The CC chemokine eotaxin, identified in guinea pigs and also recently in mice, may be a key element for the selective recruitment of eosinophils to certain inflamed tissues. Using a partial mouse eotaxin cDNA probe, the human eotaxin gene was cloned and found to be 61.8 and 63.2% identical at the amino acid level to guinea pig and mouse eotaxin. Human eotaxin protein was a strong and specific eosinophil chemoattractant in vitro and was an effective eosinophil chemoattractant when injected into the skin of a rhesus monkey. Radiolabeled eotaxin was used to identify a high affinity receptor on eosinophils (0.52 nM K d ), expressed at 4.8 ϫ 10 4 sites per cell. This receptor also bound RANTES and monocyte chemotactic protein-3 with lower affinity, but not macrophage inflammatory protein-1 ␣ . Eotaxin could desensitize calcium responses of eosinophils to RANTES and monocyte chemotactic protein-3, although RANTES was able to only partially desensitize eosinophil calcium responses to eotaxin. Immunohistochemistry on human nasal polyp with antieotaxin mAbs showed that certain leukocytes as well as respiratory epithelium were intensely immunoreactive, and eosinophil infiltration occurred at sites of eotaxin upregulation. Thus eotaxin in humans is a potent and selective eosinophil chemoattractant that is expressed by a variety cell types in certain inflammatory conditions. ( J. Clin. Invest. 1996. 97:604-612.)

A protein engineering strategy based on efficient and focused mutagenesis implemented by codon-based mutagenesis was developed. Vitaxin, a humanized version of the antiangiogenic antibody LM609 directed against a conformational epitope of the ␣ v ␤ 3 integrin complex, was used as a model system. Specifically, focused mutagenesis was used in a stepwise fashion to rapidly improve the affinity of the antigen binding fragment by greater than 90-fold. In the complete absence of structural information about the Vitaxin-

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The condor lays a couple of eggs and the ostrich a score, and yet in the same country the condor may be the more numerous of the two ; the Fulmar petrel lays but one egg, yet it is believed to be the most numerous bird in the world. One fly deposits hundreds of eggs, and another, like the hippobosca, a single one; but this difference does not determine how many individuals of the two species can be supported in a district."-Charles Darwin, The Origin of Species.The term " multiple parasitism " has been suggested by the writer* to designate that type of parasitism in which the same individual host insect is inhabited simultaneously by the young of two or more different species of primary parasites. As is well known, this phenomenon is of extremely common occurrence in nature. It appears to be almost a rule that the mother parasite does not distinguish between a parasitised and an unparasitised host and it often results, therefore, that she deposits her eggs in an individual that already bears a parasite egg or larva. If this other parasite happens to be of the same species, super-parasitism results. If, however, it is a different species, this phenomenon is known as multiple parasitism. In the case of solitary parasites such competition between two species attacking the same individual host generally results in the death of one or the other parasite. Often because of specific fitness one species is always dominant when two meet in competition. Now in the practical work of introducing entomophagous insects into new habitats to aid in the control of insect pests, one is often confronted with this condition. Should it be taken into consideration in the selection of parasites for introduction? Are two species of primary parasites, competing with each other in this way, less effective than one alone would be or can such competition safely be ignored from an economic standpoint? There seems to be a conflict of views on this question among entomologists, and while it is a matter of great complexity when everything is taken into consideration, it is essential that its significance be understood.If, as maintained by some entomologists, such competition results in a lower mortality of the host insect than would occur if only a single species were present, a grave error has been and is being made in most of the large biological control projects undertaken during the last fifty years. One frequently encounters statements by entomologists to the effect that it is a serious mistake to introduce two species which compete. It has even got into our text-books.The biological implications of multiple parasitism were first pointed out, it is believed, by Dr. L. O. Howard in his excellent study of the parasitism of the tussock moth.f In this paper he states that " many parasites suffer from this rivalry based upon erroneous instinct." He did not, however, undertake to determine the effect of this competition on the group efficiency of the parasites.Several years later Fiske § called attention to this question, although in his discussi...

We have developed a sensitive two-site immunoradiometric assay (IRMA) for intact ACTH and its precursors, pro-opiomelanocortin and 22 kDa peptide in unextracted human plasma. The assay uses two monoclonal antibodies. Antibody 1A12, specific for ACTH 10-18, is radiolabelled and antibody 2A3 specific for the C-terminal region (ACTH 24-39), is coupled to Sephacryl S300 for the solid-phase. Samples are incubated for 18 h with labelled antibody followed by 2 h with solid-phase antibody. Separation employs the sucrose layering technique. Using human pituitary ACTH 1-39 (code 74/555) in diluent containing 10% horse serum to standardize the assay, the sensitivity (upper 99% confidence limit of zero standard) is 3.5 +/- 0.8 ng/l (n - 7). The mean coefficient of variation is 5.9% within-assay and 6.7% between-assay and is less than 10% between 22 and greater than 5000 ng/l. Mean recovery of ACTH 1-39 added to dexamethasone-suppressed human plasma is 109% and endogenous ACTH behaves indistinguishably from standard ACTH on dilution. In normal subjects, mean plasma ACTH levels are 30 ng/l at 0730 h, and 15 ng/l at 1630 h at rest. ACTH concentrations are between 60 and 330 ng/l, 8-10.5 h after metyrapone (2 g orally at 2300 h), between 140 and 320 ng/l, 30-60 min after insulin-induced hypoglycaemia, and less than 4 ng/l, 8 h after dexamethasone (1.5 mg orally at 2300 h). In a range of pathological conditions ACTH concentrations accurately reflect the disorders of the pituitary-adrenal axis. Endogenous ACTH immunoactivity is stable in vitro at 22 degrees C for at least 1 h in whole blood and at least 4 h in plasma. It is concluded that this two-site IRMA for ACTH in unextracted plasma offers a reliable assay for clinical purposes.