Disease relevance of GMDS

• The human GDP-mannose 4,6-dehydratase polypeptide shares 61% identity with the enzyme from Escherichia coli, suggesting broad evolutionary conservation [1].
• GMDP for psoriasis [2].
• The released TNF-alpha was shown to prime melanoma cells, previously unable to respond to GMDP by increasing expression of melanoma-associated antigens, making them sensitive to GMDP treatment [3].
• Cloning and expression of Helicobacter pylori GDP-l-fucose synthesizing enzymes (GMD and GMER) in Saccharomyces cerevisiae [4].
• We used monoclonal antibody, generated against N-acetylglucosaminyl-beta1-4-N-acetylmuramyl-alanyl-d-isoglutamine (GMDP), and phage display libraries of random peptides to select for oligopeptides, that mimic GMDP in their biological activity [5].

High impact information on GMDS

• Our results suggest that in the fruit fly GDP-fucose, the donor for fucosyltransferase reactions, is formed exclusively via the de novo pathway from GDP-mannose through enzymatic reactions catalyzed by GDP-D-mannose 4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase/4-reductase (GMER, also known as FX in man) [6].
• GDP-d-mannose dehydratase (Gmd) converted GDP-d-mannose to GDP-6-deoxy-d-lyxo-4-hexulose, with NADP+ as cofactor [7].
• These results suggest that metabolites generated in this pathway may participate in the transcriptional regulation of the FX protein and possibly the GMD protein [8].
• We have cloned the cDNA encoding human GDP-mannose 4,6-dehydratase, the first enzyme in the pathway converting GDP-mannose to GDP-fucose [1].
• Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro [1].

Biological context of GMDS

• With the present recommendations on education and training in medical informatics the German Association for Medical Informatics, Biometry and Epidemiology (GMDS) proposes structure and contents of medical informatics curricula and courses [9].
• The results also suggest that the genomic structure encoding GMD in Lec13 cells likely has a defect different from a point mutation in the coding region [8].
• This enriched plasmid population was then screened using a human expressed sequence tag (EST AA065072) with sequence similarity to an Arabidopsis thaliana GMD cDNA [8].
• RDP has been especially valuable in providing accurate alignments for modeling active sites of proteins.RDP is part of the ToPLign system (GMD Toolbox for protein alignment) and can be accessed via the WWW independently or in concert with other ToPLign tools at http://cartan.gmd.de/ToPLign.html [10].
• OBJECTIVE AND DESIGN: The aim of the study was to evaluate the effects of GMDP on angiogenesis in vivo and as a modulator of human umbilical vein endothelial cell proliferation, cell surface antigen expression and cell adhesion in vitro [11].

Anatomical context of GMDS

• The message is expressed in all tissues and cell lines examined, and the cDNA complements Lec13, a Chinese Hamster Ovary cell line deficient in GDP-mannose 4,6-dehydratase activity [1].
• Cloning of GMD from patient and control lymphocytes ruled out any mutation affecting the amino acid GMD sequence and the purified recombinant proteins from both controls and the patient showed identical specific activities [12].
• One day after intervention, there was a strong increase of total leucocytes, monocytes and neutrophils in the groups receiving 25 or 50 mg GMDP [13].
• CONCLUSIONS: GMDP can modulate endothelial cell activity without the induction of angiogenesis in vivo which may have implications for its use as a therapeutic agent [11].
• In a double-blind placebo-controlled trial, cancer patients with an elevated activity of all five LDH isoensymes were randomized to receive either a GMDP solution or a placebo; 63 patients were evaluated every third day for the mean daily number of episodes of nausea or vomiting, changes in clinical status, cell blood count and blood chemistry [14].

Associations of GMDS with chemical compounds

• By contrast, the transcript encoding the FX protein, which forms GDP-L-fucose from the ketosugar intermediate produced by GMD, is present in increased amounts in the Lec13 cells [8].
• In the synthesis of GDP-6- deoxy-D-talose, GDP-D-mannose is first converted by GDP-mannose-4,6-dehydratase (GMD) to GDP-4-keto-6-deoxy-D-mannose and then reduced to GDP-6-deoxy-D-talose by GDP-6-deoxy-D-talose synthetase (GTS) [15].
• Results indicated that the GMD monitor, as currently manufactured, is suitable for shorter-term sampling (up to 24 h) of formaldehyde and acetaldehyde [16].
• The GMD sampler was tested for background contamination and aldehyde recoveries after 0, 1, and 7 d of storage [16].
• The GMD sampler contains a silica gel-impregnated cellulose pad coated with 2,4-dinitrophenylhydrazine (DNPH) hydrochloride [16].

Analytical, diagnostic and therapeutic context of GMDS

• Northern blot analyses indicate that the GMD transcript is absent in Lec13 cells, confirming the genetic deficiency of this locus in these cells [8].
• In addition to bioprocessing applications, GMD technology should benefit the emerging fields of cellular and gene therapy [17].
• No significant differences in post-vaccination haemagglutination inhibiting serum antibody titres were observed between the four groups, indicating that oral administration of GMDP together with influenza vaccination, does not lead to a higher vaccine efficacy [13].
• TREATMENT: GMDP [0.01-100 micrograms/ml] applied to cell cultures for 6-72 h and to the chick chorioallantoic membrane (CAM) for four days [11].
• DISCUSSION: More epidemiological studies about GMD in Puerto Rico need to be performed to better describe the prevalence of the condition in the island [18].

References