Disease relevance of DYM

• Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC) are similar, rare autosomal recessive osteochondrodysplasias [1].
• Dyggve-Melchior-Clausen syndrome (DMC) is an autosomal recessive condition characterised by short trunk dwarfism, scoliosis, microcephaly, coarse facies, mental retardation, and characteristic radiological features [2].
• In a carotid arterial-injury mouse model, p16 deficiency results in an enhanced SMC proliferation underlying intimal hyperplasia [3].
• Cytological and biochemical data indicate that the DMC syndrome is not a mucopolysaccharidosis [4].
• These data show that in vitro and in vivo exposure to hypoxia induces, via a transcriptional mechanism, 5-HTT expression in PA-SMCs, and that this effect contributes to the stimulatory action of 5-HT on PA-SMC proliferation [5].

Psychiatry related information on DYM

• However, patients with DMC exhibit significant developmental delay and mental retardation, the major features that distinguish the two conditions [1].
• Distinct patterns of Fos distribution were obtained following the freezing and escape reactions induced by MT injections of SMC and BIC, respectively [6].

High impact information on DYM

• The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair [7].
• SMC proteins are involved in chromosome condensation, sister-chromatid cohesion, sex-chromosome dosage compensation, genetic recombination and DNA repair [8].
• PPARalpha is a nuclear receptor controlling lipid metabolism and inflammation, but its role in the regulation of SMC growth remains to be established [3].
• TIMP-3 overexpression induced DNA synthesis, and promoted SMC death by apoptosis, a phenotype reproduced by adding TIMP-3 to uninfected cells, but not by a synthetic MMP inhibitor [9].
• We propose that Rad50, an SMC-like protein, promotes the use of the sister chromatid as the template for homologous recombinational repair [10].

Chemical compound and disease context of DYM

• The persistence of host-type hematopoiesis (SMC) was significantly related to a lower age of the recipient, the type of conditioning regimen, a lower total body irradiation dose, T-cell depletion of the bone marrow graft, and the use of cyclosporine A for acute graft-versus-host disease prophylaxis [11].
• These thrombi may stimulate SMC and promote the development of intimal hyperplasia and luminal narrowing [12].
• Cytological and biochemical data, notably a normal sulfate incorporation into acid mucopolysaccharides of cultured fibroblasts, indicate that the Dyggve-Melchior-Clausen syndrome is not a mucopolysaccharidosis as has been previously suggested [13].
• Only ALS patients (no controls) reacted with the visna/CNTF peptide SMC- and HSRVbcl-1/amyloid(740-751) peptide EGP-. Testing a total of 245 sera from 125 patients, three reproducible reactivities (two ALS, one OND) were observed both with and without glutaraldehyde linkage [14].
• Nitric oxide (NO) is involved in the regulation of SMC proliferation during intimal hyperplasia as has been shown by the inhibitory effect on intimal hyperplasia of adenovirus-mediated ceNOS overexpression in injured arteries in pig [15].

Biological context of DYM

• Linkage studies localized the SMC and DMC disease genes to chromosome 18q12-21.1, providing evidence suggesting that they are allelic disorders [1].
• The affected individuals in two consanguinous DMC families were homozygous for a stop codon mutation and a frameshift mutation, respectively, demonstrating that DMC represents the FLJ90130-null phenotype [1].
• Sequence analysis of the coding exons of the FLJ90130 gene, a highly evolutionarily conserved gene within the recombination interval defined in the linkage study, identified mutations in SMC and DMC patients [1].
• The radiographic features and cartilage histology in DMC and SMC are identical [1].
• Most mutations identified in DMC predict a loss of function, while those identified in SMC are mainly missense mutations, presumably associated with residual DYM activity and a less severe phenotype [16].

Anatomical context of DYM

• The DMC gene transcript is widely distributed but appears abundant in chondrocytes and fetal brain [17].
• Electron microscopy of chondrocytes have shown widened cisternae of rough endoplasmic reticulum and biochemical analyses have shown accumulation of glucosaminoglycan in cartilage, but the pathogenesis of DMC remains unexplained [2].
• BACKGROUND:Smooth muscle cell (SMC) replication plays a central role in the pathogenesis of transplant arteriosclerosis [18].
• An interaction between the two principal populations of mesodermal cells in the sea urchin embryo, primary and secondary mesenchyme cells (PMCs and SMCs, respectively), regulates SMC fates and the process of skeletogenesis [19].
• However, in several passaged VSMC lines (i.e. bovine aortic SMC, human aortic SMC, and A7r5 cells), PKG protein expression was not suppressed by cytokines or NO. sGC was highly expressed in non-passaged bovine aortic SMC but not in passaged cell lines [20].

Associations of DYM with chemical compounds

• In vivo expression of 5-HTT by PA-SMC may play a key role in serotonin-mediated pulmonary vascular remodeling [5].
• Celecoxib at both doses and DMC at 100 mg/kg had marginal impacts [21].
• We now demonstrate that mildly oxidized LDL generated by incubation with oxygen radical-producing xanthine/xanthine oxidase (X/XO) induces apoptosis in primary cultures of human coronary endothelial and SMC, as determined by TUNEL technique, DNA laddering, and FACS analysis [22].
• DNA synthesis and cholesterol synthesis by Hep G2 cells were inhibited by Pc SMC-conditioned medium [23].
• These results suggest that the chemotactic gradient by IL-8 is established between arterial intima and media in response to high glucose levels in diabetic patients, and that it may be one of the key factors for SMC migration to the intima leading to diabetic macroangiopathy [24].

Other interactions of DYM

• Even some tripeptides, such as EYE, DYM, TYS and KYE, were recognized by HPK40, while none of the tested dipeptides was recognized as substrate [25].
• Exclusion of the dymeclin and PAPSS2 genes in a novel form of spondyloepimetaphyseal dysplasia and mental retardation [26].
• It had been suggested that Dyggve-Melchior-Clausen syndrome may be due to the deficiency of a specific sulfatase and/or a protease involved in proteoglycan degradation [27].
• Abnormal serum alpha 2-macroglobulin in Dyggve-Melchior-Clausen syndrome [28].

Analytical, diagnostic and therapeutic context of DYM

• However, based on the higher risk of relapse, patients with no contraindications for SMC should not receive RIC outside of prospective randomized trials, which are needed to establish the position of RIC-based transplantation in the treatment of patients with MDS [29].
• Analysis of the tumor samples indicates that a differential reduction in the phospho-Akt/Akt ratio was noted in celecoxib- and DMC-treated groups vis-à-vis the control group [21].
• However, a correlation exists between the in vitro potency of DMC and its ability at 200 mg/kg to inhibit xenograft tumor growth through the inhibition of Akt activation [21].
• RESULTS: Use of the urgent care/emergency room and hospitalizations during the intervention year and the year prior were available for 331 patients who completed the DMCP intervention [30].
• Polymerase chain reaction (PCR) amplification of the highly polymorphic human androgen receptor gene (HUMARA) was performed on the DNA extracted from the paraffin-embedded lesional tissue microdissected to sample the admixed smooth muscle and blood vessel component (SMC/BV) and the adipose tissue component [31].

References