We have examined the sequences required in vivo to promote transcription of a cell cycle-regulated human H4 histone gene. Deletion mutants of the 5' flanking region were assayed in mouse cells or fused with the chloramphenicol acetyltransferase (CAT) gene for assay in HeLa cells. The functional limits of the regulatory sequences were shown to extend at least 6.5 kilobases (kb) upstream. Sequences sufficient for correctly initiated transcription were found in the 70 base pairs (bp) immediately 5' to the cap site. A proximal element located 200-400 bp upstream increased the level of transcription several times above the basal level, although not to maximal levels. Maximal levels of expression were achieved with 6.5 kb of 5' flanking sequence adjacent to the proximal promoter sequences or when a distal enhancer element with both position-and orientation-independent function was moved proximal to the promoter. Our results indicate that a series of 5' cis-acting sequences are functionally related to the fidelity and level of expression of this human H4 histone gene.The human histone genes encode a set of proteins essential for maintaining the integrity of eukaryotic chromosomal structure (1-4). The combined studies of several investigators have now established two basic facts: (i) most histone genes are expressed coordinately during the cell cycle in conjunction with DNA synthesis, and (ii) there are many different copies of the core and H1 histone genes being expressed concomitantly (5-8). This leads one to conclude that histone gene expression on a larger scale is coordinately controlled, but that at the level of the single gene there may be differences in the extent and timing of expression. Our previous results with H4 histone genes support this contention that not all human histone genes are expressed to the same degree during S phase (5). We and others have shown that the regulation of histone gene expression occurs at both the transcriptional and post-transcriptional levels. The two levels of regulation together serve to increase significantly the amount of histone messenger RNA during S phase (6-11). Taking these results into account, we have initiated in vivo studies to identify transcriptional regulatory sequences associated with a human H4 histone gene. The gene we have chosen to study has been previously shown to be one of the most highly expressed human H4 histone genes (5).Many studies have established that there are consensus sequences present in RNA polymerase II promoters that are necessary for expression (12)(13)(14). Sequence analysis of the F0108A H4 histone gene has demonstrated the presence of several such sequences in the 5' flanking region, including two "CAAT" boxes and a "TATA" box (15). In vitro transcription studies of this gene using whole-cell lysates have indicated that only the TATA box is necessary for correct transcript initiation (15).To establish in vivo the functional properties of 5' flanking sequences associated with the F0108 human H4 histone gene, we constructed a seri...
Unlinked autosomal microsatellites in six Jewish and two nonJewish populations were genotyped, and the relationships among these populations were explored. Based on considerations of clustering, pairwise population differentiation, and genetic distance, we found that the Libyan Jewish group retains genetic signatures distinguishable from those of the other populations, in agreement with some historical records on the relative isolation of this community. Our methods also identified evidence of some similarity between Ethiopian and Yemenite Jews, reflecting possible migration in the Red Sea region. We suggest that highresolution statistical methods that use individual multilocus genotypes may make it practical to distinguish related populations of extremely recent common ancestry.
Hypertriglyceridemia (hyperTG) is a common form of dyslipidemia and is frequently associated with premature coronary disease, and when severe, recurrent events of pancreatitis may occur. The management of hyperTG is generally medical (life style modification, medications). Plasma exchange (PE) has been reported to be useful in emergency situations particularly when acute pancreatitis results from extreme hyperTG. To our knowledge, there is only one report on long-term use of PE for hyperTG. We here report our results of long-term treatment of hyperTG in 6 patients with Frederickson Type V hyperlipidemia who had recurrent attacks of pancreatitis due to hyperTG refractory to medical therapy. PE was performed from one to eight times a month, mostly using a Cobe Spectra apparatus. In total, our center has performed a total of 1,593 PE sessions for hyperTG. There were no safety issues associated with PE for hyperTG other than occasional access problems (clotted fistula, IV access problems). Determination of plasma TG levels before and after PE demonstrated high efficiency of TG removal (42% to 58% reduction). There was marked clinical improvement in recurrent pancreatitis; patients had a major decrease in episodes (39% to 100%) while on regular PE, as long as they adhered to the treatment schedule. We conclude that long-term PE for hyperTG, while costly, is feasible and safe and may reduce recurrent attacks of pancreatitis.
Hunter disease in Israel occurs among Ashkenazi, Oriental, and Sephardic Jews and is by far more frequent than Hurler disease. None of the other mucopolysaccharidoses has been diagnosed in Ashkenazi Jews. The possibility of Hunter disease being a "Jewish" disease is discussed.
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