Extracellular calcium concentration and catecholamine release from adrenal medulla by acetylcholine and potassium

Zusammenfassung Nachweis an der isolierten perfundierten Rindernebenniere (5 ml/min), dass die Acetylcholin- oder Kalium-Stimulation der Catecholaminaus-schüttung bei fehlendem Calcium gleichmässig verhindert war. Ferner wurde die geringste Calciumkonzentration für den Ausschüttungsreiz bestimmt.

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Acknowledgment: This work was supported by an Indiana Elks Cancer Research Grant.     

Synthesis of N-(2-hydroxy-1-phenoxyacetyl) prolyproline

Ionophores consist of molecules which surround and carry positive metal ions and other ions through biological membranes. One classe of ionophores which we have been developing contains dipeptides which are encouraged to become part of a ring because of possible hydrogen bond formation between the 2-hydroxy on the phenyl group and carboxyl group (COOH) of the final amide proline. Formation of a ring should increase the complexation ability of the ionophore. We report that the synthesis of N-(2-hydroxyl-1-phenoxyacetyl) prolyproline(1), a novel ionophore is prepared from activated 2-acetoxy phenoxyacetic acid (3a) and the appropriate dipeptide ester using coupling methods such as dicyclohexyl carbodiimide with hydroxyben-ztriazole or carbonyl diimidazole. Yang Dingqiao: born in 1958, Associate professor     

Enhancement of barium- and cesium-induced adrenal catecholamine release by lidocaine

Summary Catecholamine release evoked from isolated perfused bovine adrenals by Ba⁺² or Cs⁺ is enhanced by lidocaine or by a calcium-free medium. The action of Cs⁺ therefore differs from that of K⁺ or Rb⁺ in adrenal medulla. Divalent and monovalent metallic cations of relatively large atomic weight like Ba⁺² and Cs⁺, probably penetrate the cell more easily than small highly charged ions and act intracellularly to cause adrenal catecholamine release. Local anesthetics and calcium-free media may allow greater influx of Ba⁺² and Cs⁺ into adrenomedullary cells.Acknowledgment. This work was supported by NIH, grant No. AM16153.     

Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia

Although five-year survival rates for childhood acute lymphoblastic leukemia (ALL) are now over 80% in most industrialized countries, not all children have benefited equally from this progress. Ethnic differences in survival after childhood ALL have been reported in many clinical studies, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians. The causes of ethnic differences remain uncertain, although both genetic and non-genetic factors are likely important. Interrogating genome-wide germline SNP genotypes in an unselected large cohort of children with ALL, we observed that the component of genomic variation that co-segregated with Native American ancestry was associated with risk of relapse (P = 0.0029) even after adjusting for known prognostic factors (P = 0.017). Ancestry-related differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy, indicating that modifications to therapy can mitigate the ancestry-related risk of relapse.