Blot-hybridization and DNA sequence analyses reveal the particular evolutionary conservation of a group of immunoglobulin heavy-chain variable-region (VH) genes in all mammalian species examined. These particular genes are group m genes-the VH7183 family in the mouse and the homologous VH HI family in human. This conservation is localized to sequences encoding framework regions 1 and 3 of the antibody variable region and is exerted at the nucleotide level. Because selection acting at the amino acid level alone cannot explain the conservation of these sequences, these sequences must have a noncoding function. The preferential rearrangement of VH7183 and VH HI genes, together with the similarity of the conserved sequences to elements implicated in recombination in other systems, suggest that these sequences function to target the series of rearrangements that assemble complete immunoglobulin genes.There are three major groups ofimmunoglobulin heavy-chain variable-region (VH) genes (I, II, and III) in both mouse and human (1). In both species, these groups have been further divided into families on the basis of cross-hybridization and sequence similarity (2)(3)(4)(5)(6). Homology between several human and mouse VH families in each group has been inferred from sequence similarity (Table 1). Thus, the divergence of the three major groups of VH families (and certain VH families therein) preceded the mammalian radiation 60-80 million years (Myr) ago, when contemporary orders of placental mammals last shared a common ancestor. The recent isolation of VH genes homologous to groups I and III from Xenopus (7,8) indicates that the divergence of the three major groups is considerably more ancient, over 300 Myr ago.If the three groups of VH genes were subjected to similar evolutionary pressures, then they would be expected to be similarly conserved. However, when cloned mouse VH genes were used as probes to isolate their human counterparts, mouse group III VH genes identified their human homologues more easily than did mouse group I and II VH genes (4, 5). Mouse group III probes could also identify VH genes in several other mammalian species (9, 10), the reptile Caiman (9, 11), the amphibian Xenopus (7), and the elasmobranch Heterodontus (12). Moreover, VH genes in the rabbit and chicken, which may have only one VH gene family, belong to group III (13,14). Collectively, these observations suggest that while other VH groups may evolve more freely (and in some cases even be lost), group III VH genes, in particular, are a conserved and obligatory component of heavy-chain loci in widely divergent mammalian and nonmammalian lineages.Here, we use Southern blot hybridization to show that discrete segments ofgroup III VH genes have been conserved throughout mammalian evolution. Examination of published sequences identifies specific candidate sequences in mouse VH7183 and human VH III gene families; these sequences have been conserved at the level of nucleotide sequence rather than coded protein sequence. Our results indicate ...

People experience and treat medication as though it were a person: in other words, as an object. Among the many symbolic meanings attributed to medication, this sort of personification, or object representation, is a meaning that medication is uniquely positioned to contain and convey: imbued with intentionality and influence, medication moves beyond the sphere of static, iconic representation and enters the changeable, dynamic object world of action, aim, and agency. Unlike more generic or stereotypic meanings, object representations attributed to medication may reflect the patient's specific dynamics and object relations. These representations are many and mutable, and take on shifting and overlapping forms that evolve with the analytic process. Medication may represent a third person within the framework of an analytic treatment, expanding the analytic dyad into a triad and offering new transference paradigms to explore. The defensive displacement of transferential qualities and attitudes, or split-off parts thereof, from the analyst onto medication can serve as a powerful resistance to the awareness of the transference to the analyst. Clinical examples illustrate the utility and importance of the analysis of medication as object, for both patient and analyst, with particular attention to the transference.

The myth of Apollo and Daphne, as told in Ovid's Metamorphoses, is viewed through the self-referential eye of the seicento painter, Nicolas Poussin. Collectively, the tree-metaphoric myths are argued to metaphorically represent, mourn, and negate unbearable realities, including the developmental challenges of adolescence and adulthood - in particular, loss. Examined in the context of their aesthetic precedents and a close reading of Ovid 's text, the two Apollo and Daphne paintings that bracket Poussin's oeuvre are interpreted as conveying the conflict and ambiguity inherent to Ovid, as well as connotations more personal to the artist. The poetic and aesthetic reworking of the regressive, magical experience of metamorphosis restores it to the symbolic world of metaphor: for reparation, remembrance, and return.

A close reading of Raymond Carver's stories, interviews, essays, and letters explores aspects of his relationships with his father, his teacher John Gardner, and in particular his influential editor, Gordon Lish, as they relate to his writing and to his development as a writer. It is proposed that the internalization of aspects of these relationships, along with the collaborative and symbolizing process of authorship--providing both self-exposition and screen--helped Carver move beyond his need for subjugated masochistic attachment and forge a path toward greater creative autonomy.

The evolution of variable region (Vh) gene family copy number and polymorphism was investigated by the analysis of the immunoglobulin heavy chain variable region (Igh-V) locus in 74 inbred strains and substrains of mice. Several strains were found to have slight differences from Igh-V haplotypes previously identified, usually involving the gain or loss of one or a few members of a single Vh gene family. These results indicate that the evolution of copy number in the mouse Igh-V locus proceeds largely by the accumulation of incremental changes, reflecting the clustered organization of the mouse Igh-V locus. We have found no evidence of very large or frequent duplication or deletion events indicative of rapid expansion or contraction processes. The existence of one or more particularly large Vh gene families most likely reflects random copy number variation, rather than selection for the amplification of their members. The identification of strains with recombinant Vh gene arrays demonstrates that recombination, both within and between haplotypes, appears to be the predominant mechanism generating the high restriction fragment length polymorphism in the Igh-V locus.