Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

Associative conditioning analog selectively increases cAMP levels of tail sensory neurons in Aplysia.

Bilateral clusters of sensory neurons in the pleural ganglia of Aplysia contain cells involved in a defensive tail withdrawal reflex. These cells exhibit heterosynaptic facilitation in response to noxious skin stimulation that can be mimicked by the application of serotonin. Recently it has been shown that this facilitation can be selectively amplified by the application of a classical conditioning procedure to individual sensory neurons. We now report that an analog of this classical conditioning paradigm produces a selective amplification of the cAMP content of isolated sensory neuron clusters. The enhancement is achieved within a single trial and appears to be localized to the sensory neurons. These results indicate that a pairing-specific enhancement of cAMP levels may be a biochemical mechanism for associative neuronal modifications and perhaps learning.     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.     

Hematochezia and the False Negative Meckel''s Scan: A Continued Need for Barium Studies

A patient with hematochezia and a false negative Meckel's scan is presented. A Meckel's diverticulum was subsequently diagnosed on barium small bowel follow-through. Meckel's diverticulum is discussed with emphasis on the relationship of barium and radionuclide studies.     

Human complement regulatory proteins protect swine lungs from xenogeneic injury

BACKGROUND: Pulmonary xenotransplantation is not possible because of hyperacute lung injury, the pathogenesis of which is unknown. This study evaluates complement-dependent pathways of pulmonary injury during heterologous perfusion of swine lungs. METHODS: Lungs from unmodified swine and swine expressing human decay-accelerating factor and human CD59 (hDAF/hCD59 swine) were perfused with either human plasma or baboon blood. Pulmonary vascular resistance and static pulmonary compliance were measured serially, and swine lung tissue were examined by light microscopy. Complement activation was assessed by serial measurements of baboon plasma C3a-desArg concentrations. RESULTS: Perfusion of unmodified swine lungs with human plasma and baboon blood resulted in hyperacute lung injury within minutes of perfusion. However, function was preserved in swine lungs expressing human decay-accelerating factor and human CD59. In both study groups, xenogeneic perfusion with baboon blood resulted in at least a sevenfold increase in plasma C3a-desArg levels suggesting transient activation of complement. CONCLUSIONS: Lungs from swine expressing human decay-accelerating factor and human CD59 were resistant to injury during perfusion with human plasma and baboon blood, indicating that complement mediated some of the features of xenogeneic acute lung injury.     

Current thinking on chronic renal allograft rejection: issues, concerns, and recommendations from a 1997 roundtable discussion

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic- and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival.