The distribution of the Hb Constant Spring gene in Southeast Asian populations

Summary The distribution of the hemoglobin Constant Spring (Hb CS) gene in eight populations in Southeast Asia (including Assam) was determined using oligonucleotide hybridization. Hb CS was absent in two Assamese populations with a high prevalence of Hb E. The Hb CS gene frequency was 0.033 in northern Thailand and near 0.01 in central Thailand and Cambodia. High frequencies, between 0.05 and 0.06, were observed in northeastern Thailand. The present data and a similar study in Laotians suggest that the Lao-speaking populations of the Mekong River basin in northeastern Thailand and Laos have the highest frequencies of the Hb CS gene in Southeast Asia.     

Nicotinic Agonists Regulate α-Bungarotoxin Binding Sites of TE671 Human Medulloblastoma Cells

The TE671 human medulloblastoma cell line expresses a variety of characteristics of human neurons. Among these characteristics is the expression of membrane-bound high-affinity binding sites for alpha-bungarotoxin, which is a potent antagonist of functional nicotinic acetylcholine receptors on these cells. These toxin binding sites represent a class of nicotinic receptor isotypes present in mammalian brain. Treatment of TE671 cells during proliferative growth phase with nicotine or carbamylcholine, but not with muscarine or d-tubocurarine, induced up to a five-fold increase in the density of radiolabeled toxin binding sites in crude membrane fractions. This effect was blocked by co-incubation with the nicotinic antagonists d-tubocurarine and decamethonium, but not by mecamylamine or by muscarinic antagonists. Following a 10-13 h lag phase upon removal of agonist, recovery of the up-regulated sites to control values occurred within an additional 10-20 h. These studies indicate that the expression of functional nicotinic acetylcholine receptors on TE671 cells is subject to regulation by nicotinic agonists. Studies of the murine CNS have consistently indicated nicotine-induced up-regulation of nicotinic acetylcholine receptors, thereby supporting the identification of the toxin binding site on these cells as the functional nicotinic receptor. Although a mechanism for this effect is not apparent, nicotine-induced receptor blockade does not appear to be involved.     

DNA haplotypes and frameworks associated with the beta-globin gene in the Kachari population of Assam (India)

DNA haplotypes and frameworks associated with the beta-globin gene were determined in a Tibeto-Burman group, the Kachari, from Upper Assam, India, using restriction analysis at eight restriction sites. Of the total of 59 subjects, 26 were homozygous for HBB*A and 33 homozygous for HBB*E. Complete haplotype determination in 33 subjects revealed a conspicuous difference in haplotype distribution between HBB*A- and HBB*E-bearing chromosomes. The Southeast Asian HBB*E-associated haplotype -+- +- (27-2 in the present terminology) predominated on HBB*E chromosomes. The previously established beta-globin-associated frameworks 1, 2 and 3 were evenly distributed among the HBB*A chromosomes, whereas all HBB*E chromosomes had framework 2. These findings favor a common origin of the HBB*E gene in Southeast Asia and Assam.     

Alpha-thalassemia in northern Thailand. Frequency of deletional types characterized at the DNA level

The frequency of alpha-thalassemias in northern Thailand was estimated using DNA techniques. Among 106 healthy adult Thais from the Chiangmai area, 28 were shown to carry alpha-globin gene anomalies. There were 19 heterozygotes and 1 homozygote for alpha-thalassemia-2. One of the alpha-thalassemia-2 deletions was of the -alpha 4.2 type and the remaining 20 of the -alpha 3.7 type (subtype I). Deletions of both alpha-globin genes on one chromosome (alpha-thalassemia-1) of the Southeast Asian type were observed in 5 cases, and 3 alpha-globin gene triplications were identified. Compared with a previous report on alpha-thalassemia in northern Thailand which was based on the determination of hemoglobin Bart's in cord blood, the present DNA study reveals a similar frequency of alpha-thalassemia-2 but a considerably lower frequency of alpha-thalassemia-1.     

Distribution of adult lactase phenotypes in the Tuareg of Niger.

The adult lactase phenotype, lactose absorber or malabsorber, was determined using the lactose tolerance test with breath hydrogen assay in a group of Tuareg, a traditionally nomadic pastoralist population in the central Sahara. Out of a total of 118 subjects, 103 (87.3%) were lactose absorbers and 15 (12.7%) lactose malabsorbers. The frequency of the "lactase suppression gene" in this population sample was .357 (SD .043). The low frequency of lactase suppression in the Tuareg supports the hypothesis of natural selection in favor of the "lactase persistence gene" in milk-dependent nomadic pastoralist.     

Drug-protein interactions: binding of chlorpromazine to calmodulin, calmodulin fragments, and related calcium binding proteins

The quantitative binding of a phenothiazine drug to calmodulin, calmodulin fragments, and structurally related calcium binding proteins was measured under conditions of thermodynamic equilibrium by using a gel filtration method. Plant and animal calmodulins, troponin C, S100 alpha, and S100 beta bind chlorpromazine in a calcium-dependent manner with different stoichiometries and affinities for the drug. The interaction between calmodulin and chlorpromazine appears to be a complex, calcium-dependent phenomenon. Bovine brain calmodulin bound approximately 5 mol of drug per mol of protein with apparent half-maximal binding at 17 microM drug. Large fragments of calmodulin had limited ability to bind chlorpromazine. The largest fragment, containing residues 1-90, retained only 5% of the drug binding activity of the intact protein. A reinvestigation of the chlorpromazine inhibition of calmodulin stimulation of cyclic nucleotide phosphodiesterase further indicated a complex, multiple equilibrium among the reaction components and demonstrated that the order of addition of components to the reaction altered the drug concentration required for half-maximal inhibition of the activity over a 10-fold range. These results confirm previous observations using immobilized phenothiazines [Marshak, D.R., Watterson, D.M., & Van Eldik, L.J. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 6793-6797] that indicated a subclass of calcium-modulated proteins bound phenothiazines in a calcium-dependent manner, demonstrate that the interaction between phenothiazines and calmodulin is more complex than previously assumed, and suggest that extended regions of the calmodulin molecule capable of forming the appropriate conformation are required for specific, high-affinity, calcium-dependent drug binding activity.