Disease relevance of LDB3

• Mutations in ZASP define a novel form of muscular dystrophy in humans [1].
• ZASP (a Z-band alternatively spliced PDZ motif-containing protein) is another Z-disk-associated protein, and targeted deletion of ZASP in mouse causes skeletal and cardiac myopathy [1].
• OBJECTIVES: We evaluated the role of Cypher/ZASP in the pathogenesis of dilated cardiomyopathy (DCM) with or without isolated non-compaction of the left ventricular myocardium (INLVM) [2].
• A randomized crossover efficacy trial of oral CPAP (Oracle) compared with nasal CPAP in the management of obstructive sleep apnea [3].
• CYPHER coronary stents and risk of thrombosis [4].

Psychiatry related information on LDB3

• Baseline clinical and angiographic characteristics were similar between groups, except for more Cypher stents as the initial DES that restenosed in the r-DES group than in the intravascular radiation therapy group (88.5% vs 69%, p = 0.01) [5].
• Thus the system allows for a more rapid, focused decision making approach than does AI/Consult, while it follows the trend established by QMR in that it abandons the Greek Oracle problem solving approach and instead adopts a physician-assisted hypothesis investigation approach [6].
• In the complex lesions without restenosis, 28% would have been excluded from the trials, while in complex lesions with restenosis, there were 53% (P=.05) (with a homogeneous percentage between the C and T groups) [7].

High impact information on LDB3

• The transcript coding for this Z-band alternatively spliced PDZ motif (ZASP) protein maps on chromosome 10q22.3-10q23.2, near the locus for infantile-onset spinocerebellar ataxia [8].
• We conclude that (1) mutations in ZASP cause stereotyped MFM pathology; (2) cardiomyopathy, distal more than proximal weakness, and neuropathy are in the spectrum of zaspopathy; and (3) mutations in ZASP define a novel form of autosomal dominant muscular dystrophy in humans [1].
• Ten carried either of two mutations in exon 6 (A147T and A165V) at or within a motif important in linking ZASP to the Z-disk; one carried a missense mutation in exon 9 (R268C) [1].
• This interaction has been further confirmed by immunohistochemical studies that demonstrated co-localization of Cypher and alpha-actinin at the Z-lines of cardiac muscle [9].
• Phosphorylation of Cypher by protein kinase C has demonstrated the functional significance of this interaction [9].

Biological context of LDB3

• We identified two alternative splicing variants of a novel PDZ-LIM domain protein, which we named Oracle [10].
• ZASP/Cypher also has a conserved sequence called the ZM-motif, and it is found in two alternatively spliced exons 4 and 6 [11].
• Many point mutations found in cardiomyopathy patients are located in the internal region of ZASP/Cypher [11].
• Therefore, the SEARCH database (System for Evaluation and Archiving of Radiation accidents based on Case Histories) has been developed in our department and implemented as an Oracle 8.0 database containing to date more than 800 case histories [12].
• RESULTS: We introduce BioWarehouse, an open source toolkit for constructing bioinformatics database warehouses using the MySQL and Oracle relational database managers [13].

Anatomical context of LDB3

• In vitro studies showed cytoskeleton disarray in cells transfected with mutated Cypher/ZASP [2].
• These data suggest a role for Oracle in the early development and function of heart and skeletal muscle [10].
• Solution structure of ZASP PDZ domain; implications for sarcomere ultrastructure and enigma family redundancy [14].
• METHODS AND RESULTS: A total of 500 patients with coronary artery disease were randomly assigned to receive a Cypher stent or BeStent [15].
• Here, we show that the ZASP/Cypher internal fragments containing either ZM exon 4 or 6 co-localized with alpha-actinin in cultured myoblasts and nonmuscle cells [11].

Associations of LDB3 with chemical compounds

• A 1876G>A substitution changing an aspartic acid to asparagine (D626N) was identified in LDB3 in four members of two families with LVNC [16].
• A 163G>A polymorphism was identified in LDB3, which changed a valine to isoleucine (V55I) in one patient with isolated LVNC [16].
• Eighty patients (83 lesions, 41 Cypher and 42 Taxus Express stents) were studied [17].
• This retrospective, observational study aimed to evaluate the efficacy and safety of bivalirudin compared with heparin as an antithrombotic regimen in patients treated with sirolimus-eluting stents (Cypher) and found that bivalirudin is clinically safe and feasible, with fewer vascular and ischemic complications compared with heparin [18].
• This project built a medical informatics data warehouse (MedInfo DDW) in an Oracle database to analyze medical information which has been collected through Baylor Family Medicine Clinic (FCM) Logician application [19].

Physical interactions of LDB3

• ZASP PDZ structure was used to model other members of the enigma family by homology and to predict their abilities to bind alpha-actinin-2 [14].

Regulatory relationships of LDB3

• Z band alternately spliced PDZ-containing protein (ZASP) is a sarcomere Z disk protein expressed in human cardiac and skeletal muscle that is thought to be involved in a dominant familial dilated cardiomyopathy [14].

Other interactions of LDB3

• We have determined the structure of ZASP PDZ by NMR and showed that it is a classical class 1 PDZ domain that recognizes the carboxy-terminal sequence of an alpha-actinin-2 calmodulin-like domain with micromolar affinity [14].
• ZASP/Cypher interacts through its PDZ domain with the major Z-disc actin cross-linker, alpha-actinin [11].
• The present system is implemented on a Sun Sparc Solaris 2.5 platform using Oracle 7.3.2, and the Oracle 7.3.2 Web server [20].

Analytical, diagnostic and therapeutic context of LDB3

• Cypher/ZASP was screened by denaturing high performance liquid chromatography (DHPLC) and direct deoxyribonucleic acid sequencing [2].
• In situ hybridization in mouse embryos confirmed and extended these data by showing high expression of Oracle mRNA in atrial and ventricular myocardial cells from E8 [10].
• The advantage of the Cypher stent is vastly reduced in large vessels [15].
• XTAL RES is a Macintosh program that is linked to PCRYSTAL (software used to enter details of the crystallization experiments) through an Oracle database on a VAX network [21].
• A meta-analysis of trials comparing Cypher and Taxus stents in patients with obstructive coronary artery disease [22].

References