Mutations generally occur in the DNA encoding the intracellular part (exon 11), which acts as a tyrosine kinase to activate other enzymes. Mutations make c-KITfunction independent of activation by scf, leading to a high cell division rate and possibly genomic instability. Additional mutations are likely "required" for a cell with a c-KIT mutation to develop into a GIST, but the c-KIT mutation is probably the first step of this process. Mutations in the exons 11, 9 and rarely 13 and 17 of the c-KIT gene are known to occur in GIST. The tyrosine kinase function of c-KIT is important in the medical therapy for GISTs, as described below. KIT-D816V point mutations in c-KIT exon 17 are responsible for resistance to targeted therapy drugs like imatinib mesylate, a tyrosine kinase inhibitor. KIT-p.D419del (exon 8) — A subset of gastrointestinal stromal tumors previously regarded as wild-type tumors carries somatic activating mutations in KIT exon 8 (p.D419del). PDGFRA mutations
Most GIST cells with wildtype (i.e. not mutated) c-KIT instead have a mutation in another gene, PDGFR-α (platelet-derived growth factor receptor alpha), which is a related tyrosine kinase. Mutations in c-KIT and PDGFrA are mutually exclusive [4][5]. Wild-type tumors
Lesser numbers of GISTs appear to be associated with neither c-KIT nor PDGFR-α abnormalities. : 1062  About 10-15% of gastrointestinal stromal tumors (GISTs) carry wild-type sequences in all hot spots of KIT and platelet-derived growth factor receptor alpha (PDGFRA) (wt-GISTs).
For these procedures, the surgical team will bypass the heart with a heart-lung machine and inject potassium chloride into the heart muscle to stop the heartbeat. Side effects
Side effects can include gastrointestinal discomfort, including nausea and vomiting, diarrhea, and bleeding of the digestive tract. Overdoses cause hyperkalemia, which can lead to paresthesia, cardiac conduction blocks, fibrillation, arrhythmias, and sclerosis.Because of the risk of small-bowel lesions, the US FDA requires some potassium salts containing more than 99 mg (about 1.3 mEq) to be labeled with a warning, while recommending an adult daily intake of 4700 mg (about 63 mEq). History
Slow-K is a 1950s development where the medicine is formulated to enter the bloodstream at delayed intervals. It was first only prescribed to British military forces to balance their diets while serving in Korea. Society
Brand names
Brand names include K-Dur, Klor-Con, Micro-K, Slow-K, Sando-K, and Kaon Cl, most of which are extended release medicine by mouth. Lethal injection
Potassium chloride is used in lethal injection as the third of a three-drug combination. KCl is also sometimes used in fetal intracardiac injections in second- and third-trimester induced abortions. Jack Kevorkians thanatron machine injected a lethal dose of potassium chloride into the patient, which caused the heart to stop functioning, after a sodium thiopental-induced coma was achieved.Cardiac arrest induced by potassium has been used in political assassinations in Iran, by injection or by inserting a potassium suppository into the victims rectum. References
External links
"Potassium chloride". Drug Information Portal. U.S. National Library of Medicine.