Stimulation of mitogenic pathways through kinase-impaired mutants of the epidermal growth factor receptor.

Two residues have been shown to be critical for the kinase activity of the receptor for epidermal growth factor (EGF): lysine-721, which functions in the binding of ATP by correctly positioning the gamma-phosphate for phosphoryl transfer, and aspartate-813, which functions as the catalytic base of the kinase. Mutation of either of these two residues has been shown to disrupt kinase activity of the receptor. However, studies performed in different laboratories had suggested that while EGF receptors mutated at lysine-721 are unable to stimulate significant increases of [(3)H]thymidine incorporation into DNA in response to EGF treatment, cells expressing EGF receptors mutated at aspartate-813 do stimulate significant incorporation of [(3)H]thymidine into DNA in response to EGF. In the present study, EGF receptors mutated at lysine-721 or aspartate-813 (K721R and D813A, respectively), as well as wild-type EGF receptors, were expressed in the same cellular background, Chinese hamster ovary cells, and side-by-side experiments were performed to investigate possible signaling-related differences. Our results indicate that while there are measurable differences in the abilities of the two mutant receptors to stimulate [(3)H]thymidine incorporation between 20 and 24 h after addition of EGF, these differences cannot be correlated with significant differences in EGF-stimulated tyrosine phosphorylation of mutant EGF receptor and endogenous ErbB2, the extent of receptor internalization, EGF-stimulated ion uptake, stimulation of SHC activity, or receptor association with Grb2. Flow cytometric data suggest that populations of cells expressing either kinase-impaired mutant EGF receptor progress similarly into S phase in response to addition of EGF. These observations suggest that D813A and K721R retain similar ability to stimulate mitogenic signaling events through transactivation of ErbB2 with only subtle temporal differences, and they emphasize the importance of expressing mutant receptors in an identical cellular context to make valid comparisons of functions.

Thanaka (Limonia acidissima) and deet (di-methyl benzamide) mixture as a mosquito repellent for use by Karen women.

The prevention and treatment of drug-resistant malaria is becoming increasingly difficult. On the Thai-Myanmar border multi-drug resistant strains of falciparum malaria are increasing and, because the malaria vector Anopheles bite outdoors during early evening, insecticide house-spraying or impregnated bednets provide only limited protection. Therefore, the protective efficacy of repellent formulations containing di-methyl benzamide (deet) and permethrin against local vectors was estimated, when applied to the skin, and their acceptability amongst pregnant Karen women who are at relatively high risk from malaria was assessed. Human landing catches of mosquitoes showed that almost complete protection was achieved using different formulations of 20% deet and 0.5% permethrin for up to 6 h. All-night collections from human subjects indicated that this repellent combination reduced exposure to malaria parasites by at least 65 and 85% for those transmitted by Anopheles minimus and An. maculatus, respectively, the two principal vectors in this area. Pregnant women in the camps preferred repellents which were mixed with 'thanaka', a root paste made from pulp of the wood apple tree, Limonia acidissima, used locally as a cosmetic. Apart from a temporary warming sensation where repellent thanaka was applied to the skin, the repellents were well tolerated. An intervention trial is currently in progress to determine whether deet mixed with thanaka can protect pregnant women against malaria in this part of the world. Bioassays using a laboratory strain of Aedes aegypti demonstrated that thanaka is itself slightly repellent at high dosages and the mixture with deet provides protection for over 10 h. This treatment would therefore also provide some personal protection against dengue, which is increasing locally, transmitted by Ae. aegypti and Ae. albopictus biting during the daytime.

Centrorhynchus aluconis (Acanthocephala) and other helminth species in tawny owls (Strix aluco) in Great Britain.

Observations on the distribution of Centrorhynchus aluconis (Acanthocephala) and 6 other species of helminths in the definitive host Strix aluco, in tawny owl, are presented. Infected owls were collected from 16 sites ranging from Tarbet, Strathclyde, Scotland, to Ewhurst, Surrey, in the south of England. In addition, unidentified cyclophyllidean cestodes were found in the alimentary tract of the tawny owls. Centrorhynchus aluconis was the most prevalent helminth found and had the highest intensity. It appears that C. aluconis is widely distributed in the tawny owls of Great Britain. Porrocaecum spirale (Nematoda) was the second most prevalent species of helminth. This species and C. aluconis are believed to be dependent on shrews (Sorex araneus and Sorex minutus) for their transmission to owls.

Prevalence and intensity of intestinal helminth infections from three communities in Sierra Leone

An epidemiological survey in September 1991 investigated the prevalence (per cent) and intensity (epg) of soil-transmitted helminth infections in three communities (Rowollon; Kroo Bay and Foria); Sierra Leone. Evidence was found for infections with ascaris lumbricoides; hookworm (probably necator americanus); trichuris trichiura; strongyloides stercoralis and schistosoma mansoni; using a modified kato-katz technique

The occurrence of Centrorhynchus (Acanthocephala) in shrews (Sorex araneus and Sorex minutus) in the United Kingdom.

Encysted acanthocephalans belonging to the genus Centrorhynchus were found in the body cavities of Sorex araneus (common shrew) and Sorex minutus (pygmy shrew) from Boxworth, Cambridgeshire, U.K. Fifty percent of the male S. araneus and 67% of the male S. minutus examined were found to be infected, with the mean intensity (+/-SD) being 54.3 +/- 91.3 and 14.7 +/- 18.4, respectively. The species of Centrorhynchus in the shrews may be Centrorhynchus aluconis, which is distributed widely in tawny owls, Strix aluco, in the United Kingdom. Shrews appear to serve as paratenic hosts for C. aluconis.

Availability of caecal habitat as a density-dependent limit on survivorship of Leptorhynchoides thecatus in green sunfish, Lepomis cyanellus.

Distribution of Leptorhynchoides thecatus (Acanthocephala: Rhadinorhynchidae) among the pyloric caeca and the relationship between site and rate of maturation were studied in laboratory infections of 10, 25 and 40 cystacanths fed to green sunfish, Lepomis cyanellus. After 1 week fish fed at each intensity had significantly different numbers of worms. By the 3rd week post-infection, parasites disappeared from the anterior portion of the intestine. At this time the mean numbers of worms recovered from 25 and 40-cystacanth infections were not significantly different. At the end of the 1st week, the area where caeca join the alimentary tract (between caecal area) and caeca numbered 6 and 7 contained significantly more worms than the other sites. By the 3rd week post-infection only caecum 7 contained significantly more worms, and at 5 weeks there was no significant difference between the number of worms present in any caecum or the between caecal area. Initially worms in the more intense infections matured more slowly, but by the 3rd week post-infection there was no significant difference in the states of maturity. The rate of maturation was not related to the site occupied.