Biomedical subjects

J C Roder

Publications and source records attributed to J C Roder.

148 records · Page 9Linked to original sources

PubMedDate not supplied

Spatial learning in transgenic mice expressing human presenilin 1 (PS1) transgenes.

Dominant mutations in the Presenilin 1 gene are linked to an aggressive, early-onset form of familial Alzheimer's Disease (FAD). Spatial memory of transgenic (Tg) mice expressing either mutant (lines Tg(M146L)1, Tg(M146L)76, Tg(L286V)198) or wild type (line Tg(PS1wt)195) human PS1 transgenes was investigated in the Morris water maze (WM) test at 6 and 9 months of age. The results showed that the mutated Tg mice had increased swim speed when compared to non-Tg littermates or Tg PS1 wild type mice. The swim speed difference did not, however, significantly affect the spatial learning in the WM test and all groups showed comparable search paths during training and similar spatial bias during probe trials. When re-tested at 9 months, all mice showed significantly improved learning acquisition of spatial information. The lack of progressive spatial learning impairment in mice expressing the mutated human PS1 transgene in the WM does not preclude impairments in other cognitive tasks but suggests that full phenotypic expression of mutant PS1 alleles may require co-expression of human versions of other AD-associated genes.

Alzheimer Disease↗

PubMedDate not supplied

Recognition of myelin-associated glycoprotein by the monoclonal antibody HNK-1.

Myelin-associated glycoprotein (MAG) is a quantitatively minor component in both peripheral and central myelin sheaths that is thought to have a role in cell-cell interactions within the nervous system. We show here that a mouse monoclonal antibody, HNK-1, which is directed against human natural killer cells also recognizes an antigenic determinant of human central and peripheral nervous system white matter by immunoperoxidase staining of tissue sections. Immunoblot analysis of myelin proteins and purified extracted MAG indicates that the antigen recognized is MAG.

Antibodies, Monoclonal↗

PubMedDate not supplied

Inducible cellular transformation by a metallothionein-ras hybrid oncogene leads to natural killer cell susceptibility.

Natural killer (NK) cells are lymphoid effector cells possessing spontaneous cytolytic activity against a variety of tumour targets. The fact that NK cells pre-exist at high frequency and require no lengthy activation, and the observation that differentiated and metastatic tumour cells often have a decreased sensitivity to NK cytolysis have led to the hypothesis that these cells may be involved in the earliest stages of antitumour surveillance. Central to this model is the prediction that NK sensitivity must arise during cellular transformation. To test this prediction directly, we have constructed a vector containing the transforming gene from the EJ bladder carcinoma cell line under the transcriptional control of the mouse metallothionein-I promoter. When induced with heavy metal ions, mouse fibroblast lines containing this vector become dramatically sensitive to NK-mediated cytolysis concomitant with the expression of the cellular Harvey ras (c-Ha-ras) p21 protein and with cellular transformation.

Animals↗

PubMedDate not supplied

Improved engraftment of human tumours in SCID mice pretreated with radiation and anti-asialo GM1.

The effects of sublethal radiation (3 Gy) and anti-asialo GM1 (anti-ASGM1) on engraftment of human tumour cell lines and fresh tumour were evaluated in the severe combined immunodeficient (SCID) mouse. Four tumour cell lines (colonic adenocarcinoma LS174T, malignant melanoma MEWO, lung adenocarcinoma H125, chronic myelogenous leukemia K562) and a fresh colon cancer metastasis were injected subcutaneously, intraperitoneally or intravenously into SCID mice. Tumour volume and metastatic spread of implanted tumours were evaluated 3-8 weeks following inoculation. Pretreatment with radiation and anti-ASGM1 resulted in more rapid and extensive uptake of subcutaneous and intraperitoneal tumours. Tail vein injection into pretreated animals also resulted in a greater number of lung metastases of H125, MEWO and K562 cell lines. This study demonstrates that sublethal radiation and the elimination of murine NK cell activity with anti-ASGM1 improves tumour take rates. These findings should prove useful for investigations of human cancer immunotherapy using SCID mice engrafted with human lymphocytes and human tumours.

Animals↗