A high frequency (about 60%) of ret rearrangements in papillary thyroid carcinomas of children exposed to radioactive fallout in Belarus after the Chernobyl accident, has been reported by three recent studies Ito et al., 1994;Klugbauer et al., 1995). These studies suggested that the radiation exposure may be a direct inducer of activating rearrangements in the ret gene. In order to con®rm the postulated link between irradiation and the role of the ret protooncogene in thyroid tumorigenesis, we analysed for the presence of ret activating rearrangements using RT ± PCR, XL ± PCR, Southern blot and direct sequencing techniques, 39 human thyroid tumors (19 papillary carcinomas and 20 follicular adenomas), from patients who had received external radiation for benign or malignant conditions. As controls, we studied 39 spontaneous' tumors (20 papillary carcinomas and 19 follicular adenomas). Our data concerning the radiationassociated tumors, showed that: (1) the overall frequency of ret rearrangements was 84% in papillary carcinomas (16/19) and 45% (9/20) in follicular adenomas; (2) in contrast with the results obtained in the Chernobyl tumors, the most frequently observed chimeric gene was RET/PTC1 instead of the RET/PTC3 and (3) all the tumors were negative for RET/PTC2. In the`spontaneous' tumors, only the papillary carcinomas presented a ret rearrangement (15% : 3/20): 1 RET/PTC1, 1 RET/ PTC3 and 1 uncharacterized. In conclusion, our results con®rm the crucial role played by the ret proto-oncogene activating rearrangements in the development of radiation-associated thyroid tumors appearing after therapeutic or accidental ionizing irradiation, and show, for the ®rst time, the presence of RET/PTC genes in follicular adenomas appeared after external irradiation.

Thirty-seven thyroid autonomously hyperfunctioning adenomas were screened for mutations in the TSH receptor (TSHR), G alpha s (gsp), and ras genes. Polymerase chain reaction-amplified fragments of the TSHR C-terminal part (exon 10), the G alpha s (exons 8 and 9), and the three ras genes were obtained from the genomic DNA extracted from 37 tumors and their adjacent normal tissues and were studied by direct nucleotide sequencing and hybridization with synthetic probes. A point mutation in the third intracellular loop (codon 623) of the TSHR was found in 3 of 37 adenomas studied. This mutation codes for a change (Ala to Ser) in the TSHR structure and is somatic and heterozygotic. Constitutive activation of the TSHR was demonstrated by an increase in basal cAMP levels after transfection of Chinese hamster ovary cells with a mutated Ser623-TSHR complementary DNA. Nine gsp[00ae]MDRV[00af]- and one ras-activating mutations were also detected. No simultaneous alteration of the studied genes was present. Thus, in hyperfunctioning thyroid adenomas, our data suggest that a mutational activation of the TSHR and gsp genes may play a tumorigenic role through constitutive activation of the cAMP pathway.

Seven juvenile individuals of the Australian species Crocodylus johnstoni from the Frankfurt Zoological Park were ®lmed on high-speed video, at 250 ®elds s 71 , whilst freely moving at various speeds in a long corridor. The sequences of locomotion were analysed to determine the various space and time parameters to characterize limb kinematics. We found that the animals use diverse patterns of asymmetrical gait, revealing great¯exibility in limb co-ordination. In all these gaits, the forelimb strikes the ground ®rst, in the couple made by diagonally opposite fore-and hindlimbs. Among these gaits, rotary gallop offers probably a high level of manoeuvrability, whereas transverse gallop resulted in a higher level of stability. Speed increase is achieved by half-bound and bound, the latter being the only gait used at velocities > 2 m s 71 . Speed was increased mainly by increasing the stride length of the fore-and hindlimbs by simultaneously increasing both its components, the step and swing lengths. However, in bound, the step length of each forelimb increased more than the swing length, resulting in a stronger thrust action, whereas swing length increased more than step length for the hindlimb, causing the centre of mass to accelerate forwards during its ballistic phase. The asymmetrical gaits of crocodiles such as Crocodylus johnstoni are probably not functionally equivalent to the transitional asymmetrical gaits exhibited by lizards when building up into a bipedal run. These gaits are also not entirely equivalent to mammalian gaits, despite the use of vertical movements of the vertebral axis in these crocodiles, favouring an erect dynamic posture.

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