Programmed writing and therapy with symbiotically enmeshed patients.

This paper illustrates how programmed writing lessons to be completed as homework assignments can be used in conjunction with traditional verbal psychotherapy. Each patient was involved in a symbolically enmeshed relationship. Special benefits for patients from the combination of programmed writing lessong with traditional psychotherapy were: (1) increased couple communication; (2) possibly more rapid change; (3) possibly shorter-term therapy; (4) increased forgotten trauma discovery; (5) and increased explicit and specific instructions. Patients were informed from the outset that the use of programmed writing lessons would or might: (1) help the therapist get a better idea of what was going on in regard to the development, values, rules, etc. of their symbiotic relationships; (2) decrease the time spent in therapy, and (3) encourage self-realization through self-directed assignments between sessions. For psychotherapists there are advantages of: (1) putting the responsibility for change on the shoulders of patients rather than on themselves; (2) using programs of theoretical and therapeutic approaches that may not be well known to the therapist; (3) reducing the frequency of sessions and administering written homework assignments when the therapist is on vacation; and (4) increasing the number of patients that can be seen for unit of therapist's time.

Lysosomal enzyme secretory mutants of Dictyostelium discoideum.

Dictyostelium discoideum secretes a number of lysosomal enzymes during axenic growth and upon suspension in a low ionic strength, non-nutrient buffer (standard secretion conditions). These secretory characteristics have allowed us to identify 74 lysosomal enzyme secretory mutants generated by N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The majority of these mutants fell into one of four classes, on the basis of their secretory characteristics in non-nutrient buffer. The four mutant classes indicate that a minimum of three distinct sets of genes are necessary for proper secretion of lysosomal enzymes from D. discoideum cells under standard secretion conditions: one set of genes that is involved in general lysosomal enzyme secretion, one that is involved in glycosidase type secretion, and a third that is involved in acid phosphatase type secretion. These three classes likely reflect heterogeneity in the intracellular destination of lysosomal enzymes, the secretory mechanism, or both. A fourth set of genes may be necessary for proper secretion during growth, but plays no role under standard secretion conditions. These are likely altered in the regulation of secretion or in lysosomal enzyme targeting. Of the 74 secretory mutants, 36 were also modification mutants resulting in decreased pI, thermolability, or in vivo instability of lysosomal enzyme activities. The high frequency of modification mutants indicates an integral relationship between lysosomal enzyme modification, and lysosomal enzyme targeting and secretion in D. discoideum.

Secretory mutants in the cellular slime mold Dictyostelium discoideum.

Our initial studies have shown that the cellular slime mold Dictyostelium discoideum is a particularly suitable organism for the study of lysosomal enzyme secretion. During appropriate stages in the life cycle, secretion is prominent for a number of lysosomal enzymes. The methods described here have been developed to investigate various aspects of the secretion process. Moreover, our evidence that regulation of the secretory system is influenced by environmental changes and by cell differentiation indicates that this organism may be useful for studying the functional regulation of this organellar system. To a large degree these types of studies have been limited in the past due to the lack of an appropriate experimental system. The ability to isolate secretory mutants affecting the secretion of lysosomal enzymes adds another dimension to investigations using D. discoideum. In our initial attempts we have been successful in isolating a variety of different types of mutants that alter the secretion of one or more lysosomal enzymes. While the results are in agreement with the results of our physiological investigations, they also indicate much more heterogeneity in the lysosomal system than we had previously suspected. The indications that many of our secretory mutants may also affect modification of the enzymes is also intriguing. This observation may also help to explain the fact that many of these strains are defective in normal development. Together with the immunological methods available in this organism for studying posttranslational modification, the mutants may be valuable in deciphering the relationship between modification of lysosomal enzymes and their proper localization and secretion from the cell. Thus, Dictyostelium discoideum may become as useful for the study of some questions of cell biology as it has been for development.