Chemotherapy delays progression of motor neuron disease in the SOD1 G93A transgenic mouse.

BACKGROUND: A significant proliferation of glial cells occurs in the spinal cord and brainstem of SOD1 G93A transgenic mice with familial amyotrophic lateral sclerosis (ALS). Since activated glia may contribute to motor neuron degeneration, we tested whether inhibition of gliosis using low-dose chemotherapy is beneficial in this mouse model. METHODS: Mice were administered fortnightly intraperitoneal injections of 0.1 mg/kg vincristine (VIN) or saline commencing at postnatal day 68 before disease onset. Mice were sacrificed at end-stage disease, and spinal cords were examined for histology. RESULTS: Survival of VIN-treated mice was significantly increased at 132.0 +/- 4.1 days compared to control animals at 117.8 +/- 2.1 days (p < 0.05). Furthermore, analysis of microglia and astrocyte populations suggests a reduction in the former following VIN therapy. CONCLUSION: This study suggests that chemotherapy may offer an alternative therapy or co-therapy for ALS.

A survey of lead-based paint abatement projects performed in public buildings in Erie and Crawford Counties, Pennsylvania, during the time period 1995-1997.

A survey of lead-based paint abatement projects in public buildings of Crawford and Erie Counties, Pennsylvania, was conducted during the time period January 1995 to March 1997. These survey results suggest that few lead abatement projects were performed during this time period. Projects that were performed commonly did not employ proper lead abatement practices as described by the U.S. Occupational Safety and Health Administration, U.S. Environmental Protection Agency, and U.S. Department of Housing and Urban Development. These data suggest that most contractors and public officials have misunderstandings of both environmental regulations and required procedures for safe and effective lead-based paint abatement.

Selective loss of expression of a tumor-associated antigen on a human leukemia cell line induced by treatment with monoclonal antibody and complement.

The sensitivity of a common acute lymphoblastic leukemia-associated antigen (cALLa)-positive, human leukemia pre-B-cell line to killing by antibody and complement was studied. A stable subpopulation was selected by its ability to survive four sequential treatments with excess monoclonal antibody (MoAb) directed against an Mr 24,000 glycoprotein associated with human leukemia cells and excess rabbit complement. Analysis of the antigen expression by individual cells within the parental and the selected cell populations was achieved by flow cytometry and demonstrated a marked decrease of the leukemia-associated antigen expression on individual cells within the selected subpopulation. These low-antigen-density cells were stable in subculture, and the immunoglobulin heavy-chain gene rearrangement of the parent population and the low-antigen-density subpopulation were identical, indicating that they were derived from a single cell source. The selection of this subpopulation was specific in that the expression of a second antigen recognized by a cALLa-specific MoAb was not affected. The presence of subpopulations of tumor cells with low levels of surface antigen expression that are resistant to killing upon addition of excess antibody and complement will prove to be an obstacle to the use of this approach to eliminate tumor cells from bone marrow that is to be used for autologous transplantation.

Evidence for an anticomplementary factor associated with human bone marrow cells.

Complement (C)-mediated lysis of antibody-sensitized sheep erythrocytes was inhibited by the addition of human bone marrow cells. The anticomplementary activity could be attributed to a soluble factor that was released from the bone marrow cells. This factor inhibited at an early stage in the C-cascade and showed the characteristics of a factor that accelerates decay of C2. The release of such a factor by bone marrow cells would present an obstacle to the use of antibody and C to purge tumor cells from bone marrow that is to be used for autologous transplantation.