Familial occurrence of Wilms'' tumor: nephroblastoma in one of monozygous twins and in another sibling.

We report the occurrence of pathologically documented Wilm's tumor in a 24-month-old male twin and just 9 months later in his 12-month-old male sibling. We considered the twins to be monozygotic because of their phenotypic similarities, the probability computed from analysis of blood groups, and the comparison of their dermatoglphics. There were no other persons in the kindred with either tumor or associated malformations, and the parents were not consanguineous. Because of the frequency of Wilm's tumor, the few instances of demonstrated occurrence in siblings seem insufficient to postulate monogenic determination. Concordance in monozygotic twins has simply not been proven. The monozygotic unaffected twin of our first patient has remained without evidence of tumor to 5 years, and, as long as he remains so, he appears to represent an exception to the hypothesis of the mutagenic origin of this childhood tumor.     

Carbachol stimulation of triacylglycerol lipase activity in pancreatic acinar cells.

Carbachol (CCh) reduced the levels of [3H]arachidonic acid in triacylglycerol (TG) of pancreatic acinar cells. In cells prelabeled with [14C]glycerol, CCh reduced [14C]TG and increased [14C]diacylglycerol levels. Using [3H]triolein as exogenous substrate, CCh enhanced TG lipase activity 3-fold in a particulate fraction derived from intact acinar cells. These results portray a mechanism for generating diacylglycerol and arachidonic acid in exocrine pancreas involving agonist stimulation of TG hydrolysis.     

C. elegans and H. sapiens mRNAs with edited 3' UTRs are present on polysomes

Adenosine deaminases that act on RNA (ADARs) are editing enzymes that convert adenosine to inosine in double-stranded RNA (dsRNA). ADARs sometimes target codons so that a single mRNA yields multiple protein isoforms. However, ADARs most often target noncoding regions of mRNAs, such as untranslated regions (UTRs). To understand the function of extensive double-stranded 3′ UTR structures, and the inosines within them, we monitored the fate of reporter and endogenous mRNAs that include structured 3′ UTRs in wild-type Caenorhabditis elegans and in strains with mutations in the ADAR genes. In general, we saw little effect of editing on stability or translatability of mRNA, although in one case an ADR-1 dependent effect was observed. Importantly, whereas previous studies indicate that inosine-containing RNAs are retained in the nucleus, we show that both C. elegans and Homo sapiens mRNAs with edited, structured 3′ UTRs are present on translating ribosomes.     

Dissecting functional similarities of ribosome-associated chaperones from Saccharomyces cerevisiae and Escherichia coli

Ribosome-tethered chaperones that interact with nascent polypeptide chains have been identified in both prokaryotic and eukaryotic systems. However, these ribosome-associated chaperones share no sequence similarity: bacterial trigger factors (TF) form an independent protein family while the yeast machinery is Hsp70-based. The absence of any component of the yeast machinery results in slow growth at low temperatures and sensitivity to aminoglycoside protein synthesis inhibitors. After establishing that yeast ribosomal protein Rpl25 is able to recruit TF to ribosomes when expressed in place of its Escherichia coli homologue L23, the ribosomal TF tether, we tested whether such divergent ribosome-associated chaperones are functionally interchangeable. E. coli TF was expressed in yeast cells that lacked the endogenous ribosome-bound machinery. TF associated with yeast ribosomes, cross-linked to yeast nascent polypeptides and partially complemented the aminoglycoside sensitivity, demonstrating that ribosome-associated chaperones from divergent organisms share common functions, despite their lack of sequence similarity.     

Induction of telomerase activity during development of human mast cells from peripheral blood CD34+ cells: comparisons with tumor mast-cell lines

To further characterize the development of mast cells from human hemopoietic pluripotent cells we have investigated the expression of telomerase activity in cultured human peripheral blood CD34+ cells, and CD34+ /CD117+ /CD13+ progenitor mast cells selected therefrom, with the idea that induction of telomerase is associated with clonal expansion of CD34+ /CD117+ /CD13+ cells. A rapid increase in telomerase activity preceded proliferation of both populations of cells in the presence of stem cell factor and either IL-3 or IL-6. The induction was transient, and telomerase activity declined to basal levels well before the appearance of mature mast cells. Studies with pharmacologic inhibitors suggested that this induction was initially dependent on the p38 mitogen-activated protein kinase and phosphatidylinositol 3'-kinase, but once cell replication was underway telomerase activity, but not cell replication, became resistant to the effects of inhibitors. Tumor mast cell lines, in contrast, expressed persistently high telomerase activity throughout the cell cycle, and this expression was unaffected by inhibitors of all known signaling pathways in mast cells even when cell proliferation was blocked for extended periods. These results suggest that the transient induction of telomerase activity in human progenitor mast cells was initially dependent on growth factor-mediated signals, whereas maintenance of high activity in tumor mast cell lines was not dependent on intracellular signals or cell replication.