Role in diseases

Polymorphisms have been described for all (3-adrenergic receptors while initial studies, notably of the (3i-subtype, suggested that these might be predictors of diseases as well as of therapeutic responses, these results have more recently been questioned. Alterations in responsiveness may be limited to certain compounds and a causative role in diseases has not been or remains to be substantiated in larger trials. 

Jentsch TJ (2000) Neuronal KCNQ potassium channels physiology and role in disease. Nat Rev Neurosci 1 21-30... 

PARs are coupled to multiple G-proteins and mediate a number of well-defined cellular responses via classical second messenger and kinase pathways. PARs are differentially expressed in cells of the vasculature as well in the brain, lung, gastrointestinal tract, skin as well as other highly vascularised tissues and evidence suggests distinct physiological functions and roles in disease states [2]. 

Rye K-A et al Overview of plasma lipid transport. In Plasma Lipids and Their Role in Disease. Barter PJ, Rye K-A (editors). Harwood Academic Publishers, 1999. 

Table 12.2 Criteria for free radicals as a causative role in disease...

Activated T cells begin releasing cytokines including interleukin-2 (IL-2), interferon-y, (IFN-y), tumor necrosis factor (TNF-a), and others.4,13 Cytokine activity leads to a rapid proliferation and turnover of skin cells, triggering the inflammatory process and the development of psoriatic skin lesions.4,13,14 TNF-a may have a role in disease severity it upregulates endothelial and keratinocyte expression of ICAM-1,... 

Diet plays an important role in most of the chronic diseases that are the largest causes of morbidity and mortality in the developed world. In a reductionist approach, scientists have often made the role of individual nutrients in the maintenance of health the focus of their research. This approach, and in particular the discovery of essential nutrients and their roles in disease prevention, has been instrumental in the elimination of deficiency diseases in large parts of the world. However, nutrients are not consumed in isolation, but as components of whole foods and in an infinite number of combinations. In addition, foods contain a myriad of chemicals (or non-nutrients) which either serve no role in human metabolism or for which the role has not yet been elucidated. This introduces a significant level of complexity, which may be difficult to unravel. 

Safe and effective treatment for the entire spectrum of symptoms remains a critical unmet need within the patient population [5]. Alternative avenues of pharmacological intervention are being explored, including nondopaminergic central nervous system (CNS) targets that may play critical roles in disease amelioration. 

Modified amino acid solutions are designed for patients with altered protein requirements associated with hepatic encephalopathy, renal failure, and metabolic stress or trauma. However, these solutions are expensive and their role in disease-specific PN regimens is controversial. 

The epigenetic codes set by HATs are countered by the activity of the histone deacetylases. This delicate balance has been documented to maintain the cellular homeostasis. HDACs seem to play dual opposing roles in disease manifestation. Dysfunctioning of HDACs are involved in several cancers. In some cases HDACs... 

In the candidate-gene approach - the most frequently used approach adopted to identify the predisposing or causal genes in the complex and multigenic and multifactorial diseases - genes with a known or proposed function, with the potential to influence the disease phenot)q)e, are investigated for a direct role in disease. In a small number of cases of t)q)e 2 diabetes, candidate-gene studies have identified mutations in. 

In the family of the Gramineae, which includes some of man s most important crops, active lignification seems to be of special importance for induced resistance mechanisms (19,20). This may be correlated with the nearly complete absence of phytoalexins in this family (21). In spite of an intensive search for such infection-induced fungitoxic substances, no phytoalexins have been found in wheat to date (22). Nevertheless, induced lignification has been shown to play an important role in disease resistance of wheat against a variety of fungal pathogens (4) ... 

Fowler (2005) Homocysteine overview of biochemistry, molecular biology, and role in disease processes. Semin Vase Med 5 77-86... 

Coumarins also have a C6-C3 skeleton, but they possess an oxygen heterocycle as part of the C3-unit. There are numerous coumarins, many of which play a role in disease and pest resistance, as well as UV-tolerance. The coumarin umbelliferone (1.21) is popular in enzyme assays. Umbelliferone esters can be used as a substrate for non-specific esterase enzyme assays and in fluorescent immunoassays (Jacks and Kircher, 1967). In order to quantify the enzyme activity of the popular reporter gene P-glucuronidase (GUS), plant extracts can be incubated with 4-methylumbelliferyl P-D-glucuronide (4-MUG 1.22), which upon hydrolysis... 

Models of autoimmune diabetes in nonobese diabetic mice (NOD) mice, insulin-dependent diabetes, and experimental allergic encephalyomyelitis (EAE) were also used to evaluate naked pDNA therapy. In the latter models, a predominant Thl cytokine response is thought to play a role in disease symptoms and etiology. Treatment of these mouse models with a TH2 type cytokine, such as IL-10 or IL-4, has been found to shift the immune response and lessen the severity of disease. Therefore, the efficacy of pDNA delivery of a Th2 cytokine was explored in these specific models. 

Additional substantiating evidence that calcium channel auxiliary subunits might play pivotal roles in disease processes comes from the study of mouse models. Five murine diseases with similar phenotypes to Cav2.1 P/Q-type channel mutant-associated diseases have been linked to calcium channel auxiliary subunits (Tables 9-11). 

Because PMCA1 and 4 are expressed ubiquitously, they are often co-expressed in the same cell types and their roles in disease are studied in parallel. No spontaneous mutations of either gene have been identified in either mouse or human, so insight into the independent functions of these genes has come primarily from work on targeted null mutations generated in mice. 

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