Disease relevance of Alpk3

• In an uncontrolled clinical trial the effects of repeated administration of the F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNF alpha)-antibody (MAK 195F) on cytokine levels and the cardiovascular system were studied in 20 patients with severe sepsis [1].
• The animals were given weekly injections of N,N'-dimethylhydrazine (DMH, 10 mg/kg body weight) for the initial 10 weeks to induce colon carcinogenesis, and then fed on diet with or without 5% MAK for 10 weeks [2].

High impact information on Alpk3

• These data show that function of MAK is not essential for spermatogenesis and male fertility [3].
• A member of the mitogen-activated protein kinase superfamily, MAK, has been proposed to have an important role in spermatogenesis, since Mak gene expression is highly restricted to testicular germ cells [3].
• M-CK/AK1 (MAK=/=) mutant skeletal muscle displayed aberrant ATP/ADP, ADP/AMP and ATP/GTP ratios, reduced intracellular phosphotransfer communication, and increased ATP supply capacity as assessed by 18O labeling of [Pi] and [ATP] [4].
• These results suggest that MAK=/= muscles are energetically less efficient than wild-type muscles, but an apparent compensatory redistribution of high-energy phosphoryl flux through glycolytic and guanylate phosphotransfer pathways limited the overall energetic deficit [4].
• Permanent P19CL6 cell lines overexpressing Midori more efficiently differentiated into cardiomyocytes than did parental cells, whereas those overexpressing the antisense Midori less efficiently differentiated [5].

Biological context of Alpk3

• The phenotypes and the antitumoral potentiality of MAK cells were documented [6].

Anatomical context of Alpk3

• Northern blot analysis revealed that expression of Midori was restricted to the fetal and adult heart and adult skeletal muscle in mice [5].
• In whole mount in situ hybridization, Midori was expressed in cardiac crescent and developing heart but not in somites [5].
• When the MAK RNAs are isolated by hybrid selection and translated in a cell-free system, one polypeptide of 42,000 daltons is obtained [7].
• Hormones produced by or controlled by the pituitary gland do not appear to be involved in the regulation of MAK RNA levels [7].
• Levels of MAK RNA detected in submaxillary gland, heart, brain, muscle, and testes are unaffected by testosterone treatment [7].

Associations of Alpk3 with chemical compounds

• The uninduced level of MAK mRNA in female kidneys is half of that exhibited by males and is increased 8-fold by testosterone [7].
• Androgen regulation of MAK mRNAs in mouse kidney [7].
• The first disturbances scored were only visible as retardation in the offspring, and occurred after exposure to concentrations of halothane 200-fold (1000 ppm) the MAK-value [8].

Analytical, diagnostic and therapeutic context of Alpk3

• Apparent serum monospecificity was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing gels transblotted to nylon membranes and overlayed with purified MAK 89 antibody and radioiodinated Protein A. The affinity of the antibody is high [dissociation constant (Kd) = 2.6 X 10(-11) M] [9].
• These MAK cells (10(8) to 10(9] were injected in cancer patients in pilot clinical trials and were well tolerated [10].
• MAK treatment is technically feasible, clinically safe and presents several advantages compared to other immunotherapies [10].
• MAK (5% group) significantly prolonged animal survival as compared with basal diet group (control group) after 7 Gy of X-ray irradiation at a dose rate of 2 Gy min(-1) [11].

References