Disease relevance of CDAN1

• Linkage and mutational analysis of the CDAN1 gene reveals genetic heterogeneity in congenital dyserythropoietic anemia type I [1].
• Our aim was to characterise the CDAN1 mutation in eight unrelated patients with sporadic CDA I, three of whom had complex bone disease [2].
• This study compared the feasibility, validity, and responsiveness of PCDAI vs. CDAI in the assessment of Crohn's disease activity among pediatric patients [3].
• Results demonstrate that CDAN and DOPE with and without siRNA confer low toxicity to mammalian cells, whereas lipofectAMINE2000 is clearly toxic both as a reagent and after formulation into LsiR particles [4].
• To determine the importance of systemic arterial hypertension (SAH) in the pathogenesis of coronary atherosclerosis (CA), the coronary stenosis (CSI), coronary diffuse atheromatous (CDAI) and coronary tortuosity (CTI) indices were assessed by selective coronary angiography (SCA) in 132 survivors of a definite first myocardial infarction (MI) [5].

Psychiatry related information on CDAN1

• Follow-up evaluations were scheduled at three, six and twelve months and included self-assessment as well as physicians assessment of disease activity using CDAI and laboratory parameters [6].

High impact information on CDAN1

• METHODS: Peripheral blood monocytes from healthy volunteers and patients with chronic active CD (CDAI > 250) were isolated by density gradient centrifugation methods [7].
• CDA type I (CDAI [MIM 224120], gene symbol CDAN1) is characterized by erythroid pathological features such as internuclear chromatin bridges, spongy heterochromatin, and invagination of the nuclear membrane, carrying cytoplasmic organelles into the nucleus [8].
• A cluster of 45 highly inbred Israeli Bedouin with CDAI enabled the mapping of the CDAN1 disease gene to a 2-Mb interval, now refined to 1.2 Mb, containing 15 candidate genes on human chromosome 15q15 (Tamary et al. 1998) [8].
• Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1 [8].
• These findings, and the cellular phenotype, suggest that codanin-1 may be involved in nuclear envelope integrity, conceivably related to microtubule attachments [8].

Chemical compound and disease context of CDAN1

• RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn's disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters [9].
• AIM: To study the effect of oral budesonide and prednisolone on peripheral blood natural killer (NK) cell activity in patients with active ileocaecal Crohn's disease (Crohn's disease activity index, CDAI > or = 200) [10].
• Intestinal permeability (lactulose/mannitol test), gastroduodenal permeability (urinary sucrose excretion), and postheparin plasma diamine oxidase activity were serially measured in 61 adults with Crohn's disease in remission (CDAI <150) for at least 30 days [11].
• Clinical relapses as assessed by CDAI values were observed in 37.5% of patients receiving mesalamine alone and in 6.25% of patients in the group treated with mesalamine plus the probiotic agent [12].
• Nineteen patients with active (CDAI > 200) colonic (N = 11) or ileocolonic (N = 8) Crohn's disease were assessed by colonoscopy and indium scanning [13].

Biological context of CDAN1

• Fifteen of 16 cases alive at the time of analysis showed mutations of at least one allele from exons 6 to 28 within CDAN1 [14].
• The authors recently cloned the CDAN1 gene and identified one founder missense mutation in all of their Bedouin patients [15].
• Transfection studies on HeLa and Panc-1 cells reveal that CDAN/DOPE lipoplexes are superior in efficacy to DC-Chol/DOPE lipoplexes [16].
• SNPs were genotyped (TaqMan) in two cohorts ( n= 90 and n= 444 (ACCENT I)) of active Crohn's disease patients (CDAI 220-450) [17].
• Both CD28 downregulation and CD57 expression correlated to CDAI and surrogate markers of disease activity [18].

Anatomical context of CDAN1

• Cytidine deaminase in human white blood cells has three electrophoretic phenotypes representing the homozygous and heterozygous expression of two common alleles, CDA1 and CDA2, at an autosomal locus [19].
• The following parameters were also determined in these patients: CD activity index (CDAI), erythrocyte sedimentation rate, C reactive protein, length of disease, previous surgical resection, and number of recurrences [20].
• There was no correlation with either histological findings elsewhere in the upper gastrointestinal tract or with laboratory findings, symptoms, CDAI, or medication [21].
• Among the Crohn's patients clearance was increased significantly in those with abnormal erythrocyte sedimentation rates (ESR) (greater than 15 mm/h, p less than 0.005) and diminished serum albumin (less than 35 g/L, p less than 0.005), but not in those with an abnormal Crohn's disease activity index (CDAI less than 150) [22].
• Short report: erythrocyte membranes from a patient with congenital dyserythropoietic anaemia type I (CDA-I) show identical, although less pronounced, glycoconjugate abnormalities to those from patients with CDA-II (HEMPAS) [23].

Associations of CDAN1 with chemical compounds

• Thermodynamic aspects and biological profile of CDAN/DOPE and DC-Chol/DOPE lipoplexes [16].
• After remission (CDAI < or = 150) was attained with steroid therapy, patients were randomized to receive either omega-3 fatty acids (n = 70), placebo (n = 65), or diet (n = 69) [24].
• In CD patients an acute phase treatment with prednisolone was administered for 7 weeks reaching an improvement (CDAI < 200) in 7 patients [25].
• METHODS: 27 patients with CD in remission (CDAI <150) and 22 healthy controls ingested 3.7 MBq of 51Cr-EDTA, 20 kBq of 14C-mannitol and 5 g of unlabelled mannitol in 100 ml of distilled water [26].
• There were strong correlations between PDAI, MDGA, and PGA scores at all visits (R = 0.66-0.72; p < 0.001), whereas the CDAI and HBDAI correlated poorly with PDAI (R < 0.23) [27].

Analytical, diagnostic and therapeutic context of CDAN1

• Interestingly, CDAN/DOPE liposomes undergo substantial rehydration and protonation prior to complexation with pDNA, which is observed as two discrete exothermic signals during titration [16].
• The DNA complexation and condensation properties of two established cationic liposome formulations, CDAN/DOPE (50:50, m/m; Trojene) and DC-Chol/DOPE (60:40, m/m), were investigated by using a combination of isothermal titration calorimetry (ITC), circular dichroism (CD), photon correlation spectroscopy (PCS), and turbidity assays [16].
• METHODS: In a double-blind, multicentre trial, 75 patients in clinical remission (Crohn's Disease Activity Index, CDAI, < or = 150) were randomly assigned to receive placebo, budesonide 3 mg or budesonide 6 mg daily for 12 months [28].
• Western blotting revealed that codanin-1 synthesis was 65% less than the control [2].
• The index may be used in epidemiologic studies to accurately place patients into quartiles of disease severity which correspond to similar quartiles of the CDAI [29].

References