Disease relevance of CELIAC2

• Celiac disease (CD) is a common chronic inflammatory disorder of the small intestine with a multifactorial aetiology [1].
• We have investigated DNA polymorphism of the class II alpha chain genes in HLA typed patients with insulin dependent diabetes mellitus (IDDM; n = 79), celiac disease (CD; n = 46), dermatitis herpetiformis (DH; n = 53), and controls (n = 86) [2].
• This study was designed to determine the prognostic significance of CD expression in axillary node-negative (ANN) breast cancer [3].
• Patients with CD-positive tumors developed significantly more often both soft tissue recurrences and visceral metastases (P = .0007) and had a significantly shorter disease-free survival (P < .0001) [3].
• The human colorectal tumor cell line, WiDr, was genetically modified to express either the CD gene (WiDr/CD) or the HSV-TK gene (WiDr/TK) [4].

Psychiatry related information on CELIAC2

• 0. Our results suggest that CD cleavage of tau could generate tau fragments with intact microtubule binding domains, which could have a role in the pathogenesis of paired helical filaments (PHFs) in Alzheimer's disease [5].
• It is also evident that the Chen PFMSE scale satisfies concurrent validity when compared with well-developed and tested instruments such as general self-efficacy ( GSE), perceived PFME benefits, and incontinence impact questionnaire-7 (IIQ-7) [6].
• The self-esteem of the children was measured by the global negative self-evaluation scale (GSE) [7].
• CONCLUSION: CD should be ruled out in the differential diagnosis of neurological dysfunction of unknown cause, including ataxia, epilepsy and dementia [8].

High impact information on CELIAC2

• Using a rapid assay for G- and F-actin in cell extracts, based on the inhibition of DNase I, we have found that neither short-nor long-term exposure of HEp-2 cells to CD produce net depolymerization of actin filaments [9].
• An increased frequency of a DX alpha genotype UU in all three diseases was found (IDDM 59%, DH 45%, CD 48%, compared to 21% in controls, P less than 0.001), which is not explained solely by the increased frequencies of DR3-DX alpha U [2].
• The developed protrusions, which remain relatively stable in the presence of CD, contain chiefly mono- or subribosomes, and occasionally other organelles normally resident in endoplasm; compact microfilament felt occupies their bases and extends into their proximal stalks [10].
• Zeiosis is prevented by agents that interfere with the contractile response to CD, such as inhibitors of energy metabolism or cyclic AMP [10].
• Macromarkers, such as latex spherules, migrate like the zeiotic knobs on the cell surfaces in the presence of CD [10].

Chemical compound and disease context of CELIAC2

• We investigated the efficacy of adenoviral (Ad5)-directed cytosine deaminase/5-fluorocytosine (CD/5-FC) enzyme/prodrug gene therapy to enhance selectively the tumoricidal action of ionizing radiation in human cancer xenografts derived from a human squamous carcinoma cell line (SQ-20B) [11].
• Tumor xenografts grown in hindlimbs of nude mice were transfected with an adenoviral vector (Ad.CMV.CD) containing the cytosine deaminase (CD) gene under the control of a cytomegalovirus (CMV) promoter [11].
• Estrogen greatly induces transcription of the CD gene in estrogen receptor (ER)-positive breast cancer cells [12].
• In this report, we transiently introduced a human CD promoter/chloramphenicol acetyltransferase reporter gene into human MCF-7 breast cancer cells to study the mechanisms by which the ER activates the promoter [12].
• Altogether these data suggest that: (a) the expression and the posttranslational fate of CD in HT-29 colon cancer cells are largely affected by the state of their enterocytic differentiation; and (b) in this cell line the acid-dependent mannose 6-phosphate receptor pathway is, at best, little involved in the trafficking of CD [13].

Biological context of CELIAC2

• In addition, extensive family studies have provided strong, reproducible evidence for a susceptibility locus on chromosome 5q (CELIAC2) [14].
• In contrast, CD alone was sufficient to produce changes in gamma-actin gene expression [15].
• For the 2F1 and c-myc genes, neither the GaMIg nor CD stimulus alone led to a prolonged increase in mRNA levels, whereas GaMIg plus CD allowed for continuous elevated expression of these genes [15].
• The IC50 (concentration of drug producing 50% inhibition of cell growth) for GCV was approximately 3.4 microM in WiDr/TK cells, while the IC50 for 5-FCyt was approximately 27 microM in WiDr/CD cells [4].
• The most significant prognostic information was obtained when CD expression (predicting metastatic activity) was combined with estimate of cell-proliferation rate (S-phase fraction) [3].

Anatomical context of CELIAC2

• Previously we demonstrated that stimulation of resting murine splenic B lymphocytes with goat anti-mouse immunoglobulin antibody (GaMIg) plus cytochalasin D (CD) led to DNA synthesis; GaMIg and CD added simultaneously, or GaMIg added before CD, induced this response (T. L. Rothstein, J. Immunol. 136:813-816, 1986) [15].
• An immunohistochemical method based on a new monoclonal antibody (1C11) with a distinct epitope specificity made it possible to study CD expression from archival paraffin-embedded specimens and to distinguish staining in tumor cells from the high-level expression found in tumor-infiltrating macrophages [3].
• Moreover, these modifications may lead to the amplification of gluten-specific T cell responses in the gut and consequently may be important for the development of CD [16].
• We demonstrate here that culture of human skin fibroblasts in RCG or in CD- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated monolayers resulted in the activation of an IL-1 autocrine feedback loop that was switched off by the naturally occurring IL-1 receptor antagonist (IL-1RA), a blocker of the common IL-1 receptor [17].
• Depolymerization of microtubules with colchicine (Colch) or actin microfilaments with cytochalasin D (CD) dramatically reduced the amount of caveolin-3 in buoyant (sucrose density) fractions of adult rat cardiac myocytes [18].

Associations of CELIAC2 with chemical compounds

• This augmentation, which was concentration and time dependent, was prevented by treatment with cycloheximide during exposure to CD [19].
• Cytochalasin D (CD) and monobromobimane (MB) enhanced agglutination and prevented the inhibitory action of ADP on bovine vWf-induced platelet agglutination [20].
• CD markedly inhibited the assembly of the cytoskeletal core as well as GPIIIa retention, whereas MB resulted in a large Triton-insoluble residue which contained GPIIIa [20].
• High-level CD expression was associated with large primary tumor size (P = .014), but not with histologic grade, estrogen and progesterone receptors, DNA index, or S-phase fraction, or with c-erbB-2 and p53 overexpression [3].
• This system uses the cytosine deaminase/5-fluorocytosine (CD/5-FCyt) enzyme/prodrug combination [4].

Analytical, diagnostic and therapeutic context of CELIAC2

• These results suggest that the CD/5-FC gene therapy approach is an effective radiosensitizing strategy and may lead to substantial improvement in local tumor control that would translate into improved cure rates and better survival [11].
• CONCLUSION: These results indicate that CD expression determined by immunohistochemistry is a powerful prognostic factor in ANN breast cancer [3].
• When tumor xenografts were composed of 100% of cells expressing either HSV-TK or CD, 100% tumor-free animals were observed after GCV or 5-FCyt treatment, respectively [4].
• Cell-attached and whole-cell recordings showed that activation of sodium channels was elicited within 1-3 min after the addition of 10-20 micrograms/ml CD to the bath extracellular solution or in the presence of 5 micrograms/ml CD in the intracellular pipette solution [21].
• In non-muscle (HEp-2) cell cultures, CD enhanced synthesis of beta and gamma-actin, but did not induce synthesis of alpha-actin, which is not normally present in these cells [22].

References