Molecular cause

The molecular causes of a number of heritable diseases of bone (eg, osteogenesis imperfecta) and of cartilage (eg, the chondrodystrophies) are being revealed by the application of recombinant DNA technology. 

Biebermann, H., Schoneberg, T., Krude, H., Gudermann, T, and Gruters, A. (2000) Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood. Arch. Surg. 385, 390-392. 

K. Glunde, C. Jie and Z. M. Bhujwalla, Molecular causes of the aberrant choline phospholipid metabolism in breast cancer. Cancer Res., 2004, 64, 4270-4276. 

Familial dysbetalipoproteinemia (type III) is characterized by the accumulation of chylomicron and VLDL remnants, which are enriched in cholesterol compared to their precursors. The primary molecular cause of familial dysbetalipoproteinemia (type III) is the homozygous presence of the apolipoprotein E2 (apoE2) isoform, which is associated with recessive inheritance of the disorder [62]. However, only 1 in 50 homozygotes for apoE2 will develop type III hyperlipoproteinemia, which is clinically characterized by palmar and tuberous xanthomas, arcus lipoides, and premature atherosclerosis of coronary, peripheral, and cerebral arteries. Precipitating factors include diabetes mellitus, renal disease, hemochromatosis, but also familial hypercholesterolemia. In addition, some rare mutations in the apoE gene have been found to cause dominant and more penetrant forms of type III hyperlipoproteinemia. 

Brunner et al. (1990) used the much simpler chlorine number and number of ortho chlorines to correlate KAW for PCBs, as well as connectivity indices. These correlations are primarily of interest for revealing the molecular causes of variations in KAW for this class of chemicals. They do not apply to other classes, but they do demonstrate the feasibility of producing fairly accurate correlations for a restricted class of compounds. 

Wood-Kaczmar A, Gandhi S, Woods NW. 2006. Understanding the molecular causes of Parkinson s disease. Trends Mol Med 12 521-528. 

As in previous chapters, the presentation remains restricted to kinetic principles and their applications in modeling. No attempt is made to review the intricacies of reactivities of monomers and their molecular causes or their effect on polymer structure and properties. For details of these, the reader is referred to excellent texts on the subject [G1-G12],... 

The ability to separate adsorbate-adsorbate from adsorbate-adsorbent contributions in simulations enables a clear identification of the underlying molecular causes of these features to be made. 

Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood. Arch Surg 385 390-392... 

The adrenal cortex plays a key role in regulating intermediary metabolism, fluid and electrolyte balance, and the response to stress. Molecular analyses of specific disorders resulting from either the diminished or enhanced produc-tion/action of corticosteroids have led to the identification of a number of genes that play key roles in adrenal function and corticosteroid action. These genes provide potential targets for novel therapies that may revolutionize our approaches to these rare adrenal diseases. In addition, understanding the molecular causes of these diseases has provided important insights into basic adrenal functions that may translate into improved therapy of more common disorders such as hypertension and obesity. 

Due to space restrictions this chapter will not cover in any detail the structure-based or docking methods which we have compared extensively with machine learning methods in the case of PXR. During the chapter we will highlight how our understanding of molecular causes of toxicity has allowed quantitative modeling, how various pharmaceutical companies actively use such computational models and their impact on drug discovery and toxicity-related attrition. 

Molecule-specific methods are concerned with the molecular or particle mass. The particle mass will double for a total dimerization, that is, there is a 100% change. Consequently, molecule-specific methods are much more sensitive than group-specific methods. However, molecule-specific methods only show changes when intermolecular association occurs, and they yield no information on the molecular causes of association. 

In order to establish the molecular causes of abnormal purine metabolism in various hyperuricemic patients we incubated the skin fibroblasts of the patient with different precursors and used our chromatographic system to establish how these precursors were utilized by the cell. The cells grown in tissue culture were incubated with various radio-... 

While the exact molecular causes of stress relaxation and creep are varied, they can be grouped into five general categories (2) ... 

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