Splenic and immune alterations of the Sparc-null mouse accompany a lack of immune response.

Sparc-null mice have been used as models to assess tumor-host immune cell interactions. However, it is not known if they have a competent immune system. In this study, the immune systems of Sparc wild-type and null mice were compared. Mice were assessed for differences in total body weight, spleen weight and spleen-to-body weight ratios. Spleens were compared with respect to morphology, and Sparc, Ki-67, MOMA-1 and IgM expression. Immune cells in blood, bone marrow and spleen were assessed by blood smears, automated blood panel, and flow cytometry. Additionally, the ability of Sparc-null mice to respond to immune challenge was evaluated using a footpad model. The morphological and immunohistochemical results indicated that Sparc-null spleens had more white pulp, hyperproliferative B cells in the germinal centers, and decreased marginal zones. Sparc-null spleens lacked normal Sparc expression in red and white pulp, marginal zones, endothelial and sinusoidal cells. By flow analysis, B cells were decreased and T cells were increased in the bone marrow. Finally, Sparc-null mice were unable to mount an immune response following footpad lipopolysaccharide challenge. These data confirm that Sparc-null mice have an impaired immune system.

Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase by nuclear variants of mycophenolic acid.

Structure-activity relationships in the region of the phthalide ring of the inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been explored. Replacement of the lactone ring with other cyclic moieties resulted in loss of potency, especially for larger groups. Replacement of the ring by acyclic substituents also indicated a strong sensitivity to steric bulk. A phenolic hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be essential for high potency. The aromatic methyl group was essential for activity; the methoxyl group could be replaced by ethyl to give a compound with 2-4 times the potency of mycophenolic acid in vitro and in vivo.

Recent advances in diagnosis of leukemia.

With the development of new technologies in the diagnosis of leukemia, we have modified the method of approaching individual cases. In addition to morphological examination, cytochemistry, immunophenotyping, electron microscopy and cytogenetics are now routinely used for daily practice. Furthermore, various molecular diagnostic methods are being tested, and some are already being used for diagnostic processes. The new technologies have certainly changed the diagnostic approach. When the diagnosis is supported by such multiple diagnostic methods, it is more reliable, reproducible and standardized. The communication among clinical practitioners through accurate diagnosis is valuable from both the therapeutic and prognostic point of view. In this article, the diagnostic method of leukemia is reviewed with an emphasis on practical aspects. Individual details are beyond the scope of this article. Interested readers are referred to the bibliography for more in depth treatment of the various techniques.

Model of the interactions of calichemicin gamma 1 with a DNA fragment from pBR322.

An analysis of the binding interactions of several DNA-drug complexes that utilize carbohydrates for DNA recognition has been undertaken. It is proposed that the carbohydrate residues function as general minor groove binding elements, and the stereochemistry of aglycone attachment sites is generally disposed to promote a right-handed helical geometry that is complementary to right-handed DNA. The constitution and stereochemistry of the DNA double-strand cleaving agent calichemicin gamma 1 is consistent with this analysis. Docking experiments with computer-generated models of this drug and a dodecamer duplex that was found to serve as a calichemicin cleavage site were performed to gain insight into the origin of the drug's sequence-selective binding and cutting properties. A model is presented that provides a molecular level understanding of the double-strand cleavage patterns that result from the action of calichemicin gamma 1 on DNA.

Myelodysplasia with bone marrow lymphocytosis and fibrosis mimicking recurrent Hodgkin's disease.

Myelodysplastic syndromes and acute leukemias after treatment for Hodgkin's disease (HD) are well recognized. Preleukemic changes are commonly seen. Three patients from the authors' files are found with myelofibrosis and bone marrow lymphocytosis after treatment for HD. Although somewhat unusual, the clinical impression initially was, in each case, isolated recurrence of HD involving the bone marrow, 6 to 11 years after initial diagnosis. In each case, after single or multiple marrow aspirates and biopsies were done, the differential between HD involving the marrow and myelodysplasia with myelofibrosis and lymphocytic infiltrates was made. The absence of diagnostic Reed-Sternberg (RS) cells was useful in diagnosing the latter. All three patients died of causes related to cytopenias, with two having progressed to overt acute nonlymphocytic leukemia. Myelofibrosis with lymphocytic infiltrates in the marrow, without diagnostic RS cells, in patients' status after treatment for HD, should alert one to the possibility of myelodysplasia.

Health carnival: an experiment in health education.

Some common diseases or accidents that kill or disable persons prematurely are preventable, delayable or sometimes curable if detected early. Prevention, delay or cure requires that individuals be informed of the risks and of the ways they can avoid them, and that those with habits that increase their risks change their behavior. The authors decided to attempt health education of employees and their families by using a carnival setting to make it attractive and memorable. Active participation and demonstrations were used to stimulate interest and involvement to promote learning. Attendance was satisfactory and post-carnival conversations and questionnaires suggest that this might be a useful method of promoting health and safety with employees and their families.