Bonding in Functionalized Aziridines: Nitrogen-15 and Carbon-13 Studies

Two isomeric pairs of cis- and trans-1-cyclohexyl-2-phenyl-3-benzoylaziridines have been synthesized: (1) with a nitrogen-15 labelled nitrogen, and (2) with carbon-13 labelled ring carbons. The carbon-13 to X (where X=nitrogen-15, carbon-13 or hydrogen-I) spin-spin coupling constants were measured and interpreted in terms of stereoelectronic effects. X-ray crystallographic data (earlier determined for cisand trans-1-cyclohexyl-2-phenyl-3-(p-toluyl)aziridines)1 appear in good agreement with the NMR data. Bonding is discussed for the three-ring itself (NMR studies) and for its substituents (X-ray studies). It is concluded that stereochemical interaction of the Van der Waals type is an important determinant of aziridine bond length. Three-ring to carbonyl hyperconjugation is correlated with stereoelectronic interactions in the trans isomer

Dosimetric evaluation and radioimmunotherapy of anti-tumour multivalent Fab́ fragments

We have been investigating the use of cross-linked divalent (DFM) and trivalent (TFM) versions of the anti-carcinoembryonic antigen (CEA) monoclonal antibody A5B7 as possible alternatives to the parent forms (IgG and F(ab́)2) which have been used previously in clinical radioimmunotherapy (RIT) studies in colorectal carcinoma. Comparative biodistribution studies of similar sized DFM and F(ab́)2 and TFM and IgG, radiolabelled with both 131I and 90Y have been described previously using the human colorectal tumour LS174T nude mouse xenograft model (Casey et al (1996) Br J Cancer 74: 1397–1405). In this study quantitative estimates of radiation distribution and RIT in the xenograft model provided more insight into selecting the most suitable combination for future RIT. Radiation doses were significantly higher in all tissues when antibodies were labelled with 90Y. Major contributing organs were the kidneys, liver and spleen. The extremely high absorbed dose to the kidneys on injection of 90Y-labelled DFM and F(ab́)2 as a result of accumulation of the radiometal would result in extremely high toxicity. These combinations are clearly unsuitable for RIT. Cumulative dose of 90Y-TFM to the kidney was 3 times lower than the divalent forms but still twice as high as for 90Y-IgG. TFM clears faster from the blood than IgG, producing higher tumour to blood ratios. Therefore when considering only the tumour to blood ratios of the total absorbed dose, the data suggests that TFM would be the most suitable candidate. However, when corrected for equitoxic blood levels, doses to normal tissues for TFM were approximately twice the level of IgG, producing a two-fold increase in the overall tumour to normal tissue ratio. In addition RIT revealed that for a similar level of toxicity and half the administered activity, 90Y-IgG produced a greater therapeutic response. This suggests that the most promising A5B7 antibody form with the radionuclide 90Y may be IgG. Dosimetry analysis revealed that the tumour to normal tissue ratios were greater for all 131I-labelled antibodies. This suggests that 131I may be a more suitable radionuclide for RIT, in terms of lower toxicity to normal tissues. The highest tumour to blood dose and tumour to normal tissue ratio at equitoxic blood levels was 131I-labelled DFM, suggesting that 131I-DFM may be best combination of antibody and radionuclide for A5B7. The dosimetry estimates were in agreement with RIT results in that twice the activity of 131I-DFM must be administered to produce a similar therapeutic effect as 131I-TFM. The toxicity in this therapy experiment was minimal and further experiments at higher doses are required to observe if there would be any advantage of a higher initial dose rate for 131I-DFM. © 1999 Cancer Research Campaig

Diets of the Sympatric Pacific Sheath-Tailed Bat (Emballonura semicaudata rotensis) and Mariana Swiftlet (Aerodramus bartschi) on Aguiguan, Mariana Islands

v. ill. 23 cm.Also available through BioOne: http://www.bioone.org/doi/abs/10.2984/65.3.301QuarterlyThe Pacific sheath-tailed bat (Emballonura semicaudata rotensis) and Mariana swiftlet (Aerodramus bartschi ) are two rare insectivorous taxa restricted to the southern Mariana Islands in western Micronesia. It is believed that populations of both have dwindled because of impacts to their food resources. However, there is little information on the food habits of A. bartschi and none exists for E. s. rotensis. In an effort to better understand the habits of both, we investigated their diets using guano analysis. Guano was collected from two roosts in caves during a 2-week period in June and July at the onset of the rainy season. Important orders of insects consumed (percentage volume) by bats roosting at one cave included hymenopterans (64%), coleopterans (10%), lepidopterans (8%), isopterans (8%), and psocopterans (5%), whereas those at a second cave included lepidopterans (45%), hymenopterans (41%), coleopterans (10%), and isopterans (5%). Swiftlets, which roosted in only one of the caves, fed mostly on hymenopterans (88%) and hemipterans (6%). Significant differences existed between the two taxa in several insect orders eaten, with E. s. rotensis consuming more lepidopterans and coleopterans and A. bartschi taking more hymenopterans and hemipterans. Within Hymenoptera, bats fed more on ichneumoideans, whereas swiftlets ate more formicid alates and chalicidoideans. This new information on the feeding habits of E. s. rotensis and A. bartschi provides insight on the complexity of their diets during June and July, and serves as baseline information for future studies and management of their habitat

Genetic diversity, population structure, and historical demography of a highly vagile and human‐impacted seabird in the Pacific Ocean: The red‐tailed tropicbird, Phaethon rubricauda

Many seabird breeding colonies have recovered from heavy anthropogenic disturbance after conservation actions. The widely distributed red-tailed tropicbird, Phaethon rubricauda, was used as a model species to assess potential anthropogenic impacts on the genetic diversity of breeding colonies in the Pacific Ocean. Cytochrome c oxidase subunit I and control region sequences analyses were conducted across the range of the species in the Pacific Ocean. The study sites were at islands without human-related disturbance (non-impacted islands) and with human-related disturbance (impacted islands). We hypothesized that (i) breeding colonies of the red-tailed tropicbird on impacted islands have lower genetic diversity compared with colonies on non-impacted islands, and (ii) breeding colonies of the red-tailed tropicbird show significant fine and broad-scale genetic structure across the Pacific Ocean. Bayesian skyline analyses were conducted to infer past changes in population sizes. Genetic diversity was similar between impacted and non-impacted islands. There was significant broad-scale genetic structure among colonies separated by over 6,000 km, but a lack of significant fine-scale genetic structure within Australasia and Hawai'i, although a significant level of differentiation was found within Chile with ΦST analyses. Skyline analyses showed that effective population sizes remained relatively constant through time, but experienced either a slight decrease or the end of an expansion event through the last 1,000 years. These changes may be related to the arrival of humans on Pacific islands. Impacted islands may have received immigrants from other relatively close islands, buffering the loss of genetic diversity. However, it is also possible that colonies have retained ancestral variation or that a large effective population size coupled with a long generation time (13 years) has prevented the loss of genetic diversity in human-impacted islands. Future research using higher-resolution markers is needed to resolve the population genetic structure of the red-tailed tropicbird in an ecological time-scale