Analysis of transcriptional regulation by Myc and Max proteins

The biological significance of this increase in naevus counts for these children remains to be established. RM MacKie (1) University of Glasgow, Glasgow G12 8QQ. UK Treatment of gallbladder stones by lithotripsy cholecystectomy: cost effectiveness

and open

There are several common variants of the standard treatment for gallstone disease, open cholecystectomy, such as mini-incision cholecystectomy, and laparoscopic cholecystectomy. All variants share the same approach of removing the gallbladder. An alternative, non-invasive technique is extra-corporeal shock wave lithotripsy in which the stones are shattered by shock waves and the fragments passed out of the gallbladder, possibly with the help of adjuvant bile salts, leaving the gallbladder intact. The comparative effectiveness and costs of lithotripsy and cholecystectomy were unknown until now and we have therefore evaluated them in a randomised controlled trial. Substantial and significant improvements in biliary pain experience, and other common symptoms such as fatty food upset, and also in perceived health status were found with both treatments. Cholecystectomy was a little more cost-effective than lithotripsy in patients with large stone-bulk (over 4cm3 of gallstones), but possibly less cost-effective for patients with small stone bulk. However, the differences were not large, and it was concluded that to some extent, treatment choice could be guided by patient preference. Biologically, the most striking finding was that the improvements in health in the lithotripsy patients were almost immediate and not related to the disappearance of the stones. This suggests that it is not the presence of gallstones per se which gives rise to the symptoms. JP Nicholl(2) University of Sheffield. Sheffield 510 2RX. UK Analysis proteins

of transcriptional

regulation

by Myc and Max

The human c-Myc oncoprotein (Myc) has been shown to be a sequence-specific transcriptional activator whose DNA binding is dependent on dimerisation with its partner Max by using yeast as an in vivo model system. Hetero-dimerisation and DNA-binding require the basic/ helix-loop-helixlleucine zipper (bHLH-Z) domains of Myc and Max, while transactivation is mediated by a distinct amino-terminal domain of Myc. Max can also form homodimers which bind to the same DNA sequence as Myc/Max. However, Max homodimers fail to transactivate and antagonise MyclMax activity. Moreover, the Max HLH-Z domain has a higher affinity (I) EM/ (1992) 305, 799 (2) Lamer ( 1992) 340. 801

for the Myc HLH-Z domain than for itself, suggesting that the heterodimeric Myc/Max activator forms preferentially at equilibrium. These data are consistent with a dual function of Max as an essential partner and suppressor of Myc. The Myc protein is short-lived and its expression is dependent on the presence of growth factors. In contrast, Max has a relatively long half life and appears to be constitutively expressed in resting and cycling cells. Thus, in resting cells Max homodimers may function as inhibitors of proliferation, while upon cell activation the increase in c-Myc levels leads to the preferential formation of active c-Myc/max heterodimers. This mechanism may constitute a powerful switch controlling both entry into and exit from the cell cycle. H Land (3) Imperial Cancer Research Found. London WC2A 3PX. UK HIV-infected

transfusion

recipients

During a review of all cases of HIV infection acquired through blood transfusion in New South Wales, a group of six subjects, who were identified through a single donor were identified. Throughout follow-up (range 6.8 - IO.1 years after infection), five of the recipients and the donor remained clinically free of symptoms, with normal CD4 cell counts and no p24 antigenaemia. HIV was isolated from only one recipient and this isolate did not induce syncytia in vitro. The frequency of progression to AIDS or a CD4+ cell count of less than 0.50 x 109/L was significantly lower among these six subjects (l/6) than among 101 other HIV-infected transfusion recipients, for whom a similar period of followup was available (94/lOl; P < 0.0001). These findings suggest that this group were infected by a less virulent strain of HIV-I and that non-virulent strains of HIV-I may continue to be so in a new host following transmission. These results urge the identification of other similar groups in an effort to investigate the implicated viral strains. B Tindall(4) The University of New South Wales, Sydney, NSW 2010, Australia Pregnancy

and diabetic

relaxin concentrations

Maternal serum concentrations of relaxin, an insulin homologue produced both by the corpus luteum of pregnancy and by the fetoplacental unit. are highest in the first trimester and fall to ther lowest level in the third trimester. We show that maternal serum relaxin concentrations are significantly higher at each stage of preg-

(3) Nature (1992) 359. 423

(4) Lancer (1992) 340. 863