated with shortness of the submucosal segment of the ureter due to congenital lateral ectopia of the ureteric orifice. VUR is found in 30-50% of infants and young children with a urinary tract infection. A serious concern in families with an affected patient is that approximately one half of siblings or offspring will be affected, but up to a half of these affected siblings and offspring may be asymptomatic in childhood. If left untreated, these patients may present later in life with proteinuria, hypertension or renal failure. VUR is the commonest cause of end-stage renal failure in children, and an important cause in adults. As the kidney damage resulting from severe VUR is preventable, early detection is desirable. The techniques for clinical diagnosis are invasive and costly, reinforcing the importance of identification of a gene for VUR to facilitate genetic screening. Although family studies suggest a major dominant gene, the inheritance pattern is still a matter of debate. In rare instances, VUR occurs in association with other diseases, such as the coloboma-ureteric-renal syndrome, which is caused by a PAX2 gene mutation. In this review, we present evidence that this common disorder may be caused by mutations in the developmental pathway of which the PAX2 gene forms a part.
Hum Mol Genet 1996
PMID:Unravelling the genetics of vesicoureteric reflux: a common familial disorder. 887 47

Myocardial Na+,K(+)-ATPase was studied in patients with aortic valve disease, and myocardial Na+,K(+)- and Ca(2+)-ATPase were assessed in spontaneously hypertensive rats (SHR) and hereditary cardiomyopathic hamsters using methods ensuring high enzyme recovery. Na+,K(+)-ATPase was quantified by [3H]ouabain binding to intact myocardial biopsies from patients with aortic valve disease. Aortic stenosis, regurgitation and a combination hereof were compared with normal human heart and were associated with reductions of left ventricular [3H]ouabain binding site concentration (pmol/g wet weight) of 56, 46 and 60%, respectively (p < 0.01). Na+,K(+)- and Ca(2+)-ATPases were quantified by K(+)- and Ca(2+)-dependent p-nitrophenyl phosphatase (pNPPase) activity determinations in crude myocardial homogenates from SHR and hereditary cardiomyopathic hamsters. When SHR were compared to age-matched Wistar Kyoto (WKY) rats an increase in heart-body weight ratio of 75% (p < 0.001) was associated with reductions of K(+)- and Ca(2+)-dependent pNPPase activities (mumol/min/g wet weight) of 42 (p < 0.01) and 27% (p < 0.05), respectively. When hereditary cardiomyopathic hamsters were compared to age-matched Syrian hamsters an increase in heart-body weight ratio of 69% (p < 0.001) was found to be associated with reductions in K(+)- and Ca(2+)-dependent pNPPase activities of 50 (p < 0.001) and 26% (p = 0.05), respectively. The reductions in Na+,K(+)- and Ca(2+)-ATPases were selective in relation to overall protein content and were not merely the outcome of increased myocardial mass relative to Na+,K(+)- and Ca(2+)-pumps. In conclusion, myocardial hypertrophy is in patients associated with reduced Na+,K(+)-ATPase concentration and in rodents with reduced Na+,K(+)- and Ca(2+)-ATPase concentrations. This may be of importance for development of heart failure and arrhythmia in hypertrophic heart disease.
Mol Cell Biochem 1997 Apr
PMID:Reduced concentration of myocardial Na+,K(+)-ATPase in human aortic valve disease as well as of Na+,K(+)- and Ca(2+)-ATPase in rodents with hypertrophy. 908 35

The classical pathway for MHC class-I-restricted Ag presentation processes cytosolic Ag synthesized in or delivered into the cytosol for binding to MHC class I molecules in the ER. Alternatively, Ag may be processed and bind class I molecules in endocytic compartments or at the cell surface after regurgitation of processed peptides. We show that a 69-mer synthetic polypeptide that carries the optimal 9-mer Kd-restricted epitope from the Plasmodium berghei circumsporozoite protein, PbCS 245-253, is presented to CD8+ T cells after a short incubation (1-2 h) with target cells. The presentation kinetics correlate with the length of the peptides when shorter peptide analogues are used. This presentation is independent of the transporters associated with antigen processing and presentation (TAP), does not require newly synthesized proteins and does not proceed via regurgitation of intracellularly processed peptides. In contrast, it is substantially decreased in the absence of beta2 microglobulin or serum. Taken together, these data suggest that serum components, such as proteases and beta2 microglobulin, allow the processing and loading of exogenous polypeptides onto empty cell surface class I molecules for presentation to CTL.
Mol Immunol 1999 Feb
PMID:Extracellular processing and presentation of a 69-mer synthetic polypetide to MHC class I-restricted T cells. 1037 82

The intrinsic peritrophic matrix glycoprotein, peritrophin-95, from the midgut of larvae of Lucilia cuprina can only be solubilized from the matrix using strong denaturants. This suggests that the protein has a structural role in the matrix. Consistent with this is the finding that immuno-gold and immuno-fluorescence localizations of the protein showed a uniform distribution within the peritrophic matrix. RT-PCR demonstrated that expression of peritrophin-95 mRNA was restricted to the larval cardia, a small organ located in the anterior midgut from which the type 2 peritrophic matrix originates. Immuno-blots and ELISAs demonstrated that the sera from sheep infested naturally or artificially with these larvae recognised peritrophin-95. This indicates that peritrophin-95 stimulates the ovine immune system during larval infestation even though the protein is firmly attached to the peritrophic matrix in the larval midgut and seemingly "concealed" from the ovine immune surveillance system. Analyses of larval regurgitated or excreted material by immuno-blots, immuno-affinity purification and amino-terminal sequencing demonstrated the presence of soluble monomeric peritrophin-95. These results indicate that peritrophin-95, a candidate vaccine antigen for use in sheep is not a "concealed" antigen as previously thought. The presence of soluble peritrophin-95 in the regurgitated/excreted material from larvae suggests that this protein may be involved in a maturation phase of peritrophic matrix production, a by-product of which is the excretion or regurgitation of soluble peritrophin-95.
Insect Biochem Mol Biol 2000 Jan
PMID:The intrinsic peritrophic matrix protein peritrophin-95 from larvae of Lucilia cuprina is synthesised in the cardia and regurgitated or excreted as a highly immunogenic protein. 1064 66

The uptake of natural lung surfactant into differentiated type II cells may be used for the targeted delivery of other molecules. The fluorescent anion pyranine [hydroxypyren-1,3,6-trisulfonic acid, sodium salt (HPTS)] was incorporated into a bovine surfactant labeled with [3H]dipalmitoylphosphatidylcholine ([3H]DPPC). The uptake of [3H]DPPC and of HPTS increased with time of incubation and concentration, decreased with the size of the vesicles used, and was stimulated by 8-bromo-cAMP and partially inhibited by hypertonic sucrose. However, the amount of HPTS uptake was approximately 100 times smaller than that of [3H]DPPC. This large difference was due to a more rapid regurgitation of some of the HPTS from the cells but not to leakage from the surfactant before uptake. The acidification of the internalized surfactant increased linearly over 90 min to 7.13, and after 24 h, a pH of 6.83 was measured. In conclusion, after internalization of a double-labeled natural surfactant, the lipid moieties were accumulated in relation to the anions, which were targeted to a compartment not very acidic and in part rapidly expelled from the cells.
Am J Physiol Lung Cell Mol Physiol 2001 Jul
PMID:Uptake of a natural surfactant and increased delivery of small organic anions into type II pneumocytes. 1140 57

Phospholipase Cepsilon is a novel class of phosphoinositide-specific phospholipase C, identified as a downstream effector of Ras and Rap small GTPases. We report here the first genetic analysis of its physiological function with mice whose phospholipase Cepsilon is catalytically inactivated by gene targeting. The hearts of mice homozygous for the targeted allele develop congenital malformations of both the aortic and pulmonary valves, which cause a moderate to severe degree of regurgitation with mild stenosis and result in ventricular dilation. The malformation involves marked thickening of the valve leaflets, which seems to be caused by a defect in valve remodeling at the late stages of semilunar valvulogenesis. This phenotype has a remarkable resemblance to that of mice carrying an attenuated epidermal growth factor receptor or deficient in heparin-binding epidermal growth factor-like growth factor. Smad1/5/8, which is implicated in proliferation of the valve cells downstream of bone morphogenetic protein, shows aberrant activation at the margin of the developing semilunar valve tissues in embryos deficient in phospholipase Cepsilon. These results suggest a crucial role of phospholipase Cepsilon downstream of the epidermal growth factor receptor in controlling semilunar valvulogenesis through inhibition of bone morphogenetic protein signaling.
Mol Cell Biol 2005 Mar
PMID:Congenital semilunar valvulogenesis defect in mice deficient in phospholipase C epsilon. 1574 17

An autopsy case of pseudoxanthoma elasticum is reported. A Japanese female patient complained of yellow papules on the neck, precordium, and axilla, beginning at 54 years of age. When the patient was 58 years old, in response to her visual disturbance a funduscopic examination was performed, revealing angioid streaks, and skin biopsy identified a characteristic pseudoxanthoma elasticum (PXE) lesion. The patient developed congestive heart failure, and following mitral valve prolapse and regurgitation flow into the left atrium, mitral valve replacement with a prosthetic valve was performed when the patient was 65 years old. Soon afterward, the patient complained of gait disturbance, and she died of congestive heart failure at 68 years of age. Autopsy specimen revealed fragmented, granular, and calcified elastic fibers in the middle to deep dermis and in the thickened subendocardium, and small to medium-sized muscular arteries revealed fragmented, laminated, and calcified elastic lamina; vascular changes were seen in the heart, lung, kidney, gastrointestinal tract, and iliac artery. Disrupted elastic fibers were visualized using the Weigert resorcin fuchsin method and were stained positive by antielastin and antifibronectin antibodies. Calcification was confirmed by von Kossa staining. Affected areas were PAS-positive after diastase digestion, indicating the presence of glycoprotein. Affected areas were colloidal iron-positive, indicating the presence of proteoglycan matrix.
Med Mol Morphol 2007 Sep
PMID:An autopsy case of pseudoxanthoma elasticum: histochemical characteristics. 1787 51

Elastic system fibers are composed of two distinct elements, elastin, which is an amorphous component crosslinked in the core, and microfibril, localized in the periphery of elastin. As microfibrillar proteins, fibrillins, microfibril-associated glycoproteins (MAGPs), latent TGF-beta-binding proteins (LTBPs), microfibril-associated proteins (MFAPs), and fibulins are known. Fibrillin-1 is a major microfibrillar protein and characterized by calcium binding EGF-like (cbEGF) domain. Association between fibrillin-1 and TGF-beta is a recent topic of this field and this interaction is known to inactivate and target TGF-beta action. FBN1 encoding fibrillin-1 is a responsible gene for Marfan syndrome type 1 (MIM #154700), characterized by increased height and long limbs, ectopia lentis, and cardiovascular disorders, such as mitral valve prolapse and aortic dilation and regurgitation. Animal models suggest that the abnormal TGF-beta signaling is underlying as the pathogenesis of these conditions. Besides skeletal, ocular and cardiovascular conditions, severe periodontitis is frequently seen in affected patients. To clarify the unknown function of elastic system fibers in the periodontal ligament (PDL), PDL-cells were isolated from a Marfan syndrome type 1 patient who was with the severe periodontitis and had a mutation in one of the cbEGF domain of fibrillin-1. These results suggested that wild-type fibrillin-1 was required for the normal cell alignment and tissue architecture of PDLs. Evidences are now accumulated to suggest that fibrillin-1 is one of the molecule involved in the interaction between cell and extracellular matrix.
J Exp Zool B Mol Dev Evol 2009 Jul 15
PMID:Marfan syndrome and its disorder in periodontal tissues. 1919 46

Partial monosomy 21 has been reported, but the phenotypes described are variable with location and size of the deletion. We present 2 patients with a partially overlapping microdeletion of 21q22 and a striking phenotypic resemblance. They both presented with severe psychomotor delay, behavioral problems, no speech, microcephaly, feeding problems with frequent regurgitation, idiopathic thrombocytopenia, obesity, deep set eyes, down turned corners of the mouth, dysplastic ears, and small chin. Brain MRI showed cerebral atrophy mostly evident in frontal and temporal lobes, widened ventricles and thin corpus callosum in both cases, and in one patient evidence of a migration disorder. The first patient also presented with epilepsy and a ventricular septum defect. The second patient had a unilateral Peters anomaly. Microarray analysis showed a partially overlapping microdeletion spanning about 2.5 Mb in the 21q22.1-q22.2 region including the DYRK1A gene and excluding RUNX1. These patients present with a recognizable phenotype specific for this 21q22.1-q22.2 locus. We searched the literature for patients with overlapping deletions including the DYRK1A gene, in order to define other genes responsible for this presentation.
Mol Syndromol 2010 Sep
PMID:Distinctive Phenotypic Abnormalities Associated with Submicroscopic 21q22 Deletion Including DYRK1A. 2103 Oct 80

Right ventricular (RV) enlargement and pulmonary valve insufficiency (PI) are well-known, unavoidable long term sequelae encountered by patients who undergo tetralogy of Fallot (TOF) surgery. Despite their lifelong need for cardiac surveillance and occasional re-intervention, there is a paucity of numerical data characterizing blood flows in their pulmonary arteries (PA). Specifically, although PA regurgitation is well-known to be ubiquitously present in adult repaired TOF (rTOF) patients yet, there have been only limited numerical studies to fully characterize this process. The few studies available have utilized idealized, simplistic geometric models or overly simplistic boundary conditions that fail to account for flow reversals near the arterial walls as observed in in-vitro and MRI based in-vivo studies. The objective of this study was to establish and validate a numerical methodology of PA blood flow using actual patient specific geometry and flow measurements obtained using phase-contrast MRI, employing Womersley type velocity profiles that model flow reversals near walls. The results from computation were validated with measurements. For the normal subject, the time averaged right PA pressure from computation (13.8 mmHg) and experiment (14.6 mmHg) differed by 6%. The time-averaged main PA pressure from computation (16.5 mmHg) and experiment (16.3 mmHg) differed by 1%. The numerically computed left PA regurgitant fraction was 89% compared to measured 77.5%, while the same for the rTOF was 43% (computation), compared to 39.6% (measured). We conclude that the use of numerical computations using the Womersley boundary condition allows reliable modeling of the pathophysiology of PA flow in rTOF.
Mol Cell Biomech 2011 Mar
PMID:Comparison of hemodynamic endpoints between normal subject and tetralogy patient using Womersley velocity profile and MR based flow measurements. 2139 26


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